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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.)

Aim: To describe the circumstances, causes and timing of death in extremely preterm infants., Methods: We included from the EPIPAGE-2 study infants born at 24-26 weeks in 2011 admitted to neonatal intensive care units (NICU). Vital status and circumstances of death were used to define three groups of infants: alive at discharge, death with or without withholding or withdrawing life-sustaining treatment (WWLST). The main cause of death was classified as respiratory disease, necrotizing enterocolitis, infection, central nervous system (CNS) injury, other or unknown., Results: Among 768 infants admitted to NICU, 224 died among which 89 died without WWLST and 135 with WWLST. The main causes of death were respiratory disease (38%), CNS injury (30%) and infection (12%). Among the infants who died with WWLST, CNS injury was the main cause of death (47%), whereas respiratory disease (56%) and infection (20%) were the main causes in case of death without WWLST. Half (51%) of all deaths occurred within the first 7 days of life, and 35% occurred within 8 and 28 days., Conclusion: The death of extremely preterm infants in NICU is a complex phenomenon in which the circumstances and causes of death are intertwined., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants., Methods: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days., Results: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18)., Conclusion: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC., Impact: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Early-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates., Methods: This is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019-March 2021)., Results: 108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants ( Proteus mirabilis and E. coli )., Conclusion: In neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors for early-onset sepsis (EOS)., Study Design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of EOS (ie, born after preterm labor or preterm premature rupture of membranes or from a mother who had clinical chorioamnionitis or had received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotic therapy started at day 0 or day 1 of life, irrespective of the duration and type of antibiotics. We compared treated and untreated patients using inverse probability of treatment weighting based on estimated propensity scores., Results: Among 648 very preterm infants at low risk of EOS, 173 (26.2%) had received early antibiotic treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR, 1.04; 95% CI, 0.72-1.50); however, it was associated with higher odds of severe cerebral lesions (OR, 2.71; 95% CI, 1.25-5.86) and moderate-severe bronchopulmonary dysplasia (BPD) (OR, 2.30; 95% CI, 1.21-4.38)., Conclusions: Early empirical antibiotic therapy administrated in very preterm infants at low risk of EOS was associated with a higher risk of severe cerebral lesions and moderate-severe BPD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: Birth asphyxia can lead to organ dysfunction, varying from isolated biological acidosis to hypoxic-ischemic encephalopathy (HIE). Pathophysiology of moderate or severe HIE is now well known and guidelines exist regarding the care required in this situation. However, for newborns without moderate or severe HIE, no consensus is available. Our objective was to describe the immediate neonatal consequences and need for care of asphyxiated newborns without moderate or severe HIE., Methods: Multicentre retrospective study from January 2015 to December 2017 in two academic centres, including neonates ≥37 gestational weeks with pathological foetal acidemia (umbilical arterial pH<7.00 and/or lactate≥10 mmol/L)., Results: Among 18 550 births, 161 (0.9%) had pathological foetal acidemia. 142 (88.0%) were not diagnosed with moderate or severe HIE. Among them, 82 (58.0%) were hospitalised. 13 (9.0%) had respiratory failure and required nutritional support. 100 (70.0%) underwent blood sampling, which showed at least one biological anomaly in 66 (66.0%) of cases., Conclusion: Newborns born with pathological foetal acidemia without the occurrence of moderate or severe HIE had metabolic disorders and could need organ support. A prospective study describing this vulnerable population would help to establish consensus guidelines for the management of this population., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)