Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes in up to 497,932 women

ABSTRACT Importance Higher maternal pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and perinatal outcomes. However, which of these associations are causal remains unclear. Objective To explore the relation of maternal pre-pregnancy BMI with pregnancy and perinatal outcomes by integrating evidence from three different methods (i.e. multivariable regression, Mendelian randomization, and paternal negative control analyses). Design Triangulation of multivariable regression, Mendelian randomization and paternal negative control results from up to 14 studies in the MR-PREG collaboration. Setting Europe and North America. Participants Up to 497,932 women of European ancestry. Exposure Maternal pre- or early-pregnancy BMI based on self-reported or measured weight and height. Main outcomes and Measures Miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, maternal anaemia, perinatal depression, pre-labour rupture of membranes, induction of labour, caesarean section, preterm birth, small- and large-for-gestational age, low and high birthweight, low Apgar score at 1 and 5 minutes, neonatal intensive care unit admission, and no initiation of breastfeeding. Results Multivariable regression, Mendelian randomization and paternal negative control analyses supported an association of higher maternal BMI with lower risk of small-for-gestational age and higher risk of hypertensive disorders of pregnancy, gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, large-for-gestational age, and high birthweight. As an example, higher maternal BMI was associated with higher risk of gestational hypertension in multivariable regression (OR: 1.67; 95% CI: 1.64, 1.71 per standard unit in BMI) and Mendelian randomization (OR: 1.58; 95% CI: 1.29, 1.93), which was not seen for paternal BMI (OR: 1.02; 95% CI: 0.99, 1.05). Findings did not support a relation between maternal BMI and perinatal depression. For other outcomes, evidence was inconclusive due to inconsistencies across the applied approaches or substantial imprecision in effect estimates from Mendelian randomization. Conclusions and Relevance Our findings support a causal role for maternal pre-/early-pregnancy BMI on a range of adverse pregnancy and perinatal outcomes. Pre-conception interventions to support women maintaining a healthy BMI may reduce the burden of obstetric and neonatal complications. KEY POINTS Question What is the effect of higher maternal pre-/early-pregnancy body mass index (BMI) on adverse pregnancy and perinatal outcomes? Findings We found consistent evidence that higher maternal BMI was related to higher risk of gestational hypertension, preeclampsia, gestational diabetes, pre-labour membrane rupture, induction of labour, and having a large-for-gestational-age baby, lower risk of having a small-for-gestational-age baby, and not related to perinatal depression. Meaning These findings highlight the importance of supporting women to achieve/maintain a healthy pre-conception BMI to reduce the burden of obstetric and neonatal complications.