Histologic chorioamnionitis and risk of neurodevelopmental impairment at age 10 years among extremely preterm infants born less than 28 weeks of gestation

Abstract Background Children born extremely preterm whose placenta had histologic evidence of chorioamnionitis have early brain dysfunction, but little is known about neurological development at 10 years of age. Objective We investigated the association between histologic chorioamnionitis and neurodevelopmental impairment at 10 years among children born Methods The multicenter Extremely Low Gestational Age Newborn (ELGAN) Study enrolled extremely preterm newborns from 2002-2004 at 14 U.S. hospitals. Chorioamnionitis was defined by histologic stage (early, moderate, and advanced) and grade (mild/moderate and severe) of chorionic plate and umbilical cord inflammation. The children were evaluated for cerebral palsy at 2 years, and autism spectrum disorder, cognitive impairment (intelligence quotient >2 standard deviations below the mean), and epilepsy at age 10 years by blinded evaluators using validated measures. Multivariable logistic regression with generalized estimating equations was used. Results Among 805 placenta, 43% (347/805) had histologic chorioamnionitis by moderate or advanced maternal stage, 36% (286/805) by severe maternal grade, 18% (132/737) by moderate or advanced fetal stage, and 1% (10/737) by severe fetal grade. The frequencies of impairments were 11% (88/767) for cerebral palsy, 7% (56/773) for autism spectrum disorder, 15% (120/788) for cognitive impairment, and 7% (52/763) for epilepsy. Adjusted for maternal age, body mass index, race, insurance status, maternal education, tobacco use, infant sex, and multiple gestations, the adjusted odds (AOR) for the association between histologic chorioamnionitis and cerebral palsy years was increased with advanced maternal stage (AOR 2.5, 95% CI 1.6 to 3.9), severe maternal grade (AOR 2.0, 95% CI 1.2 to 3.4), moderate fetal stage (AOR 2.20, 95% CI 2.1 to 2.2), and mild or moderate fetal grade (AOR 1.5, 95% CI 1.0 to 2.2). Similarly, the AOR for the association between histologic chorioamnionitis and epilepsy was increased with advanced maternal stage (AOR 1.5, 95% CI 1.3 to 1.6) and severe fetal grade (AOR 5.9, CI 1.9 to 17.8). In addition, the AOR for the association between histologic chorioamnionitis and autism spectrum disorder was increased with mild or moderate fetal grade (AOR 1.7, 95% CI 1.0 to 2.9). Histologic chorioamnionitis was not associated with cognitive impairment. These findings held after adjustment for gestational age at delivery. In contrast to histological chorioamnionitis, a clinical diagnosis of chorioamnionitis was not associated with neurodevelopmental impairment. Conclusion Histologic chorioamnionitis may be associated with some forms of neurodevelopmental impairment at 10 years of life among infants born