Disruption of maternal IgA by prenatal antibiotics precedes intestinalE. colicolonization and late-onset sepsis in neonates

Neonates, particularly prematurely born neonates, are particularly vulnerable to enteric pathogens. Antibiotics are widely administered during pregnancy for off-label use and prevention, but the effect on neonatal physiology has not been well characterized. Maternally derived IgA provided in milk is a predominant protective measure in the intestinal lumen of the nursing offspring. The connection between the maternal intestine and mammary IgA responses has been observed, but understanding how clinical use of antibiotics effects mammary IgA remains unclear. Here we find that prenatal cephalosporin antibiotics, but not penicillins, decrease mammary IgA in dams, and limit the availability of IgA within the lumen of nursing offspring. Decreased IgA correlated with an outgrowth of commensal E. coli and increased colonization and translocation of pathogen E. coli. Moreover, antenatal cephalosporin administration was associated with increased mortality in a model of LOS that was associated with decreased mammary IgA. Futhermore, in a clinical cohort of at-risk infants, maternal broad spectrum antibiotic treatment, including cephalosporins, increased the risk of LOS in neonates in comparison to penicillin-based treatments. This was associated with reduced IgA in the milk, and we propose maternal administration of select antibiotics could disrupt mammary IgA, leading to increased risk of LOS in infants by allowing for pathogen colonization in the neonatal intestine.