Risk of large for gestational age births at early, full and late term in relation to pre-pregnancy body mass index: Mediation by gestational diabetes status.

Abstract

Maternal pre-pregnancy body mass index (BMI) is strongly associated with infant birthweight and the risk differs in pregnancies complicated by gestational diabetes (GDM). To examine the risk of large for gestational age (LGA) (≥97th percentile) singleton births at early term, full term and late term in relation to maternal pre-pregnancy BMI status mediated through GDM. We analysed data from the 2018 U.S. National Vital Statistics Natality File restricted to singleton term births (N=3,229,783). In counterfactual models for causal inference, we estimated the total effect (TE), natural direct effect (NDE) and natural indirect effect (NIE) for the association of pre-pregnancy BMI with subcategories of LGA births at early, full and late term mediated through GDM, using log-binomial regression and adjusting for race/ethnicity, age, education, parity and infant sex. Proportion mediated was calculated on the risk difference scale and potential unmeasured confounders were assessed using the E-value. Overall, 6.4% of women had GDM, and there were 3.6% LGA singleton term births. The highest prevalence of GDM was among pre-gestational overweight/obesity that also had the highest rates of LGA births at term. The TE estimates for the risk of LGA births were the strongest across women with higher pre-pregnancy BMI compared to women with normal pre-pregnancy BMI. The NDE estimates were higher than the NIE estimates for overweight/obese BMI status. The proportion mediated, which answers the causal question to what extent the total effect of the association between pre-pregnancy BMI and LGA births is accounted for through GDM, was the highest (up to 16%) for early term births. Term singleton births make up the largest proportion in a cohort of newborns. While the percentage mediated through GDM was relatively small, health risks arising from pre-pregnancy overweight, and obesity can be substantial to both mothers and their offspring.