Prenatal inflammation may explain why some infants are more prone to neonatal sepsis

Each year, 15 million infants are born prematurely and are at high risk for short- and long-term complications, including sepsis, severe bowel inflammation, and neurodevelopmental disorders. A new report in the American Journal of Pathology demonstrates a link between prenatal inflammation and postnatal immune status and organ function in premature pigs, suggesting that early intervention (eg, antibiotics or anti-inflammatories) might be warranted in infants born prematurely with signs of inflammation of the fetal membranes.

"Our study could encourage clinicians to better know the population of premature infants with chorioamnionitis (inflammation of the fetal membrane) as they present a higher risk of systemic inflammation and neonatal sepsis," explained the investigator. Principal Per T. Sangild, DVSc, DMSc. PhD, Section of Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark, and Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.

"The data highlight the importance of barrier integrity between epithelial (intestines, lungs and skin) and circulation, which are more fragile in preterm infants and may facilitate translocation of bacteria and parasites. inflammatory molecules, leading to systemic inflammation and internal organ disorders ".

To induce prenatal inflammation, bacterial endotoxin lipopolysaccharide (LPS) was injected into the amniotic sacs of antenatal pigs. LPS and control groups were analyzed at birth, three days after birth and five days after birth (infant formula).

At birth, prenatal LPS induced benign histological chorioamnionitis and a strong innate immune response of the fetal lungs and intestines, accompanied by an elevated level of inflammatory cytokines and an infiltration of neutrophils and macrophages. "We believe that epithelial responses have probably been derived from direct exposure to cytokines induced by LPS or intra-amniotic LPS," said Dr. Sangild.

Five days later, inflammation of the intestines and lungs decreased; However, pigs exposed to LPS before birth gradually developed systemic inflammation, with high levels of blood leukocyte subgroups (neutrophils, lymphocytes, etc.) and plasma cytokines (eg, IL-1β), similar to symptoms observed in septic infants. Of those who survived, the control group pigs were standing and walked for the first time before the animals exposed to LPS. High levels of bacteria have also been found in the spleen in pigs exposed to LPS, indicating an increase in systemic infection or a decrease in the ability to eliminate transferred bacteria. In utero mortality was higher in LPS-exposed fetuses than in the control group, as was the incidence of severe diarrhea. Interestingly, intra-amniotic LPS did not increase the incidence of formula-induced necrotizing enterocolitis by the fifth day. This is important because it was suspected that systemic inflammation at birth could also predispose to subsequent NEC in the preterm gut; However, this hypothesis was not supported by this study.

"These data suggest that the postnatal systemic effects of short-term prenatal LPS were indirectly initiated from the previous local inflammation of epithelial tissues of the fetal period, and that they were progressively amplified systemically over the course of time. first days after preterm birth, "commented Dr. Sangild

The results of this study underscore the importance of early diagnosis of prenatal inflammation to facilitate nutritional, medical or pharmaceutical interventions that mitigate postnatal reactions that are detrimental to prenatal inflammation. The problem still remains that a pregnant woman with intra-amniotic inflammation may be asymptomatic and, therefore, not realize that she has an infection that could harm her baby.