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.

BACKGROUND: Maternal pre-pregnancy body mass index (BMI) is strongly associated with infant birthweight and the risk differs in pregnancies complicated by gestational diabetes (GDM).

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.