围孕期GLP-1受体激动剂暴露与不良产科结局：一项系统综述与荟萃分析。
完整摘要 · 中文译文
背景：本系统综述和荟萃分析评估在妊娠期或围受孕期暴露于胰高血糖素样肽-1受体激动剂（GLP-1 RA）是否与不良母胎结局相关。 方法：检索了Medline、Embase和Cochrane图书馆，纳入比较妊娠试验阳性前6个月内暴露与未暴露于GLP-1 RA的妊娠的观察性研究。结局包括流产、宫内死亡、先天性异常、早产（PTB）、妊娠期高血压疾病（HDP）、妊娠期糖尿病（GDM）、胎儿生长受限（FGR）、小于胎龄儿（SGA）、大于胎龄儿（LGA）和妊娠期体重过度增加。采用随机效应荟萃分析并按适应症进行亚组分析。 结果：10项研究共纳入2,118,215名女性，其中8,325名暴露，2,109,890名未暴露。合并估计值未显示流产或宫内死亡、先天性异常、早产、妊娠期高血压疾病（HDP）、妊娠期糖尿病、胎儿生长异常或妊娠期体重过度增加的明显可检测增加。观察到子痫前期的合并估计值较低（比值比（OR）：0.87，95%置信区间（CI）：0.78-0.98；p=0.02），但这基于两个数据集，应谨慎解读。亚组分析未显示按适应证的明显可检测差异。暴露窗口敏感性分析覆盖受孕前90天至孕早期结束，使用了与主要先天性畸形分析相同的四项研究，因此并非独立。 结论：现有观察性证据未发现围受孕期暴露于胰高血糖素样肽-1受体激动剂（GLP-1 RAs）后母体或围产期不良结局的明显可检测增加。然而，由于异质性、残余混杂和数据集有限，这些发现不能确证安全性。 资助：无。
完整摘要 · 英文原文
BACKGROUND: This systematic review and meta-analysis assesses whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) during pregnancy or the periconceptional period is associated with adverse maternal and perinatal outcomes. METHODS: Medline, Embase, and the Cochrane Library were searched for observational studies comparing pregnancies exposed and unexposed to GLP-1 RAs within 6 months before a positive pregnancy test. Outcomes included miscarriage, intrauterine death, congenital anomalies, preterm birth (PTB), hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), small for gestational age (SGA), large for gestational age (LGA), and excess gestational weight gain. Random-effects meta-analyses and subgroup analyses by indication were performed. FINDINGS: Ten studies included 2,118,215 women, of whom 8,325 were exposed and 2,109,890 were unexposed. Pooled estimates did not show a clearly detectable increase in miscarriage or intrauterine death, congenital anomalies, preterm birth, HDP, gestational diabetes, abnormal fetal growth, or excess gestational weight gain. A lower pooled estimate for preeclampsia was observed (odds ratio [OR]: 0.87, 95% confidence interval [CI]: 0.78-0.98; p = 0.02), but this was based on two datasets and should be interpreted cautiously. Subgroup analyses showed no clearly detectable differences by indication. The exposure-window sensitivity analysis, covering 90 days before conception through the end of the first trimester, used the same four studies as the primary congenital-malformation analysis and therefore was not independent. CONCLUSION: Available observational evidence did not identify a clearly detectable increase in adverse maternal or perinatal outcomes following periconceptional exposure to GLP-1 RAs. However, these findings do not establish safety because of heterogeneity, residual confounding, and limited datasets. FUNDING: None.