Identifying Mediators Underlying the Intergenerational Cycle of Obesity: A Causal Mediation Analysis

Abstract

Abstract Objectives To understand the mechanisms of the intergenerational cycle of obesity between women and offspring. Methods We recruited pregnant women into the Nurture study (North Carolina, US) and prospectively followed up their offspring until 1 year of age from 2013–2017. The exposure of this analysis was self-reported maternal pre-pregnancy body mass index (BMI) calculated using weight and height. The outcome was researcher-measured infant weight-for-length z-score (WFLZ) at 1 year, calculated based on the WHO Child Growth Standards. We conducted a causal mediation analysis to estimate the average mediation effect of each mediator, including gestational weight gain (GWG), delivery mode, infant birth weight-for-gestational age z-score, and duration of breastfeeding. We adjusted for maternal age, race, parity, smoking status prior to pregnancy, education, household income, food security, and gestational age (when not examining birth weight-for-gestational age z-score). Results We included 380 dyads. Among mothers, there were 65.5% black, 22.6% white, and 11.8% other/multiple race. Prior to pregnancy, 19.5% were overweight and 45.3% were obese. A 10 kg/m2 increment of pre-pregnancy BMI was associated with 0.16 (95% CI: 0.06, 0.27) higher infant WFLZ at 1 year. When examining mediators individually, birth weight-for-gestational age z-score had a statistically significant mediation effect (0.05, 95% CI: 0.02, 0.08), corresponding to 30.2% (95% CI: 20.0%, 62.9%) of the total effect of pre-pregnancy BMI on infant WFLZ. The average mediation effect by GWG was −0.04 (95% CI: −0.08, 0.00), by cesarean delivery was 0.01 (95% CI: −0.01, 0.04), and by breastfeeding duration was 0.02 (95% CI: −0.01, 0.06). Treating mediators as potential confounders for one another did not alter the results. Conclusions Infant birth weight-for-gestational age z-score mediated, in part (∼30%), the relation between maternal pre-pregnancy BMI and infant WFLZ at 1 year. In contrast, GWG, delivery mode, and breastfeeding were not mediators in our sample. This highlights the importance of primordial prevention of maternal obesity, ideally prior to conception, to mitigate the intergeneration cycle of obesity. Research exploring the potential mediating role of factors such as the gut microbiome is needed. Funding Sources The National Institutes of Health.