近日，美国麻省总医院Camille E. Powe团队研究了停用GLP-1受体激动剂后妊娠体重增加情况和妊娠结局。这一研究成果于2025年11月25日发表在《美国医学会杂志》上。

胰高血糖素样肽-1受体激动剂（GLP-1RAs）在妊娠期禁用。妊娠期停用GLP-1RAs可能影响妊娠体重增加和妊娠结局。

为了比较妊娠前或妊娠早期暴露于GLP-1RAs和未暴露于GLP-1RAs的妊娠体重增加和妊娠结局，研究组进行了一项回顾性队列研究，选择2016年6月1日至2025年3月31日期间，在单一学术卫生系统内分娩的149790例单胎妊娠。暴露因素为妊娠前3年至妊娠后90天之间的GLP-1RA顺序，每个暴露妊娠的倾向评分与3个未暴露妊娠相匹配。主要结局是妊娠期体重增加。次要结局是妊娠期体重增加过多、胎龄出生体重的大小、胎龄和性别的出生体重百分位数、出生长度、早产、剖宫产、妊娠期糖尿病和妊娠高血压疾病。

在研究期间的149790例妊娠中，共有1792例（448例暴露组和1344例非暴露组）被纳入主要分析的匹配队列。暴露组孕妇平均年龄为34.0岁（标准差4.7岁），孕前体重指数为36.1（标准差6.5；计算公式为体重公斤数除以身高米数的平方）；448例中有378例（84%）患有肥胖症，104例（23%）患有既往糖尿病；136例（30%）为西班牙裔，49例（11%）为非西班牙裔黑人，223例（50%）为非西班牙裔白人；43例（10%）享有公共医疗保险。与倾向评分匹配的非暴露组妊娠（平均10.5公斤，标准差8.0）相比，GLP-1受体激动剂暴露组的妊娠期体重增加更显著（平均13.7公斤，标准差9.2），差值为3.3公斤（95%置信区间2.3~4.2；P<0.001）。GLP-1受体激动剂暴露组出现妊娠期体重过度增加的风险更高（65% vs 49%；风险比1.32，95%置信区间1.19~1.47），新生儿平均出生体重百分位数更高（58.4% vs 54.8%；差值3.6%，95%置信区间0.2%~6.9%），早产（17% vs 13%；风险比1.34，95%置信区间1.06~1.69）、妊娠期糖尿病（20% vs 15%；风险比1.30，95%置信区间1.01~1.68）及妊娠期高血压疾病（46% vs 36%；风险比1.29，95%置信区间1.12~1.49）的发生风险也显著升高。两组在出生身长、大于或小于胎龄体重风险以及剖宫产率方面未见显著差异。

研究结果表明，在一个主要由肥胖女性组成的队列中，GLP-1RA的使用与随后的孕前或早孕停药有关，妊娠期体重增加更多，早产、妊娠期糖尿病和妊娠期高血压疾病的风险更高。

附：英文原文

Title: Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation

Author: Jacqueline Maya, Deepti Pant, Yiran Fu, Kaitlyn James, Carolina Batlle, Sarah Hsu, Diana C. Soria-Contreras, Lydia L. Shook, Christopher Mow, Marie-France Hivert, Tanayott Thaweethai, Camille E. Powe

Issue&Volume: 2025-11-25

Abstract:

Importance  Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are contraindicated in pregnancy. Discontinuation of GLP-1RAs proximal to pregnancy could affect gestational weight gain and pregnancy outcomes.

Objective  To compare gestational weight gain and pregnancy outcomes with and without exposure to GLP-1RAs before or during early pregnancy.

Design, Setting, and Participants  Retrospective cohort study of 149790 singleton pregnancies delivered between June 1, 2016, and March 31, 2025, within a single academic health system.

Exposure  A GLP-1RA order between 3 years before and 90 days after conception, with propensity score matching of each exposed pregnancy to 3 unexposed pregnancies.

Main Outcomes and Measures  The primary outcome was gestational weight gain. Secondary outcomes were excess gestational weight gain, large and small for gestational age birth weight, birth weight percentile for gestational age and sex, birth length, preterm delivery, cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy.

Results  Among 149790 pregnancies during the study period, 1792 (448 exposed and 1344 unexposed) were matched for the primary analysis. Exposed pregnancies had mean maternal age of 34.0 years (SD, 4.7 years) and prepregnancy body mass index of 36.1 (SD, 6.5; calculated as weight in kilograms divided by height in meters squared); 378 of 448 (84%) had obesity and 104 of 448 (23%) had preexisting diabetes; 136 (30%) were Hispanic, 49 (11%) were non-Hispanic Black, and 223 (50%) were non-Hispanic White; and 43 (10%) had public insurance. The GLP-1RA–exposed pregnancies had greater gestational weight gain (mean, 13.7 kg [SD, 9.2]) than propensity score–matched unexposed pregnancies (mean, 10.5 kg [SD, 8.0]), a difference of 3.3 kg (95% CI, 2.3-4.2; P<.001). The GLP-1RA–exposed group had a higher risk of excess gestational weight gain (65% vs 49%; risk ratio [RR], 1.32; 95% CI, 1.19-1.47), greater mean birth weight percentile (58.4% vs 54.8%; difference, 3.6%; 95% CI, 0.2%-6.9%), and higher risk of preterm delivery (17% vs 13%; RR, 1.34; 95% CI, 1.06-1.69), gestational diabetes (20% vs 15%; RR, 1.30; 95% CI, 1.01-1.68), and hypertensive disorders of pregnancy (46% vs 36%; RR, 1.29; 95% CI, 1.12-1.49). There was no difference in birth length, risk of large or small for gestational age birth weight, or cesarean delivery.

Conclusions and Relevance  In a cohort composed primarily of women with obesity, GLP-1RA use with subsequent prepregnancy or early pregnancy discontinuation was associated with more gestational weight gain and a higher risk of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy.

DOI: 10.1001/jama.2025.20951

Source: https://jamanetwork.com/journals/jama/fullarticle/2841781