Effect of acute histologic chorioamnionitis on bronchopulmonary dysplasia and mortality rate among extremely low gestational age neonates: A retrospective case–control study

Abstract

ObjectiveTo evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN).MethodsThis Italian single‐center case–control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage ≥2 and grade 2 HCA, (HCA‐infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no‐HCA‐infants).ResultsAmong 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA‐infants group and 33 in the no‐HCA‐infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47–13.71).ConclusionsThis is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN.

Homeostatic macrophages prevent preterm birth and improve neonatal outcomes by mitigatingin uterosterile inflammation

“…However, M2 MΦ treatment downregulated the expression of Tnfrsf1a and Nod1 in the fetal lung (Figure 5d&e). Considering that treatment with M2 MΦ did not result in a significant suppression of the inflammatory response in the fetal lung, an organ critically linked to complications in preterm neonates 13–15 , we explored whether the homeostatic effects of M2 MΦ treatment were more evident in the neonatal lung by evaluating inflammatory gene expression in this tissue. Neonates born to dams treated with M2 MΦ exhibited a diminished inflammatory profile in the neonatal lung, characterized by reduced expression of Il6 , Ccl2 , Socs3 , and Cxcl1 in comparison to offspring from untreated dams (Figure 5f&g).…”

“…Next, we focused on the fetal lung since preterm neonates born to women with intra-amniotic inflammation are at high risk of developing bronchopulmonary dysplasia 13–15 . In the fetal lung (Figure 5A), intra-amniotic injection of HMGB1 resulted in the upregulation of Il6 , Tnfrsf1a , Il33 , Nlrp6 , and Tlr9 (Figure 5B&C).…”

“…Importantly, SIAI has been linked to adverse short- and long-term outcomes for the offspring of women with this clinical condition 7,11 . Specifically, women with SIAI are at greater risk of having placentas affected by acute histologic chorioamnionitis 12 , which is linked to the development of deleterious conditions such as bronchopulmonary dysplasia 13–15 and necrotizing enterocolitis 16,17 , likely due to exposure of the fetal lungs and intestine to intra-amniotic inflammation 18–20 . Clinical studies have also shown that SIAI is associated with increased amniotic fluid concentrations of alarmins or danger signals 7,21,22 , molecules released upon cellular stress or damage 23,24 .…”

“…Importantly, in utero sterile inflammation has been linked to adverse short-and long-term outcomes for the offspring of women with this clinical condition 7,11 . Specifically, women with in utero sterile inflammation are at greater risk of having placentas affected by acute histologic chorioamnionitis 12 , which is linked to the development of deleterious neonatal conditions such as bronchopulmonary dysplasia [13][14][15] and necrotizing enterocolitis 16,17 , likely due to exposure of the fetal lungs and intestine to intraamniotic inflammation [18][19][20] . However, despite the strong associations between in utero sterile inflammation and adverse fetal and neonatal outcomes, no approved treatments currently exist.…”