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“Effect of diet on the mental performance of children”

Final Report Summary - NUTRIMENTHE (“Effect of diet on the mental performance of children”)

Executive Summary:
NUTRIMENTHE has successfully finished with strong evidence relating the importance of nutrition during early life and the long-term neurocognitive and behaviour development achieving in this moment more than 72 peer-reviewed publications. Generation R has shown that children born to mothers who did not use folic acid supplements during the first trimester of their pregnancy had a higher risk of total behaviour problems. Both, low folate level and no folic acid supplementation increased the risk of child internalising problems at 3 years of age. Structural imaging showed differences in the corpus callosum, the major white matter tract connecting the two hemispheres, depending of folate status during pregnancy. Further results from this cohort suggest that maternal thyroid function during pregnancy is an important determinant of child brain development that is sensitive to nutritional status. In ALSPAC study, maternal red blood cell long-chain polyunsaturated fatty acids (LCPUFAs) in pregnancy have been associated with child IQ at 8y. These associations suggest possible mechanisms involving neural phospholipids {docosahexaenoic acid (DHA) and arachidonic acid (AA)}. The re-analysis of WISC III at 8 years demonstrated that seafood intake >340 g/week during pregnancy is associated with higher mean scores on a ‘Verbal Comprehension’ and ‘Working Memory and Speed Processing’ index, but not on a ‘Performance Index’. Eating fish regularly and an adequate iodine intake during pregnancy are important for the neurocognitive development of the offspring. The NUHEAL follow-up demonstrated that supplementation with fish oil and/or 5-Methyltetrahydrofolate (5-MTHF) during pregnancy is positively associated with better Processing Speed and Visual Motor Coordination in children at 9 y of age. Maternal 5-MTHF supplementation is associated with child’s ability to solve response conflicts within an attention task at 9.5 y, and this may be linked to a higher activation of the right posterior mid-frontal cortex, suggesting that early nutrition may influences the functionality of brain areas involved in executive function. The CHOP Study showed that there are no differences between infants fed with high or low protein content formulas during the first year of life in cognition or behaviour at 8 y of age. This demonstrates the safety of low protein content in infant formulas regarding long-term mental performance. This information is of value for scientists and government bodies when developing policies for the nutritional value of infant products. Evidence from ALSPAC, CHOP and NUHEAL regarding child neurodevelopment supports the recommendation that children should consume at least two fish meals per week one of them being of oily/fatty fish. The SIMBA randomised controlled intervention study with a B vitamin mix in kindergarten children (aged 4-6 y) was completed in 200 children and showed that markers of biochemical status (red blood cell folate and plasma homocysteine) changed in a healthy direction after 3 months of B vitamin supplementation but no changes were observed in cognitive performance nor verbal learning ability. The supplementation with DHA in phenylketonuric children demonstrated that led to a dose dependant increase of the plasma levels of DHA (% in glycerophospholipid fatty acids), but with no relevant changes of the neurological and cognitive functions tested. Polymorphisms of the genes FADS1 and FADS2 have been analysed on an in-house genotyping platform, in NUTRIMENTHE subjects where data on dietary intake and mental outcomes were available (ALSPAC, NUHEAL, and Phenylketonuria study). FADS gene variants showed strong associations with maternal fatty acid levels during pregnancy and neonatal n-6 and n-3 fatty acids. A majority of the genetic variants showed associations in one direction only: positive associations for short chain fatty acids with fewer unsaturated bonds, negative associations for the more complex LCPUFAs. In the NUHEAL study it has been shown that if a mother is heterozygous (G/A) for FADS1 rs174556 compared to if she is homozygous (G/G) her child is 7.5 times more likely to have fast processing speed at 9 y. Therefore, these genetic variants need to be taken into account in analyses of nutritional influences on fatty acid composition and cognitive outcomes in future studies. The consumer expectations survey demonstrated that parent’s and educator’s beliefs and knowledge about the role of diet on the mental outcomes of children is associated with attention and concentration, often mediated by effects on child's mood and behaviour. Parents categorise foods as 'good' or 'bad'; they relate positive effects to a healthy balanced diet, while sugars and fatty foods are perceived to be associated with negative effects. Analysis of ALSPAC using a micro-economic approach used the finding that improving child’s cognitive skills by early nutrition (breast feeding) can increase the chance for a better educational attainment level. The economic model calculations of later income effects showed an expected future benefit from breastfeeding of ~5,000 € per child. This suggests that successful promotion activities for better early nutrition such as better maternal diet, maternal supplementation and breastfeeding as shown in NUTRIMENTHE will be highly cost-effective.
NUTRIMENTHE has raised the awareness of the public by developing the means to disseminate the work and results of the project at a scientific and societal level. WP13 used many routes to achieve this aim through print and broadcast media. Communication of the results included via two websites, publishing regular newsletters, writing articles in magazines, issuing press releases, engaging with social media and organising public events both scientific and for the general public. The NUTRIMENTHE International Conference held in Granada in September 2013, was promoted widely during the year, via regular e-mail alerts and media announcements. Furthermore, as it was included in the 20th IUNS International Congress of Nutrition programme, a wide advertisement was done all over the world. A successful press conference was organised by the UGR with the support of Beta-Technology and UNILEVER and this also contributed to the media coverage achieved. This ensured a big attendance and extensive media interest which resulted in increased visits to the website as well as coverage, and also the development of interviews in TV and radio to different speakers. The abstracts presented to the Conference were published in a supplement of Annals of Nutrition and Metabolism. Most of the results presented in the Conference have ensured information ready for publication in a supplement of British Journal of Nutrition (on-going).
The “Early Nutrition Academy”, which now continues to pursue the aims of the NUTRIMENTHE consortium after the completion of the project, has successfully linked the NUTRIMENTHE project to the internet website and also the brochure developed for such purpose, which will be continuously updated in the next years; this platform will not only announce future trainings in the area of nutrition and brain but also to serve as an international research exchange platform including an increasing number of collaborators in this field of research.
In conclusion, the project has been successfully completed after five and a half years of duration and has well provided further evidence for the potential of early nutritional factors on the later mental performance and behaviour, while at the same time indicating the need to further address research questions in the area of early nutrition.
Further information is provided on www.nutrimenthe.eu and www.nutrimentheproject.eu.

Project Context and Objectives:
NUTRIMENTHE is a research project funded by the European Commission through its 7th Framework Programme. The project is looking at the role that diet plays in the mental performance of children. The project, which began on the 1st March 2008, involves scientists from 19 organisations from nine countries worldwide.
The idea that the diet of mothers, infants and children could have an influence on long-term mental performance, has major implications for public health practice and policy development, and for our understanding of human biology, as well as for food product development, economic progress, and future wealth creation. The evidence on the effect of diet on mental performance (MP) is largely based on animal, retrospective studies, & short-term nutritional intervention studies in humans.
The current evidence of an association between gestational nutrition and brain development is becoming to be well established for folate, n-3 fatty acids and iron. Also, the positive effect of micronutrients on health, especially of pregnant women eating well to maximise their child’s outcomes, is commonly acknowledged. Recent findings highlight the fact that single nutrient supplementation is less adequate than supplementation with more complex formulae. However, the optimal content of micronutrient supplementation and whether there is a long-term impact on child’s neurodevelopment needs to be investigated further. Moreover, it is also evident, that future studies should take into account genetic heterogeneity when evaluating nutritional effects and also nutritional recommendations.

NUTRIMENTHE has addressed these areas by bringing together a multi-disciplinary team of international scientists and leaders in key areas of nutrition and mental performance from major research centres across Europe, co-ordinated through a professional management approach with horizontal, vertical and sectorial integration. This integrated approach has brought together work from robust experimental studies in humans backed by modern prospective observational studies and molecular techniques.


Figure 1. *Red star – Neuropsychological battery being fully applied in the full cohort or in a subsample; *Blue star – Some tests and examination of different domains, already included in the NUTRIMENTHE Neuropsychological Battery, were applied.

NUTRIMENTHE was designed in such a way that effects of diet/nutrition on different age ranges are addressed by the following overall objectives:

(i) Estimate the importance of nutrition for the neurodevelopment in contemporary European populations by examining the associations between early nutrition and later outcome in large well-characterised population-based prospective studies with detailed measures of diet in pregnancy and the first years of life (WP1-2).
(ii) Quantify the effects of prenatal maternal diet on foetal early programming and subsequently on later cognitive development, mental and behavioural disorders (WPs1-3).
(iii) Specify and understand the role and mechanisms of specific nutrients effects on early programming and different genetic polymorphisms, and how the nutrients interactions within the maternal, infant and childhood diet influence the child’s neurodevelopment, mental performance and behaviour disorders (WPs1-6,8).
(iv) Explore the quantitative requirements and role of some nutrients in improving mental performance in children and their subsequent outcomes (WPs 5,6,7)
(v) Develop an appropriate standard neuropsychological battery to improve a comparable methodology for cognitive assessment in EU children (WPs 2,3,4,5,6,7).
(vi) Explore the public health impact of how knowledge about diet affects mental development on the consumer behaviour and its impact on the economic progress of EU countries (WPs10,11).
(vii) Establish a multi-disciplinary training programme and disseminate the results to ensure that the project promotes best practice in dietary advice to pregnant women and parents with newborn babies, infants and children in Europe, optimising as far as possible future brain health, mental performance, behaviour and well-being (WP13).

The NUTRIMENTHE Workplan is comprised of thirteen WPs (Figure 1), each one has clearly defined objectives & tasks, but with a cohesive approach with the rest of the project. All objectives planned in the project have been achieved during these 5 years, and even more, all those new approaches designed in the course of the Project have been reached too. There has been achieved a strong integration and harmonisation between the WPs; this fact has increased so much the possibilities to get new and important results. The strategy in developing the work plan has been to ensure the structure will best achieve the overall goals of NUTRIMENTHE through the different tasks in each WP, whilst ensuring a cohesive approach with the rest of the project.
• WORKPACKAGE 1: “Long term effects of maternal dietary intake in pregnancy on cognitive and behavioural development within 7,000 multi-ethnic preschool children”. The Generation R Study”.

The objective of WP1 was to examine and quantify nutrient effects (maternal dietary intake and nutritional status in early childhood) on early behaviour and cognitive development. This WP is embedded within a large multi-ethnic population-based prenatal cohort study known as the Generation R Study. The Generation R study has nearly 7,000 active participants and the children are currently between the ages of 5 and 9 years. The primary goal of WP1 is to assess whether maternal dietary intake in pregnancy is associated with behaviour and cognitive problems in the offspring.

• WORKPACKAGE 2: Interaction of fish intake and genetic variation in determining child behaviour – the Avon Longitudinal Study of Parents and Children (ALSPAC)

The Avon Longitudinal Study of Parents and Children is a longitudinal cohort study based in Bristol, UK which has followed subjects from before birth and for over 20 years. It has collected data on diet from pregnancy onwards, biological samples for genetic and biochemical analysis and assessed childhood growth and cognitive and behaviour development. Child IQ at age 8 years was associated with greater intake of fish by the mother during pregnancy; one possible factor related to these results is fish intake by the mother, which is a good dietary source is the omega-3 long-chain polyunsaturated fatty acid (LC-PUFAs), docosahexanoic acid (DHA) or similar FAs. Further investigation of what factors in fish may be affecting this outcome and whether there is a genetic component has been demonstrated. The effect of an iodine rich diet during pregnancy on the improvement of child mental health was also explored.

• WORKPACKAGE 3 “Follow-up of school age children whose mothers received n-3 LCPUFA and or 5-methyl-tetrahydrofolate during pregnancy”

The main objective of WP3 is to determine whether during childhood there are long-term effects on cognitive development, mental performance and behaviour as a consequence of DHA and folic acid supplementation during pregnancy. This WP proposes a long-term follow-up (7-9.5 years) of the 270 children whose mothers were participants in the “Nutraceuticals for a Healthier Life” Project (NUHEAL) previously funded within the EU 5th FP and EARNEST EU FP6. The children were invited to revisit the local study centre at the ages 7.5 8, 9 and 9.5 years.

• WORKPACKAGE 4 “Follow-up of school age children with different protein intakes in early childhood”

WP4 consists on the follow-up of school-aged children who were randomly assigned to be fed with an infant and follow-on formula with higher or lower protein content during the first year of life. The Childhood Obesity Project (CHOP) was previously funded by the 5th and 6th Framework Programmes, with the objective to analyse if early higher protein supply may increase later obesity risk. During the first 6 years of follow-up, anthropometrical measurements were taken regularly, dietary intake, feeding behaviour and mental performance (Culture Fair Intelligence Test and the Strengths and Difficulties Test) were assessed. Within NUTRIMENTHE, we follow the children until the age of 8 years, focusing on the assessment of mental performance.

• WORKPACKAGE 5 “Evaluation of the effects of a micronutrient supplement on mental function in pre-school children”

The primary objectives of WP5 were i) to perform an intervention study with B vitamins in kindergarten age (4-6 years) children with cognitive performance outcomes and ii) to apply learnings from this study and other insights from NUTRIMENTHE into new consumer products. A key feature of the study was to identify children having a relatively low dietary folate intake from a sample population of 1,000 children.

• WORKPACKAGE 6 “Quantitative requirements of n-3 LCP for neural function in children”

Patients with phenylketonuria (PKU) have an inborn error in the metabolism of the amino acid phenylalanine (Phe) and thus must follow a strictly controlled protein-restricted diet from early infancy, devoid of natural dietary sources of n-3 LC-PUFA, such as eggs, meat, milk or fish. A multicentric double-blind randomised trial has been conducted within WP6 of NUTRIMENTHE to determine quantitative DHA requirements for optimal neural function in PKU children; patients with classical PKU from Munich, Santander, Milan, Birmingham, Heidelberg, Istanbul, were randomised to receive between 0 to 15 mg of DHA/kg/day during 6 months. Plasma concentrations of DHA were considered by investigating their relationship to DHA intake (dose dependence) and on the other hand by studying their relationship to the neurological outcome.

• WORKPACKAGE 7: “Cross-cultural standardisation of a neuropsychological battery for cognitive assessment in EU children”

The main objective of WP7 was to facilitate comparison between the childhood studies by designing a standardised neuropsychological protocol (NP) in different languages, and taking into account cultural differences. WP7 was designed to be a transversal WP with the main goal of harmonisation between different Projects with a common tool to assess mental performance.
WP7 together to the Working Group of Mental Performance led the development of the Global NUTRIMENTHE database. For such purpose, the NUTRIMENTHE Neuropsychological Battery designed by UGR was fully applied in children 8 years old from a subsample of WP1 and in all children participants in WP3 and WP4; in total, 1050 children from 7 different countries were examined with the same NP.
WP7 was also involved in a new integrated activity with WP2: Re-analising the WISC results from the ALSPAC project to study the effect of early diet on brain domains and executive functions development.

• WORKPACKAGE 8: “Analysis of genetic polymorphisms as co-variables in determining interaction of nutrition and mental health”

Tissue contents of n-3 LC-PUFA in children may be influenced by placental supply during pregnancy, by dietary supply in infancy and childhood, and by endogenous conversion of the precursor essential fatty acid α-linolenic acid. We have previously shown that common polymorphisms of the genes FADS2 and FADS1 found in about one quarter of the European population, encoding for the key enzymes regulating endogenous LC-PUFA synthesis, i.e. δ-6-desaturase and δ-5 desaturase, are associated with markedly reduced plasma LC-PUFA concentrations. Therefore, WP8 set up to measure polymorphisms of the FADS genes in WP2, WP3 and WP6, and additionally genes involved in folate metabolism in WP5. These polymorphisms are being related to plasma fatty acid concentrations and together with dietary data linked to the information on child behaviour, performance, and mental health.

WORKPACKAGE 9: “Quantitative analysis of biochemical markers”

In the various NUTRIMENTHE workpackages biochemical status markers have to be determined using very different analytical techniques, e.g. B-vitamins, trace elements, n-3 LC-PUFAs, amino acids, endocrine markers. Centralised performance of the assays provides standardised procedures and is cost effective. Partners involved in the development of standard operation procedures for sample collection and handling were LMU-Müenchen sharing his expertise and facilities in fatty acid and vitamin analysis, CI WARSAW offered the methods for hormone analysis and UGR contributed the resources for urine analysis. This pool of available methodologies allowed flexibility in respect to the determination of biomarkers not foreseen in the initial planning.

• WORKPACKAGE 10. “Consumer expectations - survey among parents and educators”

The overall objective of WP10 was to gain an understanding of how parents and teachers perceive that food affects the mental performance of children. Parents influence all aspects of a child’s life including the development of food choices as well as controlling the availability and types of food in the home. As children grow and attend school others, including teachers, become more important influences.

• WORKPACKAGE 11: Economic Impact of improving mental function

WP11 has been involved in the NUTRIMENTHE project to show the economic impact of improving mental function. The main objective was to perform a comprehensive health economic analysis of pre- and postnatal nutritional interventions with proven or proposed long-term programming effects on the mental development. For three early nutrition interventions with proposed effects on mental development, systematic literature reviews of randomised controlled trials (RCTs) as the “gold standard of evidence” were conducted and published as basis for economic assessment. Together with WP2 a new aim was established in the last period of NUTRIMENTHE project framework, to explore the economic consequences of early nutrition using the ALSPAC study data.

• WORKPACKAGE 12: Project Management and Reporting to the EC

The Management of the project has been developed by the WP 12 and its role is to carry out the legal, ethical, financial and administrative themes. The coordinator and the management team have: a) Administered the Community financial contribution regarding its allocation between beneficiaries and activities, in accordance with the grant agreement and the decisions taken by the consortium; b) Reviewed the report to verify consistency with the project tasks before transmitting them to the Commission; c) Monitored the compliance by beneficiaries with their obligations under this grant agreement; d) Prepared the Fifth periodic report; e) Developed the Final report.

• WORKPACKAGE 13: Training, dissemination and exploitation

The main focus of WP13 was on raising awareness to the public about NUTRIMENTHE and developing the means to disseminate and communicate the work and results of the project. WP13 used many routes to achieve this aim through print and broadcast media. Communication of the results included via two websites, through developing key messages to the public area, publishing newsletters, writing articles in magazines, issuing press releases, engaging with social media and organising events. Additionally, WP13 provided training to members of the NUTRIMENTHE consortium on media engagement and the use of social media.


Project Results:

NUTRIMENTHE has significantly improve the knowledge regarding the effect of diet on the mental performance and behaviour in children, through studying the role, mechanisms, risks & benefits of specific nutrients & food components to respond to specific needs and influencing positively on the MP of children. The research has included quantification of the nutrient effects of early programming on later cognitive and mental disorders, effects of food on mental state and MP such as mood, activation, attention, motivation, effort, perception, memory & intelligence and the effects of food on mental illness. Extensive data from human and animal studies indicate that early diet and specific nutrients (e.g. iron, zinc, B-vitamins, folate, LC-PUFA) have a long-term impact on the function and structure of the brain.
Due to the large and excellent cohort studies involved, the wealth information generated permitted to link food intake data to biochemical measurements and to mental performance and behaviour in a large population across Europe (more than 20000 children). This allowed the establishment of dietary recommendations and key messages for the European population.

Several nutrients have been identified as important factors related to mental performance and behaviour, such as LC-PUFAs, Folic Acid, other B-vitamins and micronutrients. However, for all these nutrients there are a lack of clarity and little consensus on their role in neurodevelopment, mental performance and mental illness. NUTRIMENTHE has created new important scientific evidence on this field. Furthermore, NUTRIMENTHE has developed a more mechanistic insight by specific work on genotyping to unravel uncertainties in the role of LCPUFA’s and also by extensive bio-analytic work. Moreover, neurophysiological measures included in several workpackages have been linked to brain imaging techniques for all the nutrients concerned.

Another approach in NUTRIMENTHE recognises the difficulty of cognitive and behavioural test methodologies in nutrition studies. NUTRIMENTHE has brought key experts together from the field of child psychology and child psychiatry to assist in developing the most optimal neuropsychological tool to assess cognition and behaviour in the different studies.

Finally, NUTRIMENTHE has taken a great deal of care to ensure that dissemination of the results is most effective. Now that the European Food Safety Authority (EFSA) has initiated legislation for health claims and given the public is increasingly aware of health benefits of foods, NUTRIMENTHE is implementing a thorough dissemination programme. This includes content on the development of food products, data to qualify health and nutrition claims and an effective communication programme to consumers and the public, based on economic analyses, consumer data and systemic literature reviews.

Since the beginning of the project more than 70 papers have been published, and many others are in draft (Appendix 3). As a result of this strong work, different key messages have been drafted too (Deliverable 13.5).


OVERALL WORKPACKAGES RESULTS

Workpackage 1 - “Long term effects of maternal dietary intake in pregnancy on cognitive and behavioural development within 7,000 multi-ethnic preschool children. The Generation R Study”

The objective of WP1 was to examine and quantify nutrient effects (maternal dietary intake and nutritional status in early childhood) on early behaviour and cognitive development. This WP was embedded within a large multi-ethnic population-based prenatal cohort study known as the Generation R Study. The Generation R study has nearly 7,000 active participants and the children are currently between the ages of 5 and 9 years. The primary goal of WP1 was to assess whether maternal dietary intake in pregnancy is associated with behaviour and cognitive problems in the offspring.

Nutritional intake in early pregnancy has been assessed in 4324 women using a Food Frequency Questionnaire. This deliverable has been described in detail in the second periodic report. Primarily, we focused in our analyses of maternal dietary intake on mothers of Dutch national origin as the FFQ was designed to tap into Dutch eating habits and nutrition assessment must be tailor-made for each ethnic group. Data from another 2500 women was, however, used for specific questions such as iodine intake.

There was considerable progress over the years within NUTRIMENTHE WP1. The progress has been presented covering the three specific domains of (1) the laboratory analyses of serum-derived factors; (2) acquisition of behaviour and cognitive measures; (3) Data analyses and publication of results.

