Periodic Reporting for period 2 - AIR-NB (Pre-natal exposure to urban AIR pollution and pre- and post-Natal Brain development)
Okres sprawozdawczy: 2020-03-01 do 2021-08-31
Air pollution is the main urban-related environmental hazard. It appears to affect brain development, although current evidence is inadequate given the lack of studies during the most vulnerable stages of brain development and the lack of brain anatomical structure and regional connectivity data underlying these effects. Of particular interest is the prenatal period, when brain structures are forming and growing, and when the effect of in utero exposure to environmental factors may cause permanent brain injury. I and others have conducted studies focused on effects during school age which could be less profound. I postulate that: pre-natal exposure to urban air pollution during pregnancy impairs foetal and postnatal brain development, mainly by affecting myelination; these effects are at least partially mediated by translocation of airborne particulate matter to the placenta and by placental dysfunction; and prenatal exposure to air pollution impairs post-natal brain development independently of urban context and post-natal exposure to air pollution. I aim to evaluate the effect of pre-natal exposure to urban air pollution on pre- and post-natal brain structure and function by: i) establishing a new pregnancy cohort and evaluating brain imaging (pre-natal and neo-natal brain structure, connectivity and function), and post-natal motor and cognitive development; ii) measuring total personal exposure and inhaled dose of air pollutants during specific time-windows of gestation, noise, paternal stress and other stressors, using personal samplers and sensors; iii) detecting nanoparticles in placenta and its vascular function; iv) modelling mathematical causality and mediation, including a replication study in an external cohort. The expected results will create an impulse to implement policy interventions that genuinely protect the health of urban citizens.
AIR-NB has created a new population-based cohort named Barcelona Life Study Cohort (BiSC, www.biscproject.org) of around 1,050 (at March 15 update) pregnant women with singleton gestations who reside in Barcelona (Catalonia, Spain). Women were recruited during their first prenatal visit. Follow-up during pregnancy comprised of trimestral ultrasound evaluations of fetal anthropometry and placental function, trimester 3 evaluation of fetal brain development, and maternal blood and urine collection. Last delivery to be included is planned for end of September 2021, and around 1,100 pregnant women are planned to be involved. Air-NB has created a child birth cohort including all BISC newborns (around 800 by March 15, expected more than 1000 by September 2021). Assessment of motor and cognitive development and eye tracking at months 6 and 18 has been conducted using questionnaires, psychometric exams and tests. Air-NB has created biobank including maternal blood (at each trimester and at delivery), maternal urine (two urine voids per day during a week in each trimester) and hair, rectal and vaginal swap at week 32, cord blood, placenta biopsies, and infant urine and feces at 6 and 18 months. A new methodology for neonatal brain MRI capture has been successfully developed and implemented for the acquisition of anatomical T2-weighted MRI, DTI, and functional MRI for the BiSC newborns during their first 28 days of life. The exam was conducted at Betabrain, a pioneering brain research setting, that provides all the infrastructure for attending infants. As of March 15, we have obtained MRI data from 70 newborns of a total of 100.
Air-NB has measured time-activity patterns for all pregnant women twice (1st and 3rd trimesters) using a combination of smartphones to record the time-stamped geolocation and personal monitors to record time-stamped physical activity level. Personal, indoor and outdoor air pollution levels of PM2.5 PM2.5 elements, black carbon and NO2 have been measured for pregnant women whose first and third trimesters of pregnancy were assessed before the start of the COVID-19 pandemic. We also obtained measures of home-outdoor noise and home-indoor temperature/humidity as well as a very detailed characterization of the home indoor and outdoor environments. After the start of the pandemic, we activated a contingency plan by limiting the fieldwork to obtaining measures of personal, indoor and outdoor NO2, time-activity pattern, and home-indoor temperature for all pregnant women. We are developing an air pollution exposure assessment framework integrating data on time-activity patterns with a hybrid geographical modeling and personal and home-outdoor air pollution monitoring to estimate maternal exposure level as well as inhaled dose of NO2, PM2.5 black carbon and PM2.5 constituents at the main microenvironments for pregnant women for each participant during each week of her pregnancy. Post-natal personal exposure to NO2 is measured for all infants at 6 and 18 months. Air-NB also assess maternal exposure to noise by integrating noise levels and noise peak indicators measured at participants’ bedroom window using noise monitors together with modeled microenvironmental levels of noise to all pregnant women.
Air-NB has established a database on placental function (uteroplacental and fetoplacental vascular resistances) using Doppler ultrasound measurements for all pregnant women. Air-NB collected placenta biopsies of fresh placenta tissue from the maternal and foetal side of cotyledons and stored sealed at −80°C, including some biopsies for DNA and RNA extraction, for more than 600 women. Black carbon particles in placentas is being measured in the lab of Prof. Nawrot at University of Hasselt, Belgium. A pilot study showed detectable levels in all samples and a notable variability of concentrations.
Data cleaning and data set preparation is ongoing.
