Grandmaternal body mass index in early pregnancy and risk of grandoffspring stillbirth: a nationwide, 3-generation cohort study

Abstract

We investigated the association between maternal grandmaternal early pregnancy body mass index (BMI) and grandoffspring stillbirth risk in a Swedish population-based 3-generation cohort of 176 908 grandmothers (F0), 197 579 mothers (F1), and 316 459 grandoffspring (F2) born 1997-2016. There were 998 stillbirths (risk, 3.2 per 1000 births). Compared with grandmaternal BMI 18.5-24.9, adjusted relative risks (RRs) of grandoffspring stillbirth for BMIs of 25.0-29.9 and ≥30.0 were, respectively, 1.41 (95% CI, 1.15-1.72) and 1.62 (95% CI, 1.14-2.30). RRs for corresponding maternal (F1) BMI categories were, respectively, 1.32 (95% CI, 1.06-1.65) and 1.77 (95% CI, 1.39-2.25). Maternal BMI mediated only 19% of this relationship. Grandmaternal preeclampsia and maternal small-for-gestational age (SGA) birth were related to increased F2 stillbirth risk but did not mediate the association between grandmaternal BMI and grandoffspring stillbirth risk. To explore whether this association was explained by factors shared within families, we studied the relationship of maternal full sisters' BMI and stillbirth risk in 101 368 pregnancies. Stillbirth RRs for full sisters' BMI 25.0-29.9 and ≥30.0 compared with 18.5-24.9 were, respectively, 0.76 (95% CI, 0.51-1.13) and 0.88 (95% CI, 0.55-1.40). In conclusion, grandmaternal overweight and obesity were associated with grandoffspring stillbirth. This association is not fully explained by shared familial factors.