1) Laboratory quantification of serum-derived nutritional factors: Quantification of serum folic acid, Vitamin B12, and maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) have been performed in 5,800 mothers within the Generation R study. Assessment of fatty acid levels is now complete and involves the following fatty acids:

Saturated FAs
Trans FAs
Cis Monounsaturated FAs n-9 Polyunsaturated FAs n-6 Polyunsaturated FAs n-3 Polyunsaturated FAs
C14:0
C16:0
C17:0
C18:0 C16:1t
C18:1t
C18:2tt
C22:1t C15:1n-5
C16:1n-7
C18:1n-7
C18:1n-9
C20:1n-9 C20:3n-9 C18:2n-6
C18:3n-6
C20:2n-6
C20:3n-6
C20:4n-6
C22:4n-6
C22:5n-6 C18:3n-3
C20:3n-3
C20:5n-3
C22:5n-3
C22:6n-3

2) Measures of child behaviour collected using the Child Behaviour Checklist, Strength and Difficulties Questionnaire, and Social Responsiveness Scale has been performed at 5-6 years of age in 6680 children. In addition to these measures, the same number of children has participated in the Berkeley Puppet Interview and a non-verbal IQ assessment. Family function has been measured using the Family Assessment Device and measures of child activity, TV and video game observation, height, weight, and bullying and victimisation have also been obtained. In 200 children we have completed collection of the neuropsychological assessment designed in WP7.

3) There have been 14 published papers (all in PubMed, all explicitly mentioning “NUTRIMENTHE” – See Appendix 3) and multiple abstracts to date that describe the relationship between nutritional factors and neurodevelopment, emotion, and behaviour within the Generation R Study. Furthermore, Generation R has participated in the development of the NUTRIMENTHE Global database with 200 children.

ADVANCE

• Prenatal Folate affects Brain Development and Behaviour: We completed three important studies examining brain development in children exposed to low maternal folate during fetal life. Taken together these studies provide a very important message regarding folate and brain development. The message is that even in the absence of major neurological problems, such as neural tube defects, low folate can have more subtle negative consequences on brain development and child behavior (Steenweg-de Graaf J, et al., 2012; 2013). The results have shown that maternal dietary patterns during pregnancy affect the risk of the behavioural problems during childhood. Children of mothers who did not use folic acid supplements during the first trimester of their pregnancy had a higher risk of total problem behaviour at 18 months; the data also showed that low folate level, as well as no folic acid supplement used, increase the risk of child internalising problems at 3 years old, even when adjusted for maternal characteristics such as age, national origin, educational level and psychopathology. Data collection and analyses have been performed on 5,945 mothers who received three ultrasound measures during pregnancy as well as a subgroup of 320 children who received postnatal ultrasounds six weeks after birth. Children exposed to lower levels of maternal folate had smaller head growth and postnatal ultrasound measures show smaller length of the corpus callosum. Noteworthy was that these changes persisted into later childhood, with children exposed to low folate during fetal life also showing decreased total brain volume on MRI (Nijs, et al. Pediatrics, 2014) and more emotional problems. Folate plays a major role in key processes of neurodevelopment, and during fetal life the brain undergoes the greatest amount of growth than any other period of life. Thus, the key public health message is to assure that women of childbearing years and who are planning (or even not planning) to become pregnant consume enough folate to prevent being folate deficient.

• Prenatal Fish intake and Fatty Acid status in relation to child behavioural and cognitive development: We completed analyses examining the relations of maternal fish intake and fatty acid levels during pregnancy with offspring behavior and cognitive development in the offspring. Our results suggest that higher maternal (fatty) fish intake during pregnancy is associated with less internalising problems in the offspring, which may be explained by subsequent higher omega-3 fatty acids, in particular DHA. Whereas most studies report associations between cord blood fatty acid levels and child problem behavior, we found an effect of maternal DHA and omega-3/omega-6 ratio measured in mid-pregnancy from 6999 participants. We did not find strong evidence however for an association of maternal fish intake and fatty acid levels with child IQ. After adjusting for confounders, we found that low (lowest quartile versus the other 3 quartiles) maternal levels of AA to be associated with higher child non-verbal IQ (B=1.02 P=0.035 and high (highest quartile versus the other 3 quartiles) levels of AA to be associated with lower non-verbal IQ (B=-1.39 P=0.005). Currently, the Dutch Health Council advises an average LC-PUFA intake from fish of 450 mg/day (i.e. 2 portions of fish per week, of which at least one fatty fish; http://www.gezondheidsraad.nl/sites/default/files/200621N.pdf) regardless of pregnancy. Also, despite extensive research on marine oil supplementation during pregnancy, there are no recent guidelines yet available that have been approved by the WHO Guidelines Review Committee (http://www.who.int/elena/titles/fish_oil_pregnancy/en/). Our findings are a step forward for the growing body of literature in the field of child cognitive and behavior development. Possible adverse effects of very high LC-PUFA concentrations, however, are not clear yet. Therefore, for now, the key public health message is that pregnant women should adhere to the current guidelines for LC-PUFA intake. Further research is needed to identify LC-PUFA-sensitive periods of fetal brain development, optimal intake of LC-PUFAs during pregnancy, and the specific effects of inadequate prenatal LC-PUFA status on behavior and cognitive development in the offspring.

• Mild maternal thyroid hormone insufficiency, iodine, child’s non-verbal intelligence and brain morphology: This study has proved that poor maternal thyroid function during pregnancy is an important risk factor for children's brain development. We performed the first MRI study addressing the effect of mild maternal thyroid hormone insufficiency on brain morphology of children in the general population. We did not find any differences in brain volumetric measures, cortical thickness, and surface area between children exposed prenatally to hypothyroxinemia and controls. In 3,727 mother-child pairs, we showed that the children exposed to maternal hypothyroxinemia in early pregnancy had a nonverbal IQ 4.7 points lower than the children whose mothers had normal thyroid status in pregnancy (adjusted model for confounders: 95%CI: -7.2 -2.2; p<0.001). When we reran the analysis in a subsample of children excluding those with high autistic symptoms, the association between maternal hypothyroxinemia in early pregnancy and child’s nonverbal IQ remained essentially unchanged (B=-4.48 95%CI: -7.16 -1.81 p=0.001). Thus, the key message to the clinicians is that the current guidelines and fortification policy in the Netherlands regarding the management of mild thyroid insufficiency should remain unchanged. Clinical trials to test efficacy of screening women during very early pregnancy for mild thyroid insufficiency must be conducted.
As part of a joint project with ALSPAC study (WP2), urinary iodine secretion (and creatinine levels) of 2337 pregnant women was assessed in spot urine samples collected in early pregnancy (<18 weeks of gestation). The results show that the Generation R participants are iodine sufficient, with median urinary iodine levels of 229.9 µg/L (IQR 130.4 395.4). The median (IQR) for iodine to creatinine ratio in the Generation R sample was 298.5 µg/g (200.3 432.3). In total, 30% of pregnant women in Generation R had urinary iodine levels lower than the value recommended by the World Health Organization (<150 µg/L) (Van Mil et al. 2012). Preliminary analyses in 1460 mother-child pairs with data on urinary iodine and nonverbal IQ revealed that there was a relation between maternal urinary iodine levels lower that 150 µg/L and children’s non-optimal nonverbal IQ at age 6 years (unadjusted model OR=1.56 95% 1.07-2.26 p=0.02). However, after adjustment for confounders, maternal urinary iodine levels in early pregnancy was not associated with children’s nonverbal IQ at age 6 years (adjusted model OR=1.37 95% 0.92-2.05 p=0.10). Similar results emerged in the analysis of language comprehension score at age 6 years. These results will be drafted as a joint manuscript with the ALSPAC study and will be submitted in spring 2014.


WORKPACKAGE 2: Interaction of fish intake and genetic variation in determining child behaviour – the Avon Longitudinal Study of Parents and Children (ALSPAC)

The Avon Longitudinal Study of Parents and Children is a longitudinal cohort study based in Bristol, UK which has followed subjects from before birth and for over 20 years. It has collected data on diet from pregnancy onwards, biological samples for genetic and biochemical analysis and assessed childhood growth and cognitive and behaviour development. Previous to the start of Nutrimenthe it had shown that child IQ at age 8 years was associated with fish eating by the mother during pregnancy: greater intake of fish by the mother being associated with better cognitive outcome in their offspring. One possible factor for which fish is a good dietary source is the omega-3 long-chain polyunsaturated fatty acid, docosahexanoic acid (DHA) or similar FAs. There are many theoretical reasons for thinking the DHA may be involved in neurodevelopment. Further investigation of what factors in fish may be affecting this outcome and whether there is a genetic component was warranted. Work package 2 in Nutrimenthe was set up to take this work forward.

DNA samples were extracted from mothers and children and a set were shipped to Munich for determination of an agreed set of polymorphisms in the fatty acid desaturase (FADS) genes cluster, under WP8. Work was done to compute dietary variables from questionnaires collected previously on the mother’s diet in pregnancy and the child’s diet at various ages in childhood. From other funding sources, data became available for the fatty acid composition of blood for the mother’s in pregnancy, the child’s cord blood and blood at 7.5 years of age. IQ had been assessed using WISC, in both verbal and performance domains at age 8y and behaviour assessed by a ‘Strengths and Difficulties Questionnaire’ (SDQ) completed by parents about the child at age 7y. These data were combined for analysis.
ALSPAC study within NUTRIMENTHE has been the first to investigate the relationship between iodine status in UK pregnant women and offspring cognition. The paper shows the importance of adequate iodine status during early gestation and emphasises the risk that iodine deficiency can pose to the developing infant and child cognitive development, even in a country classified as only mildly iodine deficient. The study demonstrates that iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention.

ADVANCE:

FADS gene cluster and neurodevelopment and asthma

• The analysis of maternal fatty acids showed strong associations with variants in the FADS gene cluster even after correction for multiple testing. A majority of the genetic variants showed associations in one direction only. The ALSPAC results have shown that there is a genetic control of the pathways in the body that produce LCPUFAs and these are important in both the pregnant woman and the foetus. Positive associations tended to be observed for the shorter chain fatty acids with fewer unsaturated bonds while negative associations were observed for the more complex fatty acids. Other analyses on four SNPs associated with fatty acid binding and transport proteins showed no associations with maternal or newborn fatty acid levels. There is initial evidence that FADS variants modulate nutritional influences on complex phenotypes such as asthma and neurodevelopment; ALSPAC study has proved that FADS gene polymorphisms are associated with FA levels in maternal and cord blood. FA levels in maternal blood during pregnancy showed a minor relationship with development of child’s IQ at 8 years. However, it has been demonstrated a selective benefits of LC-PUFAs on IQ linked to FADS2 gene polymorphisms, being of special importance in children fed with an infant formula no supplemented with LC-PUFAs (Steer et al., 2013).

Effect of diet during pregnancy on child neurodevelopment: specially focus on fatty acids and iodine
- Maternal polyunsaturated fatty acids in pregnancy have been associated with child IQ at 8y. These associations suggest possible mechanisms involving neural phospholipids (DHA and AA).
- Evidence from ALSPAC is consistent in finding that regular dietary intake of fish in pregnancy is important for child neurodevelopment and that many constituents of fish not just long-chain omega-3 fatty acids may be involved. So, evidence from ALSPAC supports the recommendation that pregnant women should consume at least two fish meals a week, one of them being of oily/fatty fish.
- ALSPAC further shows that consumption of fish in children is associated with better long-chain omega-3 fatty acid status. Dietary ALA intake is associated with plasma DHA only if no fish is eaten but sources of long chain omega-3 fatty acids can provide additional benefits. These may come from supplements which contain DHA and EPA. Evidence from ALSPAC, CHOP and NUHEAL supports the recommendation that children should consume two fish meals per week one of them being of oily/fatty fish, to have better behaviour outcomes. Fish is a good source of long-chain polyunsaturated fatty acids, iodine and many other important nutrients. Our evidence supports the consumption of fish rather than any individual constituent.
- The ALSPAC study has shown the importance of adequate iodine status during early gestation and emphasises the risk that iodine deficiency can pose to the developing infant and child cognitive development, even in a country classified as only mildly iodine deficient (Bath et al. The Lancet, 2013). The study also demonstrates that iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention. A joint publication is on-going with the Generation R data (WP1). The effect on maternal iodine status in pregnancy of the development of hearing was also investigated and the results presented by Dr Sarah Bath at the Young Scientists’ Forum Competition (placed 3rd in the competition), at the NUTRIMENTHE International conference in Granada, Spain 13th September 2013. Iodine status was significantly higher in those women with a higher consumption of milk, seafood and eggs; it is well known that severe iodine deficiency is associated with hearing impairments and even deafness, but this is the first study to investigate the relationship between mild-to-moderate iodine deficiency during pregnancy and hearing threshold in the offspring. This study showed that children born to mothers with low iodine status in pregnancy were more likely to have hearing threshold in the top quartile in a least one ear at age seven years than those born to mothers with a higher iodine status. This remained significant after adjustment for potential confounders. Further analysis are planned to investigate the relationship between iodine status and hearing in the offspring. As well, adequate iodine intake in pregnancy has been shown to be important for child cognitive development at 8 years old.

ALSPAC collaboration with other WPs
Other 2 studies have been developed in the last 2 years of NUTRIMENTHE; these studies have been the result of collaborations with WP7 and WP11 (results are shown in their respective sections).

WORKPACKAGE 3 “Follow-up of school age children whose mothers have received n-3 LCPUFA and or 5-methyl-tetrahydrofolate during pregnancy”

The main objective of WP3 is to determine whether during childhood there are long-term effects on cognitive development and mental performance as a consequence of a supplementation with fish oil {FO: 500 mg/day of DHA + 150 mg/day of eicosapentaenoico (EPA)}, 400 µg/day of 5-Methyltetrahydrofolate (5-MTHF), placebo or both during pregnancy. This workpackage proposes a long-term follow-up (7-9.5 years) of the 270 children whose mothers were participants in the “Nutraceuticals for a Healthier Life” Project (NUHEAL, QLK1-CT-1999-00888), funded by the EU in the 5th Framework Programme, and being followed up within “Early Nutrition Programming Project (EARNEST FP6 Integrated Project, www.metabolic-programming.org FOOD-CT-2005-007036) and currently within NUTRIMENTHE.

Children whose mothers participated in the NUHEAL trial were invited to revisit the local study centre at the ages 7.5 8, 9 and 9.5 years (NUHEAL-Follow-up within NUTRIMENTHE). The data obtained within the NUHEAL Project and the follow-up within EARNEST Project was combined to obtain a global knowledge about the long-term effects in the children whose mothers were supplemented with DHA and/or folate during pregnancy. For these reviews the protocol of assessment in the four moments was developed in agreement between the three centres participants in the study and harmonised with WP4 and partially with WP1:

- Neuropsychological assessment: all tests from the Neuropsychological Battery were translated into German, Hungarian and Spanish, and have been available in each country for the NUHEAL children follow-up. The training for the NUHEAL teams from the 3 centres was developed in January 2010 in Granada. Two full days of training including practical activities with children were performed, to optimise quality control of the procedures. The level of harmonisation achieved with WP4 is around 95%.
- Diet assessment: CHOP Food frequency adaptation to NUHEAL follow-up and training of fieldworkers Children’s food habits, and in particular the consumption of marine foods and folate intake, has been assessed by executing structured interviews following the standardised food questionnaire developed under the supervision of Dr. Pauline Emmet (ALSPAC - leader of the NUTRIMENTHE Working Group of Diet). This food questionnaire has been also harmonised with WP4.
- Anthropometric and Physical Activity assessment: the establishment of the procedures for physical activity and physical condition assessment and training in agreement with partners participants in CHOP follow-up study was done. The same procedures have been applied in WP3 and WP4. The integration of anthropometric assessment and Medical History was also performed. All protocols were very similar in WP3 and WP4.
- Cognitive Potentials assessment (EEG/ERP) and MRI: UGR has developed the methodology, procedure (including conditions for EEG), paradigms and revised technology to develop EEG/ERP in children. This exam was performed as well in Hungary and Germany (n:136). To facilitate the implementation of the EEG/ERP, UNILEVER has led the BIOSEMI active machine to Hungary and Germany, just the same model being used in UGR. The selected tasks designed as paradigms for children at 8y and repeated at 9.5y were those to study Attention Networks (ANT) and Working Memory (WM) and were designed by UGR expertise’s. In the Spanish children (n:108) resting and Language comprehension task were also performed using the EEG/ERP technique to assess the brain areas involved. As well, brain MRI neuroimaging study was done in 80 Spanish children.
ADVANCE
The NUHEAL follow-up study has had a big progress over the years within NUTRIMENTHE framework. The progress has been presented covering the three specific domains of (1) The acquisition of cognitive, behaviour and brain morphological measures: neuropsychological assessment, EEG/ERP and MRI; (2) Dietary intake in childhood, fatty acid in cheek cells and metabolomic analyses in urine samples; (3) Data analyses and publication of results (See Appendix 3).

1) Acquisition of Cognitive, behavior and brain morphological measurements

• There is an important change in processing speed maturation between 7.5y and 9y in the children analyzed in all intervention groups; however, those whose mothers received Placebo during pregnancy, spent significantly more time to solve the task than those born to FO, 5-MTHF or FO+5-MTHF supplemented mothers, in both tests, the Symbol Digit Modality Test (SDMT) and the Colour Trails Test (CCTT) – (Task 1). FO supplementation during pregnancy have a positive long-term effect on Speed Processing in the offspring up to 9 years old, as have been shown with the SDMT and CCTT tests. The most important factor influencing speed processing in the children at 9 years are the ratio AA/DHA in the mother at delivery; most interestingly, offspring of mothers who were heterozygote regarding the FADS1 genetic variant rs174556, showed 7.47 more often a better T score in the Symbol Digit Modality Test (SDMT) (so better processing speed) at 9 years old than those children of mothers with homozygous major alleles. These two factors determine better scoring in SDMT and CCTT tests, so higher velocity, and more hits in SDMT. As the connection between white matter integrity and speed processing in cognitive tasks is consistently established, these results show positive and strong long-term effects of perinatal LC-PUFAs and FADS1 polymorphism on cognitive development, suggesting an increase of white matter volume and better integrity. Another important factor influencing the speed processing development is the cultural level of the mother; higher cultural level in the mother is related to have an offspring with a better speed processing developed being between the 75 percentile. On the other side, an increase of total homocystein (tHcy) was demonstrated to be related to worse speed processing development at 9 years. So, maternal LC-PUFAs and folate requirements should be within normal ranges till the end of pregnancy to avoid undesirable long-term effects. A paper has been sent to BJN (suppl.).

• A positive long-term effect of FO and/or 5-MTHF supplementation during pregnancy was shown on the development Visual Motor Coordination in children at 9 years old, especially with dominant hand, seems to have an important relationship with the strength and agility; even more, sex is another important factor, girls had better results in flexibility and boys in agility. All correlations found were between visuomotor coordination and fitness at 9y, but not at 7.5y. The long-term effects of the prenatal supplementation with FO and 5-MTHF seem to be related to other neuropsychological abilities at 9 years old. Further analyses are on-going. A paper has been submitted to BJN (suppl.).

• The data analysis from EEG/ERP in the NUHEAL Follow-up also proved that folate supplementation during pregnancy improves children’s ability to solve response conflicts, giving better attention abilities. We observed that the Folate supplemented group solved faster the conflict than the remaining groups (all p<0.05). The same effect was observed for ERP amplitudes. Low resolution electromagnetic tomography analysis showed higher activation of a cluster of voxels located at right posterior mid-cingulate cortex for the Folate supplemented group. However we observed significant slowing down of response speed and alertness for this group. We conclude that Folate supplementation rather than FO or the combination of both supplements improves the children ability to solve response conflicts. This advantage seems to be based on the higher activation of right posterior mid-cingulate prefrontal cortex, indicating that early nutrition influences the functionality of brain areas involved in executive functions. These results are included in a paper sent to J Neurosci (see Appendix 3).

• On the other hand, we performed MRI and used voxel-based morphometry and surface area to determine potential influences on brain structure. After image processing, the volumes of white (WMV), gray matter (GMV) and cortical surface area were determined in 80 Spanish children aged 9.14. At 4y, HC was strongly associated to GMV of bilateral anterior areas, including several frontal gyrus, anterior cingulate, bilateral temporal, encompassing temporal pole, superior and middle temporal gyrus and limbic areas, insular cortex, parahippocampal gyrus, hippocampus, amygdala, and small clusters in bilateral occipital areas. We also observed that the volume of a cluster of voxels in the prefrontal cortex (BA9) is significantly correlated with mental global performance, as assessed by the Kaufman battery. So, our conclusion is that HC, especially at 4y, makes a long-term outstanding fitting of brain size, cognition and GMV and WMV distribution in the brain at 9.5 y. So, the MRI study in the NUHEAL Spanish children showed that head circumference (HC) at 4 years predicts long-term grey and white matter volumes, total brain volume, total inner surface area and grey matter distribution in the brain. These results are included in a paper already sent to Trends Cogn Sci.

2) Dietary intake in childhood, fatty acid in cheek cells and metabolomic analyses in urine samples
• The study of dietary intake of NUHEAL children from different European countries has demonstrated that many European children at 4 years are eating diets that are low in nutrient content but high in fat and sugar. A paper has been published in EJCN (see Appendix 3).

• FADS1 gene variants modulate tracking of cheek cell samples fatty acids profile in children aged 9.5 y. FADS1 rs174556 polymorphisms seemed to be predictive of levels of 20:3n6 (%) in cheek cells at 8y and of 18:2n6 at 9.5y; rs174561 of 20:3n6 at 8y and, 18:3n3 and 18:2n6 at 9y; rs3834458 of 20:3n6 at 8y, 18:3n3 and 18:2n6 at 9y, and of 18:2n6 at 9.5y; rs968567 of 20:3n6 at 8y, and 18:3n6 and 20:3n6 at 9y. From all cofactors included in the model, sex was the most significant predictor of the FA levels at school age. Therefore, these genetic variants need to be taken into account as potential confounders when it comes to the analysis of nutritional influences on fatty acid composition and cognitive outcomes. Our data will be used to assess gene-nutrition interactions in the smaller intervention studies and enhance the precision of the study evaluation to understand the relationship between nutrition and neurodevelopment in better detail. These results are included in a paper drafted for the BJN supplement currently in press.
• NUTRIMENTHE Metabolomics approach has been developed in urine samples in the NUHEAL study. A total amount of 536 urine samples were analyzed from the 4 timepoints studied in the NUHEAL children in NUTRIMENTHE framework. Apparently, there is a not long-term effect of DHA and 5-MTHF supplementation in pregnant women on the metabolomics profile of their children at different time points at school age. However, the regression model showed a different evolution in the metabolomics profile of the urinary samples from children participants in the FO+5-MTHF study group. The analysis of all urinary samples obtained at school age, demonstrated that the differences found between them in the metabolomics profile are strongly related to the country of origin, and therefore probably to diet, culture and lifestyle. The urinary compounds found such as Hippuric or Citric acids are the most influential metabolites useful for the discrimination of the metabolomics profile according to country of origin. More statistical analyses are ongoing at the moment to evaluate the possible relationships between metabolic profiles and neurodevelopment data. 2 papers are being drafted in this moment containing these results.
3) Data analyses and publication of results
At the moment 8 publications has been delivered (see Appendix 3). Further analyses of the data are on-going. Furthermore, WP3 has participated in the NUTRIMENTHE Global Database, determining new results.


