Maternal Profiles Account for Birth Weight Differences Across Ethnicities: Results from Three Canadian Birth Cohorts

Background Marked differences in birth weight (BW) between South Asian and White European-origin populations are well-documented and pose public health concerns. Methods We analyzed fetal BW, the fat mass (FM), and fat-free mass (FFM) components in South Asian (n=938) and White European (n=3,044 and 804) newborns from three Canadian birth cohorts, examining the contribution of 16 maternal factors to observed BW differences using epidemiological and Mendelian randomization analyses. Findings South Asian newborns had on average, a significantly lower BW (3.3±0.4kg) than White Europeans (3.5±0.5kg), even after accounting for birth length (p<0.001). FFM was the primary driver of this difference, contributing to 0.22kg lower BW (p<2.2E-16), while FM had a significant but weaker counteracting effect of 0.01kg higher BW in South Asians (p=0.006). Five maternal factors demonstrated a direct maternal genetic influence: pre-pregnancy weight primarily increased BW via FFM, it also had a non-negligible increasing effect on FM. On the other hand, maternal glucose and gestational diabetes mellitus (GDM) causally increased BW through FM accumulation. Maternal height had a minimal effect only on FFM. After adjusting for these 5 maternal predictors, roughly 50% of the ethnic difference in BW (0.1kg; 95% CI: 0.067-0.13kg) was accounted for. Interpretation Different maternal factors influence specific components of BW. Targeting body fat reduction and maternal glucose regulation in South Asian mothers may help reduce the intergenerational transmission of increased FM and its associated adverse health outcomes. Funding This study was funded by the Canadian Institutes of Health Research DOHaD Team Grant: MWG-146332.