OBJECTIVE To estimate the association between maternal metformin use for the treatment of early gestational or pre-existing type 2 diabetes and preterm preeclampsia. METHODS This is a planned secondary analysis of the MOMPOD study (Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy), a randomized trial comparing the effect of adding metformin with insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational or type 2 diabetes. Participants were randomized at 11-23 weeks of gestation to 1,000 mg metformin twice daily or placebo until delivery. A subset of participants had maternal blood collected at 24-30 weeks of gestation, and serum soluble endoglin, apolipoprotein B, vascular cell adhesion molecule-1, soluble fms-like tyrosine kinase 1, placental growth factor, high-sensitivity C-reactive protein, adiponectin, and vascular endothelial growth factor levels were measured. Our primary outcome was preterm preeclampsia , defined as preeclampsia requiring delivery before 37 weeks of gestation. Secondary outcomes included preterm preeclampsia requiring delivery before 34 weeks of gestation and differences in serum biomarkers. Multivariable regression analysis was used to estimate the associations between metformin use and primary or secondary study outcomes. RESULTS Of 831 participants, 119 (14.3%) developed preeclampsia requiring delivery before 37 weeks of gestation: 57 of 416 (13.7%) in the placebo group and 62 of 415 (14.9%) in the metformin group. Thirty-seven (4.4%) developed preeclampsia requiring delivery before 34 weeks of gestation: 15 (3.6%) receiving placebo and 22 (5.3%) receiving metformin. Compared with placebo, metformin was not associated with a significant difference in the occurrence of preeclampsia before 37 weeks of gestation (adjusted odds ratio [aOR] 1.04, 95% CI, 0.70-1.56) or before 34 weeks (aOR 1.43, 95% CI, 0.73-2.81). Similarly, there was no association between maternal metformin use and serum biomarker levels. CONCLUSION Among parturients with early gestational or pre-existing type 2 diabetes, the addition of metformin to insulin was not associated with lower odds of preterm preeclampsia or with serum biomarkers associated with cardiovascular disease risk.

中文翻译：

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二甲双胍在妊娠早期或 2 型糖尿病中的使用与早产子痫前期之间的关联。


目的 评估母体使用二甲双胍治疗早期妊娠期或预先存在的 2 型糖尿病与早产子痫前期之间的关联。方法 这是对 MOMPOD 研究（妊娠期显性 2 型糖尿病管理的医学优化）的计划二次分析，这是一项随机试验，比较了添加二甲双胍与胰岛素治疗对早期妊娠或 2 型糖尿病单胎妊娠复合新生儿结局的影响。参与者在妊娠 11-23 周时被随机分配到 1,000 毫克二甲双胍组，每天两次或安慰剂组，直至分娩。一部分参与者在妊娠 24-30 周采集母体血液，并测量血清可溶性内皮糖蛋白、载脂蛋白 B、血管细胞粘附分子-1、可溶性 fms 样酪氨酸激酶 1、胎盘生长因子、高敏 C 反应蛋白、脂联素和血管内皮生长因子水平。我们的主要结局是早产子痫前期，定义为需要在妊娠 37 周前分娩的子痫前期。次要结局包括需要在妊娠 34 周前分娩的早产子痫前期和血清生物标志物的差异。多变量回归分析用于估计二甲双胍使用与主要或次要研究结果之间的关联。结果在 831 名参与者中，119 名 （14.3%） 发生子痫前期需要在妊娠 37 周前分娩：安慰剂组 416 名患者中有 57 名 （13.7%），二甲双胍组 415 名患者中有 62 名 （14.9%）。37 例 （4.4%） 发生子痫前期需要在妊娠 34 周前分娩：15 例 （3.6%） 接受安慰剂，22 例 （5.3%） 接受二甲双胍。 与安慰剂相比，二甲双胍与妊娠 37 周前 （校正比值比 [aOR] 1.04,95% CI，0.70-1.56） 或 34 周前 （aOR 1.43,95% CI，0.73-2.81） 子痫前期发生率无显著差异。同样，母体二甲双胍的使用与血清生物标志物水平之间没有关联。结论 在早期妊娠期或已有 2 型糖尿病的产妇中，在胰岛素中添加二甲双胍与早产儿痫前期的较低几率或与心血管疾病风险相关的血清生物标志物无关。