Neonatal and obstetric outcomes following periconceptional exposure to glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis

Early pregnancy exposure was not linked to major adverse outcomes.
*Systematic review and meta-analysis of observational studies; Level 2a.

Citation

Hakim J, Rajesh D, Tello JA. Neonatal and obstetric outcomes following periconceptional exposure to glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis. American Journal of Obstetrics & Gynecology. 2026; October:800-816.

Background

Use of glucagon-like peptide-1 receptor agonists is rising among reproductive-age women with obesity or type 2 diabetes. Animal studies raised concern, but human pregnancy safety data have been limited.

Patients

Human singleton pregnancies with exposure from 3 months before conception through the first trimester. Exclusions included animal studies, multiple gestations, fetal chromosomal disorders, known teratogenic co-medications, and exposure stopped more than 3 months before conception.

Intervention

Periconceptional glucagon-like peptide-1 receptor agonist exposure, including semaglutide, liraglutide, dulaglutide, exenatide, and related drugs.

Control

Unexposed pregnancies, often matched or grouped by obesity, type 2 diabetes, insulin use, metformin use, or general population controls.

Outcome

Congenital malformations, pregnancy loss, live birth, preterm birth, fetal growth, hypertensive pregnancy disorders, cesarean delivery, and neonatal outcomes.

Follow-up Period

Mostly through delivery; neonatal follow-up was limited.

Results

Twenty-two studies included 49,395 exposed pregnancies; 10 comparative studies entered meta-analysis.

OR: odds ratio; CI: confidence interval; NS: not statistically significant.

The renal finding was largely driven by one large cohort with baseline differences in obesity, diabetes control, hypertension, and kidney disease.

Limitations

All comparative evidence was observational, so residual confounding is likely. Exposure was often based on prescriptions, not confirmed use. Long-term child outcomes were largely unavailable, and rare defects remain hard to assess.

Funding

Jisc and University of St Andrews; no conflicts reported.

Clinical Application

Reassure after inadvertent early exposure, but continue advising discontinuation before conception and avoid routine use during pregnancy.