Sex-specific mediating effect of gestational weight gain between pre-pregnancy body mass index and gestational diabetes mellitus

Background Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific. Methods This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM. Results A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Z(a) x Z(b) confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Z(a) x Z(b) CIs 0.00422-0.01977), but not male fetuses (Z(a) x Z(b) CIs -0.00085 to 0.01236). Conclusions Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM.