We have shown widespread metabolomic change on becoming pregnant that returns to pre-pregnancy status after delivery. This is more extreme in obese pregnant women. Using RCT evidence we show that a lifestyle intervention can ameliorate adverse atherogenic lipid changes in obese pregnancy. We also find that South Asian women have a more marked glycaemia response to pregnancy than White European women, whilst White European women have a more dyslipidemia response.
By comparing results from different studies and analytical methods we have robustly demonstrated that higher maternal pregnancy BMI, circulating glucose, inflammatory markers and some amino acids increase fetal growth and birthweight. Traditional clinical chemistry measured lipids (total cholesterol, LDLc, HDLc, and triglycerides) did not appear t to influence birthweight, but exploratory results using a novel analysis method suggest that maternal total lipids in VLDL particles and in medium LDL particles causally increase birthweight. Using genetic variants related to metabolically favorable adiposity we demonstrate that in the absence of metabolic disruption, higher maternal adiposity does not result in fetal overgrowth, and indeed is related to lower mean birthweight.
Beyond the effects seen in infancy we did not find evidence of an effect of higher maternal BMI on offspring adiposity and cardiometabolic outcomes across childhood and into early adulthood. Whilst RCT evidence suggested randomized change to a healthier diet and physical activity, and consequent reduced maternal gestational weight gain, resulted in lower offspring birthweight and adiposity at 6-months, this was attenuated to the null by age 3-years.
In offspring whose mothers experienced gestational diabetes (GD) and those born large for gestational age, we have observed disrupted metabolism, with a more atherogenic profile, in childhood, adolescence and early adulthood. To explore this further, we have recently conducted the largest genome-wide association study to date (a trans-ethnic GWAS of 5,485 women with GD and 347,856 without), and identified Multiple lines of evidence pointed to genetic contributions to the shared pathophysiology of GD and type 2 diabetes. We are now under taking Mendelian randomization (MR) analyses of the effects of in utero exposure to GD on offspring future cardiovascular health.
In a UK three generation cohort, we have shown that the current generation of pregnant women have higher mean BMI and are more likely to be obese, than their mothers’ generation. We have further shown that the effect of maternal higher gestational BMI on offspring birthweight extends across generations, such that higher maternal grandmother BMI is related to higher offspring birthweight and length. Other transgenerational outcomes including of grandmaternal pregnancy BMI on lipids, fatty acids and blood pressure in infancy and early childhood are being explored .
We have engaged participants and the public in disseminating our findings. For example, through social and conventional media, running community scientific fairs, contributing to ‘a pint of science’, the Cheltenham Science festival and Einstein garden at the Greenman Festival
