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

Abstract

BACKGROUND: Extremely preterm infants whose placenta had histologic evidence of chorioamnionitis have early brain dysfunction, but little is known about neurologic development at 10 years of age. OBJECTIVE: We investigated the association between histologic chorioamnionitis and neurodevelopmental impairment at 10 years among children born <28 weeks' gestation (extremely preterm). STUDY DESIGN: The multicenter Extremely Low Gestational Age Newborns study enrolled extremely preterm newborns from 2002 to 2004 at 14 hospitals in the United States. 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 examined for cerebral palsy at 2 years and for autism spectrum disorder, cognitive impairment (intelligence quotient >2 standard deviations below the mean), and epilepsy at the age of 10 years by blinded evaluators using validated measures. Multivariable logistic regression with generalized estimating equations was used. RESULTS: Among 805 placentas, 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. After adjustment for maternal age, body mass index, race, insurance status, maternal education, tobacco use, infant sex, and multiple gestations, the adjusted odds ratio for the association between histologic chorioamnionitis and cerebral palsy years was increased with advanced maternal stage (adjusted odds ratio, 2.5; 95% confidence interval, 1.6e3.9), severe maternal grade (adjusted odds ratio, 2.0; 95% confidence interval, 1.2e3.4), moderate fetal stage (adjusted odds ratio, 2.20; 95% confidence interval, 2.1e2.2), and mild or moderate fetal grade (adjusted odds ratio, 1.5; 95% confidence interval, 1.0e2.2). Similarly, the adjusted odds ratio for the association between histologic chorioamnionitis and epilepsy was increased with advanced maternal stage (adjusted odds ratio, 1.5; 95% confidence interval, 1.3e1.6) and severe fetal grade (adjusted odds ratio, 5.9; 95% confidence interval, 1.9e17.8). In addition, the adjusted odds ratio for the association between histologic chorioamnionitis and autism spectrum disorder was increased with mild or moderate fetal grade (adjusted odds ratio, 1.7; 95% confidence interval, 1.0e2.9). Histologic chorioamnionitis was not associated with cognitive impairment. These findings held after adjustment for gestational age at delivery. In contrast to histologic 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 <2...

Developmental Trajectories in Very Preterm Born Children Up to 8 Years: A Longitudinal Cohort Study

“…On the other hand, a significant difference was found in socio-economic status between infants with and without follow-up, with a higher SES score in the children that did have follow-up. This finding is similar to findings in previous studies, showing that drop-out was more likely to occur in families with social disadvantages, while preterm children from socially disadvantaged families may have poorer neurodevelopment ( 3 , 32 , 43 ). However, considering the high follow-up rate in this study, limited influence on the presented results is expected.…”

Chorioamnionitis and neurodevelopmental outcome in very preterm infants from 2007 to 2017—a population‐based study

“…The clinical diagnosis of chorioamnionitis has different definitions and parameters without specific thresholds. 9,10 It is found only in a minority of cases with histological or microbiological chorioamnionitis 10 and is therefore neither sensitive nor specific.…”

“…The discrepancy in the results can be explained by the heterogeneity of the study populations (born at term vs. preterm infants), differences in the definition of chorioamnionitis (clinical vs. histological), differences in recommended therapeutic strategies and differences in reported outcome parameters, ultrasound abnormalities or cerebral palsy. The clinical diagnosis of chorioamnionitis has different definitions and parameters without specific thresholds 9,10 . It is found only in a minority of cases with histological or microbiological chorioamnionitis 10 and is therefore neither sensitive nor specific.…”

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis

“…Preterm infants have a distinct immune profile in umbilical cord blood and cerebrospinal fluid that includes higher levels of pro-inflammatory cytokines and lower levels of growth factors when compared to term-born controls, but there is uncertainty about the extent to which this is influenced by antenatal factors, environmental exposures and/or developmental regulation (4)(5)(6). Histologic chorioamnionitis (HCA), defined as inflammation of the chorioamniotic membranes, is strongly associated with preterm birth (7,8) and increases the risk of neonatal morbidities including lung disease, intraventricular hemorrhage, sepsis and necrotizing enterocolitis (9)(10)(11)(12)(13)(14). HCA has also been implicated in the development of white matter injury, cerebral palsy and neurodevelopmental impairment (15-18) and we have previously reported that this may be mediated by a distinct cord blood immune profile in preterm infants (19).…”