Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
Am J Obstet Gynecol. 2024 Sep;231(3):308-314.e6. doi: 10.1016/j.ajog.2024.02.316. Epub 2024 Mar 7.
This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes.
MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023.
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.
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.
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.
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.
本研究旨在探讨母亲在怀孕期间使用二甲双胍对后代神经发育结局的影响。
从建库至 2023 年 7 月 1 日，对 MEDLINE、Embase 和 Web of Science（核心合集）进行了检索。
纳入了在妊娠任何阶段因任何适应证接受二甲双胍治疗并可获得后代神经发育数据的女性患者的研究。排除了无对照组的研究。综述纳入了随机对照试验、病例对照研究、队列研究和横断面研究。
由 2 名评审员独立筛选纳入研究并提取数据。使用改良版的纽卡斯尔-渥太华量表（针对非随机研究）和随机试验的风险偏倚 2 工具评估偏倚风险。
共有 7 项研究符合纳入标准，其中包括 14042 名儿童的合并队列，其中 7641 名儿童接受了随访，随访时间长达 14 年。在婴儿期（相对风险，1.09；95%置信区间，0.54-2.17；3 项研究；9668 名儿童）或 3 至 5 岁时（相对风险，0.90；95%置信区间，0.56-1.45；2 项研究；6118 名儿童），怀孕期间使用二甲双胍与神经发育迟缓无关。与未暴露的同龄人相比，怀孕期间使用二甲双胍与运动评分的改变无关（平均差异，0.30；95%置信区间，-1.15 至 1.74；3 项研究；714 名儿童）或认知评分的改变无关（平均差异，-0.45；95%置信区间，-1.45 至 0.55；4 项研究；734 名儿童）。纳入的研究质量较高，被认为偏倚风险较低。
在儿童 14 岁之前，子宫内暴露于二甲双胍似乎与不良神经发育结局无关。这些发现为考虑在怀孕期间使用二甲双胍的临床医生和孕妇提供了保证。
