The involvement of maternal and fetal gene, metabolic, and lifestyle interactions on newborn birth weight and adiposity in South Asian and white European offspring.

There is an inverse association between birth weight (across most of its distribution) and risk of diabetes and coronary heart disease in adulthood1,2. This is likely a reflection of maternal and offspring genetics, intrauterine environments, and foetal exposures, which influence birth weight (BW) and adiposity, and contribute to future risk. Along with maternal and offspring genetics, maternal lifestyle (e.g., diet) is important to support a healthy intrauterine environment and offspring growth, offering a modifiable opportunity to encourage healthy newborn anthropometrics. However, the moderating effect and interaction of maternal health and lifestyle (e.g., diet, physical activity) on newborn BW and adiposity is currently unknown.
South Asians (SAs) are up to 4-fold greater risk of cardiometabolic diseases, compared to white Europeans (WE)2-4, with health complications and diagnoses often arising earlier in SAs and at a lower BMI2-5. Evidence demonstrates that (i) SA newborns tend to be born of lower BW but higher adiposity and show early markers of metabolic risk6-8, and (ii) the direction of association between maternal diet and BW differs between SAs and WEs9. Collectively, this suggests that SA newborns are guided towards a low BW and high adiposity that puts them at increased risk of cardiometabolic disease in adulthood, compared to WEs.
Using polygenic risk scores (PRS), the HAPO cohort demonstrated robust associations (P<10-19) between newborn genetics, and BW and adiposity10 in infants of European, Afro-Caribbean, Mexican, and Thai ancestry. More recently11, a consortium of SA cohorts in India, Bangladesh, and the UK, demonstrated robust associations between maternal and offspring PRSs and newborn BW (34g and 51g per standard deviation PRS, respectively). This suggests that maternal and foetal genetics both contribute to newborn anthropometrics. However, no studies have (i) reported on the differences in the maternal and newborn genetic determinants of newborn BW and adiposity between WEs and SA; (ii) reported on the differences in the maternal and newborn genetic determinants on growth trajectory in WEs and SA; (iii) evaluated the role of maternal genetically-predicted metabolism on offspring growth; or (iii) investigated the moderating effect of maternal lifestyle (e.g., diet), cardiometabolic health (e.g., blood glucose and lipids), or pharmacological variables on newborn growth in WEs and SAs. This level of understanding would offer (i) biological rationale for the differences in BW and adiposity that are observed between WE and SA newborns and young infants; (ii) insight regarding the malleability of BW and adiposity in newborns; and (iii) guidance on the use of maternal lifestyle and health as moderators of newborn growth in WEs and SAs.