Grandmaternal Obesity and Risks of Birth Asphyxia-Related Complications in Grand-Offspring: A Countrywide Three-Generation Study

Abstract

Objective: We investigated the associations of grandmaternal early pregnancy BMI with grand-offspring risks of birth asphyxia-related complications. Methods: In a nationwide three-generation Swedish cohort, we estimated adjusted relative risks (RRs) of Apgar score 0–3 at 5 min and neonatal seizures for categories of grandmaternal BMI among 315,461 maternal and 203,522 paternal singleton live-born grand-offspring. To address unmeasured confounding by shared familial factors, we used the parental full sisters' BMI as a negative control exposure. In the maternal line, we assessed whether associations with grandmaternal obesity were mediated through maternal obesity. Results: Compared with normal maternal grandmaternal BMI, RRs (95% CI) of low Apgar score were, respectively, 1.29 (1.06, 1.57) and 1.53 (1.03, 2.28) for overweight (BMI 25.0 to 29.9) and obesity (BMI ≥ 30.0). For neonatal seizures, the corresponding RRs (95% CI) were 1.32 (1.05, 1.66) and 1.81 (1.17, 2.79). Maternal sisters' BMI was unrelated to both outcomes. Maternal obesity mediated < 25% of the associations with maternal grandmaternal obesity. Paternal grandmaternal obesity was related to an increased risk of neonatal seizures; paternal sisters' BMI was unrelated to this outcome. Conclusions: Grandmaternal overweight and obesity are related to increased risks of severe birth asphyxia-related complications in grand-offspring, independent of unmeasured shared familial factors.