WORKPACKAGE 4 “Follow-up of school age children with different protein intakes in early childhood”

Workpackage 4 consisted on the follow-up of about 600 school-aged children from 5 European countries, who were randomly assigned to be fed with an infant and follow-on formula with higher or lower protein content during the first year of life. The study sample was recruited to take part in the Childhood Obesity Project. This project was previously funded by the 5th and 6th Framework Programmes (to follow the children until the age of 2 and 6 years, respectively), with the objective to analyze if early higher protein supply may increase later obesity risk. The study showed that lower protein formula during the first year of life led to significant lower body mass index at 2 years (Koletzko B et al, AJCN 2009), and therefore to a lower obesity risk.
In term well-nourished infants, there was no data from large prospective follow-up studies on the possible effect of different levels of protein intake early in life on later neurodevelopment. In the last years, trends on protein recommendations during infancy and childhood tend to be lower than in the past, as shown by a significant reduction recommended by the last World Health Organization (WHO) and the Food and Agriculture Organization (FAO) (Joint Report Report of a Joint WHO/FAO/UNU Expert Consultation, 2007). Within Nutrimenthe, funded by the 7th Framework Programme, we followed the children until the age of 8 years, focusing on the assessment of mental performance. This study aimed to assess the effect of feeding healthy term infants with different amounts of protein (within a normal range) during the first year of life (a critical period for brain growth and development) on mental performance later in life (at 8 years). To pose this question, we were based on the existing literature showing improved mental performance among preterm and undernourished children who had been protein supplemented. The importance of such study lies on the recent trends to lower protein intakes recommendations, as for example to prevent obesity risk. In a scenario in which reduced protein intake is recommended, and this reduction seems to have preventive effects on obesity but not deleterious effects on growth, it remains necessary a safety analysis confirming the similar neurodevelopment in childhood, of those who have been fed with a lower protein formula in early life.
Together with this main objective, the workpackage aimed:
• To analyse the association between dietary intake and blood levels of essential LC-PUFA and specific micronutrients (vitamins B1, B2, B6, B12 and folic acid, iron and zinc) and neurodevelopment at 8 years.
• To analyse the association between different protein intakes (from birth to 8 years-old), IGF-1 and IGFBP-3 plasma levels at different time points and cognitive and neurological development at 8 y old.
• To analyse the association between neurodevelopment at 8 years with other factors as growth, physical activity, socioeconomic level and familiar status.

To test our hypothesis we used the NUTRIMENTHE Neuropsychological Battery including tests for different domains and functions rather than a test assessing overall ability (i.e. Intelligence quotient). In nutrition studies, one particular domain may be affected differently than others at different ages, and an overall ability test may not detect these differential patterns.
The neuropsychological battery was the same used in other WPs within NUTRIMENTHE and developed by the UGR. In short, the functions (and domains) assessed were: visual episodic memory, verbal memory (memory), sustained & focussed attention, Spatial attention (attention), visual-perceptual integration (perception), semantic fluency, verbal comprehension (language), Processing speed, visual-motor coordination, impulsivity/ inhibition, selective attention, Flexibility/ shifting, Working memory, Reasoning, selective and focused attention and decision making.
The degree of internalising and externalising behavioural problems was assessed administering to mothers the Child Behaviour Checklist 4-18 (CBCL).
ADVANCE
• Children participants in the CHOP study, in which as infants were randomised to have a higher protein (HP) (infant formula 2.9 g protein/ 100 Kcal and follow‐on formula 4.4 g protein/100mL) or lower protein content formula (LP) (infant formula 1.77g protein/ 100 Kcal and follow‐on formula 2.2g protein/100mL) during the first year of life were followed up at the age of 8 years with the NUTRIMENTHE Neuropsychological Battery. To obtain comparable data, all descriptive results are presented as country z-scores. Summarised results are shown below. The results from this randomised clinical trial showed no significant differences between 8 years-old children who had been fed with the lower and the higher protein content formula during the first year of life in memory (verbal and visual), attention (spatial, focused and sustained), perception, language (fluency and comprehension), processing speed, motor coordination and executive functions (shifting/ flexibility, inhibition/impulsivity, working memory, reasoning, selective and focused attention, visual-spatial skills or decision making, confirming the safety of the lower protein content formula. Previous studies reporting different mental performance in children fed higher protein intakes, had been undertaken in special populations with special needs, never before in term, well-nourished children.
• Herewith it has been demonstrated the safety of lower protein content in infant formulas according to long-term mental performance. This information is of great value for both the scientific community and the government bodies and committees in charge developing policies for nutritional value of infant products.
Neuropsychological functions scores and behaviour problems scores by feeding group:

Workpackage 5 - “Evaluation of the effects of a micronutrient supplement on mental function in (pre-) school children”

The primary objectives of workpackage 5 were i) to perform an intervention study with B vitamins in kindergarten age (4-6 years) children with cognitive performance outcomes and ii) to apply learnings from this study and other insights from NUTRIMENTHE into new consumer products. The first objective has been achieved with the intervention study completed and most outcomes clear. During year 1 of NUTRIMENTHE the protocol was developed jointly between the WP5 partners UNILEVER and LMU. A key feature of the study was to identify children having a relatively low dietary folate intake from a sample population of 1,000 children. This meant that it was necessary to first develop and validate new methodology for a marker of folate status in urine (para-aminobenzoylglutamate (p-ABG)) as it was considered unfeasible to obtain blood samples from children of such young age. The method development and validation were successful and the assay applied within the study using urine samples from 1,002 children sent by post.
The intervention study was performed during year 2 of the project in ~80 kindergartens in the Munich area. As mentioned above, we initially screened 1,002 children aged 4-6 years for suboptimal folate status by assessing the para-aminobenzoylglutamate excretion in urine. Based on these results, 250 low ranking subjects were recruited into the double blind, randomised, controlled trial providing for 3 months daily sachets with 221µg folate, 1.1 mg vitamin B2, 0.729 mg B6, 1.2µg B12 and 135 mg calcium, or calcium only. The primary outcome measures were changes of short and long term memory combined with measures of cognitive speed between baseline and study end. Secondary endpoints were changes of urinary markers of B vitamin status, and in a subgroup (100 children) full blood folate and plasma homocysteine. Several subtests of two well-known intelligence test systems for preschool children were used. We applied the “Hannover-Wechsler-Intelligenztest für das Vorschulalter-III” (HAWIVA-III), the German version of the Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III). This version is especially designed for children from the age of 2 y 6 mo to 6 y 11 mo. A full scale IQ is provided as well as several subtest scores in verbal and performance cognitive domains. In addition, subscales of the Kaufman-Assessment Battery for Children (K-ABC) in the German Version by P. Melchers and U. Preuß, were chosen, an instrument for assessing the cognitive development in children ages 2.5 to 12.5 y. It is comprised of four global test scores that include sequential processing scales, simultaneous processing scales, achievement scales and mental processing composite. A key aim of the NUTRIMENTHE project is the use of harmonised methods for cognitive testing and in WP5 we aimed for as much overlap with the WP7 Neuropsychological battery as was possible. But as children in this study were at such a young age not all tests were applicable and we needed to limit the testing time to a maximum of 45 minutes.
ADVANCE

• The randomised, controlled intervention study was successfully completed in more than 200 young children and showed that biochemical status markers (red blood cell folate and plasma homocysteine) changed in a healthy direction after three months of B vitamin supplementation, but there were no changes were observed in cognitive performance. We then applied a Neuropsychological Test Battery which was focused on verbal learning ability as there were literature indications that this domain could be most susceptible to B vitamin status, but no differences were shown. So, it may be that an intervention period of three months was insufficient to enable the structural or functional changes in neuronal tissue which may have been required to be neuropsychologically detectable.

• Analysis of the biochemical parameters in urine and blood samples, data screening and statistical analysis of the large data set was performed during the remaining period of year 2 and into year 3 by the Munich WP5 team. Compliance to the study intervention was shown to be good. Urine p-ABG and red blood cell folate levels significantly increased in the treatment group and plasma homocysteine significantly reduced (new findings in children of this age). Unfortunately B vitamin consumption was not associated with significant improvements in cognitive performance in this study population and there could be a number of potential explanations for this which were addressed in a published article. This neutral study outcome lead to the re-definition of WP5 objectives as it was not considered feasible to develop a functional product for cognitive performance based on data obtained.

Workpackage 6 - “Quantitative requirements of n-3 LCP for neural function in children”
Patients with phenylketonuria (PKU) have an inborn error in the metabolism of the amino acid phenylalanine (Phe) and thus must follow a strictly controlled protein-restricted diet from early infancy. This protein-restricted diet is devoid of natural dietary sources of n-3 long chain polyunsaturated fatty acids (LC-PUFA), such as eggs, meat, milk or fish. Therefore, blood concentrations of n-3 LC-PUFA, especially of docosahexaenoic acid (DHA) are reduced in PKU children compared to healthy controls. DHA availability is considered important for optimal neurological function. Previous studies have shown that neural function of PKU children is improved by high dose supplementation of fish oil providing DHA, as shown by significant improvements of both visual evoked potential latencies and of fine motor skills and coordination, but no dose response relationship has been established so far.

This multicentric double-blind randomised trial conducted within WP6 of NUTRIMENTHE aimed at determining quantitative DHA requirements for optimal neural function in PKU children. Patients with classical PKU from several major treatment centres in Europe (Munich, Santander, Milan, Birmingham, Heidelberg, Istanbul) are randomised to receive between 0 and 15 mg of DHA per kg body weight daily for a duration of 6 months. Biochemical (fatty acid composition of plasma phospholipids, lipoprotein metabolism), and functional testing (visual evoked potentials, fine motor skills, cognitive function and markers of immune function) are performed at baseline and after 6 months. DHA intake per kg body weight will be related to outcome parameters and thus, the dose response relationship can be investigated. As an intermediate parameter between intake and neurological outcomes plasma concentrations of DHA are considered by investigating their relationship to DHA intake and on the other hand by studying their relationship to the neurological outcome.

ADVANCE
• The study was completed with almost the anticipated number of study participants, who met the pre-defined inclusion criteria. Although it is challenging to collect data for functional outcome parameters in a clinical setting data from almost 75% of the participants could be evaluated. The major focus was on the relationship between outcome and DHA supplementation per kg body weight. In respect to the biomarker plasma level of DHA a dose response curve could be established, which suggests that an increase of the supplementation above 8 mg DHA per kg body weight per day does not lead to much further increase of DHA-percentages.





• In contrast to the DHA levels no doses – response relationship could be established for the visually evoked potentials. This is expected from the finding that DHA supplementation did not lead to a significant increase of functional outcome in any of the supplemented groups. Observations for the further functional outcome parameters were similar and were not changed by including genotype into the evaluation. Thus, the major conclusion is that DHA from algal oil effectively increases plasma levels of DHA in the PKU patients, but functional outcome could not be improved. This may be related to the unexpected high basal levels of DHA in the study participants.

Workpackage 7 - “Cross-cultural standardisation of a neuropsychological battery for cognitive assessment in EU children”

This workpackage has been designed to facilitate the comparison between the childhood studies (WPs 1-5) by designing a harmonised neuropsychological protocol in different languages, and taking into account cultural differences. This has been a long process counting with the suggestions from the EC reviewers, NUTRIMENTHE partners and external advisory board members.

There was performed a large training in Granada 2010 with real children with all representative researchers from the partners involved in the assessment. To avoid any problems with the neuropsychological assessment, other training sessions have been organised during the Munich and York NUTRIMENTHE Meetings in 2010. The objective of these trainings was to provide instructions, procedures and scoring of the neuropsychological tests especially to WP1 and WP4 psychologists and others professionals involved in the examination.

A NUTRIMENTHE blog was developed and placed in the NUTRIMENTHE website with all information about procedures for assessment, videos and the answer to the most common questions. Furthermore, the partners could ask also through this way all remaining questions about potential doubts related to the assessment. We have been controlling following-up of the implementation of the Neuropsychological Battery (NP) and the establishment of a common database for the NP data.

ADVANCE

• We were able to design and implement a NUTRIMENTHE Neuropsychological Battery, specifically designed for this project, to establish a common database integrating the neuropsychological samples of Generation R Cohort (WP1), NUHEAL Study (WP3) and CHOP Study (WP4). The criteria used to choose the tests were as follows: 1) Tests to assess the main neuropsychological domains (Lezak et al., 2004); 2) Tests appropriate for 7-9 year old children; 3) Tests with low verbal stimulus in order to reduce the influence of language; 4) When possible, tests with reduced cultural influence. The battery comprised different tests to evaluate Motor Coordination (Grooved Pegboard Test), Processing Speed: Symbol Digit Modalities Test –SDMT); Perception (Hooper Visual Organization Test- HVOT); Attention: Continuous Performance Test – CPT and Pair Cancellation Test; Memory: The Rey Auditory Verbal Learning Test (RAVLT), Recall of Object Test (ROT); Language: Categorical Fluency Test and NEPSY Comprehension of Instructions; Executive Functions: Matrix Analogies Test, Reversal Digits Subtest, Children’s Colors Trail Test (CCTT) Parts 1 and 2, Stroop Color and Word Test, Hungry Donkey Task (HDT); Behavioural problems and psychopathology: Child Behavior Checklist (CBCL) (see, Deliverable 7.9).

• Report with the description of the neuropsychological methodology, including criteria for choosing the test, translation procedure and each neuropsychological test was given. List of standardised neuropsychological variables and SPSS and STATA databases containing the standardised neuropsychological scores are included in this WP. The UGR has been given support to all other partners discussing and helping them to interpret the data and so improving the possibilities for new publications.

• As a result of that, and together with the Working Group of Mental Performance, neuropsychological performance of 1050 children from 7 different countries has been merged. However, due to differences in the script programming for CPT and Go-No Go task for WP3 and the rest, reaction time was not comparable in those tasks for all WPs. Global hits and errors for those tasks were merged. Thus, a full neuropsychological battery was obtained for 833 children (WP1, n: 201; WP3, n: 266; WP4, n: 366) and 173 variables of 6 neuropsychological domains (speed processing, visual-motor coordination, attention, memory, language and executive function). The NUTRIMENTHE Global Database was built up with neuropsychological variables and other common data from 1050 children from 8 European countries, participants in Generation R, NUHEAL and CHOP, examined using the NUTRIMENTHE Neuropsychological Battery. This big approach has permitted to demonstrate that to standardise (by country and sex) the neuropsychological scores is an appropriate procedure to avoid the influence of culture on multicultural studies (see, Deliverable 7.11).

Joint work between WP7 and WP2: Re-analysis of the WISC III test performed in the ALSPAC children at 8 years of age.

• The work performed together between WP7 and ALSPAC database (WP2) including data from the 7415 children at 8 years old which were neuropsychologically assessed with the WISC III test, and their mothers during pregnancy where included in this analysis.The data have been re-analysed from a neuropsychological point of view, considering multiple confounder factors as co-variables. The factorial analysis of the WISC III tests determined the establishment of 3 different factors, the Verbal Comprehension (F1) (Vocabulary, Similarities, Comprehension and Information), Performance Index (F2) (Picture Completion, Picture Arrangement, Block Design, Object Assembly) and Working Memory and Speed Processing (F3) (Digits forward, Digits backward, Arithmetic and Coding). The factorial analysis of the WISC III tests performed determined the establishment of 3 different factors, the Verbal Comprehension (F1) (Vocabulary, Similarities, Comprehension and Information), Performance index (F2) (Picture Completion, Picture Arrangement, Block Design, Object Assembly) and Working Memory and Speed Processing (F3) (Digits forward, Digits backward, Arithmetic and Coding). The results showed that: a) Mother’s plasma phospholipids n3 fatty acids were positively associated to higher scores on Verbal Comprehension (F1) and Working Memory and Speed Processing (F3). b) Seafood intake than 340 g/week during pregnancy and maternal education determine higher mean scores on F1 and F3, but not for the F2. c) Parity ≥2 was related to reduce scores in Verbal Comprehension and Performance Index. d) In addition, Paternal social class was a major factor related to the three factors.


Workpackage 8 - “Analysis of genetic polymorphisms as co-variables in determining interaction of nutrition and mental health”

The main objective of this work package together with the cohorts was to find a relation between concentrations of long-chain omega-3 fatty acids (n-3 LC-PUFA) in tissues of the foetus and/or the child and behaviour and cognitive outcomes.

We have previously shown that common polymorphisms of the genes FADS1 and FADS2 found in about one quarter of the European population, encoding for the key enzymes regulating endogenous LC-PUFA synthesis, are associated with plasma LC-PUFA concentrations in adult populations. It is therefore well accepted that these genetic variants are an important factor for the determination of endogenous fatty acid concentrations in addition to nutritional influences.

Our aim was to measure polymorphisms of the genes FADS1 and FADS2 in children studied in other work packages where data on dietary intake and mental outcomes are available, from cohort and from randomised intervention studies. These polymorphisms should be related to plasma fatty acid concentrations and linked to the information on child behaviour, performance, and mental health.

ADVANCE

• In the NUTRIMENTHE Project the FADS1 and FADS2 gene polymorphisms were analysed in “mothers-baby pairs” in the ALSPAC and NUHEAL studies, but also in SIMBA and Phenylketonuric children studies; these analyses were performed on an in-house genotyping platform to study the influence of such polymorphisms on n-6 and n-3 fatty acid levels in the subjects studied. FADS gene variants were demonstrated to be an important factor determining maternal n-6 and n-3 fatty acid levels and foetal supply with during pregnancy.

Our main results from work package 8 together with the study cohorts are:

• FADS genetic variants influence the composition of long chain polyunsaturated fatty acids in maternal as well as fetal tissues and by this determine the foetal supply with these important fatty acids during pregnancy in addition to the nutritional supply. In other words, there is genetic control of the pathways in the body that produce long chain polyunsaturated fatty acids and these are important in both the pregnant woman and the foetus.
• There is initial evidence that FADS variants modulate nutritional influences on complex phenotypes such as allergies and cognitive function, but further studies are required as gene-nutrition interactions are hard to assess due to power limitations and the complexity of the research question.
• Together with WP3, an analysis plan was established and the first focus will be on a longitudinal analysis of maternal plasma DHA levels during the second half of pregnancy dependent on maternal FADS genotype and DHA / folate supplementation. This first analysis showed that carriers of the minor FADS alleles had consistent lower levels of plasma DHA over the analysed gestation period and the differences between the genotype groups increased with advanced gestational age.
• During the complete project period, WP8 was involved in the preparation and publication of 13 manuscripts in direct or very close connection to the NUTRIMENTHE objectives (see Appendix 3).


Workpackage 9 - “Quantitative analysis of biochemical markers”

In the various workpackages of NUTRIMENTHE biochemical status markers have to be determined using very different analytical techniques, e.g. B-vitamins, trace elements, n-3 long chain polyunsaturated fatty acids, amino acids, endocrine markers. Centralised performance of the assays provides standardised procedures and is cost effective. Thus, the work in respect to biochemical markers is centralised at partners providing the required analytical techniques. Furthermore, these partners are involved in the development of standard operation procedures for sample collection and handling. Partner LMU-Müenchen shares his expertise and facilities in fatty acid, and vitamin analysis, while CI WARSAW has available the methods for hormone analysis and UGR contributes the resources for urine analysis. This pool of available methodologies allows flexibility in respect to the determination of biomarkers not foreseen in the initial planning.

During the first years of Nutrimenthe biochemical parameters to be determined in WPs 3 (NUHEAL follow up), 4 (CHOP follow up), 5 (SIMBA- B-vitamin supplementation) and 6 (NUTRIMENTHE PKU study) were defined by the principal investigators. In co-operation between WP 9 and the investigators standard operation procedures for sample collection were implemented.

ADVANCE

• Experience from NUTRIMENTHE and other studies showed that venous blood sampling is not well accepted by children and their parents. To overcome this limitation WP9 set out to investigate possibilities of less invasive measurements of biomarkers. Thus a procedure for the analysis of fatty acids from whole blood GPL in dried blood spots was successfully developed based on a method previously established for plasma (Glaser et al. 2010). Data on the precision of GPL fatty acid analysis have been published for plasma, RBC and cheek cells, with CVs ranging from 1.0 to 10.5% for plasma and RBC GPL, and 1.4 to 9.7% for cheek cells (Glaser et al. 2010; Klingler et al. 2011; Klem et al. 2012). The repeatability of the GPL fatty acid analysis in whole blood was consistent with those data. This showed that the 2-step analysis for plasma GPL is also applicable for the analysis of GPL in dried blood samples.
• For WP3 (NUHEAL follow up) within the NUTRIMENTHE study 390 cheek cell samples collected at ages 8, 9 and 9.5 years were analysed for their glycerophospholipid composition and about 530 urine samples (collected at ages 7.5 8, 9 and 9.5 years) were analysed by liquid chromatography mass spectrometry for metabolites. Cheek cells collected at age 7.5 years could not be analysed, as the collection procedure could not be implemented in time.
• From the blood samples collected in WP4 (CHOP follow-up) a huge number of specific analyses were performed besides the metabolomic characterisation with a targeted, liquid chromatography – tandem mass spectrometry based approach, including amino acids, carnitine ester, phosphatidylcholines and sphingomyelins. Fatty acid status, including LCPUFAs of the n-3 and n-6 series was determined by the analysis of red blood cells (355 analyses) (See Deliverable 9.8).
• In WP5 previously from more than 1000 children screened for inclusion into the study the urinary concentration of the folate catabolite para-aminobenzoylglutamate had been determined. From the 250 children enrolled into the study the corresponding urine analyses have been performed twice (pre and post study), as well as determination of methyl-malonic acid in urine. As far as participants consented to blood sampling (n=120), small volumes of blood were available for the measurement of whole blood folate and plasma homocysteine concentrations. For the folate and homocysteine analyses in WP5 the same microbiological assay and liquid chromatography - mass spectrometry method, respectively, were applied as for the samples collected in WP4.
• In WP6, blood was collected pre- and post- a supplementation with different dosages DHA or a placebo, respectively. From the available plasma the fatty acid composition of plasma glycerophospholipids was determined as fatty acid status marker including concentration of DHA. Samples from 114 children were analysed.
• NUTRIMENTHE advanced the state of the art with the development of innovative biochemical techniques, such a procedure for the analysis of fatty acids from whole blood GPL in dried blood spots, the determination of fatty acids in cheek cells or the untargeted metabolomics analysis in urine searching for new biomarkers related to cognition and behaviour. The work package for biochemical analyses was a valuable and integrating part of the whole NUTRIMENTHE study, increasing the scientific output of the studies and being involved in many papers. Although with delays, WP9 increases the scientific output of the studies.

