A major German study finds that early repeated antibiotic use in very low-birth-weight infants can have lasting effects on lung health, highlighting the importance of antibiotic stewardship and preventive care for preterm children.
Study: Perinatal Antibiotic Exposure and Respiratory Outcomes in Children Born Preterm. Image Credit: mi_viri / Shutterstock
In a recent study published in JAMA Network Open, researchers assessed whether repeated perinatal antibiotic exposure in very low-birth-weight (VLBW) preterm newborns born via cesarean delivery is associated with obstructive airway disease.
Animal models have revealed that antibiotic exposure contributes to obstructive airway disease, and human observational studies have found associations between childhood asthma and prenatal antibiotic exposure. Preterm newborns and infants have a higher risk of chronic lung disease than those born at term, for various reasons, including preterm lung anatomy, nutritional deficits, and exposure to oxygen and invasive ventilation.
Nevertheless, the pulmonary outcomes of preterm newborns vary greatly given various modifying factors, such as genetics, gestational age (GA), and a higher risk of recurrent pulmonary infections. While antibiotic therapy is associated with asthma development in later childhood, no study has yet assessed the links between obstructive airway disease and early antibiotic exposure in preterm infants born via cesarean delivery, who face distinct microbiome disruption risks due to surgical birth and antibiotic protocols.
About the Study
In the present study, researchers examined the associations between multiple antibiotic exposures in VLBW preterm neonates born via cesarean delivery and obstructive airway disease at early school age. The German Neonatal Network (GNN) conducted this multicenter, population-based cohort study, which enrolled 22,557 preterm infants, narrowing to 16,232 eligible for follow-up after exclusions. From this group, 3,820 VLBW newborns (born between 22 and 36 weeks of gestation with a birth weight under 1,500 g) underwent follow-up assessments at five to seven years of age.
The analysis focused exclusively on cesarean-delivered infants to isolate the effects of perinatal antibiotic exposure, as vaginal births were excluded. Parents completed questionnaires about their children’s respiratory health, and spirometry tests measured lung function.
The primary endpoint was the forced expiratory volume in one second (FEV₁) z-score. Children were stratified into three antibiotic risk score (ARS) groups: ARS I (single exposure: maternal surgical antimicrobial prophylaxis [SAP]), ARS II (SAP + postnatal antibiotics), and ARS III (antenatal antibiotics + SAP + postnatal antibiotics).
Findings
Higher ARS levels were associated with progressively lower FEV₁ z-scores (β = −0.27 per exposure level; 95% CI, −0.40 to −0.13). Compared to ARS I, ARS II and III showed worsening lung function: ARS II was linked to a −0.31 reduction in FEV₁ z-scores (95% CI, −0.59 to −0.02), while ARS III showed a −0.27 reduction (95% CI, −0.46 to −0.08) compared to ARS II.
Secondary outcomes included a 91% higher risk of asthma episodes in ARS III versus ARS II (odds ratio = 1.91; 95% CI, 1.32–2.76) and reduced forced vital capacity (FVC) z-scores.
The study noted limitations, including potential selection bias due to a 23.5% follow-up rate, exclusion of infants unable to perform spirometry (e.g., those with severe cerebral palsy), and lack of data on antibiotic types or durations. Researchers emphasized that while associations were clear, causality could not be proven due to the observational design.
While the study discusses the potential role of breastfeeding and a healthy microbiome in respiratory outcomes, and mentions probiotic exposure as an adjusted confounder, it does not explicitly recommend probiotics as a mitigation strategy for antibiotic-associated risks. The primary recommendations in the conclusion focus on antibiotic stewardship and structured prevention bundles to support respiratory health.
Conclusions
In summary, repeated antibiotic exposures in cesarean-born VLBW infants were associated with wheezing and impaired lung function at early school age. While causality remains unproven, the findings underscore the need for antibiotic stewardship programs to minimize unnecessary neonatal exposures and targeted respiratory monitoring for high-risk infants. The study suggests that further research and prevention strategies, including the support of breastfeeding, are warranted.