Chorioamnionitis and elevated cord blood inflammatory cytokine concentrations are associated with detectable disturbances of systemic and cerebral hemodynamics in premature newborns. Fifty-five infants (25-31 wk gestation) were enrolled. Chorioamnionitis was defined by placental histology. IL-6, IL-1␤, and tumor necrosis factor-␣ were quantified by ELISA. Blood pressure, heart rate, cardiac output, stroke volume, fractional shortening, and middle cerebral artery blood flow velocities were measured at 3 Ϯ 1 h after birth. Chorioamnionitis was evident in 22 placentas and was associated with increased IL-6 (p Ͻ 0.001), IL-1␤ (p ϭ 0.035), and heart rate (p ϭ 0.027); and with decreased mean and diastolic blood pressure (p ϭ 0.026 and p ϭ 0.019, respectively). IL-6 concentration correlated inversely with systolic, mean, and diastolic blood pressures. Right ventricular cardiac output was elevated (p ϭ 0.028) in infants with fetal vessel inflammation. Maternal temperature Ն38.0°C and newborn immature-to-total white blood cell ratio Ն0.4 were associated with significant decreases in left ventricular fractional shortening (p ϭ 0.001 and p ϭ 0.005, respectively). Neither chorioamnionitis nor elevated cytokine concentrations were associated with changes in middle cerebral artery Doppler blood flow velocities. Chorioamnionitis and elevated cord blood IL-6 concentrations are associated with decreased blood pressure in premature newborns. Inflammation of the fetal vessels and nonspecific indicators of infection are associated with disturbances in cardiac function. Infants with chorioamnionitis and elevated cytokine concentrations do not manifest changes in cerebral Doppler indices within the first few postnatal hours. We speculate that cytokine-associated systemic hemodynamic disturbances in premature infants born after chorioamnionitis predispose such infants to perinatal brain injury. Hemodynamic abnormalities among premature infants are recognized to be important factors in the pathogenesis of perinatal brain injury. For example, IVH is more common in very low birth weight infants with hypotension (1) and fluctuating cerebral blood flow velocities (2). PVL may denote white matter ischemia (3) that results from compromised cerebral blood flow during a critical developmental period in which oligodendroglia undergo myelogenesis (4) in the presence of a tenuous vascular supply (5, 6). In fact, animals at a stage of brain development comparable to the Ͻ32-wk human fetus display a distinct and selective reduction of white matter blood flow in response to hypotension (7), confirming the predisposition for periventricular white matter ischemia at this gestational age.The ischemia theory of white matter injury has been challenged (8 -11) by the epidemiologic observation that chorioamnionitis is a strong predictor of subsequent PVL (12, 13) and cerebral palsy in both term (14) and preterm (13) infants. Although the mechanism of white matter injury in the context of infection has not been fully elucidated, evidence suggests that the p...

IMPORTANCE Umbilical cord milking as an alternative to delayed umbilical cord clamping may provide equivalent benefits to preterm infants, but without delaying resuscitation. OBJECTIVE To determine whether the rates of death or severe intraventricular hemorrhage differ among preterm infants receiving placental transfusion with umbilical cord milking vs delayed umbilical cord clamping. DESIGN, SETTING, AND PARTICIPANTS Noninferiority randomized clinical trial of preterm infants (born at 23-31 weeks' gestation) from 9 university and private medical centers in 4 countries were recruited and enrolled between June 2017 and September 2018. Planned enrollment was 750 per group. However, a safety signal comprising an imbalance in the number of severe intraventricular hemorrhage events by study group was observed at the first interim analysis; enrollment was stopped based on recommendations from the data and safety monitoring board. The planned noninferiority analysis could not be conducted and a post hoc comparison was performed instead. Final date of follow-up was December 2018. INTERVENTIONS Participants were randomized to umbilical cord milking (n = 236) or delayed umbilical cord clamping (n = 238). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of death or severe intraventricular hemorrhage to determine noninferiority of umbilical cord milking with a 1% noninferiority margin. RESULTS Among 540 infants randomized, 474 (88%) were enrolled and completed the trial (mean gestational age of 28 weeks; 46% female). Twelve percent (29/236) of the umbilical cord milking group died or developed severe intraventricular hemorrhage compared with 8% (20/238) of the delayed umbilical cord clamping group (risk difference, 4% [95% CI, −2% to 9%]; P = .16). Although there was no statistically significant difference in death, severe intraventricular hemorrhage was statistically significantly higher in the umbilical cord milking group than in the delayed umbilical cord clamping group (8% [20/236] vs 3% [8/238], respectively; risk difference, 5% [95% CI, 1% to 9%]; P = .02). The test for interaction between gestational age strata and treatment group was significant for severe intraventricular hemorrhage only (P = .003); among infants born at 23 to 27 weeks' gestation, severe intraventricular hemorrhage was statistically significantly higher with umbilical cord milking than with delayed umbilical cord clamping (22% [20/93] vs 6% [5/89], respectively; risk difference, 16% [95% CI, 6% to 26%]; P = .002). CONCLUSIONS AND RELEVANCE In this post hoc analysis of a prematurely terminated randomized clinical trial of umbilical cord milking vs delayed umbilical cord clamping among preterm infants born at less than 32 weeks' gestation, there was no statistically significant difference in the rate of a composite outcome of death or severe intraventricular hemorrhage, but there was a statistically significantly higher rate of severe intraventricular hemorrhage in the umbilical cord milking group. The early study termination and resulti...

DCC in premature infants is associated with potentially beneficial hemodynamic changes over the first days of life.