A recent study published in JAMA Network Open highlights a concerning association between repeated perinatal antibiotic exposure and obstructive airway disease in very low-birth-weight (VLBW) preterm infants delivered via cesarean section.
Previous animal research and human observational studies have linked antibiotic exposure to the development of asthma and other respiratory issues. Preterm infants, particularly those born at very low birth weights, face an inherently higher risk of chronic lung disease due to factors such as immature lung anatomy, nutritional challenges, and exposure to oxygen therapy and invasive ventilation. However, the specific impact of early antibiotic exposure on lung health in cesarean-delivered preterm newborns—who experience unique microbiome disruptions related to surgical birth and antibiotic use—has not been thoroughly explored until now.
Study Design and Population
Conducted by the German Neonatal Network (GNN), this large multicenter cohort study initially enrolled 22,557 preterm infants. After exclusions, 16,232 infants were eligible for follow-up, with 3,820 VLBW infants (born between 22 and 36 weeks gestation, weighing less than 1,500 grams) assessed between five and seven years of age. The study focused exclusively on cesarean-born infants to isolate the effects of perinatal antibiotic exposure from those related to vaginal delivery.
Parents provided detailed information on their children’s respiratory health via questionnaires, while lung function was objectively measured using spirometry. The primary outcome was the forced expiratory volume in one second (FEV₁) z-score, a standard measure of airway obstruction.
Antibiotic Exposure Categories and Findings
Researchers categorized infants into three antibiotic risk score (ARS) groups based on the timing and extent of exposure:
ARS I: Single exposure to maternal surgical antimicrobial prophylaxis (SAP)
ARS II: SAP plus postnatal antibiotics
ARS III: Antenatal antibiotics, SAP, and postnatal antibiotics
The study found a clear dose-response relationship: higher ARS levels correlated with progressively lower FEV₁ z-scores, indicating worsening lung function. Compared with ARS I, children in ARS II showed a significant decrease in lung function (−0.31 z-score), while those in ARS III experienced a similar decline (−0.27 z-score) relative to ARS II.
Secondary analyses revealed that children in the highest exposure group (ARS III) had a 91% greater risk of asthma episodes compared to ARS II, along with reductions in forced vital capacity (FVC).
Study Limitations and Interpretations
The authors acknowledged several limitations, including a modest follow-up rate (23.5%), potential selection bias from excluding infants unable to perform spirometry, and lack of detailed data on antibiotic types and durations. Given the observational design, the study cannot definitively establish causality between antibiotic exposure and respiratory outcomes.
While breastfeeding and maintaining a healthy microbiome were discussed as important factors influencing lung health, the study stopped short of endorsing probiotics as a definitive intervention. Instead, it emphasized the critical need for prudent antibiotic use and structured preventive measures to protect vulnerable preterm infants’ respiratory health.
Conclusions and Implications
This study provides compelling evidence that repeated antibiotic exposure in cesarean-born VLBW preterm infants is linked to wheezing and impaired lung function during early childhood. Although causality remains to be proven, these findings underscore the importance of antibiotic stewardship programs aimed at reducing unnecessary neonatal antibiotic use. Additionally, enhanced respiratory monitoring for high-risk infants and support for breastfeeding are recommended as part of comprehensive care strategies. Future research should explore targeted prevention and intervention approaches to improve long-term respiratory outcomes in this vulnerable population.
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