Genetic and maternal environmental contributions to estimated fetal weight at 20 weeks gestation compared with birthweight

Abstract Introduction: Birthweight reflects fetal growth from conception. The complications arising from the extremes of fetal growth are well known, but addressing these effectively depends on understanding how and when fetal growth is affected by various maternal and fetal factors. We aimed to compare associations of fetal genetic and maternal environmental factors with fetal weight mid-pregnancy and birthweight. Material and methods: We studied 3110 mother-child pairs from three population-based birth cohorts (UK and China). Estimated fetal weight at ~20 weeks gestation (EFW20) and birthweight were the outcomes of interest. Exposures were fetal genetic factors (fetal sex and fetal birthweight genetic score [BW GS]) and maternal factors (maternal BW GS, BMI, fasting plasma glucose [FPG], smoking, age, and parity). Associations were studied using multivariable linear regressions within cohorts and meta-analysed. Results: All exposures were associated with both EFW20 and birthweight, apart from maternal FPG and smoking which were associated with birthweight only. Male fetal sex and a higher maternal BW GS were consistently associated with higher EFW20 and birthweight, whereas the fetal BW GS, maternal FPG, BMI and smoking showed more marked associations later in pregnancy. Maternal age and parity showed directionally opposite associations with EFW20 and birthweight. Conclusions: Fetal genetic and maternal environmental factors vary in their effect on fetal growth in mid-pregnancy compared with late pregnancy. These findings contribute to our understanding of growth across pregnancy and may inform the timing of clinical monitoring of fetal growth and interventions targeting modifiable maternal factors.