Pondugula Nishita, Culhane Jennifer F, Lundsberg Lisbet S, Partridge Caitlin, Merriam Audrey A
Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Obstet Gynecol. 2025 Jul 3. doi: 10.1097/AOG.0000000000005995.
To evaluate the associations among peripregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure with hypertensive disorders of pregnancy (HDP) and gestational weight gain.
We conducted a retrospective cohort study that included patients who delivered between 2014 and 2024 and had GLP-1RA exposure up to 1 year before pregnancy. Participants were identified through electronic medical record query with manual medical record abstraction to confirm exposure stop dates. Exposure to GLP-1RAs was classified by indication: pregestational diabetes mellitus or weight management. Unexposed control groups for each indication cohort were identified from an existing institutional data repository from 2021 to 2022. Demographic and clinical characteristics and obstetric outcomes were compared. The two primary outcomes were gestational weight gain and HDP. Gestational weight gain was quantified as below, meeting, or exceeding recommended gestational weight gain. Crude odds ratios and adjusted odds ratios (aORs) were estimated using multivariable modeling. Regression analysis was stratified as GLP-1RA exposure prepregnancy only or during pregnancy.
We included 243 patients who were exposed to GLP-1RA up to 1 year before pregnancy, with 65.4% having evidence of use during pregnancy. Overall, 103 (42.4%) patients used GLP-1RA for pregestational diabetes and 140 (57.6%) patients used it for weight management, compared with 175 unexposed patients in the pregestational diabetes control group and 200 unexposed patients in the weight-management control group (body mass index [BMI] 30-39.9: n=100; BMI 40 or higher: n=100). Exposure to GLP-1RAs was not associated with gestational weight gain in the pregestational diabetes cohort but was associated with decreased odds of gestational weight gain below recommendations (aOR 0.38, 95% CI, 0.18-0.80) in the weight-management cohort. Exposure to GLP-1RAs was associated with lower odds of HDP when compared with unexposed individuals with pregestational diabetes (aOR 0.52, 95% CI, 0.30-0.90) and with unexposed individuals who were undergoing weight management (aOR 0.51, 95% CI, 0.30-0.87). These associations were slightly more robust among patients exposed during pregnancy.
In individuals undergoing weight management, peripregnancy GLP-1RA exposure was associated with decreased risk of gestational weight gain below recommendations, which may reflect rebound weight gain after cessation. Peripregnancy GLP-1RA exposure was associated with lower odds of developing HDP for both the pregestational diabetes and weight-management cohorts. Additional studies are needed to guide GLP-1RA use in pregnancy and to better elucidate any risks of exposure.
评估孕期前使用胰高血糖素样肽-1受体激动剂（GLP-1RA）与妊娠高血压疾病（HDP）及孕期体重增加之间的关联。
我们进行了一项回顾性队列研究，纳入了2014年至2024年间分娩且在怀孕前1年内使用过GLP-1RA的患者。通过电子病历查询并人工提取病历以确认暴露终止日期来确定参与者。根据用药指征对GLP-1RA的暴露情况进行分类：孕前糖尿病或体重管理。从2021年至2022年现有的机构数据存储库中确定每个指征队列的未暴露对照组。比较人口统计学和临床特征以及产科结局。两个主要结局是孕期体重增加和HDP。孕期体重增加量化为低于、符合或超过推荐的孕期体重增加量。使用多变量模型估计粗比值比和调整后的比值比（aORs）。回归分析按仅在孕前暴露GLP-1RA或在孕期暴露进行分层。
我们纳入了243名在怀孕前1年内暴露于GLP-1RA的患者，其中65.4%有孕期使用的证据。总体而言，103名（42.4%）患者因孕前糖尿病使用GLP-1RA，140名（57.6%）患者因体重管理使用GLP-1RA，而孕前糖尿病对照组有175名未暴露患者，体重管理对照组有200名未暴露患者（体重指数[BMI]30 - 39.9：n = 100；BMI 40或更高：n = 100）。在孕前糖尿病队列中，暴露于GLP-1RA与孕期体重增加无关，但在体重管理队列中，与低于推荐的孕期体重增加几率降低相关（aOR 0.38，95%CI，0.18 - 0.80）。与未暴露的孕前糖尿病个体相比（aOR 0.52，95%CI，0.30 - 0.90）以及与未暴露的进行体重管理的个体相比（aOR 0.51，95%CI，0.30 - 0.87），暴露于GLP-1RA与HDP几率较低相关。这些关联在孕期暴露的患者中略强。
在进行体重管理的个体中，孕期前暴露于GLP-1RA与低于推荐的孕期体重增加风险降低相关，这可能反映了停药后的体重反弹。孕期前暴露于GLP-1RA与孕前糖尿病和体重管理队列中发生HDP的几率较低相关。需要进一步研究以指导孕期GLP-1RA的使用并更好地阐明任何暴露风险。
