(54) Impact of Prenatal Antibiotic Exposure on Late-Onset Sepsis Risk in a Mouse Model of Premature Rupture of Membranes

Background: Pregnant women experiencing premature rupture of amniotic membranes (PROM) are routinely treated with broad-spectrum antibiotics to mitigate the risk of ascending infections, which can significantly increase morbidity and mortality for both the mother and the fetus. The standard antibiotic regimen includes intravenous ampicillin and gentamicin, followed by oral amoxicillin and erythromycin for a total duration of seven days. While early life antibiotic exposure is known to elevate the risk of late-onset sepsis and necrotizing enterocolitis in premature neonates, the effects of prenatal antibiotic administration on these complications remain unclear.

Objectives: The goal is to better understanding of the potential risks associated with antibiotic use during pregnancy in cases of PROM. Our research also seeks to elucidate the impact of prenatal antibiotic administration on the susceptibility to late-onset sepsis by studying the effect of prenatal antibiotics on GAP activity and bacterial translocation.

Design/Methods: We developed a mouse model to simulate PROM antibiotic exposure. In this model, specific pathogen-free (SPF) housed C57BL/6 pregnant dams receive amoxicillin and erythromycin in their drinking water from embryonic day (E) 14 to 21. We further expanded on the model by gavage feeding E. coli ST69, a highly pathogenic variant, and assessing for its translocation rates to mesenteric lymphatic lymph node, liver, and spleen in pups exposed to antibiotics prenatally vs control.

Results: Our preliminary data indicates that pups exposed to prenatal antibiotics exhibit impaired growth relative to control pups. Immunohistologic and hematoxylin & eosin staining of the small intestine and colon shows inflammatory changes and altered small intestinal villi architecture in exposed pups when compared with controls.

Conclusion: Using a mouse model of PROM antibiotic exposure, our preliminary data indicate that prenatal antibiotics can lead to impaired growth and significant inflammatory changes in the intestinal architecture of exposed pups. This research aims to further explore how prenatal antibiotic exposure influences the risk of late-onset sepsis, providing critical insights that could inform clinical practices and improve outcomes for both mothers and their infants.