A Role for the Pregravid Maternal Milieu in the Intergenerational Transmission of Obesity

Abstract Objectives Maternal obesity increases the risk for adverse pregnancy and offspring outcomes; however, with large heterogeneity. We hypothesize that in mothers with obesity, the heterogeneity of offspring adiposity is due to prolonged exposure to excess maternal substrates, namely glucose and triglycerides, which promote fetal fat accretion. The aims of this prospective observational study were to 1) examine the maternal metabolic milieu in pregnant women with metabolically unhealthy obesity, MUO and metabolically healthy obesity, MHO; and 2) identify if these maternal metabolic phenotypes in women with obesity influence infant adiposity. Methods During early pregnancy, 51 women with obesity were classified to have MUO (n = 9) or MHO (n = 13) based on the presence of zero (MHO) or ≥ 2 (MUO) risk factors for metabolic syndrome (SBP > 130 or DBP > 85, HDL < 50 mg/dL, LDL ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, and glucose ≥ 100 mg/dL). Area under the pregnancy concentration curve (AUC) for glucose and triglycerides, gestational weight gain (GWG), fat accretion, and energy intake and expenditure from early (13–16 wks), mid (24–27 wks) to late (35–37 wks) pregnancy and infant fat mass were compared between groups. Results Compared to women with MHO, women with MUO were not different with respect to maternal BMI, GWG, fat accretion, energy and macronutrient intake, and energy expenditure. In both groups, maternal substrates changed similarly from ∼13 to ∼37 weeks of pregnancy, however MUO resulted in greater pregnancy AUC for glucose (+2169.7 ± 381.5 p < 0.001 mg/dL · day) and triglycerides (+12,210.5 ± 3916.1 mg/dL · day, p < 0.001). The offspring of women with MHO had significantly lower birth weight (−620.8 ± 204.6 g, p = 0.01), body fat percentage (−5.8 ± 2.1%, p = 0.02), and total fat mass (−268.8 ± 88.4 g, p = 0.01). Conclusions Differing obesity phenotypes in pregnancy may explain the heterogeneity of offspring adiposity. Metabolically unhealthy obesity resulted in a more prolonged exposure of fetal fat promoting substrates and increased adiposity at birth. This study identifies a population of women with obesity most in need of prenatal interventions and suggests that obesity phenotypes need to be considered when evaluating intervention effect on offspring outcomes. Funding Sources R01DK099175.