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Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers

ABSTRACT: Preeclampsia is both a vascular and inflammatory disorder. Since the placenta is a conduit for fetal development, preeclampsia should be a presumed cause of adverse infant outcomes. Yet, the relationship of placental pathology, inflammation and neurological outcomes after preeclampsia are understudied. We prospectively examined a cohort of maternal-infant dyads with preeclampsia for maternal inflammatory cytokines at time of preeclampsia diagnosis and delivery, and fetal cord blood cytokines (IL-1β, IL-6, IL-8, and TNF-α). Placentas were analyzed for inflammatory and vascular pathologies. Neurodevelopmental assessment of infants utilizing the Pediatric Stroke Outcome Measure (PSOM) was conducted at 6-month corrected gestational age. Eighty-one maternal-newborn dyads were examined. Worse neurological outcomes were not associated with elevated maternal / fetal cytokines. Early preterm birth (gestational age ≤ 32 weeks) was associated with worse neurological outcomes at 6-months regardless of maternal/ fetal cytokine levels, placental pathology, or cranial ultrasound findings (OR 1.70, [1.16–2.48], p = 0.006). When correcting for gestational age, elevated IL-6 approached significance as a predictor for worse developmental outcome (OR 1.025 [0.985–1.066], p = 0.221). Pathological evidence of maternal malperfusion and worse outcomes were noted in early preterm, although our sample size was small. Our study did not demonstrate an obvious association of inflammation and placental pathology in preeclampsia and adverse neurodevelopmental outcome at 6-month corrected age but does suggest maternal malperfusion at earlier gestational age may be a risk factor for worse outcome.

SUBMITTER: Sotiros A

PROVIDER: S-EPMC8592443 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To evaluate the impact of maternal hypertensive disorders of pregnancy (HDP) on mortality and neurological outcomes in extremely and very preterm infants using a nationwide neonatal database in Japan. This population-based retrospective study was based on an analysis of data collected by the Neonatal Research Network of Japan from 2003 to 2015 of neonates weighing 1,500 g or less at birth, between 22 and 31 weeks' gestation. A total of 21,659 infants were randomly divided into two groups, HDP (n = 4,584) and non-HDP (n = 4,584), at a ratio of 1:1 after stratification by four factors including maternal age, parity, weeks of gestation, and year of delivery. Short-term (neonatal period) and medium-term (3 years of age) mortality and neurological outcomes were compared between the two groups by logistic regression analyses. In univariate analysis, HDP was associated with an increased risk for in-hospital death (crude odds ratio [OR], 1.31; 95% confidence interval, 1.04-1.63) and a decreased risk for severe intraventricular haemorrhage (0.68; 0.53-0.87) and periventricular leukomalacia (0.60; 0.48-0.77). In multivariate analysis, HDP was significantly associated with a lower risk for in-hospital death (adjusted OR, 0.61; 0.47-0.80), severe intraventricular haemorrhage (0.47; 0.35-0.63), periventricular leukomalacia (0.59; 0.45-0.78), neonatal seizures (0.40; 0.28-0.57) and cerebral palsy (0.70; 0.52-0.95) at 3 years after adjustment for covariates including birth weight. These results were consistent with those of additional analyses, which excluded cases with histological chorioamnionitis and which divided the infants into two subgroups (22-27 gestational weeks and 28-31 gestational weeks). Maternal HDP was associated with an increased risk for in-hospital death without adjusting for covariates, but it was also associated with a lower risk for mortality and adverse neurological outcomes in extremely and very preterm infants if all covariates except HDP were identical.

Project description:BackgroundInfants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).MethodsPreterm infants (N = 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBF i ) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i ). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.ResultsSteeper increases in CBF i (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBF i , and CMRO2i from birth to TEA were not associated with neurological examination at TEA.ConclusionIn this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBF i and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

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Inflammatory cytokines, placental pathology, and neurological outcomes in infants born to preterm preeclamptic mothers

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