Impact of semaglutide exposure on fetal and neonatal outcomes in pregnant women: a systematic review

Abstract

Background: Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used for obesity and type 2 diabetes treatment. As its use rises among women of reproductive age, understanding its impact on fetal and neonatal health is essential.

Objectives: To assess fetal and neonatal outcomes associated with semaglutide exposure during pregnancy or within two months before conception.

Search strategy: PubMed, Embase, and ClinicalTrials.gov were searched for relevant studies.

Selection criteria: Studies reporting fetal and neonatal outcomes following semaglutide exposure before or during pregnancy were included, with no language restrictions.

Data collection and analysis: Two reviewers independently screened and extracted data. Due to study heterogeneity, a narrative synthesis was used, and bias risk and study quality were assessed.

Main results: Five studies involving a total of 1,128 semaglutide exposed pregnancies, showed mixed results. One study reported adverse outcomes including spontaneous abortion and preeclampsia. Another study found spontaneous abortion rate of 23%, comparable to diabetes- and obesity-groups. A third study observed a prevalence of congenital malformations of 8.3%, with no significant risk increase compared to insulin. One study linked semaglutide discontinuation to fetal macrosomia and neonatal hypoglycaemia. Another noted preterm birth and large-for-gestational-age infants, with no increased congenital malformation risk. No clear association with birth defects was identified, however the evidence is limited by study variability and bias risk.

Conclusions: The limited number of available studies precludes firm conclusions nevertheless current evidence does not indicate a consistent increased risk of major congenital malformations associated with semaglutide exposure.

Keywords: Congenital malformation; Fetal and neonatal adverse outcomes; GLP-1 receptor agonist; Pregnancy; Semaglutide; Systematic review.