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Objective: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm., Study Design: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24 0/7 and 34 6/7  weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively., Results: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8)., Conclusions: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane., Competing Interests: Declaration of Competing Interest The EPIPAGE 2 study was funded with support from the French Institute of Public Health Research/Institute of Public Health, and its partners. Partners include the French Health Ministry, National Institute of Health and Medical Research (INSERM), National Institute of Cancer, and National Solidarity Fund for Autonomy (CNSA); National Research Agency through the French EQUIPEX programme of investments in the future (reference ANR-11-EQPX-0038, ANR-19-COHO-001); PREMUP Foundation; Foundation of France (reference 11779); Foundation for Medical Research (SPF20160936356); and hospital clinical research programme Epinutri (DGOS13-040). Ministère de l'Enseignement Supérieur, De La Recherche et de L'Innovation (G13129KK); Apicil Foundation (R20065KK). The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval the manuscript; and the decision to submit the manuscript for publication. The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether acute histologic chorioamnionitis (HCA) diagnosed in the placenta may be associated with an increased occurrence of bronchopulmonary dysplasia (BPD) or death among extremely low gestational age neonates (ELGAN)., Methods: This Italian single-center case-control retrospective study involved ELGAN admitted to the neonatal intensive care unit between January 2019 and June 2022. Infants born from pregnant women with acute and severe HCA, identified as stage ≥2 and grade 2 HCA, (HCA-infants) were compared with infants of pregnant women without chorioamnionitis or with stage 1, grade 1 chorioamnionitis (no-HCA-infants)., Results: Among 101 eligible ELGAN, 63 infants had complete clinical and histologic data relevant to the study: thirty infants were included in the HCA-infants group and 33 in the no-HCA-infants group. Neonatal and maternal demographic and clinical characteristics were similar between the two groups. Infants born from mothers with acute and severe HCA had significantly higher occurrence of composite BPD or death (18 [60%] vs. 9 [27%]; P = 0.012), as well as higher incidence of severe forms of BPD (6 [30%] vs. 2 [6%]; P = 0.045). In multiple logistic regression analysis, after adjustment for confounding covariates, HCA was an independent risk factor for BPD or death (OR, 4.49; 95% CI: 1.47-13.71)., Conclusions: This is the first study showing that in utero exposure to acute and severe HCA is an independent risk factor for the occurrence of composite BPD or death among ELGAN., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Purpose: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age., Methods: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer)., Results: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates., Conclusions: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age., Methods: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes., Results: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05)., Conclusions: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes., (© 2024 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Objective: To determine the impact of clinical and/or histological chorioamnionitis on neurodevelopmental outcomes in premature infants., Methods: A review of the literature appeared in PubMed between 1997 and 2016 was conducted to examine the association between clinical and/or histological chorioamnionitis and neurologic impairment in the neonates (intraventricular hemorrhage, periventricular leukomalacia and white matter damage) and in infants (cerebral palsy and neurodevelopmental delay)., Results: The first meta-analysis published in 2000 observed that clinical chorioamnionitis was associated with cystic periventricular leukomalacia and cerebral palsy and that histologic chorioamnionitis was associated with periventricular leukomalacia only. A second meta-analysis in 2010 found that cerebral palsy was associated with both clinical and histological chorioamnionitis. But most recent studies over the last decade based on large cohorts found no effect of chorioamnionitis on neurological outcomes, even if they had several methodological limitations., Conclusion: According to the findings of the most recent studies, clinical or histological chorioamnionitis does not seem to be associated with neonatal white matter injuries, or with cerebral palsy. Further studies are needed to assess the impact of chorioamnionitis on long-term neurological development., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: The study compares neurodevelopmental outcome at 24 months corrected age of very preterm infants exposed to chorioamnionitis and controls. Peripartal parameters which may influence outcome are also investigated., Methods: In this observational population-based study, very preterm infants born between 2007 and 2017 were eligible (n = 466) and included if a histological placental examination and a complete neurodevelopmental assessment (Bayley Scale of Infant Development II or III) (n = 168) were performed. Secondary analyses were calculated to identify peripartal factors that significantly influence mental and psychomotor outcome., Results: Included infants showed a mean MDI of 91.2 (SD = 20.7) and a mean PDI of 99.4 (SD = 14.8). Infants with (n = 71) and without (n = 97) chorioamnionitis did not statistically differ either with mean MDI (91.8 vs. 90.3 points; p = 0.29) or mean PDI (98.3 vs. 100.9 points; p = 0.81), even after controlling for gestational age, mean APGAR scores and administration of antenatal steroids. Bronchopulmonary dysplasia was identified as the most influential factor for both MDI (p = .024) and PDI (p = .004)., Conclusion: We could not find an effect of chorioamnionitis on neurodevelopmental outcome of very preterm infants over an eleven-year period. Analysis shows that postnatal factors have higher impacts than does chorioamnionitis., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Developmental adaptive processes during gestation that are known to be involved in permanent changes in physiology and metabolism or "early life programming" can adversely affect fetal brain development, impacting both brain structure and function. Data: Emerging evidence strongly supports the developmental origin of schizophrenia, which may potentially be a result of prenatal exposure to a diversity of factors, especially infections, in genetically predisposed subjects. Structural and functional brain changes during development of schizophrenia are determined by genetic components, altered expression of schizophrenia risk genes and epigenetic dysregulation. However, the precise mechanisms underlying these relationships remain unclear. Findings from human and animal studies suggest that inflammatory-immune responses and activation of oxidative stress pathways are crucial in mediating intrauterine infection-induced neurodevelopmental and neuropsychiatric diseases. Aim: Considering the high prevalence of intrauterine inflammation in the context of chorioamnionitis during human pregnancy and the paucity of knowledge on fetal programming of schizophrenia, this mini review aims to exclusively consolidate the current evidence supporting a potential association between chorioamnionitis and schizophrenia. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether some associations between histological chorioamnionitis (HCA) and favorable neonatal outcomes might be linked to those of antenatal steroids (AS) by determining the separate as well as the combined associations of HCA and AS with neonatal outcomes in very low birth weight infants (VLBWIs). This was a population-based study of VLBWIs born at 20–33 weeks' gestation between January 2013 and December 2015 from the Korean Neonatal Network. A total of 4652 VLBWIs were enrolled for prevalence study. Of these, 2900 singleton VLBWIs were used for outcome analyses to evaluate individual associations of HCA and AS simultaneously with correction for potential perinatal factors and an interaction term of HCA and AS. The overall prevalence of HCA was 34.9% (1623 VLBWIs). Multivariable logistic regression demonstrated that HCA was associated with decreased mortality (adjusted odds ratio [aOR], 0.51; 95% confidence interval [CI], 0.29–0.91; P = 0.022), AS were associated with reduction in mortality (aOR, 0.59; 95% CI, 0.39–0.90; P = 0.014) and neonatal seizure (aOR, 0.57; 95% CI, 0.37–0.86; P = 0.008), and a combination of HCA and AS was associated with remarkably lowered severe intraventricular hemorrhage by interacting with each other (aOR, 0.47; 95% CI, 0.25–0.88; P = 0.019). We suggest that in VLBWIs HCA and AS may be favorable independent factors for neonatal outcome and may also work in synergy for neuroprotection. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are still at an increased risk for suboptimal neurodevelopmental outcomes when compared with term born infants. The development of a child born preterm can be jeopardized by suboptimal conditions during pregnancy, in addition to the suboptimal growth environment postnatally compared to the normal in utero environment. This review summarizes the literature on the role of chorioamnionitis, placental insufficiency, and maternal smoking on the developmental outcomes of preterm infants. Methods: A systematic database search was performed to identify all original articles published on or before September 12, 2018 that evaluated the impact of clinical or histological chorioamnionitis, abnormal prenatal fetal and placental blood flow, and prenatal smoking exposure on the neuropsychological and cognitive outcomes of preterm infants. We identified a total of 54 studies. Thirty five original articles evaluated the effects of clinical or histological chorioamnionitis; 15 studies evaluated the effects of abnormal blood flow patterns; and four studies evaluated the effects of maternal smoking during pregnancy. Results: The studies on prenatal risk factors showed conflicting results about the impact on the neurodevelopment of preterm infants. The majority of the studies did not show that chorioamnionitis poses a direct risk to the development of preterm infants. The role of abnormal prenatal placental and fetal blood flow on the development of preterm infants remained inconclusive because the sample sizes were often small and methodological problems complicated the interpretation of the data. Maternal smoking during pregnancy was assessed only in one cohort which showed that maternal smoking is a risk for suboptimal cognitive and neuropsychological development in preterm infants. Conclusions: This review summarizes the data on several prenatal risk factors which play a role in the developmental outcomes of preterm infants. To optimize the developmental outcomes, we need to first optimize the fetal wellbeing before birth. More research that extends from the fetal life to long-term developmental outcomes is needed. [ABSTRACT FROM AUTHOR]