Workpackage 10 - “Consumer expectations - survey among parents and educators”

The NUTRIMENTHE Project studied “Consumer expectations- survey among parents and educators” where qualitative interviews with one hundred parents and teachers in each of the four partner countries, England, Germany, Hungary and Spain have been conducted in order to assess their attitudes, beliefs and knowledge of the effects of food and nutrition on children’s mental state and performance. The overall objective of WP10 was to gain an understanding of how parents and teachers perceive that food affects the mental performance of children. Parents influence all aspects of a child’s life including the development of food choices as well as controlling the availability and types of food in the home. As children grow and attend school others, including teachers, become more important influences.

The workpackage consisted of two principal tasks:
Task 10.1 Conduct qualitative interviews with parents and teachers to assess their attitudes, beliefs and knowledge of the effects of food and nutrition on children’s mental state and performance.
Task 10.2 Quantitative data collection and analysis using a questionnaire.

ADVANCE

The first study (Task 10.1) qualitatively examined the current perceptions and beliefs of parents and teachers employing interview techniques to gain a broad understanding of parents’ knowledge and attitudes through discussion of topics such as the physical, mental and behavioural impact of diet and more specific aspects such as certain meals, types of food and supplements. Two different interview approaches were used (semi-structured interviews and a card-sorting exercise), involving 100 parents and teachers in each of the four countries. Participants were parents and teachers of children aged 4-10 years old, in mainstream education and preferably without diagnosed pathologies such as Attention deficit hyperactivity disorder (ADHD). Participants were recruited via schools in the state sector and where possible selected to reflect some differences in socio-economic status.

Principal themes and subthemes were identified from the semi-structured interviews, using thematic analysis. Four main themes emerged from the analysis, namely the effects of diet, healthiness of diet, food choices and eating habits and sources of information on nutrition. The results of this study have been published in the journal Appetite.

• In the card-sorting study the factors that could influence mental performance in children were categorised into six broad groups, Biological, Educational, Food-related, Physical, Psychological and Social. Results from that study reveal that parent’s ranking of factors for their impact on mental performance was: physical i.e. activity and sleep (mean 1.77); psychological i.e. mood and behaviour (1.69); education (1.57); food (1.33); social (1.11) and biological (0.91).

• Parents in this study were initially asked to explain what they understood by the term “mental performance”. Parents in three countries most often used general expressions when describing their understanding of mental performance. Definitions relating to “attention and concentration” occurred frequently in England (42 %) and Germany (44 %), in Spain only 2% of parents mentioned these terms. A number of parents across countries spoke of mental performance in terms of learning and memory and general expressions included academic performance, mental development and problem solving.

In Task 10.2 a questionnaire was distributed online to parents and teachers of primary school children in England, Germany, Hungary and Spain. As in the previous task participants were parents and teachers of children aged 4-10 years old, in mainstream education and preferably without diagnosed pathologies such as Attention deficit hyperactivity disorder (ADHD). Data were collected using an online questionnaire from a total of 1606 parents and 403 teachers in the four countries.

The questionnaire was designed to collect information on:
1. Parents/teachers knowledge, attitudes and beliefs about the effect of nutrition on children’s mental performance.
2. Whether those beliefs affect the food choices offered to children by parents.
3. Respondents’ personal characteristics e.g. household composition and demography, socioeconomic status, education, ethnicity.

The analysis of the quantitative data collected in the questionnaire study has been completed and the results were presented at the NUTRIMENTHE International Conference in Granada in September 2013. A number of publications, based on these data, were prepared:

• Publications
1. Brands, B; Egan, B; Gyorei, E; Lopez-Robles, JC; Gage, H: Campoy, C; Decsi, T; Koletzko, B and Raats MM (2012). A qualitative interview study on effects of diet on children’s mental state and performance. Evaluation of perceptions, attitudes and beliefs of parents in four European countries. Appetite; 2012; 58: 739-746.
2.Gage H; Egan, B; Williams, P; Györei, ; Brands, B; López-Robles, JC; Campoy, C; Koletzko, B; Decsi, T; and Raats, MM (2014). Views of parents in four European countries about the effect of food on the mental performance of primary school children. EJCN 2013; 68, 32–37; doi:10.1038/ejcn.
3. López-Robles, JC; Egan, B; Györei, ; Brands, B; Gage, H; Decsi, T; Koletzko, B; Raats, MM and Campoy. Teacher’s beliefs of the influence of diet on children’s mental performance – a qualitative study in four European countries (Submitted to Health Promotion International).

• Posters
Three posters were presented at the Nutrimenthe International Congress and one at the IUNS 20th International Congress of Nutrition (Granada, 2013).
1. Egan B, Gage H, Williams P, Gyoerei E, Brands B, Lopez-Robles JC, Campoy C, Koletzko B, Desci T, Raats M. Association between diet and mental performance of children: views of parents and teachers in four European countries. Annals of Nutrition and Metabolism 2013; 63: 1862-1862.
2. Gage H, Egan B, Williams P, Lopez-Robles JC, Brands B, Gyoerei E, Campoy C, Desci T, Koletzko B, Raats M. Association between diet and physical and mental development of children: views of parents and teachers in four European countries. Annals of Nutrition and Metabolism 2013; 63: 1863-1863.
3. Egan B, Gage H, Williams P, Brands B, Gyoerei E, Lopez-Robles JC, Koletzko B, Campoy C, Desci T, Raats M. Factors affecting food choices of parents of children aged 4-10 years in four European countries. Annals of Nutrition and Metabolism 2013; 63: 1862-1862.
4. Gage H, Egan B, Williams P, Gyoerei E, Brands B, Lopez-Robles J-C, Brown KA, Campoy C, Koletzko B, Decsi T, Raats M. Views of parents in four European countries about the effect of food on the mental performance of primary school children. Annals of Nutrition and Metabolism 2013; 63:1132-1132.

• We have demonstrated that mental outcomes are related to diet, with the effects perceived to be associated with attention and concentration, often mediated by effects on children's mood and behaviour. Parents categorise foods as 'good' or 'bad' with positive effects related generally to a healthy balanced diet while negative effects are perceived to be associated with sugary and fatty foods.

• Findings indicate that diet is regarded as a less important determinant of mental development than physical development by parents and teachers in the four European countries studied with parents perceiving diet as a less important influence on mental performance than teachers. Generally parents and teachers think that food factors are less important influences on mental performance than sleep and quality of teaching. The most important of the food factors considered in this study were having breakfast and regular meals. Parents rely primarily on their own experience to make food choices for their children and the healthiness of food is considered most important, followed by the taste of the food, serving variety and the effect of food on energy levels. The impact of diet on mental performance is viewed as less important, though cost and convenience of preparation are the least important.

Workpackage 11 - “Economic Impact of improving mental function”
Workpackage 11 was involved in the NUTRIMENTHE project to show the economic impact of improving mental function. Its objective is to perform a comprehensive health economic analysis of pre- and postnatal nutritional interventions with proven or proposed long-term programming effects on the mental development. As first step of WP11 activity systematic literature reviews and meta-analyses of the biological effect sizes were the inevitable basis to enable the aimed economic assessment. For three early nutrition interventions with proposed effects on mental development, systematic literature reviews of randomised controlled trials (RCTs) as the “gold standard of evidence” were conducted and published in the following papers.


ADVANCE

The results were published in the following papers:
− Szajewska H, Ruszczynski M, Chmielewska A. “Effects of iron supplementation in nonanemic pregnant women, infants, and young children on the mental performance and psychomotor development of children: a systematic review of randomised controlled trials” Am J Clin Nutr 2010 91: 6 1684-1690.
− Dziechciarz P, Horvath A, Szajewska H. “Effects of n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on neurodevelopment and visual function in children: a systematic review of randomised controlled trials” J Am Coll Nutr. 2010 Oct;29(5):443-54.
− Skórka A et al. “Effects of prenatal and/or postnatal (maternal and/or child) folic acid supplementation on the mental performance of children” Critical Reviews in Food Science and Nutrition, Available online.

• For all three nutritional interventions, no or very limited available evidence was found in the systematic reviews as well as in additionally literature reviews of the effect of breastfeeding on mental development.

Without proven effect sizes of any early intervention the calculation of specific cost effectiveness analysis was not feasible, but at least a health economic model calculation of the potential economic effect was conducted. Therefore the coherence of cognitive development and society’s economical outcome was reviewed in the economic literature. For estimating the benefit from improved schooling achievements, the different economic approaches (human capital growth theory versus microeconomic individual income calculation) were analysed about their suitability for the planned economic model. In the next step, the causal relationship and design of the economic model were developed. A Model was designed, analysing the economic benefit that derives from the impact of improved cognitive skills and educational performance on the later working-life income of the individuals. Available economic baseline data on income distribution and educational attainment rates were implemented into the model, calculating the later lifetime gross incomes (consisting of the net income, income tax payments and contributions to social security services) stratified for gender and for the different levels of educational attainment. For calculating the whole economic benefit for the society’s point of view, the corresponding employers social security contributions were added to the income and the differences in educational cost were included. The amounts, which mainly occur in the far future, had to be discounted to their present value. Finally, the results of the model calculations were compared to show the economic benefit of the different levels of educational attainment.

• Within NUTRIMENTHE we have evaluated the long term effects of early nutrition and economic consequences of improved cognitive development. A decision model was constructed with a micro-economic approach comparing the educational attainment level and the corresponding expected value of average income in later life. This model calculation of health economic effects from improved mental development demonstrated a great economic potential of early nutrition interventions, given that the proposed effectiveness on improved cognitive skills. However, this model showed only the theoretical economic benefit of improving neurodevelopment by early nutrition.

• For the joint data analysis of Workpackages 2 and 11, the association of different early nutrition variables with the later school achievements was examined as indicator for the effectiveness in improving cognitive development. Therefore early nutrition data and attainment levels of more than 10,000 children of the ALSPAC cohort were analysed. Together with WP2, we performed an analysis of ALSPAC data showing a positive effect of being breastfed on achieving a higher educational outcome at age 16, which remained significant, even after adjusting for possible confounders. Children who were breastfed up to six months had an OR of 1.30 (1.13 1.51) for having 5 or more GCSEs at grade C or above compared to never breastfed children. With an extended duration of breastfeeding (>6 months) the OR increased to 1.72 (1.46 2.05). Based on the present nominal income statistics for the UK, the present value of later lifetime gross income was calculated to be 67,500 £ higher for children achieving 5 or more GCSEs at grade C or above. The resulting economic benefit of breastfeeding (< 6 months) would be £ 4,208 (~ 5,000 €) per child and even more than doubled with £ 8,799 (~ 10,500 €) for 6+ months of breastfeeding. The model calculation shows that breastfeeding - in addition to many other positive effects - may improve a child’s cognitive skills and educational achievements which then has a positive economic impact. This can generate a great economic impact for the society even from only a small increase of the breastfeeding rate among mothers. In the ALSPAC cohort with ~ 10,000 children and a share of 26 % that were never breastfed, a reduction of this share by only 1%-point to 25 % would generate a total economic benefit of more than £ 400,000 (~ € 500,000). Transferring this to a total UK birth cohort of ~ 800,000 children per year, the same increase of the breastfeeding rate would generate a gain of more than 33 million GBP (€ 50 million Euro). So, successful promotion activities for better early nutrition will therefore be highly cost-effective.




Workpackage 12 - “Project Management and Reporting to the EC”

The Management of the project was developed by the WP 12 and its role was to carry out the legal, ethical, financial and administrative themes.

General tasks of the consortium management

The coordinator and the management team have:
a) Administered the Community financial contribution regarding its allocation between beneficiaries and activities, in accordance with the grant agreement and the decisions taken by the consortium.
b) Reviewed the report to verify consistency with the project tasks before transmitting them to the Commission;
c) Monitored the compliance by beneficiaries with their obligations under this grant agreement.
d) Prepared the Periodic and Final Reports
e) Financial Management
f) Annual Reviews

The Project coordinator (Prof. Cristina Campoy, UGR) has put to good use the reporting structure and systems for the financial recording and reporting systems. The management of NUTRIMENTHE has been supported by the use of IT tools (IKEIS), which has facilitate the project management, co-ordination and dissemination of information between members of the consortium.

The management activities of the project have been carried out in WP12:
1) Co-ordinate and manage the consortium and its members, over and above the technical management of the research work packages.
2) Make use of the management framework previously created to gather together all project components, maintain overall consortium communication and act as the communication channel for all dialogue with the Commission.
3) Keep regular contact and interaction with the Steering group members.
4) Employ the General Assembly, a decision-making body comprising a representative from each participant, to make coordinated decisions in relation to the work being developed by each NUTRIMENTHE partner.
5) Support for the organisation of the meetings and ensure representation at all project Steering Group and General Assembly meetings.
6) Maintain close communication with the four NUTRIMENTHE Working Groups as they support the Project Co-ordinator and Steering Group in the management of the project. The Working Groups ensure that standard working practices are implemented throughout the project and will be responsible for bringing together some cross cutting activities such as dissemination.
7) Organise and implement project communication channels.
8) Conduct the periodic and final reports.
9) The management team has controlled that all the studies had their ethical approvals of the national authorities or local ethic committees prior to starting the studies, which must be in agreement to the national regulations and the FP7 ethical rules.
10) Coordinate, with the help of the Steering Group, the External Advisory Board (EAB) which comprises international experts who can provide a high level of critical analysis leading to added value and validation of the research approach. The involvement of these ‘outside project’ advisors is critical to the success of the project and the public dissemination of the project research and outcomes.

The EAB has met at least once a year, although not all the members have meet at the same time. The members of the EAB have been:
- Prof. Tomas Paus. Professor in Developmental Cognitive Neuroscience (University of Nottingham, UK) tomas.paus@nottingham.ac.uk. Member of the Brain and Body Centre in the same place.
- Dr. Elizabeth Baillie Isaacs, Senior Research Fellow at the Childhood Nutrition Research Centre, Institute of Child Health UCL; research area: Neuropsychologist, Neuroscience. e.isaacs@ich.ucl.ac.uk
- Prof. Wim Saris. Professor of Human Nutrition (University of Maastricht, The Netherlands) W.Saris@hb.unimaas.nl. He is coordinator of the EU 6th Framework research project DiOGenes “Diet, Obesity and Genes” and he is member of the European Technology Platform Food for Life.
- Prof. Olle Hernel. Professor in Paediatrics. Department of Clinical Sciences (University of Ümea, Sweden). Ex-member of the ESPGHAN Committee on Nutrition. Olle.Hernell@pediatri.umu.se
- Dr. Jan-Willem van Klinken. MD PhD, Columbia University, New York ex-senior project leader at Unilever leading the Child Nutrition Programme at Unilever R&D; expertise in the field of cognitive testing, mood and nutrition during childhood. Janwillemvanklinken@planet.nl
- Prof. Marcella Rietschel, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, Germany.
marcella.rietschel@zi-mannheim.de
- Prof. Mijna Hadders-Algra, professor of Developmental Neurology at the Beatrix Children’s Hospital of the University Medical Centre Groningen, Groningen, the Netherlands.
m.hadders-algra@med.umcg.nl

Project Meetings, dates and venues
• NUTRIMENTHE Kick-off meeting in Granada, 2008
• 1st NUTRIMENTHE MEETING in Amsterdam, 2008
• 2nd NUTRIMENTHE MEETING (Bristol, UK 11th - 12th of March, 2009)
• 3rd NUTRIMENTHE MEETING (Tarragona, Spain 21st - 23rd of October, 2009)
• 4th NUTRIMENTHE Biannual Meeting (Munich, Germany 6th - 8th of May, 2010)
• 5th NUTRIMENTHE Biannual Meeting (York, UK 6th – 8th of October, 2010)
• 6th NUTRIMENTHE Biannual Meeting (Warsaw, Poland 17th - 18th of March 2011)
• 7th NUTRIMENTHE Biannual Meeting (Madrid, Spain 25th – 26th of October, 2011)
• 8th NUTRIMENTHE Biannual Meeting (Rötterdam, Holland 26th - 88th of May 2012)
• 9th NUTRIMENTHE Biannual Meeting: November 2011 (Milan, Italy). Host: UNIMI
• 10th NUTRIMENTHE Biannual Meeting (Granada, Spain 12th – 15th of September, 2013)

- For Agendas and Minutes, please see Appendix 7 of this report.
- For General Assembly presentations, please see project website www.nutrimenthe.eu

Training sessions:
• ENA GRANADA POSTGRADUATE SCHOOL 2009, “Role of nutrition on brain development and behaviour” (Granada, 1st-4th October 2009)
• ANTHROPOMETRIC TRAINING, 21st October 2009 – Tarragona, Spain
• SYSTEMATIC LITERATURE REVIEW AND METAANALYSES, 21st October 2009 – Tarragona, Spain
• Public Engagement Training, 23rd October 2009 – Tarragona, Spain
• INTERACTION BETWEEN NUTRITION, GENETICS AND MENTAL PERFORMANCE - Interactive activity meeting promoted by the NUTRIMENTHE`s Working Group of Mental Performance (Lanzarote, 3-10 January 2010)
• NUTRIMENTHE WORKING GROUP OF DIET MEETING AND TRAINING. Barcelona, 18th February 2010.
• TRAINING ON NEURODEVELOPMENTAL ASSESSMENT IN CHILDREN FOR NUTRIMENTHE WP3 – NUHEAL FOLLOW UP, 22nd of January, Excellence Centre for Paediatric Research EURISTIKOS-Centre for Biomedical Research. University of Granada. Technological Park of Health Science (Spain).
• ENA CANTABRIA POSTGRADUATE SCHOOL 2010 - “EARLY NUTRITION AND PHYSICAL ACTIVITY: DETERMINANTS FOR METABOLIC PROGRAMMING” (Santander, Spain 15-18 September, 2010)
• TRAINING ON NEURODEVELOMENTAL ASSESSMENT (organised by the working group mental performance and WP7), 5th of May 2010 – Munich, Germany
• Neuropsychological Training, (organised by the working group mental performance and WP7), 8th of October 2010 – York, UK
• SOCIAL MEDIA Training, (organised by the working group communications and WP13), 6th of October 2010 – York, UK
• THE WEEK OF PROF. KOLETZKO AT THE UNIVERSITY OF GRANADA: Promoting Early Programming of the Brain.
• FORUM DISCUSSION: “Nutrition and Omics in Human Development”. (Granada, 12th April 2011)
• NUTRIMENTHE SYMPOSIUM: “Nutrition and Cognitive Function” at the 11th European Nutrition Conference, Madrid, October 2011.
• ENA SYMPOSIUM: “Nutritional Programming, from theory to practice” (Reus, 18-20 April 2012)
• Rötterdam SYMPOSIUM of May 2012
• II FORUM DISCUSSION: “Lipids and Programming” (11th Granada, June 2012)
• NUTRIMENTHE INTERNATIONAL CONFERENCE of September 2013 (Granada, Spain), closed to the 20th IUNS International Congress of Nutrition.
• YOUNG SCIENTISTS COMPETITION of September 2013 (Granada, Spain)
• Further involvement of NUTRIMENTHE has been promoted through other important events such as The Power of Programming (Münich, May, 2010) and MILANO Pediatria (November, 2012)

Co-operation with other projects/programmes

The consortium is interacting with different Research and Development Programmes. Some of the partners are involved or interacting with other Projects such as:

- MyNewGut (FP7) - Microbiome Influence on Energy balance and Brain Development-Function Put into Action to Tackle Diet-related Diseases and behavior
- EarlyNutrition (PF7) - Long term effects of early nutrition on later health.
- TORNADO (FP7) - Molecular Targets Open for Regulation by the gut flora New Avenues for improved Diet to Optimise European health.
- iFamily (FP7) - The I Family Study – helping families make healthy choices
- CONTAMED (FP7) - Contaminant mixtures and human reproductive health - novel strategies for health impact and risk assessment of endocrine disrupters.
- TOYBOX (FP7) - Multifactorial evidence based approach using behavioural models in understanding and promoting fun, healthy food, play and policy for the prevention of obesity in early childhood.
- EuroFIR (FP7) - European Food Information Resource Network.
- OPTiMiSE (FP7) - Optimisation of Treatment and Management of Schizophrenia in Europe.
- SUMMIT (FP7) - Surrogate markers for Micro and Macro-vascular hard endpoints for Innovative diabetes Tools.
- ATHERO REMO (FP7) - European Collaborative Project on Inflammation and Vascular Wall Remodelling in Atherosclerosis.
- BIOSHARE (FP7) - Biobank Standardisation and Harmonisation for research excellence in the European Union.
- BIO NET project (FP7) – A Network of National Contact Points providing cutting-edge NCP services to the Knowledge Based Bio-Economy research community.
- EARNEST EU Project (FP6) - “Early programming and long term consequences”
- EURREKA European Network (FP6) - Harmonising nutrient recommendations across Europe with special focus on vulnerable groups and consumer understanding.
- PREVENTCD - Influence of the dietary history in the prevention of coeliac disease: possibilities of induction of tolerance for gluten in genetic predisposed children.
- EVASYON – Development, application and evaluation of the efficiency of a therapeutically and nutritional programme to teenagers with obesity.
- PREOBE Excellence Project - The role of nutrition and maternal genetics on the programming and development of foetal fatty tissue. Search for obesity biomarkers
- CIBERESP - Network-Centre for Biomedical Research in Public Health – ISCIII - Spain).
- BRAINOBE - SAS-Junta de Andalucía-Spain).

