Maternal Infection, Fetal Inflammatory Response, and Brain Damage in Very Low Birth Weight Infants

Abstract

Echolucent images (EL) of cerebral white matter, seen on cranial ultrasonographic scans of very low birth weight newborns, predict motor and cognitive limitations. We tested the hypothesis that markers of maternal and feto-placental infection were associated with risks of both early (diagnosed at a median age of 7 d) and late (median age = 21 d) EL in a multi-center cohort of 1078 infants <1500 x g. Maternal infection was indicated by fever, leukocytosis, and receipt of antibiotic; fetoplacental inflammation was indicated by the presence of fetal vasculitis (i.e. of the placental chorionic plate or the umbilical cord). The effect of membrane inflammation was also assessed. All analyses were performed separately in infants born within 1 h of membrane rupture (n = 537), or after a longer interval (n = 541), to determine whether infection markers have different effects in infants who are unlikely to have experienced ascending amniotic sac infection as a consequence of membrane rupture. Placental membrane inflammation by itself was not associated with risk of EL at any time. The risks of both early and late EL were substantially increased in infants with fetal vasculitis, but the association with early EL was found only in infants born > or =1 after membrane rupture and who had membrane inflammation (adjusted OR not calculable), whereas the association of fetal vasculitis with late EL was seen only in infants born <1 h after membrane rupture (OR = 10.8; p = 0.05). Maternal receipt of antibiotic in the 24 h just before delivery was associated with late EL only if delivery occurred <1 h after membrane rupture (OR = 6.9; p = 0.01). Indicators of maternal infection and of a fetal inflammatory response are strongly and independently associated with EL, particularly late EL.

Bronchopulmonary Dysplasia Is Not Associated with Ultrasound-Defined Cerebral White Matter Damage in Preterm Newborns

“…Others, however, have reported that chorioamnionitis is an antecedent of echolucency (50). Virtually all placentas and umbilical cords that have fetal vasculitis also have inflammation of the membranes, but only approximately half of placentas with membrane inflammation have fetal vasculitis (21,51). This and other findings have led to our view that fetal vasculitis is an indication of the severity and progression of the inflammatory process that tends to involve the membranes before it involves the chorionic plate and umbilical cord.…”

Chorioamnionitis: a multiorgan disease of the fetus?

“…13 In clinical studies, antenatal exposure to inflammation has been associated with an increased risk for periventricular leukomalacia and cerebral palsy. [14][15][16] Moreover, neurodevelopmental delay has been linked with previous exposure to chorioamnionitis by some studies, although others have failed to reproduce these findings. 10 Animal experimental evidence.…”

Proteomic Biomarkers of Intra-amniotic Inflammation: Relationship with Funisitis and Early-onset Sepsis in the Premature Neonate

“…Our research was motivated by the fact that histologic chorioamnionitis and funisitis has been previously linked with neonatal morbidity in preterm infants (27,28). We have previously shown that proteomic profiling of the AF can rapidly and accurately diagnose intra-amniotic inflammation, and can identify women at risk of premature delivery (14).…”