Hemodynamic Disturbances in Premature Infants Born after Chorioamnionitis: Association with Cord Blood Cytokine Concentrations

Abstract

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...

Cerebral autoregulation in the first day after preterm birth: no evidence of association with systemic inflammation

“…In contrast, fetal vasculitis was not associated with hypotension. This is in line with the findings of some published studies (12,13), but contrary to those of others (10,21). In a large cohort of preterm infants Been et al (12).…”

“…Hypotension has generally (4,(8)(9)(10), but not consistently (11)(12)(13), been associated with intrauterine inflammation. The effect on cerebral hemodynamics is still unclear.…”

“…The effect on cerebral hemodynamics is still unclear. Steady-state levels of cerebral blood flow (CBF) (10) and cerebral oxygenation (13) are unaffected. By contrast, a lower variability in cerebral oxygenation indicates that cerebrovascular responsiveness is altered (14).…”

Management of hypotension and low systemic blood flow in the very low birth weight neonate during the first postnatal week

“…29 This presentation suggests that their systemic vascular resistance is low and these alterations in cardiovascular function correlate with cord blood interleukin-6 levels. 29 However, even in these patients, the presence of maternal fever or a neonatal immature-to-total white blood cell ratio over 0.4 may be associated with decreased left ventricular fractional shortening. These findings indicate that, in VLBW neonates born after chorioamnionitis, hypotension is primarily caused by vasodilation, although a variable degree of myocardial dysfunction may also contribute to the hemodynamic disturbance.…”

Respiratory support for premature neonates in the delivery room: effects on cardiovascular function and the development of brain injury

“…Increased systemic proinflammatory cytokines not only cause direct cerebral injury but may also alter postnatal hemodynamics as cord blood IL-6 levels are inversely related to systolic, mean, and diastolic blood pressures (68). Increased circulatory disturbances in the first 24 h of life are evident in extremely preterm infants exposed to fetal inflammation (69).…”