There is already a contact with Project VIVA (NIH-USA) searching for common goals. Other projects are being considered such as Australian Healthy Neighbourhoods Project and other conducted by Godfrey K in Southampton.

The efforts made by UGR within NUTRIMENTHE EU Project, led to the development of a Neuropsychological Battery (NB) for children and adolescents translated into 8 different languages, which will permit the neuropsychological and cognitive assessment in many countries. This tool has been demonstrated as very useful to explore the effect of diet on the mental performance of children and adolescents and has been the baseline to build up a multicentre database including data from 1.050 European children which has been assessed with this tool which is now producing important results.

This tool is linked to other Projects which are actually being implemented in developing countries, to evaluate the effect of malnutrition and violence on the mental performance and behaviour: 1) Risk factors influencing neurodevelopment in 7-9 year old Moroccan children (1/12/2011–1/12/2013) – UGR International Cooperative Program and Chefchauen Town Hall, Morocco (23500 €); 2) Observatory for neurodevelopment and quality of life in children and adolescents (1/3/2011–1/3/2013) – UGR - University of Guayaquil, Ecuador - AECID (Agencia Española de Cooperación Internacional y Desarrollo) (Spanish Agency for International Cooperative Programs) (48000 €); 3) Canelones Project: Growth with you (Canelones Crece Contigo – CCC): Evaluation of the impact of home visits on children’s growth and development living in a low socioeconomic and food insecurity environment. (1/3/1999-1/12/2012) - Stunting, Overweight and Child Development Impairment go hand in hand as key problems of early infancy: Uruguayan case. Uruguay Catholic University (120000 €) / University of Granada (48000 €) - PNUD/Uruguay Project “MDGl” - Municipality of Canelones Uruguay, Uruguay Monesia Group - Erasmus Mundus External Cooperation Window


Workpackage 13 - “Training, dissemination and exploitation”

The main focus of WP13 was on raising awareness to the public about NUTRIMENTHE and developing the means to disseminate and communicate the work and results of the project.

WP13 used many routes to achieve this aim through print and broadcast media. Communication of the results included via two websites, through publishing newsletters, writing articles in magazines, issuing press releases, engaging with social media and organising events. Additionally, WP13 provided training to members of the NUTRIMENTHE consortium on media engagement and the use of social media.

In the context of the project as a whole, WP13 was an integral part of NUTRIMENTHES’s strategy of enabling the project to meet its objectives in terms of directing the results and key messages to the public area. In brief, the objectives of WP13 were to:
• Set up, maintain and update the website
• Set up a secure partner area accessible from the website
• Establish requirements for intellectual property protection
• Disseminate the knowledge generated by the project
• Organise and attend events
• Organise training activities

These activities were undertaken by WP13 throughout the lifetime of the project.

Dissemination
The website and IKIES (extranet)
These were delivered by month 3. The website is updated regularly by partner 18 (Beta Technology) with news, events and achievements of NUTRIMENTHE. The website is www.nutrimenthe.eu

Newsletters
10 project newsletters were planned over the five years of the project. All have been delivered to date.

Fact sheets
A number of fact sheets were planned to be delivered to different stakeholder groups for example, parents, industry, health practitioners, policy makers and researchers. To date, fact sheets have been produced for Researchers and Parents available on the website http://www.nutrimenthe.eu/fact_sheets

Posters
WP13 has produced two main posters for display at events attended or organised by Nutrimenthe. A Project Overview poster providing basic details about the aims and objectives of NUTRIMENTHE, the funding and number of partners and contact details and a Project Progress poster which includes key results emerging from the Workpackages.

Participation in activities for dissemination of results from NUTRIMENTHE
Beta Technology has represented NUTRIMENTHE at a number of events over the first three years of the project and has displayed posters at all of them.

Nutrevent, Lille, June 2009
Nutrevent is a biannual event dedicated to disseminating information about the latest scientific and clinical results on nutrition and health. It can attract up to 2500 delegates from academia, the food industry, investors, and professional associations and networks. Nutrimenthe submitted an abstract and was accepted to present a poster in the exhibition space. The A0 poster (Project Overview poster) designed by Beta Technology was displayed in the event track – ‘Challenges and issues in nutrition health’ for the two days.
European Food Science Day, Brussels, October 2010
The aim of this event day was to disseminate the results of EU-funded projects in the field of food and nutrition science and was attended by over 100 participants. Speakers included high level representatives from the EC, EFSA, the Confederation of the Food and Drink Industries and the European Consumers’ Organisation. Beta Technology displayed the Project Overview poster.

Power of Programming, Munich, May 2010
This event was organised by the EARNEST project, the Early Nutrition Academy and the International Society for Developmental Origins of Health and Disease. 585 delegates attended from 51 countries. Overall, the NUTRIMENTHE consortium presented nine posters and hosted one symposium, Programming of Neurodevelopment which featured presentations on the role of folate and LC-PUFA intake during pregnancy and later mental development. WP13 displayed the Project Progress poster.

Euroscience Open Forum Turin, July 2010
ESOF is Europe’s largest meeting place for researchers, stakeholders, students and science journalists, the theme for which is “Passion for Science” The event takes place biennially. The 2010 event attracted more than 4000 delegates. NUTRIMENTHE was represented by Beta Technology at an exhibition booth funded by 10 projects (including NUTRIMENTHE) from the CommNet network. Visitors to the booth could talk to representatives from the CommNet projects and collect information about the projects. The Nutrimenthe Overview poster was displayed in the booth.

Organising events

WP13 organised and assisted the events highlighted below.
1) Power of Programming Conference, Munich, May 2010
2) The Open Forum event in York (UK) in October 2010.
3) NUTRIMENTHE at the 11th European Nutrition Conference, Madrid, October 2011
4) Rotterdam 25th May 2012
5) NUTRIMENTHE International Conference 13th and 14th September 2013
6) Young Scientist Competition, Granada, September 2013

WP13 join together with the Communications Working Group organised NUTRIMENTHE’s first stand-alone event in York the aim of which was to showcase NUTRIMENTHE’s results to date. In total, 42 delegates attended the event in which partners from NUTRIMENTHE presented an overview of their work, and results to date. Delegates included partners from NUTRIMENTHE, academics from UK universities, university undergraduates, dieticians, a school’s healthy eating advisor and a representative from the UK’s government’s Food and Environment Research Agency (FERA). Following on from this event, the presenters were interviewed by a freelance journalist and the clips were edited and placed on NUTRIMENTHE’s YouTube channel.
A novel activity was undertaken, the organisation of a competition, for Young Scientists, run within the NUTRIMENTHE International Conference. There was an extension of the engagement in Social Media and international associations of consumers were contacted as required by the project reviewers.

Publicity for the Open Forum Event in York
Intended to be a general dissemination event to promote NUTRIMENTHE and present the research findings to date from a number of the workpackages. The event was aimed at academia, health professionals, policy makers, consumers and industry. Delegates included partners from NUTRIMENTHE, academics from UK universities, university undergraduates, dieticians, a school’s healthy eating advisor and a representative from the UK’s government Food and Environment Research Agency (FERA).
After the York Open Forum the partners that presented work at the event took part in one-to-one interviews with a freelance journalist. The clips are uploaded at the NUTRIMENTHE’s new You Tube channel http://www.nutrimenthe.eu/nutrimenthe_on_you_tube_.

Publicity for the Rötterdam Symposium
In the weeks preceding NUTRIMENTHE’s symposium in Rotterdam, WP13 assisted in the publicity by designing the event flyer and distributing this through via the NUTRIMENTHE website, newsletter and to the NUTRIMENTHE partners, who were encouraged to circulate the information to their contacts. Following the event, notes taken during the presentations were written-up and posted on the website (see link below) and circulated to the newsletter subscribers.
http://www.nutrimenthe.eu/nutrimenthe_sympsium_in_rotterdam,_the_netherlands,_may_2_12

Publicity for the NUTRIMENTHE International Conference
Publicity regarding the International Conference was started in the months preceding the event.
Printed flyers. Flyers were designed and added to the delegates’ packs of the Milano Pediatria event that took place in November 2012 and also sent to an event organised by the British Nutrition Foundation that took place in London in May 2013.
Website. The event was posted on the NUTRIMENTHE website and on the IUNS website.
Newsletters. The event was added to the March 2013 and July 2013 newsletters
Targeted e-mails. Additional e-mails were sent specifically to other FP7 projects, nutrition societies and other professional organisations in the months preceding the event to publicise the event and to attract more delegates.
Press releases: Press releases were issued via CORDIS.
Social Media: Facebook and Twitter were used to send updates about the project and the event to NUTRIMENTHE’s followers on Twitter and Facebook.

It was noted that the International Conference appeared on the following websites between others:

The Nutrition Society.
http://www.nutritionsociety.org/events/nutrimenthe-international-conference

Council for Health Research for Development
http://www.cohred.org/2013/05/nutrimenthe-international-conference-13th-to-14th-september-2013/

Sociedad Española de Nutrición
http://www.sennutricion.org/en/2013/09/13/nutrimenthe-international-conference

NUTRIMENTHE conference flyer on Europa
http://ec.europa.eu/research/bioeconomy/pdf/nutrimenthe_conference_flyer_.pdf

The ID Consortium
http://idconsortium.es/en/news/nutrimenthe-international-conference-granada-spain-0

The CommNet project
http://commnet.eu/06_Events/Completed_Events/Young_Scientists_Forum_Competition.kl

The Albion Alliance
http://blog.albionalliance.org.uk/2013/09/nutrimenthe-international-conference-granada-spain/

International Confederation of Dietetic Associations
http://www.internationaldietetics.org/Newsletter/Vol20Issue2/Calendar-of-Events.aspx

The Tornado project
http://www.fp7tornado.eu/


Articles (see also Appendix 5)

International Innovation magazine
This magazine is the “leading global dissemination resource for the wider scientific, technology and research communities” it gives subscribers access to “bespoke interviews and insightful comment from leading figures in science, technology and administration” and “exclusive content and presentations from leading research teams and institutes”. The NUTRIMENTHE article was based upon a bespoke interview with Cristina Campoy with an added two-page editorial on NUTRIMENTHE titled “Food for thought” The article appears in full on the Nutrimenthe website.

Families Oxfordshire
This magazine is part of the Families Online group, a group of local magazines produced throughout the UK that provide support to families through features covering a wide range of parental issues, events listings, local contacts and forums. WP13 collaborated with a journalist from Families Oxfordshire to produce an article called “Food for thought” which featured an overview of Nutrimenthe and results from WP1 (the effect of folic acid supplementation during pregnancy on mental performance) and WP2 (the benefits of eating oily fish during pregnancy). The article was followed up with information about what to eat and what to avoid during pregnancy using information from the UK’s Food Standard Agency. The article appears in full on the Nutrimenthe website.

Other publications in this area are:

A write-up of NUTRIMENTHE’s symposium at FENS 2011 was posted on the Public Information page which was picked up and reproduced on the following website.
A NUTRIMENTHE article that appeared in Complete Nutrition magazine was reproduced in the journal of Nutrition and Health 2013

Expert Omega-3 (see in the website)
http://www.expertomega3.com/en/omega3-news-item.asp?NoticiaID=191

Two additional short articles, written by Beta and reproduced in full below, were posted on the website in the information and fact sheet section;
1) A brief overview of Omega-3 and Omega-6 Fatty Acids (based on papers published by NUTRIMENTHE)
2) The role of diet in the mental performance of children, what do parents think? Feedback from NUTRIMENTHE’s Consumer Surveys.

Press releases

The following press releases have been written during the framework of the project:

Year
2008 1) The effect of diet on the mental performance of children, the Nutrimenthe FP7 project investigates.
2) An infant’s future mental abilities and susceptibility to mental illness can be permanently altered by dietary changes in early life
2010 3) Folic acid supplements taken during pregnancy may benefit toddler behaviour.
4) Are brainer children better fed?
5) Alimentando a las generaciones futuras para mejorar su desarrollo mental.
2011 6) Lack of folic acid linked to emotional problems in children
7) Lack of thyroid hormones linked to language delay in childhood.
8) Fish eating in pregnancy, genes, omega-3 fatty acids and the impact on “brain power” in children – the NUTRIMENTHE Project.
9) Come pescado y desarrolla la capacidad intelectual
10) The first 1000 days
11) Policies for a healthier European diet: are they effective?
12) The role of diet in the mental performance of children, what do parents think? Feedback from NUTRIMENTHE’s Consumer Surveys of parents.
13) The effect of food on learning: views of parents in four European Countries.
2012 14) Food for thought
15) Are brainier children better fed?
2013 16) Nutrimenthe o cómo la nutrición influye en el desarrollo de los niños
17) La alimentación durante los primeros años determina nuestro comportamiento
18) La alimentación de las embarazadas determina el desarrollo del niño
19) NUTRIMENTHE project subject of a documentary “Food for Thought”
20) Good food for babies the earlier, the better
21) Brain power from brain food for children
22) Brain development Nature or Nurture?

All appear on the Project website here: http://www.nutrimenthe.eu/press_releases

Trainings

Training in the first three years has been given on the use of the website and extranet folder system; public engagement training, which was delivered by Beta Technology at the Post-graduate training school in Granada (October 2009) and at the Nutrimenthe partner meeting in Tarragona, September 2009. Also, an introduction to and use of, social media, was given at the York partner meeting in October 2010.


Content of the Public Engagement training
The training comprised a 45 minute presentation on the basics of communication and the importance of communicating scientific research, media relations, writing press releases organising press conferences and good practice with respect to setting up websites and generating project literature. The presentation was followed by two practical sessions which included the appraisal of written material (messages and style) and role plays involving communication with parents and the media.

Take home messages included:
• Consideration must be given to the level of understanding of the target audience
• Develop a communication strategy, assign a budget and evaluate regularly

Social Media training
The Communications Working Group organised a training session at the York partner meeting (October 2010) “Social Media for Nutrimenthe” looking at different social media and how Nutrimenthe might engage with them. The company, Science Communications Ltd was engaged to provide the training and to write a report “Using social media for dissemination and public engagement in the Nutrimenthe project” The training ran for two hours and 11 partners attended. The main social media addressed were Twitter, Facebook, LinkedIn. Also commented on were in You Tube, blogging, social bookmarking and Foursquare. From this training session, WP13 drafted a social media policy for consideration.

Exploitation
The exploitation strategy is included in the Communication Strategy document. Essentially, the principles of the coordination and handling of exploitable results are specified in the Consortium Agreement (CA) (pages 17-21). If there are any changes to the procedures for IP from those in the Consortium Agreement the General Assembly must approve them and then specify the necessary changes to the consortium agreement. In the first three years of the project, the exploitation strategy has not been implemented.
• Throughout the lifetime of the project, WP13 Leader, Beta Technology, has maintained a connection with the CommNet project. CommNet began as an informal network of Communication Managers from Food projects funded through the EC’s 6th and 7th Framework Programmes. CommNet received formal funding from FP7 in 2012 and is running until the end of 2014.
• Through Beta’s engagement with CommNet, a number of good contacts have been maintained which led to the opportunity for NUTRIMENTHE to participate in meetings (for example the European Science Open Forum in Turin, 2010) and training events run by CommNet and the invitation to present the work of the NUTRIMENTHE project at the Second Bioeconomy Forum on the 1st October 2013. In addition, through this collaboration, Beta Technology became a host organisation for the Erasmus Programme and hosted an entrepreneur from Austria in November 2013. This individual is due to return to Beta for two months in 2014.
• As a partner in NUTRIMENTHE, Beta Technology has benefited by being invited to become a partner in other proposals for funding from the European Commission namely, from the KBBE programme and the EuropeAid programme, with members of the NUTRIMENTHE consortium. It is hoped that through participation in NUTRIMENTHE, additional opportunities will arise for Beta to become a partner in proposals for funding from Horizon 2020.

WORK PROGRESS AND ACHIEVEMENTS OF THE WORKING-GROUPS
The Working Groups ensure that standard working practices are implemented throughout the project and are the responsible of bringing together some cross cutting activities such as dissemination. The four Working Groups identified to support this function are:

• Mental Performance Working Group, led by UGR (Cristina Campoy, Miguel Pérez), to focus on gathering consensus and sharing experience during the development of the cross-cultural neuropsychological battery.
• The Diet and Nutrition Working Group, led by UNI BRI (Pauline Emmett), to coordinate the dietary data analysis. The output was to develop a consistent food frequency questionnaire and daily intake questionnaire for children for all EU countries participating in NUTRIMENTHE.
• The Anthropometrics & Physical Activity Working Group, led by URV (Veronica Luque), to focus on the development of a protocol for anthropometric measurements in the different ages included in this project.
• The Communications Working Group, led by BETA (Jayne Evans) to coordinate on a consistent approach to how information and results are disseminated to incorporate all relevant stakeholders.

The main objective of the working groups was to achieve an harmonisation in the different protocols between the workpackages. The structure of this harmonisation in the different phases of the study has been the following:
1. Development of common protocols (whenever is possible)
2. Writing Standard Operating Procedures (SOPs)
3. Training study personnel
4. To define common hypothesis to be studied to integrate cross-workpackage results
5. To perform statistical plans

The major achievement of the work performed by the Working Groups, have been the generation of the NUTRIMENTHE Global Database after the integration performed between some of the WPs. Moreover, the Statistical Plan approved by all partners involved, includes the joint publications programmed, some of them already in draft. This approach has been an extra effort of the consortium in order to achieve a better integration and to obtain further common results.

To achieve this goal, there was a specific Meeting held in Granada in September 2012. A NUTRIMENTHE Committee formed by the coordination group, statisticians and the leaders of the different Working Groups (Mental Performance, Dietary assessment and Anthropometry & Physical Activity) met in Granada to develop a list of common hypotheses to study through the NUTRIMENTHE Global Data Base. There, a Strategy plan for the development of the Global Data Base, for statistical analyses and outline publications was discussed. Then this plan was presented at Milano Meeting for its final approval.


WORKING GROUP OF MENTAL PERFORMANCE
Leaders: Prof. Cristina Campoy and Prof. Miguel Pérez (UGR)

Work progress and major achievements (More information available in Appendix 2)

This Working Group (WG) started working in Granada in April 2008 during the Kick-off meeting of NUTRIMENTHE. The main objective of this working group was the integration of knowledge emerging from the different Work Packages related to mental performance and behaviour in the NUTRIMENTHE children, stimulating the discussions to improve the procedures, harmonisation and the added value coming from the whole consortium.

The WG mental performance has been involved in maintaining the harmonisation process and assisting all partners with any issue related to the Neurodevelopment tests battery including the development of a common database. Moreover, the WG has been sharing experiences, solving doubts and developing the agreement between partners to perform the cross-cultural analysis. Currently, the WG is leading the statistical study of the NUTRIMENTHE Global Database (see Appendix 2), given support to the other partners involved to develop the papers agreed.

It has also been leading the preparation and publication of the article entitled:

Anjos, T., S. Altmae, et al. (2013). "Nutrition and neurodevelopment in children: focus on NUTRIMENTHE project." Eur J Nutr 52(8): 1825-1842.

Furthermore, the WG of Mental Performance has been crucial for the development of the NUTRIMENTHE International Conference held in Granada in September 2013, joined to the IUNS International Congress of Nutrition. It was a successful event, with more than 180 participants, 5 Symposiums, 34 speakers, 4 Keynote Lectures, 50 posters, and the Young Scientist Competition Forum, where this WG has taken an important role in the organization of this event.

In conclusion, the Mental Performance WG has demonstrated to be an important and strong structure to increase the harmonisation and integration between partners. The results already obtained from this approach are really of substantial interest. The expected new results after further statistical studies seem that will be of high relevance.

Mental performance assessment within NUTRIMENTHE
A Neuropsychological battery has been designed especially for NUTRIMENTHE children. This battery was prepared to evaluate different domains of cognitive development of the children. There has been an agreement between WP1, WP3 and WP4 to assess the children in the same way with the NUTRIMENTHE neuropsychological battery the mental performance and behaviour development & problems at 8 y; a total sample of 1050 children was assessed with this tool. However, other numerous neuropsychological measurements were done in some of the WP involved in NUTRIMENTHE. So, the WP of Mental Performance was working to update this information in order to find synergies for further harmonized analysis.

To ensure the correct application of this battery several trainings were performed by the WG Mental Performance and a NUTRIMENTHE Blog (www.nutrimenthenablog.org) was also developed, where all WPs involved could discuss any issues relate with the application of the Neuropsychological Battery.

A Strategic Statistical Plan for the analysis of the Global NUTRIMENTHE database has been developed and agreed stimulated form the WG of Mental Performance (Appendix 2).

The following common hypotheses were finally chosen to be analysed from the Global Data Base as final outlines from the Working Group on Mental Performance:

HYPOTHESES AIMS
Early nutritional, genetic and environmental factors are related to neurodevelopment and behaviour. To perform feature selection, selecting the most informative items obtained in the NUTRIMENTHE assessment, to detect patterns of association between selected variables and rates of neurodevelopment and behavioural problems in European children.
Modulator factors such as gender, parental smoking, socio-economic factors or FADS genetic polymorphisms affects mental performance and behaviour.
To determine the role of confounding factors during foetal life, infancy and childhood, on brain development, mental performance and behaviour in children up to 8 years in a European sample; To evaluate how genetic polymorphisms, gender differences, smoking during pregnancy or socio-economic factors could determine long-term effects on mental performance and behaviour.
Project Months 66 and 67, these 2 hypothesis of the Working Group of Mental Performance were tested through the Global Data Base.

These preliminary analyses were presented at the NUTRIMENTHE International Conference organised in Granada (September 2013). As well UGR gave statistical support for the Working Group of Anthropometry and Physical Activity to prepare their paper. The working group Mental Performance has promoted and implemented the harmonised collaboration between the partners and is working towards the neurodevelopmental analysis. All this information has been placed in the intranet of the NUTRIMENTHE website.


