Grandmaternal pre-pregnancy body mass index and infant birthweight: a mediation analysis of maternal pre-pregnancy body mass index.

The objectives of this study were to examine the total effect of grandmaternal [G0] pre-pregnancy body mass index (BMI) on infant [G2] birthweight z-score and to quantify the mediation role of maternal [G1] pre-pregnancy BMI. Data were extracted from the Nova Scotia 3G Multigenerational Cohort. The association between G0 pre-pregnancy BMI and G2 birthweight z-score and the mediated effect by G1 pre-pregnancy BMI were estimated using g-computation with adjustment for confounders identified using a directed acyclic graph and accounting for intermediate confounding. 20822 G1-G2 dyads from 18450 G0 were included. Relative to G0 normal weight, G0 underweight decreased mean G2 birthweight z-score (-0.11, 95% confidence interval (CI) -0.20, -0.030), while 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]). G1 pre-pregnancy 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 pre-pregnancy BMI was associated with infant birthweight z-score. Maternal pre-pregnancy 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.