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.

Neonatal Outcomes in Extremely Preterm Newborns Admitted to Intensive Care after No Active Antenatal Management: A Population-Based Cohort Study.

OBJECTIVE: To evaluate the association between active antenatal management and neonatal outcomes in extremely preterm newborns admitted to a neonatal intensive care unit (NICU). STUDY DESIGN: This population-based cohort study was conducted in 25 regions of France. Infants born in 2011 between 220/7 and 266/7 weeks of gestation and admitted to a NICU were included. Infants with lethal congenital malformations or death in the delivery room were excluded. A multilevel multivariable analysis was performed, accounting for clustering by mother (multiple pregnancies) and hospital plus individual characteristics, to estimate the association between the main exposure of no active antenatal management (not receiving antenatal corticosteroids, magnesium sulfate, or cesarean delivery for fetal indications) and a composite outcome of death or severe neonatal morbidity (including severe forms of brain or lung injury, retinopathy of prematurity, and necrotizing enterocolitis). RESULTS: Among 3046 extremely preterm births, 783 infants were admitted to a NICU. Of these, 138 (18%) did not receive active antenatal management. The risk of death or severe morbidity was significantly higher for infants without active antenatal management (crude OR, 2.60; 95% CI, 1.44-4.66). This finding persisted after adjustment for gestational age (OR, 2.08; 95% CI, 1.19-3.62) and all confounding factors (OR, 1.86; 95% CI, 1.09-3.20). CONCLUSIONS: The increased risk of severe neonatal outcomes for extremely preterm babies admitted to a NICU without optimal antenatal management should be considered in individual-level decision making and in the development of professional guidelines for the management of extremely preterm births.

Procalcitonin to reduce the number of unnecessary cystographies in children with a urinary tract infection: a European validation study.

OBJECTIVE: To validate high serum procalcitonin (PCT) as a predictor of vesicoureteral reflux (VUR) in children with a first febrile urinary tract infection (UTI). STUDY DESIGN: This secondary analysis of prospective hospital-based cohort studies included children ages 1 month to 4 years with a first febrile UTI. RESULTS: Of the 398 patients included in 8 centers in 7 European countries, 25% had VUR. The median PCT concentration was significantly higher in children with VUR than in those without: 1.6 versus 0.7 ng/mL (P = 10(-4)). High PCT (> or =0.5 ng/mL) was associated with VUR (OR: 2.3; 95% CI, 1.3 to 3.9; P = 10(-3)). After adjustment for all cofactors, the association remained significant (OR: 2.5; 95% CI, 1.4 to 4.4; P = 10(-3)). The strength of the relation increased with the grade of reflux (P = 10(-5)). The sensitivity of procalcitonin was 75% (95% CI, 66 to 83) for all-grade VUR and 100% (95% CI, 81 to 100) for grade > or =4 VUR, both with 43% specificity (95% CI, 37 to 48). CONCLUSIONS: High PCT is a strong, independent and now validated predictor of VUR that can be used to identify low-risk patients and thus avoid one third of the unnecessary cystourethrographies in children with a first febrile UTI.