WORKING GROUP DIET AND NUTRITION
Leader: Prof. Pauline Emmett (UNIBRI)

Diet is an integral part of the NUTRIMENTHE project both as an input and a confounding variable. What mothers eat in pregnancy and the supplements they take can play an important role in the neurodevelopment of their infant and thus in the child’s later mental performance. What children eat during infancy and childhood can also affect their mental performance both short and long-term. Therefore it is important to assess diet as accurately as possible in the mother and child at various ages.

The working group on dietary assessment and dietary data analysis has been successful in supporting the nutritional aspects of NUTRIMENTHE. In particular, devising strategies for analysis of the FFQ and food records collected in different studies and the harmonisation of the data for the purpose of making meaningful comparisons between countries and studies. The scientists have worked well together and produced publications both individually and across countries and studies. The working group has made an important contribution to the success of NUTRIMENTHE.

In a collaborative project it is important to harmonise the measurement of diet between projects to allow comparisons to be made. However, it is also important to recognise that different foods and food habits are found in different countries in Europe so assessment of diet must take this into account. Methods need to be found that allow comparisons across study and country and that do not obscure the similarities or differences that may exist between food and nutrient intakes that may relate to measured NUTRIMENTHE outcomes. The WG of diet and nutrition had the objective to harmonise dietary data collection between studies and facilitate meaningful analysis of dietary data between studies and countries. In order to achieve this objective, all nutritionist involved in the collection of longitudinal dietary data from WP1 (Generation R), WP2 (ALSPAC – all dietary data were collected prior to NUTRIMENTHE and are therefore being used as a baseline), WP3 (NUHEAL) and WP4 (CHOP), had several productive meetings (More information in Appendix 6). All pregnancy and infancy data were collected previously, NUTRIMENTHE has concentrated on collecting mid childhood dietary data.

Two dietary assessment methods have been used; food frequency questionnaires and records of all foods eaten by children. The working group has discussed and implemented ways of maximising the details obtained from parents and children themselves.

To aid comparability of the dietary data we have had detailed discussions to harmonise the food group classification of all foods eaten in different countries and studies. This has involved discussion between nutritionists and statisticians to make sure that analysis of the datasets is facilitated. The implementation of the decisions is on-going. We have discussed the use of classification into nutrient-rich core and nutrient-poor non-core foods to give us a way of presenting analysis which will facilitate communication with the public; a key objective for NUTRIMENTHE.

Work progress and major achievements (More information available in Appendix 2)

At the first meetings, it was clear that there was a need to work on standard procedures to be used for diet assessment in the older children. To this end the CHOP team obtained funding for Dr Pauline Emmett to travel to Reus in July 2012 to discuss in detail the harmonisation of the CHOP dataset. The classification of food groups was discussed in detail and it was decided that the German food composition data base would be used as the template for this objective. Possible ways of analysing the dietary data were also discussed with input from the CHOP nutrition team and Veit Grote regarding statistical methods. Decisions were made about how to deal with missing nutrient data. Finally, dietary data has been collected from children in the NUTRIMENTHE work packages and analysis of nutrients and food groups have been done.

NUTRIMENTHE nutritionists from Generation R, ALSPAC and CHOP reported back on a meeting of EUCCONET which had focused on nutrition data and analysis in longitudinal datasets. This had been a useful meeting at which our work was shown. Pauline Emmett presented some ideas about ways of analysing dietary data that can help to maximize its interpretation from a public health perspective.

It was decided that in order to progress with the dietary data collected in NUHEAL María José Piqueras would travel to Bristol to work with Pauline Emmett for three months at the beginning of 2012; she was granted by the Research Plan of the UGR.

Regarding the analysis of the NUTRIMENTHE Global Database, the following common hypothesis was finally chosen to be analysed as final outlines from this Working Group on Diet and Nutrition:

HYPOTHESES AIM
Fish consumption improves mental performance and mental health in childhood.
To analyse the relation between fish intake and cognition in children aged 8 in a European sample.
Project Months 66 and 67, this hypothesis of the Working Group of Diet and Nutrition was tested through the Global Data Base.

During 2013, a new grant was achieved for brain mobility; in this case it was Mrs. Mariona Gispert-Llauradó who went to Bristol to work on the NUTRIMENTHE Global Database from month 63 to 69, specifically with the records regarding dietary assessment in children from CHOP and NUHEAL and also analysing the diet impact on mental performance in children at 8 years.

ADVANCE

The two stays mentioned, facilitated the development of the following papers:
1. Piqueras MJ, Campoy C, Miranda MT, Decsi T, Koletzko B and Emmett PM (2014). Comparison of childhood size and dietary differences at age 4 years between three European countries and associations. Eur J Clin Nutr (2014), 1–7.
http://dx.doi.org/10.1038/ejcn.2014.43
2. Gispert-Llauradó M, Miguel Perez, et al. Fish consumption in mid-childhood and its relationship to neuropsychological outcomes measured in children in 7 European countries using a standardised battery. 2014 (drafted).
3. Emmett P, Luque V, et al. Effective ways to involve children in recording their own diet; experience in 6 European countries. BJN (suppl.) (in draft).

Comparative analysis of diet within core and non-core food groups has been performed for NUTRIMENTHE year 5. The Working Group of Diet and Nutrition facilitated the correct assessment and dietary data analysis, and has built up a good collaboration between the partners which have been working towards harmonisation of dietary analysis.

Some of the results of this Working Group were presented at the IUNS International Congress of Nutrition and the NUTRIMENTHE International Conference held in Granada (September, 2013).


WORKING GROUP ANTHROPOMETRICS & PHYSICAL ACTIVITY
Leader: Prof. Ricardo Closa, Prof. Joaquín Escribano and Dr. Verónica Luque (URV)

Work progress and major achievements: Anthropometry and Physical Activity Assessment (More information available in Appendix 2)

The “body physical status” may be related to mental performance (including both cognitive development and mental health). Both growth and physical activity are considered important factors for mental development in Nutrimenthe that may act as confounders in the relation diet-neurodevelopment as well. Several WPs in NUTRIMENTHE take records and measures of anthropometry and physical activity. WP1 (Generation R) and WP2 (ALSPAC) collected most of the data prior to NUTRIMENTHE, and WP3 (NUHEAL) and WP4 (CHOP) have collected longitudinal data prior and during NUTRIMENTHE. The main objectives of the Working Group on anthropometry and physical activity has been the harmonisation of methodologies used to assess anthropometry and physical activity and to integrate the results obtained between workpackages.

To achieve the harmonisation between the different WPs, partners from the different WPs have participated in meetings organised in:
1. Amsterdam (where the objectives and plans of the WG were defined)
2. Tarragona (where the SOPs document was presented and distributed among partners and the study personnel was trained)
3. Madrid (where common hypothesis for the different WPs were defined) and
4. Rotterdam (where a draft document called “Integrated Statistical Plan” was presented).
5. Milano (where the “Integrated Statistical Plan” was approved).

In Granada, September 2012: a NUTRIMENTHE Committee formed by the coordination group, statisticians and the leaders of the different Working Groups (Mental Performance, Dietary assessment and Anthropometry & Physical Activity) met in Granada to develop a list of common hypotheses to study through the Nutrimenthe Global Data Base. There, a strategy development of the Global Data Base, for statistical analyses and outline publications were discussed.

The following common hypotheses were finally chosen to be analysed from the Global Data Base as final outlines from the Working Group on Anthropometry and Physical Activity:

HYPOTHESES AIMS
Head circumference growth rate during the first 4y of life is related with neurodevelopment in childhood. To analyse the relationship between head growth velocity during the first 4 years of life with later mental performance
Overweight and obesity are related with the mental performance and mental health of children at 8y of age To analyse the relation between BMI, BMI z-score, diagnose of overweight and obesity with mental performance and mental health
Excessive sedentary activities have negative effects on mental performance and behaviour of children. To demonstrate the role of sedentary activities (i.e. TV watching) on cognition and behaviour in children.
Project Months 66 and 67, the first hypothesis of the Working Group was tested through the Global Data Base (Head circumference growth during the first 2 years of life may be a predictor of later mental performance).

The preliminary analyses of the NUTRIMENTHE Global database regarding the Anthropometry and Physical Activity data, were presented at the NUTRIMENTHE International Conference organised in Granada (September 2013).

ADVANCE
The conclusions by topic of the working group meeting were:
1. Neonatal anthropometry: It is well known that preterm and small for gestational age infants may have a relative impaired mental performance in the future in relation to term and healthy born infants. It would be very difficult to show any interesting result in relation to neonatal anthropometry and mental performance. Therefore, the WG agrees not to spend resources in the study of this relation, although neonatal anthropometry will be used as confounder for all analyses.
2. Head circumference: It was seemed very promising the proposal to analyse head circumference in relation to mental performance in all the cohorts. Evidence from ALSPAC, CHOP and NUHEAL has been confirmed that postnatal head size is a marker for brain development in healthy, term, children; as well, it has been shown that specific cognitive functions may be related to head growth during specific periods of childhood. Head circumference measured at birth might not be a good measure (because of the head shape adopted for the delivery channel). The main point is that the most important head growth takes place during the first 2 years of life and this could be related to latter brain size. This has become a very good hypothesis to be explored, as all WPs have measured head circumference at different time points and could relate this with later mental performance (in different countries at different ages).
3. Growth velocity/growth faltering: There is no many published literature comparing growth faltering/growth velocity in term newborns in relation to latter mental performance. This is also being explored in the NUTRIMENTHE cohorts.
4. Overweight/Obesity: It seems to be very clear that overweight/obese children could have mental performance problems and higher risk of psychopathology. Although the percentage of overweight and obese children in the studied samples might not be very large (given that the studied samples are “originally healthy”), this is a very interesting topic which is already being studied pooling the different cohorts.
5. Physical Activity: All WPs present at the meeting have collected physical activity data. This is related to both mental performance and overweight & obesity. All the groups agreed to analyse these relations in the NUTRIMENTHE cohorts.


COMMUNICATION WORKING GROUP
Leader: Claire Horton, Jayne Evans and Ben Mico (Beta-Technology)

Work progress and major achievements: Communication/Dissemination of NUTRIMENTHE results (More information is available in Appendixes 2,5,6,7)
The dissemination of the results obtained within NUTRIMENTHE has been the main objective of the Communication Working Group (CWG) by providing the overall strategy for dissemination, training and public engagement.

Overall, we have tried throughout the project to raise awareness to the public about NUTRIMENTHE and developing the means to disseminate and communicate the work and results of the project. We have used many routes to achieve this aim through print and broadcast media. Communication of the results included via two websites, through publishing newsletters, writing articles in magazines, issuing press releases, engaging with social media and organising events. Furthermore, several videos have been developed and placed in internet (youtube), and one of them has been disseminated in television (Euronews) to more than 200 countries (Appendix 6).

The drafting of the key messages of the project was been coordinated by the CWG and progress was made regarding the delivery of D13.8 the project brochure. A novel activity was undertaken, the organisation of a competition, for young scientists, run within the NUTRIMENTHE International Conference. There was an extension of the engagement in Social Media and international associations of consumers were contacted as required by the project reviewers.

Main achievements:
• Improvement of the NUTRIMENTHE website (www.nutrimenthe.eu)
• Development and implementation of the Dissemination and Exploitation Strategy Plan
• Publication of 10 Newsletters
• Publications in magazines:
- Enhancing Mental Performance: Food for thought: www.researchmedia.eu pp.25-27
- Horton C. An overview of the NUTRIMENTHE Project. Journal compilation © 2012 British Nutrition Foundation Nutrition Bulletin, 37, 152–156.
- Horton C. Does prenatal nutrition affect mental performance of childhood?. NHDmg.com May 2013 – Issue 84; pp. 28-29.
- Horton C. Nutrition and Mental Performance in children. Complete Nutrition 2013; vol 13 (3): 33-34.
- Brain Power from brain food for children. The CommNet Innovation Catalogue 2013. pp. 10-11.
• Different publications in different bulletins and magazines.
• The development of a series of videos for the NUTRIMENTHE Project dissemination
• The development of a Video clip produced by Futuris which appeared in Euronews
• Promoting interviews in the radio and TV, and press releases published in the media (more than 15.000 citations in internet)
• Engagement in Social Media
• The Young Scientists Competition
• Progressing the key messages of the project
• Deliverable 13.8 – A brochure delivering the key messages of the project (www.nutrimentheproject.eu)
• Engaging International Associations of Consumers

Extension of the Engagement with Social Media

NUTRIMENTHE engaged with two additional social networks, Facebook and Twitter. Prior to this, NUTRIMENTHE had set up a profile on LinkedIn and a channel on You Tube, to post videos of the project. Links to these social networks was place on the project website.

The Facebook and Twitter profiles were set up in April 2013, with the aim of promoting the NUTRIMENTHE International Conference and the Young Scientists Competition (Appendix 2). These networks were also useful in the posting of NUTRIMENTHE articles, NUTRIMENTHE newsletters and other success stories of the project for example, the Paediatric Nutrition Research Award for Young Investigators won by Eva Reischl of HELMUC. Twitter proved useful in re-tweeting interesting news and articles and also in the following of conference proceedings for example the World Congress of Nutrition conference in Granada (September 2013), the Feeding Healthy Minds event in London (October 2013), the Developmental Origins of Health and Disease event in Singapore (November 2013) and the Nutrigenomics EU event in Ireland (November 2013). Plus, the potential for NUTRIMENTHE Tweets to be re-tweeted by follower’s means, potentially, a large audience can be reached. The CWG is aware of the transient nature of Twitter in that the number of followers can easily rise and decline. By the end of the project, NUTRIMENTHE had sent 107 Tweets and picked up 80 followers. The more notable followers include other EU projects (ToyBox, Food4Me, iFamily, HelixEpisome, CommNet), the British Nutrition Society, La Leche League, the GAIN Alliance, University of Granada, the JRC for Nutrition, International Life Science Institute, Nestle’s EU Affairs, the Foundation for Mother and Child Research and individual dieticians and nutritionists. The Facebook and Twitter social networks continued to be used following the end of the project on 31st December 2013.

Engaging International Associations of Consumers

More than 25 Associations, Companies and Stakeholders related to consumers have been contacted, and from these contacts 85% have been successful. In this moment several important actions as an extension of NUTRIMENTHE are on-going in China and South America (Appendix 2).


Potential Impact:
The potential impact (including the socio-economic impact and the wider societal implications of the project so far) and the main dissemination activities and exploitation of results (not exceeding 10 pages).

We foresee that NUTRIMENHTE Project will have even more direct impact on the population. The key messages developed will offer now broad possibilities for further impact on the European Society, as well as an extension of the knowledge generated in the NUTRIMENTHE Project and bigger impact all over the world. For such purpose, a new website www.nutrimentheproject.eu has been developed in order to disseminate key messages and papers published to provide evidence for them. The NUTRIMENTHE website www.nutrimenthe.eu will be alive for one more year, and at the same time the new website will be available also from the ENeA website http://www.early-nutrition.org/enea.html for as long time as possible while the new papers will being published. Further information is provided on the websites above.

Socio-economic impact and the wider societal implications of the project so far
NUTRIMENTHE includes a number of key studies that define, quantify and time the impact of specific nutritional interventions on long-term cognitive, neurophysiologic and behavioural outcomes. The potential impact of nutrition on the brain would affect the whole of society and its effects would reach every age group. This includes effects on:
(i) Intelligence, and therefore education, economic productivity and economic growth.
(ii) Acquisition.
(iii) Mental illness and disturbed behaviour.
(iv) Dietary intake of the nutrients concerned during early life and childhood and attitudes/beliefs of consumers towards the effects of nutrition on mental performance.

NUTRIMENTHE Project has having impact through:
(i) Increasing knowledge of nutrient effects in mental performance, and so stimulating technological innovation and improving research methodologies in this area.
(ii) Providing sound scientific data to substantiate health and nutrition claims and to develop harmonised dietary recommendations for specific population groups.
(iii) Enhancing the cooperation and dialogue between different scientific disciplines (nutrition, food science, paediatrics, neurosciences, etc.).
(iv) Increasing the excellence and innovative potentials of the European nutrition research communities by means of stronger links to cognitive and behaviour neurosciences.

NUTRIMENTHE has had a strong impact on the programme towards the topics, because it includes a number of key epidemiological studies with large cohorts in the EU, which has enhance the knowledge about the long-term effects of early, infant and children nutrition on mental performance. The first way in which NUTRIMENTHE yield increased knowledge is by combining dietary intakes, nutritional status and FADS genetic polymorphisms from several large cohorts (Generation R, ALSPAC, CHOP, NUHEAL) across Europe and linking them to newly performed measures on mental performance. NUTRIMENTHE also includes a number of key studies that define, quantify and time the impact of specific nutritional interventions on long-term cognitive, neuromotor, mental performance and behavioural outcomes; moreover, NUTRIMENTHE has offered the opportunity to assess not only mental performance or behaviour related to diet, but also general health status (diet, physical activity,..), as well as other confounding factors. These examples indicate that the studies involved in NUTRIMENTHE has been able to demonstrate that early nutrition (early programming) is one of the most important influences on long-term cognitive and mental disorders. This knowledge is invaluable to public health practice (impact on general health), but also for consumers, parents, institutions, policy advisers and product development. Furthermore, NUTRIMENTHE has make a strong effort to impact in Europe by providing information on public awareness across Europe of the important role of nutrition on mental performance in children; it has contributed to the demonstration of the need to develop programmes to increase the understanding of how adults can act to promote better nutrition during pregnancy and infancy and health food choice in children (consumers-social impact) for an optimal cognitive and behaviour development.

NUTRIMENTHE has brought together researchers specialising in paediatrics, nutrition, child psychiatry as well as child psychology, and this has created harmonised approaches to the test methodologies used (cooperation between different disciplines). The project has also transfer as much knowledge as possible on neuroscience measures between the various research groups concerned (improvement of research methodology). The results achieved in NUTRIMENTHE will impact on the development of new products for the market and will stimulate technological innovation. A large quantity of data has been generated on dietary intakes and nutritional status from pregnancy up to childhood, and linked to measures of cognition, mental state and illness. Moreover, the data obtained will lead to the development of several claims on food products (dietary recommendations). The dissemination WP has ensured effective publication of the project results across the EU, and targeted at specific stakeholder groups, on time along the NUTRIMENTHE Framework. The evaluation of the economic impact of better cognitive and mental performance has been very innovative since it has assessed the impact of newly identified preventive measures, such as the improvement of early nutrition. NUTRIMENTHE has demonstrated that improving neurocognitive function, mental performance and behaviour development of the EU community increase education, productivity and economic growth (economic impact).

With the Generation R we were able to demonstrate that children born to mothers who did not use folic acid supplements during the first trimester of their pregnancy had a higher risk of total problem behaviour and even structural differences in the brain at the corpus callosum. As well with this cohort we have shown that poor maternal thyroid function during pregnancy is an important risk factor for children's brain development.

From the ALSPAC study a very clear message has been developed about that eating fish regularly and an adequate iodine intake during pregnancy are important for the neurocognitive development of the offspring at 8 years. Recommendations about fish intake during pregnancy are being also supported by the joint effort made by UGR and UNIBRI. The reanalysis of the WISC III test performed in the ALSPAC children at 8 years old, demonstrated that mother’s plasma phospholipids and seafood intake higher than 340 g/week during pregnancy will have a positive long term effects on Verbal Comprehension and Working Memory and Speed Processing on their offspring. This information is very valuable for the scientific community and committees in charge reviewing the policies and recommendations for pregnant women and also for the products already available in the market and the development of new ones.

NUTRIMENTHE`s NUHEAL follow-up Study has demonstrated that supplementation with fish oil and/or 5-Methyltetrahydrofolate (5-MTHF) during pregnancy will determine positive effects on the development of Processing Speed and Visual Motor Coordination in children at 9 years old. 5-MTHF supplementation improves children’s ability to solve response conflicts within the attention task at 9.5 y, and this advantage seems to be linked to a higher activation of right posterior mid-frontal cortex, indicating that early nutrition influences the functionality of specific brain areas involved in executive functions; these results confirm those obtained from Generation R. Again, this information is of great value for revising the policies and recommendations for pregnant women and will have a direct impact on the population worldwide.

With the CHOP study, we were the first to demonstrate the similar performance of children fed with different protein intakes (within a normal range) in a critical period of brain development. Given the current trends to reduce protein intake recommendations from early infancy, this information is of great value for the scientific community and the government bodies and committees in charge developing policies for nutritional value of infant products. These results may serve as a basis for development of infant products, as a confirmation of safety. It can be foreseen that this study will have a direct impact on the population, both through the scientific recommendations and through the commercial products for infants in the market.

From the genetic results, there is currently no direct societal impact, and dissemination of our results is currently mainly taking place on the scientific community level by participation at scientific conferences; however it is hoped that our results contribute to future more precise dietary recommendations taking an individual’s genetic susceptibility into account, so the development of new individualised therapies. We have demonstrated that: 1) FADS gene variants showed strong associations with maternal fatty acid levels during pregnancy and neonatal n-6 and n-3 fatty acids; 2) mother`s heterozygous (G/A) for FADS1 rs174556 seems to be an important factor determining 7.5 times more likely to have fast processing speed at 9y in their offspring than those homozygous (G/G), and 3) other preliminary statistical analysis are showing different important effects of these polymorphisms in different brain domains. So, it is suggested that there will be a very important impact of our research in the future development of new nutritional therapies for early life. Therefore, our recommendation is that these genetic variants need to be taken into account in analyses of nutritional influences on fatty acid composition and cognitive outcomes in future studies.

The evidence from ALSPAC, CHOP and NUHEAL about the daily intake in European children supports the recommendation that children should consume at least two fish meals per week one of them being of oily/fatty fish. Parents of primary school children in four European countries rely largely on their own experience to make food choices for their children and the impact of diet on mental performance is viewed as less important than food related factors. This information has implications for public health policy too. These results are for sure very important to be taken into account during childhood and adolescence to facilitate a better neurodevelopment. New clear recommendations and policies for this age group of population are needed. The dissemination of this information to the consumers has been done and still is on-going regarding the key messages developed within the Project; we believe that the impact on the general population will be high and will serve to promote the delivery of new products for toddlers and children based on this information.

