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Intrauterine metformin exposure and adiposity outcomes in children: a systematic review and meta-analysis

Jennifer Fu, N. Tabbara, G. Tomlinson, Kellie E. Murphy, J. Hamilton, D. Feig

BMJ Open, 2025

7,975 participants · 13 citations

Abstract

OBJECTIVE: The study aims to assess the effect of intrauterine metformin exposure on offspring adiposity measures in childhood.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: Medline, Embase and Cochrane Central were searched from inception to 4 October 2024.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Follow-up studies of randomised-controlled trials and observational studies involving metformin use in pregnancy for any insulin-resistant maternal condition were included.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and completed risk-of-bias assessments using either Cochrane Risk-Of-Bias tool V.2 or Risk of Bias in Non-Randomised Studies of Exposure depending on study design. Meta-analyses were conducted using the generic inversed variance method in a random-effects model. Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess certainty of evidence.

RESULTS: 18 studies reporting on 7975 children with metformin exposure in utero and over 1 million children without metformin exposure were included. At the oldest age of follow-up reported (weighted mean age of 4.4 years), children with metformin exposure for any maternal indication had comparable body mass index (BMI) with their non-exposed peers (standardised mean difference (SMD) -0.02; 95% CI: -0.11, 0.07; low certainty). When stratified by age at follow-up, while metformin-exposed children had slightly higher BMI at 1-3 years of age (SMD…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 7,975 participants or records.

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