Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis - 01/04/24
, Jessica A. Atkinson, BBiomedSc (Hons) a, b, Stephen Tong, PhD a, b, Parinaz Mehdipour, PhD a, b, Catherine Cluver, PhD a, b, c, Susan P. Walker, MD a, b, Anthea C. Lindquist, DPhil a, b, Roxanne M. Hastie, PhD a, bAbstract |
Objective |
This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes.
Data Sources |
MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023.
Study Eligibility Criteria |
Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review.
Methods |
Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials.
Results |
A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54–2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56–1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, −1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, −0.45; 95% confidence interval, −1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias.
Conclusion |
In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.
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Key words : child development, gestational diabetes mellitus, metformin, offspring
Plan
| A.C.L. and R.M.H. contributed equally as supervising authors. |
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| The authors report no conflict of interest. |
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| H.G.G. was supported by a Postgraduate National Health Medical Research Council Research Scholarship. H.G.G. and J.A.A. were supported by the Australian Government Research Training Program Scholarships. R.M.H (#1176922), S.T. (#1136418), S.P.W., and A.C.L. were all supported by the National Health and Medical Research Council. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. |
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| The protocol for this study was prospectively registered with the International Prospective Register of Systematic Review under identifier CRD42023432183 on June 13, 2023. |
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