The emerged knowledge about that head circumference (HC) especially at 4 years makes a long-term outstanding fitting of brain size, grey (GMV) & white matters volume (WMV) distribution in the brain at 9.5 y, and cognitive development. This information again is of importance and should be included as an obligatory and regular measurement in toddlers to prevent deviations of neurodevelopment in order to achieve the better cognitive level already foreseen for each child. At 4 years, preventive actions should be designed in relation to diet and neurodevelopment in European children, because probably these actions will have also a very high economic impact.

The intervention studies in toddlers and phenylketonuric children probably did not shown any functional changes in neuronal tissue which may have been required to be neuropsychologically detectable, despite modifications of B vitamins (SIMBA study) in plasma or DHA increase within doses-dependent curve. In respect to the biomarker plasma level of DHA, higher amount than the cut-off point of 8 mg DHA/Kg/day established in the curve, does not lead to much further increase of DHA-percentages. The lack of neuropsychological differences could be because a period of three months in the first case, or 6 months in the phehylketonuric study was insufficient at these ages to be detectable; however, these results clearly shown the need for further studies including fMRI to demonstrate functional differences.

The results obtained from WP10 are very important. Although most of the parents interviewed associated diet to mental outcomes, and specially attention and concentration to diet, in general diet is regarded as a less important determinant of mental development by parents and teachers. Our expectations are that our work trying to translate the information emerged from NUTRIMENTHE arrive correctly and soon to parents and teachers, helping to improve their understanding and knowledge. So, NUTRIMENTHE approaches in this field will serve to change in parents habits regarding cost and convenience of food preparation which currently are the least important factor regarding their children neurodevelopment.

The design and development of a NUTRIMENTHE Neuropsychological battery has been a very important approach. The criteria taken into account for tests’ selection were a key question; the children neuropsychological evaluation must be based on the study of brain domains, specifically designed for 7-9 y old children and with low verbal stimulus in order to reduce language influences, and also as much as possible cultural ones. The Neuropsychological performance of 1050 children from 7 European countries has been a strong effort and very valuable task within the consortium working as a global team. The Working Group of Mental Performance has been the base to integrate and harmonise all partners involved to work together in this common approach. This big study has permitted to demonstrate that standardizing (by country and sex) the neuropsychological scores is an appropriate procedure to avoid the influence of culture on multicultural studies. The impact of this effort, had immediate consequences, and now new ideas for epidemiological studies are being implemented, and the NUTRIMENTHE partners are being involved in other different studies about nutrition and brain. This approach has been very important because it will have an exponential effect all over the world on the future studies relating nutrition, cognition and behaviour, which are currently a hot topic of the year in many countries.

In relation to the economic evaluation, NUTRIMENTHE has performed an explicit calculation of the future economic impact from improving mental development and school performance by early nutrition programming effects. So decision-makers (politicians, physicians, and patients) get better knowledge and arguments for supporting the recommended early nutrition alternative. The model calculation shows that breastfeeding - in addition to many other positive effects - may improve a child’s cognitive skills and educational achievements which then has a positive economic impact of ~5,000 € per child. A shift increase by only 1%-point of breast fed infants in a one year birth cohort in the UK would generate a total economic benefit of more than 33 million GBP (€ 50 million Euro). Based on our findings, any public financed breastfeeding promotion activity would be highly cost-effective and should be supported as well as further research on the field of early nutrition. Furthermore, it is important to point out, that any additional positive health effect of the improved early nutrition strategy will bring an extra economic benefit for the individual or the society. Hence, the current analysis of the economic impact from breastfeeding and improved mental function will rather underestimate the real benefit that can be gained.

NUTRIMENTHE advanced the state of the art with the development of innovative biochemical techniques, such a procedure for the analysis of fatty acids from whole blood GPL in dried blood spots, the determination of fatty acids in cheek cells or the untargeted metabolomics analysis in urine searching for new biomarkers related to cognition and behaviour. The work package for biochemical analyses was a valuable and integrating part of the whole NUTRIMENTHE study, increasing the scientific output of the studies and being involved in many papers. Although with delays, WP9 increases the scientific output of the studies.
From the NUTRIMENTHE Project new ideas are emerging to be implemented in developing countries. There is a growing up demand about the optimal diet during early periods of life to improve mental development in children. In many countries this idea is seeing as a very positive and important action to be taken for the global development. Different ONGs and stakeholders have contacted us to deliver some actions in the next months in China, Middle East, Africa and South America.

Further Expected Results from NUTRIMENTHE
As it is shown in the present report, important results have been obtained already from the different studies; these results have been the baseline for more than 70 papers currently published and others publications. However, this is the beginning. The broad possibilities for exploitation of new analysis and results will appear in the next future.
Due to the large and excellent cohort studies involved, a wealth of information are being generated, making possible to link food intake data to biochemical & genetic measurements and to mental performance measurements in a large population across Europe. This has enabled us to the establishment of positive dietary recommendations for the European population, and also to generate important information for the scientific community. This information has been drafted as key messages (see below), some of them are already dietary recommendations supported by strong evidence, and others reveal new insights which will be the baseline for future studies.
NUTRIMENTHE is showing specific results regarding key issues in cognition and mental health in European children, indicating the important role of the diet during early life. The project has assessed the effects of early nutrition and lifestyle on cognition/cognitive development (perception, memory, intelligence etc.), emotional problems (anxiety/stress, Attention Deficit Hyper Activity (ADHD) syndrome, depression,..) and other related areas.
NUTRIMENTHE has developed a more mechanistic insight by specific work on genotyping to unravel uncertainties in the role of LCPUFA’s and other nutrients also by extensive bio-analytic work including untargeted metabolomics in urine. Moreover, the neuropsychological battery has been demonstrated to be a very important tool to harmonise the work performed; the neuropsychological results obtained from the different WPs generating the NUTRIMENTHE Global Database, and the study by brain imaging techniques and EEG/ERP, has offer the opportunity to achieve new interesting and important results about the impact of early nutrition on brain development, cognition and behaviour. Finally, NUTRIMENTHE has taken a great deal of care to ensure that dissemination of the results is produced in the most effective way.
By the end of the project we got some important results from many of the workpackages. These results have already been published or presented to different scientific events. Most of them were presented to the Scientific Community (September 2013) in the NUTRIMENTHE International Conference (Granada). Other dissemination activities to the scientific community are planned, as communication of results in other international congresses, publication in peer-review journals and dissemination through the 2 websites (www.nutrimenthe.eu and www.nutrimentheproject.eu).

There is still much work to carry out taken into account the huge amount of data generated within NUTRIMENTHE framework by the different workpackages; as well, more extensive analysis are ongoing regarding the NUTRIMENTHE Global Database, with the new emerging results about how nutrition, socio-economic factors and physical activity may affect different aspects of cognition and behaviour in childhood.
Finally, NUTRIMENTHE has developed a list of important Key Messages (Recommendations):
Diet and nutrition during pregnancy:- Potential audience
Folate intake during pregnancy (WP1)
Fortification of food with folate is needed to help women achieve sufficient folate intake during pregnancy. Science community, parents, health professionals, policy makers, industry, general public.
Encouraging women to take folate supplements during pregnancy is important to optimise brain growth. Science community, parents, health professionals, general public.
The effects of low folate during pregnancy can have long-term effects on brain growth and development. Science community, parents, health professionals, general public.
Low folate status during pregnancy is a risk factor for the development of behavioural and emotional problems during childhood. Science community, parents, health professionals, general public.
Iodine intake during pregnancy (WP2)
Adequate iodine intake in pregnancy is important for child cognitive development. Science community, parents, health professionals, general public.
Maternal dietary patterns during pregnancy (WP1)
Maternal dietary patterns during pregnancy affect the risk of the behavioural problems during childhood. Science community, parents, health professionals, general public.
Eating fish during pregnancy (WP2)
Eating fish regularly during pregnancy is important for the neuro-cognitive development of the offspring. This could be due to its fatty acid content or its iodine content or some other constituent of fish or a combination of these factors. Science community, parents, health professionals, general public.
Evidence from ALSPAC supports the recommendation that pregnant women should consume at least two fish meals a week, one of them being of oily/fatty fish. Science community, parents, health professionals, general public.
Dietary ALA can be important if no seafood is consumed but sources of long chain omega-3 fatty acids can provide additional benefits. These may come from supplements which contain DHA and EPA. Science community, parents, health professionals, general public.
Fish oil/folate supplementation during pregnancy (WP3)
Supplementation with fish oil and/or 5-MTHF during pregnancy will determine a positive effect on the development of Processing Speed and Visual Motor Coordination in children at 9 years old. Science community.
Metabolomic signatures in urine of children at 8 years born to mothers supplemented with DHA, 5-MTHF, placebo or both during pregnancy, are different between different countries. Hippuric acid is the most important metabolite identified. Science community.
Supplementation with fish oil and/or 5-MTHF during pregnancy may affect the development of different neuropsychological abilities. Science community.
Folate supplementation during pregnancy improves children’s ability to solve response conflicts, giving better attention abilities. This advantage seems to be based on the higher activation of the right posterior mid-frontal cortex, indicating that early nutrition influences the functionality of the specific brain areas involved in executive functions. Science community.
Diet and nutrition during early childhood (WP5, WP3)
Supplementation of B-vitamins, including folic acid, to healthy preschool children in Germany for three months, reduced blood levels of homocysteine, but it did not change cognitive function. Science community.
There is evidence of differences in growth between children in different European countries. This was investigated using standardised anthropometric measurements and the results were linked to plausible dietary differences. Science community, parents, health professionals, general public.
Many European children at 4 years are eating diets that are low in nutrient content but high in fat and sugar. Science community, parents, health professionals, general public.
Supplementation with DHA (WP6)
Provision of the preformed omega-3 fatty acid DHA, to school aged children increases DHA levels in their blood in a dose-dependent manner. Science community.
Protein intake during early life (WP4)
Lowering protein intake in infant formulas during the first year of life does not hamper mental performance in childhood, in well-nourished populations. Science community, parents, health professionals, general public.
Eating fish in childhood (WP2, WP3, WP4)
Evidence from ALSPAC, CHOP and NUHEAL supports the recommendation that children should consume at least two fish meals per week, one of them being of oily/fatty fish. Science community, parents, health professionals, general public.
Other messages

Maternal and foetal genetic variation (WP8, WP2, WP3)
There is genetic control of the pathways in the body that produce long chain polyunsaturated fatty acids and these are important in both the pregnant woman and the foetus. Science community.
There is initial evidence that FADS variants modulate nutritional influences on complex phenotypes such as asthma and neurodevelopment. Science community.
Evidence of selective benefits of long-chain polyunsaturated fatty acids on IQ comes from examination in ALSPAC of polymorphisms in the FADS2 gene. Science community.
Among children, who were fed only infant formula containing no long-chain polyunsaturated fatty acids, the presence of a gene variant that was associated with lower endogenous production of these fatty acids, was associated with substantially lower IQ compared to children with a gene variant that enables higher endogenous production of these fatty acids. Science community.
Maternal polyunsaturated fatty acids in pregnancy have been associated with child IQ at 8 years. These associations suggest possible mechanisms involving neural phospholipids (DHA and AA). This study found no evidence supporting a role for oleic acid or myelination. Science community.
Spanish and German children’s fatty acids composition in cheek cells is different between 8 years and 9.5 years of age. FADS2 gene variants modulate tracking of cheek cell samples fatty acids profile increasing the levels of DGLA at 8 years of age, GLA, DGLA, ALA and LA at 9 years. DGLA levels increases at 9.5 years influenced by SNPs in FADS1 and FADS2 genes. Science community.
Offspring of mothers who were heterozygote regarding the FADS1 genetic variant rs174556, showed 7.47 more often a better T score in the SDMT test (so better processing speed) at 9 years old than those children of mothers with homozygous major alleles. Science community.
Maternal thyroid function during pregnancy (WP1)
Poor maternal thyroid function during pregnancy is an important risk factor for children's brain development. Science community, parents, health professionals, general public.
Anthropometry (WP4, WP1, WP3)
Post natal head size is a marker for brain development in healthy, term, children. Science community, health professionals.
Specific cognitive functions may be related to head growth during specific periods of childhood. Science community, health professionals.
Head circumference (HC) at 4 years predicts long-term grey and white matter volumes, total brain volume, and total inner surface area of the brain. Science community.
Measuring mental performance (WP7, WP2)
Standardised (by country and sex) neuropsychological scores are an appropriate procedure to avoid the influence of culture on multicultural studies. Science community.
The factorial analysis of the WISC III tests determined the establishment of 3 different factors, the Verbal Comprehension (F1) (Vocabulary, Similarities, Comprehension and Information), Performance Index (F2) (Picture Completion, Picture Arrangement, Block Design, Object Assembly) and Working Memory and Speed Processing (F3) (Digits forward, Digits backward, Arithmetic and Coding) Science community.
Seafood intake higher than 340 g/week during pregnancy and maternal education determine higher mean scores on Verbal Comprehension and Working Memory and Speed Processing, but not for the Performance Index. Science community, health professionals, general public.
Consumers (WP10)
A broad, deep, evidence base is needed before messages and interventions can be developed, to reduce the level of scientific uncertainty in this domain, perceived by consumers. Science community, policy makers.
There is a need to know how consumers relate to the term - mental performance, before making decisions about developing interactions and strategy. Science community, policy makers.
For messages to be effective they need to use language that is understood/relevant to consumers and may need to be framed in terms of overall health and wellbeing. Science community, policy makers.
Economics (WP11, WP2)
Improving children’s cognitive skills by early nutrition can increase the chance for a better educational attainment level. Science community, policy makers.
Analyses of ALSPAC data and economic model calculations of later income effects showed an expected future benefit from breastfeeding of ~ 5,000 € per child. Science community, policy makers.
Successful promotion activities for better early nutrition will therefore be highly cost-effective. Science community, policy makers.
Meta-analyses (WP11)
There are problems and limitations with meta-analyses: Failure to identify all relevant studies; unpublished data; quality of included trials; inconclusive systematic reviews; opposite conclusions; discrepancies between the results of a meta-analysis and a large RCT. Science community.

The key messages (recommendations) will be published and disseminated to the identified potential audiences over the coming months via the NUTRIMENTHE website, the new project website www.nutrimentheproject.eu which will be placed at the Early Nutrition Academy too, along with several targeted press releases, and the continuation of social media feeds via Facebook, Twitter and LinkedIn.

Main dissemination activities

A key role later in the life of NUTRIMENTHE has been the integration of knowledge and results arising from research in the individual work packages into a uniform pool of new knowledge that will form the basis of the dissemination and training activities which are being undertaken.

Nutrimenthe Website www.nutrimenthe.eu – the website has been recently improved making abstracts of NUTRIMENTHE peer-reviewed publications, more accessible to the general public. Project results have been disseminated via the website.

A wide range of activities have been organised in order to promote the NUTRIMENTHE project and to disseminate its results (see also Appendix 2,3,4,5 and 6):
Dissemination activities Summary
Websites Project website www.nutrimenthe.eu
Project results and key messages website www.nutrimentheproject.eu

Articles More than 70 peer-reviewed papers (see Appendices 3 and 4)

Non-reviewed articles (see Appendices 5 and 6):
- Food for thought. Claire Horton, Jayne Evans and Cristina Campoy (2010). International Innovation magazine;
- An overview of the NUTRIMENTHE project, Claire Horton (2012) Nutrition Bulletin, 37 148-152.
- Does pre-natal nutrition affect mental performance in childhood? Claire Horton (2013), Network Health Dieticians magazine, issue 84.
- Nutrition and Mental Performance in Children. Claire Horton (2013), Complete Nutrition magazine, Vol 13 No. 3.
- Nutrition and Mental Performance in Children. Claire Horton, Nutrition and Health Journal (2014 in press).

Videos and films
NUTRIMENTHE Open Forum, York 2010
https://www.youtube.com/watch?v=eyV0i-9HyAA
https://www.youtube.com/watch?v=8Ge9cUNktLM
https://www.youtube.com/watch?v=RiOQFAB0jKM
https://www.youtube.com/watch?v=McG1hXVdLbc
https://www.youtube.com/watch?v=OrlblH_BcXY
https://www.youtube.com/watch?v=yKlYoQUF1RA
https://www.youtube.com/watch?v=87m4f_aG6DE
https://www.youtube.com/watch?v=FkKX1vUv1OU
https://www.youtube.com/watch?v=dDUlbumSpHQ

http://www.nutrimenthe.eu/nutrimenthe_on_you_tube_

FILM FUTURIS Euronews
http://www.euronews.com/2013/10/14/eu-project-aims-to-set-the-standard-for-healthy-eating-from-pregnancy-to-/
https://www.youtube.com/watch?v=8a5EeMbEvn4

NUTRIMENTHE International Conference, Granada 2013
http://player.vimeo.com/video/74975159

https://www.youtube.com/watch?v=cgi2akkUgDQ
https://www.youtube.com/watch?v=IHFWfxj7lIE
https://www.youtube.com/watch?v=hQMFN6KZSMU
https://www.youtube.com/watch?v=440hYaO4bNU
https://www.youtube.com/watch?v=23gozpf1Rg4
https://www.youtube.com/watch?v=0FhSve4P12g
https://www.youtube.com/watch?v=31aYEJMwLbU
https://www.youtube.com/watch?v=uNPflIHcc14
https://www.youtube.com/watch?v=WOufTM8ctG8
https://www.youtube.com/watch?v=aRmWQxJWfGg

BBC News Health: TV Interview to Sarah Bath
http://www.bbc.com/news/health-22607161

Third party articles (see Appendices 4 and 5)

“Food for Thought” International Innovation magazine October 2010; pp. 25-29. www.researchmedia.eu.

“Food for Thought – new insight into the importance of good early nutrition” Families Oxfordshire magazine (November 2010)

“Good food for babies the earlier the better” Horizon magazine (October 2013)

“2013 Innovation Catalogue: Selected bioeconomy research projects”: Brain power from brain food for children. Pp. 10-11. www.commnet.eu

Newsletters NUTRIMENTHE issues two newsletters a year (10 in total) providing readers with an update of our research findings to date, nutrition news, reports from events we have attended or organised, forthcoming events and a focus on individual NUTRIMENTHE studies or partners.
1. Newsletter issued May 2009.
2. Newsletter issued December 2009.
3. Newsletter issued August 2010.
4. Newsletter issued December 2010
5. Newsletter issued July 2011
6. Newsletter issued January 2012.
7. Newsletter issued August 2012
8. Newsletter issued March 2013
9. Newsletter issued July 2013.
10. Final newsletter issued December 2013
Flyers and fact sheets DL flyers to promote the work of the project and publicise project events were produced during the lifetime of the project. In addition, other flyers were produced (see Appendix 6)

“The effect of diet on the mental performance of children, information for parents” (June 2010 in English and Spanish)
“Our healthy eating recipe card” (In English and Italian, August 2010)
“The effect of diet on the mental performance of children – information for researchers” (September 2010)
“The effect of diet on the mental performance of children” (Project progress leaflet, June 2011)
“A brief overview of omega-3 and omega- fatty acids” (July 2011)
“The role of diet in the mental performance of children – what do parents think?” (December 2011)

Presentations See Appendix 4
Press releases See Appendix 5
Many press releases has been written and disseminated mainly through the UGR.
Six were written by WP13 during the lifetime of the project.
Press releases impacted generating notes at newspapers, and different radio and TV interviews in different countries
Events We have organised (see Appendix 6):
- the Granada Scientific Week on Healthy Lifestyle and Nutrition in Europe: From Conception to Adolescence, Including the International Symposium: “Demonstrating Early Nutrition Programming in Human and Animal Models” and the NUTRIMENTHE Kick-off Meeting.
- the ENA Winter School 2009: “Pregnancy and Programming” (9-13 February, 2009)
- the ENA Autumn School 2009: “Role of Nutrition of Brain Development and Behaviour” (Granada, 1-4 October, 2009)
- the NUTRIMENTHE at the first European Food Science Day, Brussels November 2009
- the ENA Cantabria Postgraduate School 2010: “Early Nutrition and Physical Activity: Determinants for metabolic programming” (Santander, 15-18 September, 2010).
- the Open Forum event in York (UK) in October 2010.
- the Week of Prof. Koletzko at the University of Granada: Promoting Early Programming of the Brain.
- the Forum Discussion: “Nutrition and Omics in Human Development”. (Granada, 12th April 2011)
- The NUTRIMENTHE Symposium: “Nutrition and Cognitive Function” at the 11th European Nutrition Conference, Madrid, October 2011.
- the ENA Symposium: “Nutritional Programming, from theory to practice” (Reus, 18-20 April 2012).
- the Rötterdam Symposium of May 2012
- the II Forum Discussion: “Lipids and Programming” (11th Granada, June 2012)
- the NUTRIMENTHE International Conference of September 2013 (Granada, Spain), closed to the 20th IUNS International Congress of Nutrition.
- the Young Scientists Competition of September 2013 (Granada, Spain)
- Further involvement of NUTRIMENTHE has been promoted through other important events such The Power of Programming (Münich, May, 2010) and MILANO Pediatria (November, 2012)

Social media We have also set up a Facebook page and Twitter account, plus, uploaded NUTRIMENTHE project videos to You Tube (www.nutrimenthe.eu).


Press releases
Different press releases, which impacted generating notes at newspapers, and different radio and TV interviews in different countries within this period. Whole information is recopiled in the website and their results in Appendix 5. Here we include the latest ones.
Press release to promote the NUTRIMENTHE International Conference
Date: 3rd May 2013
Does nutrition during pregnancy and in early childhood influence later mental performance?
This is the question being addressed by the NUTRIMENTHE project in research that began in 2008. The answers will be discussed at a conference in Granada, Spain, later this year that will showcase the results of the project, providing delegates with a wealth of new information and key messages about how diet during pregnancy and childhood influences later mental performance. Now in its final few months, the project involved hundreds of European families with young children. Researchers addressed the effect of specific nutrients, including B-vitamins, folic acid, breast milk versus formula milk, iron, iodine and omega-3 fatty acids, on the cognitive, emotional and behavioural development of children from before birth to age eight. The question of gene-nutrient interaction has also been explored, likewise, how parents and teachers perceive that food effects children’s mental function, and the economic impact of improving mental performance.

