Grandmaternal prepregnancy body mass index and infant birthweight: a mediation analysis of maternal prepregnancy body mass index.

The objectives of this study were to examine the total effect of grandmaternal (G0) prepregnancy body mass index (BMI) on infant (G2) birthweight z score and to quantify the mediation role of maternal (G1) prepregnancy BMI. Data were extracted from the Nova Scotia 3G Multigenerational Cohort. The association between G0 prepregnancy BMI and G2 birthweight z score and the mediated effect by G1 prepregnancy BMI were estimated using g-computation with adjustment for confounders identified using a directed acyclic graph and accounting for intermediate confounding. A total of 20 822 G1-G2 dyads from 18 450 G0 participants were included. Relative to G0 normal weight, G0 underweight decreased mean G2 birthweight z score (-0.11; 95% CI, -0.20 to -0.030), whereas G0 overweight and obesity increased mean G2 birthweight z score (0.091 [95% CI, 0.034-0.15] and 0.22 [95% CI, 0.11-0.33], respectively). G1 prepregnancy BMI partly mediated the association, with the largest effect size observed for G0 obesity (0.11; 95% CI, 0.080-0.14). Estimates of the direct effect were close to the null. In conclusion, grandmaternal prepregnancy BMI was associated with infant birthweight z score. Maternal prepregnancy BMI partly mediated the association, suggesting that factors related to BMI may play an important role in the transmission of weight across the maternal line.