Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

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 240/7 and 346/7 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.

Early Antibiotic Exposure and Adverse Outcomes in Very Preterm Infants at Low Risk of Early-Onset Sepsis: The EPIPAGE-2 Cohort Study.

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.

Neurodevelopmental Outcomes after Premedication with Atropine/Propofol vs Atropine/Atracurium/Sufentanil for Neonatal Intubation: 2-Year Follow-Up of a Randomized Clinical Trial.

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov: NCT01490580.

Volume of Neonatal Care and Survival without Disability at 2 Years in Very Preterm Infants: Results of a French National Cohort Study.

OBJECTIVES: To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. STUDY DESIGN: The EPIPAGE-2 (Etude Epidémiologique sur les Petits Âges Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. RESULTS: Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. CONCLUSIONS: These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization.

The influence of fetal growth reference standards on assessment of cognitive and academic outcomes of very preterm children.

OBJECTIVE: To compare 3 methods of identifying small-for-gestational-age (SGA) status in very preterm children as related to cognitive function and academic outcome. STUDY DESIGN: There were 1038 singletons in the Epipage Study, born before 33 weeks in 1997 without severe neurosensory impairment, who were classified as SGA when birth weight was below the 10th percentile according to: (1) birth weight (bw) reference: SGA(bw)/appropriate for gestational age (AGA)(bw); (2) intrauterine (intraut) reference: SGA(intraut)/AGA(intraut); and (3) intrauterine reference customized (cust) according to individual characteristics: SGA(cust)/AGA(cust). Cognitive function was assessed by the mental processing composite (MPC) score of the Kaufman Assessment Battery for Children at age 5 and academic achievement by a parental questionnaire at age 8. RESULTS: Of the children, 15% were SGA(bw), 38% were SGA(intraut), and 39% were SGA(cust). All children SGA(bw) were also SGA(intraut) and SGA(cust). MPC was <85 in 32% of children and 27% had low academic achievement. AGA(bw)/SGA(intraut) children had a significantly increased risk of MPC <85 (adjusted OR 1.74, 95% CI 1.22-2.28) or low academic achievement (adjusted OR 1.64, 95% CI 1.05-2.55) compared with AGA(bw)/AGA(intraut) children. The SGA(cust) group was only slightly different from the SGA(intraut) group. CONCLUSIONS: An intrauterine reference identified very preterm infants at risk of poor cognitive or academic outcomes better than a birth weight reference. Customization resulted in only slight modifications of the SGA group.