Intrauterine Inflammation and the Onset of Peri-Intraventricular Hemorrhage in Premature Infants

Abstract

Background: Peri-intraventricular hemorrhage (P/IVH) is a common neonatal morbidity among premature infants. The aim of the study was to examine the association between placental and/or fetal inflammation and the onset of P/IVH in premature infants. Methods: A prospective study included 125 infants with gestational age 23–29 weeks. Placentas were examined for the presence of chorioamnionitis and funisitis, cord blood was sampled for the measurement of cytokines (IL-6 and IL-8). Fetal inflammation was defined as levels of IL-6 higher than 7.6 pg/ml. P/IVH was defined as early if diagnosed within the 1st day after birth; thereafter P/IVH was defined as late. Results: Adjusted for the influence of gestational age, early-onset sepsis (OR 3.2, p = 0.045) and no or incomplete antenatal steroid course (OR 6.0, p = 0.001) significantly predicted early P/IVH. Funisitis (OR 1.6, p = 0.06) and fetal inflammation (OR 2.6, p = 0.06) were only partially associated with early hemorrhage. Contrary to that, respiratory distress syndrome (OR 3.4, p = 0.04), mechanical ventilation (OR 5.9, p = 0.008), low blood pressure (OR 3.5, p = 0.02), and vasopressors (OR 5.7, p = 0.002) were associated with late P/IVH. In multivariate analysis no or incomplete steroid course remained independent predictors for early and use of vasopressors for late P/IVH. The interaction of fetal inflammation and vaginal delivery with no or incomplete steroid course increased the risk of early P/IVH. Conclusions: These results indicate different risk factors for early and late P/IVH. Neither funisitis nor fetal inflammation independently predicts the onset of P/IVH. However, the interaction of fetal inflammation and vaginal delivery with no or incomplete antenatal steroid course increase the risk of early but not also late P/IVH.

Outcome of Early-Onset Sepsis in a National Cohort of Very Low Birth Weight Infants

“…[15][16][17] A number of mechanisms may explain EOS-related brain injury. Cerebral damage may be caused by a direct bacterial effect, by cytokine-mediated inflammatory response 14,18,19 ; alternatively, brain injury may also reflect a poorer initial condition of infants with EOS, as evident from the increased need for deliveryroom resuscitation. PVL has been associated with inflammation and infection, 14-16 but we did not find an increased risk for PVL in infants with EOS.…”

Placental histology related to fetal brain sonography

“…Although clinical chorioamnionitis is frequently implicated in the aetiology of abnormal neonatal cranial ultrasound findings,14 31 32 several recent studies failed to include histological chorioamnionitis as an independent causative factor of perinatal brain injury,33 PIVH17 18 34 or cerebral palsy 19 20. It has been hypothesised that only a pre-existing infection, eliciting a fetal inflammatory response is related to fetal brain injury 4 6 8 35.…”

“…Both chronic intrauterine hypoxia10–12 and chorioamnionitis have been associated with white matter (WM) injury1 4 13 and periventricular and intraventricular haemorrhage (P/IVH) in preterm neonates 14–16. Several recent studies, however, failed to include histological chorioamnionitis as an independent causative factor in IVHs17 18 or cerebral palsy 19 20…”

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

“…Intra-amniotic inflammation is found in approximately 40% of patients with preterm premature rupture of membranes (PPROM) [1,2,3,4,5]. Fetuses who are exposed to intra-amniotic inflammation can develop fetal inflammatory response syndrome (FIRS) [6] that is defined by an elevation of umbilical cord plasma interleukin-6 (IL-6) concentration [2] and/or funisitis (a histopathologic hallmark of FIRS) [7].…”

“…Definition of FIRS with clinical and biomarker criteria has also been proposed [8]. FIRS is an independent risk factor for perinatal morbidity/mortality and is associated with long-term sequelae such as bronchopulmonary dysplasia and impaired neurological outcomes [1,2,3,4,5,6,7,8,9]. Although derangements in several biomarkers have been reported in umbilical cord blood of fetuses/neonates born to mothers with PPROM [9], prospective studies of diagnostic and prognostic markers of FIRS in neonates born to asymptomatic women with PPROM are lacking.…”