Genetically determined body mass index and maternal outcomes of
pregnancy: a two-sample Mendelian randomization study
Abstract
Objective: Observational studies have described associations between
obesity and adverse outcomes of pregnancy. Mendelian randomization (MR)
takes advantage of the ‘natural’ genetic randomization to risk of an
exposure such as body mass index (BMI) to study the effects of the
exposure on outcomes. Similar to randomization in a clinical trial, this
limits the potential for confounding and bias. Design: A two-sample MR
study. Setting: Summary statistics from published genome wide
association studies (GWAS) in European ancestry populations. Population
or Sample: Instrumental variants for body mass index (BMI) were obtained
from a study on 434,794 females. Female-specific genetic association
estimates for outcomes were extracted from the sixth round of analysis
of the FINNGEN cohort data. Methods: Inverse-variance weighted MR was
used to assess the association between BMI and all outcomes. Sensitivity
analyses with weighted median and MR-Egger were also performed. Results:
A 1-SD increase in BMI was associated with higher risk of pre-eclampsia
(OR 1.68, 95%CI 1.46-1.94, p=8.74x10-13), gestational diabetes (OR
1.67, 95%CI 1.46-1.92, p=5.35x10-14), polyhydramnios (OR 1.40, 95%CI
1.00-1.96, p=0.049). There was evidence suggestive of a potential
association with higher risk of premature rupture of membranes (OR 1.16,
95%CI 1.00-1.36, p=0.050) and postpartum depression (OR 1.12, 95%CI
0.99-1.27, p=0.062). Conclusions: Higher maternal BMI is associated with
marked increase in risk of pre-eclampsia, gestational diabetes and
polyhydramnios. The relationship between BMI and premature rupture of
membranes and postpartum depression should be assessed in further
studies. Our study supports efforts to target BMI as a cardinal risk
factor for maternal morbidity.