Latency in preterm premature rupture of membranes (PROM): A risk factor for neonatal white matter damage?

Gestational age at delivery and spontaneous prematurity are independent risk factors for white matter damage (WMD). However, among infants delivered spontaneously after PROM, latency of PROM has been inconsistently correlated with risk of WMD. Because latency of PROM is related to gestational age at membrane rupture, we evaluated whether duration of membrane rupture independently predicts risk of WMD. From a cohort of 659 consecutive singleton neonates born at 24.0 - 33.6 weeks from 1/1993 to 12/2002, we extracted the obstetric and histopathologic placental variables of those with PROM (n = 196), and compared those who developed WMD (n = 15) with those who did not (n = 181). WMD was defined as intraventricular hemorrhage grade 3 plus, periventricular leucomalacia, or ventriculomegaly not associated with hydrocephaly. Excluded were stillbirths, infants with congenital anomalies and neonates who died before 7 days. Statistical analysis included Fisher's exact test, Student t-test, and unconditional logistic regression analysis, with a two-tailed P < 0.05 or odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. We observed a significantly lower gestational age at PROM, gestational age at delivery and birth weight, and a longer latency between PROM and delivery in those with WMD. Unconditional logistic regression analysis demonstrated that only gestational age at PROM (P < .001, OR = .79) and prenatal steroids (P = .016, OR = .19) were significantly associated with WMD, whereas latency interval (P = .69), gestational age at delivery (P = .99), and birth weight (P = .62) were not. Similar results were obtained when we used stepwise logistic regression analysis in which the variables approaching significance at univariate analysis were entered in the chronological order in which they normally occur. Among premature infants born at < 34 weeks after PROM, gestational age at PROM and lack of prenatal administration of steroids are the only predictors of WMD.