Histological Characteristics of the Fetal Inflammatory Response Associated with Neurodevelopmental Impairment and Death in Extremely Preterm Infants

Abstract

To test the hypothesis that increasing severity of the fetal inflammatory response would have a dose-dependent relationship with severe neurodevelopmental impairment (NDI) or death in extremely preterm infants. Study design We report 347 infants 23 to 28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or NDI at 18–22 month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1: phlebitis; stage 2: arteritis with or without phlebitis; stage 3: subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis). Results A fetal inflammatory response was detected in 110 placentas (32%). Severe NDI/death rate was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs. 35%; p<0.05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with higher rates of severe NDI/death (47% vs. 23%; p<0.05). After adjustment for confounding factors, only subacute necrotizing funisitis (RR: 1.87; 95% CI: 1.04 – 3.35; p=0.04) and chorionic plate vasculitis with thrombosis (RR: 2.21; 95% CI: 1.10 – 4.46; p=0.03) were associated with severe NDI/death. Conclusions Severe fetal inflammatory response characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis are associated with severe NDI/death in preterm infants.

Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model

“…Our observations of decreased basal survival in neonatal pups may have relevance to the increased mortality observed in human preterm neonates exposed to chorioamnionitis (27). The observed trend toward decreased survival in LPS-exposed, SeV-infected weanling mice in our studies might yield a clue to the enhanced mortality of preterm infants with RSV (reviewed in ref.…”

“…(28)). The possibility of an association between antenatal inflammation and RSV-related mortality in human infants is intriguing and merits investigation, particularly given the often-subclinical fetal inflammation in the preterm population (27).…”

Correlation of preterm infant illness severity with placental histology

“…[21] identified that fetuses with plasma IL-6 greater than 11 pg/mL had significantly higher rates of overall severe neonatal morbidity, as well as RDS and proven or suspected sepsis. Further studies have reported the significant relationship between umbilical arteritis/severe fetal inflammatory response and severe neonatal morbidity [22; 23]. Our findings are in agreement with the prior reports that the fetal inflammatory response is highly correlated with neonatal morbidity.…”

Antenatal factors modulate hearing screen failure risk in preterm infants

“…In contrast to the maternal inflammatory response, FIRS, defined as cord IL-6 >11 pg/mL, significantly increased the risk for hearing screen failure in the study cohort, and has been associated with adverse neonatal outcomes, particularly intraventricular haemorrhage and early onset sepsis 25. Increasing severity of fetal vasculitis was associated with severity of composite neurodevelopmental impairment/death at 18–22 months’ adjusted age in infants 23–28 weeks’ gestation 26. Neither prior study reported hearing outcomes.…”