“We welcome you to Granada for this important conference” said NUTRIMENTHE’s Coordinator Professor Cristina Campoy, from the University of Granada. “We have many results to discuss which will help everyone understand the importance of early nutrition in mental performance”

The Conference will take place in Granada on the 13th and 14th September 2013, in advance of the 20th IUNS International Congress of Nutrition taking place at the same venue from the 15th to 10th September 2013. Delegates to the NUTRIMENTHE International Conference can submit abstracts for exhibition as posters or, for oral presentation.

Abstract submission deadline: 10th May 2013.

Abstracts accepted for the NUTRIMENTHE conference will be published in a supplement of the journal, Annals of Nutrition and Metabolism being prepared for the 20th International Congress of Nutrition.

Delegates of the NUTRIMENTHE Conference can enjoy a reduced rate to attend the 20th International Congress of Nutrition.

Press release for the NUTRIMENTHE press conference.
Date: Friday 13th September 2013
Diet during pregnancy and early life affects children’s behaviour and intelligence.
The statement “you are what you eat” is significant for the development of optimum mental performance in children as evidence is accumulating to show that nutrition pre-birth and in early life “programmes” long term health, wellbeing, brain development and mental performance and that certain nutrients are important to this process. Researchers from the NUTRIMENTHE project have addressed this in a five-year study involving hundreds of European families with young children. Researchers looked at the effect of, B-vitamins, folic acid, breast milk versus formula milk, iron, iodine and omega-3 fatty acids, on the cognitive, emotional and behavioural development of children from before birth to age nine. The study has found that folic acid, which is recommended in some European countries, to be taken by women during the first three months of pregnancy, can reduce the likelihood of behavioural problems during early childhood. Eating oily fish is also very beneficial, not only for the omega-3 fatty acids they which are ‘building blocks’ for brain cells, but also for the iodine content which has a positive effect on reading ability in children when measured at age nine. A long-term study was needed as explained by Professor Cristina Campoy, who led the project “Short term studies seem unable to detect the real influence of nutrition in early life”, explained Prof Cristina Campoy, “NUTRIMENTHE was designed to be a long-term study, as the brain takes a long time to mature, and early deficiencies may have far-reaching effects. So, early nutrition is most important.” Many other factors can affect mental performance in children including; the parent’s educational level, socio-economic status of the parents, age of the parents and, as discovered by NUTRIMENTHE, the genetic background of the mother and child. This can influence how certain nutrients are processed and transferred during pregnancy and breastfeeding and in turn, affect mental performance. In giving advice to parents, Cristina Campoy explained, “it is important to try to have good nutrition during pregnancy and in the early life of the child and to include breastfeeding if possible, as such ‘good nutrition’ can have a positive effect on mental performance later in childhood.” She went on to explain, “however, in the case of genetics, future studies should include research on genetic variation in mothers and children so that the optimum advice can be given. This area is relatively new and will be challenging!” The knowledge obtained by NUTRIMENTHE will contribute to the science base for dietary recommendations for pregnant women and children for improving mental performance. The work and results of NUTRIMENTHE will be presented and discussed at the NUTRIMENTHE International Conference taking place at the Granada Conference and Exhibition Centre on the 13th and 14th of September.
ENDS


Additional publicity
In addition to the articles, press releases, oral presentation and assistance to conferences WP13 has also been involved in the following activities to disseminate the results of NUTRIMENTHE.

Social Media:
NUTRIMENTHE set up profiles on two additional social media sites, Twitter and Facebook. The updating of these sites was the responsibility of Beta Technology. These social networks were regarded as an additional means of disseminating the results and activities of the project and also to post information and news from third parties.

Twitter: A Twitter account was set up in May 2013 to act as an additional route to disseminate the activities of the project, news from other sources (including following nutrition events on Twitter) and also to help publicise the International Conference and Young Scientists Competition. In the time to the end of the project, NUTRIMENTHE has sent 107 Tweets and picked up 80 followers. The more notable followers include other EU projects (ToyBox, Food4Me, iFamily, HelixEpisome, CommNet), the British Nutrition Society, La Leche League, the GAIN Alliance, University of Granada, the JRC for Nutrition, ILSI, Nestles EU Affairs, the Foundation for Mother and Child Research and individual dieticians and nutritionists.

Facebook
NUTRIMENTHE joined Facebook in April 2013. Activities, articles, events and news from the project are published here in short posts with links to the project website.

Website:
The NUTRIMENTHE project website was updated throughout the 5th reporting period with external news and events plus information about the activities of the project. Links were provided to the social media sites set up by NUTRIMENTHE.

Newsletters.
Four project newsletters were issued to the newsletter subscribers in the 5th reporting period, bringing the total to 10 newsletters issued throughout the lifetime of the project. Following the International Conference, the conference delegates were added to the newsletter list.

Additional messages, using the newsletter manager software, were also sent to the newsletter subscribers, nutrition societies, other professional organisations and other EU nutrition projects as follows. Two to promote the Young Scientist Competition, three to promote the International Conference, one each to promote the publication of the NUTRIMENTHE review paper, the symposium in Rotterdam, the press release regarding the ALSPAC work concerning effect of iodine deficiency in pregnancy on cognitive outcome in children and the documentary on Euronews. Information about NUTRIMENTHE and the International Conference was also circulated via the Beta Technology website and newsletter, which is received by over 1000 subscribers in the UK and Internationally.

NUTRIMENTHE filmed interviews
A series of interviews with pre-prepared questions was filmed in Granada on 13th September 2013. The questions were prepared by WP13 and circulated to the interviewees in advance of the filming to enable them to amend the questions as necessary. Individuals from the following partner organisations were involved:
University of Granada, Spain; Erasmus Medical Center, The Netherlands; Helmholtz Zentrum Munich German Research Centre for Environmental Health; University of Bristol, UK; University of Surrey, UK; Institute for Market Research, Strategy and Planning, Germany; University Rovira I Virgili, Spain. The interviews were uploaded to YouTube and are accessible via the NUTRIMENTHE website here:
http://www.nutrimenthe.eu/nutrimenthe_on_you_tube_

Second Bioeconomy Forum
The NUTRIMENTHE project was represented by Beta Technology at the Second Bioeconomy Forum organised by the CommFABnet EC project. At the Forum, representatives of 12 EC projects presented their business outlooks to a panel of experts from retail, consumers, technology transfer and industry. The panellists provided feedback on each project. The projects also have a two page article in CommFABnet’s Innovation Catalogue.
http://www.nutrimenthe.eu/UserFiles/File/CommNet_Innovation_Catalogue_final_wb.pdf
Following the Bioeconomy Forum presentation, Beta Technology was a guest speaker at the CommFABnet communication training that followed. The subject was “challenges for communicating bioeconomy research. The delegates were individuals responsible for the dissemination of results from other EU projects.

Press cuttings
When a press release is issued, WP13 searches the internet to determine where the information has been picked up. A Google alert was also set up with the search term NUTRIMENTHE. Following the issue of the press release on the 13th September, at the NUTRIMENTHE press conference in Granada, it was noted that the press release was picked up by the following websites.



Mom`s diet during pregnancy can affect kid`s behaviour and intelligence
http://zeenews.india.com/news/health/tags/NUTRIMENTHE.html

Diet During Pregnancy and Early Life May Affect Children's Behavior and Intelligence
http://www.sciencedaily.com/releases/2013/09/130913101815.htm

Mother's diet during pregnancy affects children's intelligence
http://machineslikeus.com/news/mothers-diet-during-pregnancy-affects-childrens-intelligence

Maternal diet linked to children’s behaviour, IQ.
http://www.foodproductdesign.com/news/2013/09/maternal-diet-linked-to-children-s-behavior-iq.aspx

Diet during pregnancy and early life affects children’s behaviour and intelligence
http://www.thisisreallyinteresting.com/diet-pregnancy-early-life-affects-childrens-behaviour-intelligence/

Study: Diet during pregnancy and early life affects children’s behavior and intelligence
http://natmonitor.com/2013/09/16/study-diet-during-pregnancy-and-early-life-affects-childrens-behavior-and-intelligence/

Diet during pregnancy and early life affects children's behavior and intelligence
http://press-news.org/113065-diet-during-pregnancy-and-early-life-affects-children-s-behavior-and-intelligence.html

Pregnancy diet impacts child development and intelligence
http://naturallysavvy.com/nest/pregnancy-diet-impacts-child-development-and-intelligence

Diet During Pregnancy and Early Life Affects Children’s Behaviour and Intelligence
http://www.nutritionhorizon.com/news/Diet-During-Pregnancy-and-Early-Life-Affects-Childrens-Behaviour-and-Intelligence.html
The Brain Benefits of Healthy Diet and Fitness in Early Life
http://www.psychologytoday.com/blog/the-athletes-way/201309/the-brain-benefits-healthy-diet-and-fitness-in-early-life

Family Survival Protocol – Microcosm news
http://familysurvivalprotocol.com/2013/09/17/researchers-from-the-nutrimenthe-project-in-a-five-year-study-have-found-that-folic-acid-can-reduce-the-likelihood-of-behavioural-problems-during-early-childhood/

The Armenian Medical Network
http://www.health.am/ab/more/diet-during-pregnancy-and-early-life/

Weight Loss Triumph
http://www.weightlosstriumph.com/proper-nutrition-starts-early-both-mother%E2%80%99s-pregnancy-diet-and-baby%E2%80%99s-diet-can-affect-childs-behavio

Every Reason Diets
http://everyreasondiets.com/diet-during-early-life-affects-childrens-behaviour-and-intelligence/

Bio-Medicine
http://www.bio-medicine.org/biology-news-1/Diet-during-pregnancy-and-early-life-affects-childrens-behavior-and-intelligence-31680-2/


Broadcast media
Euronews
Euronews produced a documentary called “Food for Thought” that included information about NUTRIMENTHE. Euronews contacted NUTRIMENTHE on the recommendation of the European Commission, during September 2013. Filming took place at the University of Granada and at the Erasmus Medical Center in Rotterdam. The film included interviews with NUTRIMENTHE researchers and also parents and children involved in NUTRIMENTHE’s studies. The film, produced in cooperation with European Commission DG Research and DG CONNECT, was aired for a week on the Futuris news channel. The documentary was 12 minutes long, and was broadcast to 155 countries in Euronews' thirteen broadcasting languages (English, German, French, Italian, Russian, Spanish, Portuguese, Arabic, Turkish, Persian, Ukrainian, Greek and Hungarian). To access the documentary, visit this website:
http://www.euronews.com/2013/10/14/eu-project-aims-to-set-the-standard-for-healthy-eating-from-pregnancy-to-/

Broadcasts of the NUTRIMENTHE International Conference
Filming took place during the NUTRIMENTHE International Conference and the result is this short video that captures the spirit of the conference and the key messages from the presentations.
http://player.vimeo.com/video/74975159


Third party publicity
Articles
WP13 is aware of three other articles that have been written about NUTRIMENTHE in this reporting period.

• This article appeared on CORDIS in July 2012: http://ec.europa.eu/research/infocentre/article_en.cfm?id=/research/star/index_en.cfm?p=ss-nutrimenthe&item=Infocentre&artid=26273
• This article appeared in the EC’s Horizon magazine in October 2013 “Good food for babies, the earlier the better” http://horizon-magazine.eu/article/good-food-babies-earlier-better_en.html
• An article about pregnancy and babies was written by Nancy Ripton of Just the Facts for the Canadian Living magazine. However, repeated requests to provide a link to this article have yielded nothing.
• Interview by Lic. Silvana Buján for: “Radio Universidad Nacional de Mar del Plata” and Argentina.

Other
Sidiga Washi, who attended the NUTRIMENTHE International Conference, provided this write-up.
http://ffa.uaeu.ac.ae/news/08102013_SpainDrSidiga.shtml



List of Websites:
The address of the project public website
Further information is provided on www.nutrimenthe.eu

The project website (www.nurimenthe.eu) has been developed as an interactive web site providing information on the project activities, background information on nutrition research and links to other sites relating to research or commercial activities in the area. The website includes information on the NUTRIMENTHE project, work plan/partners/contacts, alongside wider Nutrition and mental performance information. The website also includes relevant news/events and links to other European projects in this area (EARNEST, DIOGENES, PERILIP…). The project website is constantly updated and provides details about the project and it is the main tool to maintain the Information and Knowledge Exchange and Integration System (IKEIS) that enable effective communications among consortium partners and between the project and the public. An extranet system has been designed and implemented to fulfil the Information and Knowledge exchange requirements of the project. The IKEIS allows partners to view/upload/download information/documents and exchange knowledge relevant to the project in a hierarchical access structure based on Work Package/Management level.



Standard reference and master documents are also available in the system for the use of the partners. The list of Master/reference documents on the NUTRIMENTHE IKEIS: Description of Work, Work package list, Overall budget, Eligible costs and requested contribution, Acknowledgments for Publications, Project Months, Person-Months per WP per Partner, Person-Months per activity per Partner, New Guidance on Project Reporting, EC letter signed Grant Agreement, EC signed Grant Agreement, Financial guide. Further IKEIS sections for deliverables and milestones of the project are in place: Work package, Advisory/Steering groups, Meetings, Training. Information sourced from the work package outputs is disseminated and integrated fully via the IKEIS and the information documents can be uploaded directly by the consortium members as they are produced. Email alerts are sent to the consortium members when new documents are uploaded.
The project logo


Future plans for NUTRIMENTHE Website
Both the NUTRIMENTHE project website www.nutrimenthe.eu and the project results and key messages website www.nutrimentheproject.eu/ currently fall under the dissemination activities undertaken by WP13 (Beta Technology).
The NUTRIMENTHE project micro-website is now highly developed and ‘user friendly,’ plus accessible via Google searches http://www.nutrimentheproject.eu The new project results and key messages website can be accessed via a link on the homepage.
The new website describes the NUTRIMENTHE project, the consortium, background to the research that was carried-out, the achievements and key messages of the project. As more results are published, this website will be updated with new information.
Over the coming months, the management of both websites will be taken over by the Early Nutrition Aacademy (http://www.early-nutrition.org/). Both NUTRIMENTHE websites are licensed until 2015.
The home page of the new website is below:


The boxes at the base of the home page lead to more information about the individual areas of research of the project.
Background The influence of a woman’s diet during pregnancy The effect of post natal nutrition Measuring mental performance, physical activity and body composition
Studies on genetics What do consumers think Economic factors Summary and key messages



These boxes at the base of the home page lead to the work of the individual cohorts and other studies, taking part in NUTRIMENTHE as follows:

Box Sub-headings
Background Generation R
Children of the 90s
The childhood obesity programme
The cognitive effects of B-vitamins
Omega-3 fatty acids for brain function in children
The influence of a woman’s diet during pregnancy Folate and folic acid
Iodine intake and maternal thyroid function
Dietary intervention during pregnancy
Eating fish during pregnancy
The effect of post natal nutrition The cognitive effects of B-vitamins
Omega-3 fatty acids for brain function in children
Protein intake in early life
Measuring mental performance, physical activity and body composition Global database
Body composition
Physical activity
Studies on genetics None
What do consumers think None
Economic factors Meta-analyses
Summary and key messages Messages for parents
Messages for health professionals
Legacy
Other outputs

A link has been placed on the NUTRIMENTHE project website, linking to the new website where the results and key messages are placed.




The home page of the existing NUTRIMENTHE website is below:

Navigation tabs include: About the project, NUTRIMENTHE publications, Media and Links. The NUTRIMENTHE publications tab provides access to the abstracts of peer-reviewed publications and posters and PowerPoint presentations given by NUTRIMENTHE partners or, on behalf of NUTRIMENTHE partners, at national and international conferences. The abstracts of research papers are easily accessible. The Media tab gives general details about the project for visitors from the media to the website and gives downloadable press releases generated by the project. The Links tab gives details of related projects and International networks and organisations.



Information about the NUTRIMENTHE consortium is located on the About the Project tab which also contains a project summary, project structure and an overview of the Workpackages. The Project Summary text includes information about NUTRIMENTHE studies, namely the SIMBA study, PKU study, Consumer attitudes and the Economic analysis. The Public Information page has been updated with information about NUTRIMENTHE activities. Articles in which NUTRIMENTHE has featured can be downloaded here as well as NUTRIMENTHE’s biannual newsletter, the most recent issue of which is also accessible from the Home Page.

There is a Modal box: A ‘pop up’ box on the home page. This function is only be used periodically when NUTRIMENTHE has important events or news to highlight. Video clips: NUTRIMENTHE has its own You Tube channel where video clips can be viewed. The NUTRIMENTHE website has a number of links with other relevant websites.

The home page of The Early Nutrition Academy, who will be taking over the management of both NUTRIMENTHE websites can be found below:

The NUTRIMENTHE websites will continue to be updated with relevant information over the coming months.


Video clips:

Video clip produced by Futuris which appeared in Euronews:

NUTRIMENTHE project subject of a documentary “Food for Thought”
October 21, 2013
The NUTRIMENTHE project, which includes Beta Technology as the partner responsible for communication and dissemination, is the subject of a documentary “Food for Thought” appearing on the Euronews channel, Futuris, that broadcasts news from leading European scientific and technological research projects. The documentary is being broadcast for one week from 14th October 2013.
Producers from Euronews visited project co-ordinator, the University of Granada and one of the partners, The Erasmus Medical Center in Rotterdam in September to make the documentary. Project Coordinator, Professor Cristina Campoy and researchers Cristina Martinez-Zaldivar Moreno, Professor Henning Tiemeier and Dr Tonya White, appear in the film talking about the work of the project and the importance to brain development of nutrition during pregnancy and early life. The film also includes interviews with some of the parents and children involved in the clinical studies which give an interesting insight into the views of the families whose continuing participation is integral to the success of the project.
Click here to watch the film. https://www.youtube.com/watch?v=8a5EeMbEvn4



The film, which was produced in cooperation with the European Commission, is currently available in Euronews’ thirteen broadcasting languages (English, German, French, Italian, Russian, Spanish, Portuguese, Arabic, Turkish, Persian, Ukrainian, Greek and Hungarian) in 155 countries.

Video clips produced during the NUTRIMENTHE International Conference in Granada, September 2013


https://www.youtube.com/watch?v=cgi2akkUgDQ
https://www.youtube.com/watch?v=IHFWfxj7lIE
https://www.youtube.com/watch?v=hQMFN6KZSMU
https://www.youtube.com/watch?v=440hYaO4bNU
https://www.youtube.com/watch?v=23gozpf1Rg4
https://www.youtube.com/watch?v=0FhSve4P12g
https://www.youtube.com/watch?v=31aYEJMwLbU
https://www.youtube.com/watch?v=uNPflIHcc14
https://www.youtube.com/watch?v=WOufTM8ctG8
https://www.youtube.com/watch?v=aRmWQxJWfGg


BBC News Health: TV Interview to Sarah Bath
Iodine deficiency 'may lower UK children's IQ'
By James Gallagher Health and science reporter, BBC News Health; Dr. Sarah Bath told the BBC: "We saw a three-point IQ difference between children who were born to mothers with low iodine in early pregnancy and children who were born to mothers above the cut-off." http://www.bbc.com/news/health-22607161



Dr Sarah Bath: "Good sources of iodine are fish, milk and dairy products"


Video clips generated during the Open Forum in York, 2010:


https://www.youtube.com/watch?v=eyV0i-9HyAA
https://www.youtube.com/watch?v=8Ge9cUNktLM
https://www.youtube.com/watch?v=RiOQFAB0jKM
https://www.youtube.com/watch?v=McG1hXVdLbc
https://www.youtube.com/watch?v=OrlblH_BcXY
https://www.youtube.com/watch?v=yKlYoQUF1RA
https://www.youtube.com/watch?v=87m4f_aG6DE
https://www.youtube.com/watch?v=FkKX1vUv1OU
https://www.youtube.com/watch?v=dDUlbumSpHQ

Relevant contact details

Nr COUNTRY Participant Name Contact person e-mail
1 Spain University of Granada (UGR) Cristina Campoy ccampoy@ugr.es
2 Germany University of Munich (LMU-MUENCHEN) Berthold Koletzko berthold.koletzko@med.uni-muenchen.de
3 The Netherlands UNILEVER Sheila Wiseman Sheila.Wiseman@unilever.com
4 The Netherlands Erasmus University Medical Center (ERASMUS MC) Frank Verhulst f.verhulst@erasmusmc.nl
5 Spain University Rovira I Virgili (URV) Ricardo Closa ricardo.closa@urv.cat
6 UK University of Surrey (UNIS) Monique Raats m.raats@surrey.ac.uk
7 Hungary University of Pécs (UNIPECS) Támas Décsi tamas.decsi@aok.pte.hu
8 Italy University Degli study di Milano (UNIMI) Marcello Giovannini marcello.giovannini@unimi.it
9 Poland University of Warsaw (MUW) Hania Szajewska hania@ipgate.pl
10 UK Birmingham Children’s Hospital (BCH) Anita McDonald anita.macdonald@bch.nhs.uk
11 Poland The Children´s Memorial Health Institute (CI WARSAW) Dariusz Grusfeld d.gruszfeld@czd.pl
13 Germany Institute for Market Research, Strategy and Planning (IMSP) Neils Straub straub@imsp.de
14 Belgium Université Libre de Bruxelles (ULB) Philippe Goyens pgoyens@ulb.ac.be
15 UK SHS International (SHS) Sandra Giffen sgiffen@shsint.co.uk
16 UK University of Bristol (UNIBRI) Jean Golding jean.golding@bristol.ac.uk
17 Germany Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH (HELMUC) Thomas Illig illig@helmholtz-muenchen.de
18 UK Beta Technology Limited (BETA) Jayne Evans jayne.evans@betatechnology.co.uk>;
19 US Martek Biosciences Corporation (MARTEK) Rob Winwood RWinwood@martek.com
21 Spain Servicio Cantabro de Salud Luz Mª Garcia Piqueres Ifimav.otri@fmdv.org
Third
Party Spain Research Institute Hospital Marques de Valdecilla (IFIMAV) Miguel García-Fuentes pedgfm@humv.es
Third
Party Germany Klinikum der Universitaet Nicole D’Este berthold.koletzko@med.uni-muenchen.de