Air-NB has measured time-activity patterns for all pregnant women twice (1st and 3rd trimesters) using a combination of smartphones to record the time-stamped geolocation and personal monitors to record time-stamped physical activity level. Personal, indoor and outdoor air pollution levels of PM2.5 PM2.5 elements, black carbon and NO2 have been measured for pregnant women whose first and third trimesters of pregnancy were assessed before the start of the COVID-19 pandemic. We also obtained measures of home-outdoor noise and home-indoor temperature/humidity as well as a very detailed characterization of the home indoor and outdoor environments. After the start of the pandemic, we activated a contingency plan by limiting the fieldwork to obtaining measures of personal, indoor and outdoor NO2, time-activity pattern, and home-indoor temperature for all pregnant women. We are developing an air pollution exposure assessment framework integrating data on time-activity patterns with a hybrid geographical modeling and personal and home-outdoor air pollution monitoring to estimate maternal exposure level as well as inhaled dose of NO2, PM2.5 black carbon and PM2.5 constituents at the main microenvironments for pregnant women for each participant during each week of her pregnancy. Post-natal personal exposure to NO2 is measured for all infants at 6 and 18 months. Air-NB also assess maternal exposure to noise by integrating noise levels and noise peak indicators measured at participants’ bedroom window using noise monitors together with modeled microenvironmental levels of noise to all pregnant women.
Air-NB has established a database on placental function (uteroplacental and fetoplacental vascular resistances) using Doppler ultrasound measurements for all pregnant women. Air-NB collected placenta biopsies of fresh placenta tissue from the maternal and foetal side of cotyledons and stored sealed at −80°C, including some biopsies for DNA and RNA extraction, for more than 600 women. Black carbon particles in placentas is being measured in the lab of Prof. Nawrot at University of Hasselt, Belgium. A pilot study showed detectable levels in all samples and a notable variability of concentrations.
Data cleaning and data set preparation is ongoing.
AIR-NB will provide evidence on the most important urban-related determinants of brain development during one of the most vulnerable periods for its development, and will thereby have important implications for developing community interventions in urban planning.
Studying the structural and functional brain effects of air pollution exposure during foetal and neurodevelopment during early life is important. These pre-natal and early-life effects could have long-lasting consequences and an accompanying societal burden, which is important both for the general public and for policymakers. Demonstrating its impact on infant’s brains could create an impulse to definitively implement policy interventions that genuinely protect the health of urban citizens glob, and the pregnant women and infants particularly.
For public health interventions, there is a need to disentangle the effects of the various anthropogenic pollutants in urban air, and the underlying sources that cause the observed association with brain damage. For example, it is important to distinguish the effect on brain development of NO2 from that of particles, especially in European cities with large fleets of diesel-powered vehicles.
By understanding the role of the placenta in how air pollution leads to impaired brain development, I will be able to discover part of the causal nature of this relationship, which, among others benefits, will provide solid evidence to reinforce arguments for obstetricians and policymakers in implementing feasible and achievable individual- and community-level interventions to protect pregnant women.
I will enhance the quality of the exposure measurement during pregnancy and accurately identify specific time windows of susceptibility for brain development during pregnancy. Detecting these critical periods is fundamental for preventive purposes during pregnancy. Interventions have been shown to be more efficient when carried out during earlier vulnerability windows.
I will contribute to our understanding of pre-natal and post-natal brain development in one of the largest studies in the general population to date, and which will use the most advanced imaging techniques based on ultrasound and MRI brain measures. This work will impact research on the brain connectome (map of neural connections) and neuroscience in general.
Studying the structural and functional brain effects of air pollution exposure during foetal and neurodevelopment during early life is important. These pre-natal and early-life effects could have long-lasting consequences and an accompanying societal burden, which is important both for the general public and for policymakers. Demonstrating its impact on infant’s brains could create an impulse to definitively implement policy interventions that genuinely protect the health of urban citizens glob, and the pregnant women and infants particularly.
For public health interventions, there is a need to disentangle the effects of the various anthropogenic pollutants in urban air, and the underlying sources that cause the observed association with brain damage. For example, it is important to distinguish the effect on brain development of NO2 from that of particles, especially in European cities with large fleets of diesel-powered vehicles.
By understanding the role of the placenta in how air pollution leads to impaired brain development, I will be able to discover part of the causal nature of this relationship, which, among others benefits, will provide solid evidence to reinforce arguments for obstetricians and policymakers in implementing feasible and achievable individual- and community-level interventions to protect pregnant women.
I will enhance the quality of the exposure measurement during pregnancy and accurately identify specific time windows of susceptibility for brain development during pregnancy. Detecting these critical periods is fundamental for preventive purposes during pregnancy. Interventions have been shown to be more efficient when carried out during earlier vulnerability windows.
I will contribute to our understanding of pre-natal and post-natal brain development in one of the largest studies in the general population to date, and which will use the most advanced imaging techniques based on ultrasound and MRI brain measures. This work will impact research on the brain connectome (map of neural connections) and neuroscience in general.