Each year, 15 million infants are born preterm and are at high risk of short- and long-term complications, including sepsis, severe bowel inflammation and neurodevelopmental disorders. This report presented in the American Journal of Pathology reveals and demonstrates, in animals, a link between prenatal inflammation, and the function of internal organs and postnatal immune status. These findings suggest that early intervention, eg, antibiotics or anti-inflammatories may be warranted in infants born preterm with evidence of fetal membrane inflammation.
Thus, intra-amniotic inflammation—here caused by short-term prenatal exposure to endotoxins—leads first to an acute immune response in the fetal lungs and intestine, followed by systemic inflammation after birth. , according to this study from the University of Copenhagen. The study thus sensitizes clinicians to better understand the group of premature infants with chorioamnionitis (inflammation of the fetal membrane) because they are at higher risk of systemic inflammation and neonatal sepsis, comments its lead author, Dr Per T. Sangild, from the Department of Pediatrics and Nutrition at the University of Copenhagen.
The integrity of the barriers between the epithelial tissues (intestinal, lungs and skin) and the circulation appears here as a key factor: because these barriers are more fragile in premature newborns and can allow the translocation of bacteria and inflammatory molecules which will lead to systemic inflammation and dysfunction of internal organs.
The study , conducted in pigs, first consisted in inducing prenatal inflammation, by prenatal injection of endoxins (LPS) into the amniotic sacs of pigs. The “LPS” group and the control group were analyzed at birth, 3 days after birth and 5 days after birth. This analysis shows that:
- at birth, animals in the intervention group exhibit mild histological chorioamnionitis and a strong innate immune response of the fetal lungs and intestines, accompanied by elevated inflammatory cytokines and neutrophil and macrophage infiltration;
- 5 days later, inflammation of the intestines and lungs is reduced, however, the animals gradually develop systemic inflammation, with elevated levels of blood leukocyte subgroups (neutrophils, lymphocytes, etc.) and plasma cytokines ( eg, IL-1β), similar to symptoms seen in septic infants;
- finally, the survivors stand up, for the first time, much later than the control animals;
- elevated levels of bacteria are found in the spleen of exposed pigs, suggesting increased systemic infection or decreased ability to eliminate transferred bacteria;
- the in utero mortality rate is higher in fetuses exposed to “LPS” than in fetuses from the control group.
" Taken together, these data suggest that these systemic effects are related to local inflammation of epithelial tissues in the fetal period ", conclude the researchers, " and that these effects were progressively amplified systemically over the first few days after preterm birth .
In summary, the study highlights the importance of early diagnosis of prenatal inflammation to facilitate nutritional, medical, or pharmaceutical interventions that mitigate adverse postnatal responses to prenatal inflammation. With a challenge: a pregnant woman with intra-amniotic inflammation may be asymptomatic.
