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Genetically determined body mass index and maternal outcomes of pregnancy: a two-sample Mendelian randomization study
  • Dorothea Geddes-barton,
  • Anita Banerjee,
  • Maddalena Ardissino
Dorothea Geddes-barton
University of Oxford Nuffield Department of Population Health

Corresponding Author:[email protected]

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Anita Banerjee
Guy's and St Thomas' Hospitals NHS Trust
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Maddalena Ardissino
University of Oxford Nuffield Department of Population Health
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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.
10 Aug 2022Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
22 Aug 2022Submission Checks Completed
22 Aug 2022Assigned to Editor
02 Oct 2022Reviewer(s) Assigned
27 Mar 2023Review(s) Completed, Editorial Evaluation Pending
01 May 2023Editorial Decision: Revise Major
22 May 20231st Revision Received
29 May 2023Assigned to Editor
29 May 2023Submission Checks Completed
29 May 2023Review(s) Completed, Editorial Evaluation Pending
11 Jun 2023Reviewer(s) Assigned
31 Jul 2023Editorial Decision: Revise Minor
01 Aug 20232nd Revision Received
02 Aug 2023Assigned to Editor
02 Aug 2023Submission Checks Completed
02 Aug 2023Review(s) Completed, Editorial Evaluation Pending
13 Aug 2023Editorial Decision: Accept