The relationship between placental and other perinatal risk factors for neurologic impairment in very low birth weight children

Placental abnormalities reflect antenatal disease processes that may intera ct with other perinatal risk factors to affect long-term outcome. We perfor med a nested case control analysis of placental and clinical risk factors a ssociated with neurologic impairment (NI) at 20-mo corrected age (60 cases and 59 controls) using data collected in a prospective study of very low bi rth weight (less than 1500 g) infants born between 1983 and 1991. In a prel iminary analysis we explored the relationship between clinical infection an d histologic chorioamnionitis (CA). Only histologic CA with a fetal vascula r response correlated with either clinical CA or early onset neonatal sepsi s, We then assessed the relative contribution of the nine risk factors (fou r placental and five clinical) associated with NI at the univariate level b y multiple logistic regression. Three risk factors were independent predict ors of NI: severe cranial ultrasound abnormalities (odds ratio 13.6, 95% co nfidence intervals 4.5-66.7), multiple placental lesions (odds ratio 13.2, 95% confidence intervals 1.3-137.0), and oxygen dependence at 36 wk (odds r atio 4.2, 95% confidence intervals 1.2-14.6). Finally, a series of logistic regressions was conducted with the dependent variable changing as we-moved back along the causal chain to explore the relationships between risk fact ors operating at different stages. This analysis suggested that antenatal v ariables that were not independent predictors of NI by multiple logistic re gression exerted their effects through the following intermediate pathways: fetal grade 3 histologic CA via chorionic vessel thrombi, clinical CA via grade 3 villous edema, and grade 3 villous edema via severe cranial ultraso und abnormalities.