Maternal antibiotic use during pregnancy increases the risk of offspring airway infections: a systematic review and meta-analysis

Background Antibiotics are widely prescribed during pregnancy, yet their impact on offspring infection risk remains unclear. This study synthesises all available data and evaluates the association between maternal antibiotic use during pregnancy and the risk of infections in offspring during childhood. Methods We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, registered with PROSPERO. We searched PubMed, Embase, Ovid, ISRCTN registry, ClinicalTrials.gov and Cochrane Library for English language studies without publication date restrictions. Studies reporting quantitative data on prenatal antibiotic exposure and childhood infections after the neonatal period were included. Two authors screened and extracted data from published reports. Risk of bias was evaluated using the Newcastle-Ottawa Scale. The primary outcome was any childhood infection risk, analysed using random-effects meta-analyses with sensitivity analyses by infection type and study quality. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results From 7317 records, 14 cohort studies (n=5 011 183 children) were included, of which 12 (n=4 995 449) provided data for meta-analysis. Prenatal antibiotic exposure was associated with an increased risk of any offspring infection (OR 1.33, 95% CI 1.01 to 1.76, p=0.04). A sensitivity analysis (n=3 647 296) of six high-quality studies showed a stronger association (OR 1.48, 95% CI 1.13 to 1.95, p<0.01). Specifically, ear, nose and throat infections were significantly increased (n=2 841 644 children) (OR 1.40, 95% CI 1.18 to 1.65, p<0.0001). The risk of bias was low in the majority of the included studies and the certainty of evidence was high for any offspring infection from the GRADE assessment. Conclusions Prenatal antibiotic exposure was associated with increased offspring infection risk and in particular upper airway infections. These findings indicate a need for cautious antibiotic prescribing during pregnancy, although potential confounding cannot be excluded. PROSPERO registration number CRD42024599699. No data are available.