In the latest research into early antibiotic exposure and development of childhood conditions, a study of infants born preterm suggests that repeated pre- and postnatal antibiotic exposure is associated with impaired lung function at early school age, German researchers reported this week in JAMA Network Open.
In the population-based, multicenter cohort study, very low birth weight (VLBW) preterm babies were enrolled at 58 German neonatal intensive care units (NICUs) from January 2009 through March 2017 and received follow-up at 5 to 7 years of age. The authors defined VLBW as less than 1,500 grams, or 3.3 pounds.
The researchers were interested in examining this cohort because previous studies have found that prenatal antibiotic exposure and antibiotic treatment at an early age are linked to the development of asthma. But to their knowledge, no studies have examined a potential link between antibiotic use in preterm infants—who are vulnerable to life-threatening bacterial infections and have high antibiotic exposure rates—and obstructive airway disease.
"Antibiotics remain lifesaving in the NICU, as delayed or omitted administration can lead to neonatal death or severe organ damage," the study authors wrote. "However, antibiotic exposure enhances the risk for microbiome distortions (gut dysbiosis)—that is, reduction of microbial diversity and key taxa, such as Bifidobacteria. In turn, dysbiosis may precede sepsis, brain injury, and systemic and sustained inflammation, all of which contribute to long-term pulmonary morbidities."
Lower lung function, increased asthma risk
The infants were stratified by an antibiotic risk score (ARS), with the low-risk (ARS 1) group exposed only to surgical antibiotic prophylaxis (SAP) given to the mother prior to cesarean delivery, the intermediate-risk group (ARS 2) exposed to SAP and postnatal (after-birth) antibiotic treatment, and the high-risk group (ARS 3) additionally exposed to antenatal (before-birth) maternal antibiotic treatment.
The primary outcome of the study was the forced expiratory volume in 1 second (FEV1) score—a measurement of lung function—at 5 to 7 years of age. Secondary outcomes included forced vital capacity (FVC) z score and childhood asthma episodes.
A total of 3,820 VLBW preterm-born infants with follow-up (median gestational age, 28.4 weeks; 36.2% from a multiple birth; 81.4% born via cesarean delivery) were included in the study. Of these infants, 292 (9.4%) were in the ARS 1 group, 1,329 (42.7%) in the ARS 2 group, and 1,488 (47.9%) in the ARS 3 group. Linear regression analysis revealed a significant decline in FEV1 scores at early school age that was associated with increasing ARS levels (ARS 2 vs 1: β, −0.31; 95% confidence interval [CI], −0.59 to −0.02 and ARS 3 vs 2: β, −0.27; 95% CI, −0.46 to −0.08).
Although we could not demonstrate a causal link, our data can make a case for balancing the priorities of immediate health concerns of invasive infection and potential long-term consequences when clinicians determine the need for antibiotic treatment.
A secondary analysis found that a higher exposure level (ARS 3 vs 2) was associated with impaired FVC z scores (β, −0.23; 95% CI, −0.43 to −0.03) and an increased risk of early childhood asthma episodes (odds ratio, 1.91; 95% CI, 1.32 to 2.76).
"Although we could not demonstrate a causal link, our data can make a case for balancing the priorities of immediate health concerns of invasive infection and potential long-term consequences when clinicians determine the need for antibiotic treatment," the authors wrote. They add that while there are various factors that affect lung development in preterm infants, early identification of high-risk children could enable healthcare professional to counsel parents on lung-protective strategies.
"Evidence-based programs and prevention bundles are needed to support respiratory health and optimize long-term outcomes in the vulnerable group of preterm individuals."
