Jean‐Christophe Rozé

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.

OBJECTIVES: We compared the frequency of behavioral problems in very preterm and term children at 5 years of age. We hypothesized that behavioral problems would be associated with cognitive impairment and environmental factors and that differences between the 2 groups would be reduced but persist after adjusting for cognitive performance and environmental factors. PATIENTS AND METHODS: The Etude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE) study was a prospective population-based cohort study that included all births occurring between 22 and 32 weeks' gestation and a control group of infants born at 39 to 40 weeks' gestation in 1997 in 9 French regions. Neonatal and obstetrics data were collected at birth. At 5 years of age, sociodemographic status and neurodevelopmental and cognitive development of the children, as well as maternal mental well-being, were assessed. The behavioral problems of 1102 very preterm and 375 term singletons without major impairments were studied by using the parent-completed Strengths and Difficulties Questionnaire. RESULTS: Parents of very preterm children reported significantly more behavioral problems, with a twofold higher prevalence compared with term children for hyperactivity/inattention, emotional symptoms, and peer problems. Behavioral problems were associated with low cognitive performance, developmental delay, hospitalizations of the child, young maternal age, and poor maternal mental well-being. Very preterm children were still at higher risk of behavioral problems compared with term children after adjustment for cognitive performance and all others factors. CONCLUSIONS: Behavioral problems were strongly related to cognitive impairment, but very preterm children were still at higher risk even after adjusting for cognitive performance. Early screening for behavioral problems should be encouraged for all very preterm children, and maternal well-being should also be the focus of special attention.

OBJECTIVES: To describe neurodevelopment at age 5 among children born preterm. DESIGN: Population based cohort study, EPIPAGE-2. SETTING: France, 2011. PARTICIPANTS: 4441 children aged 5½ born at 24-26, 27-31, and 32-34 weeks MAIN OUTCOME MEASURES: Severe/moderate neurodevelopmental disabilities, defined as severe/moderate cerebral palsy (Gross Motor Function Classification System (GMFCS) ≥2), or unilateral or bilateral blindness or deafness, or full scale intelligence quotient less than minus two standard deviations (Wechsler Preschool and Primary Scale of Intelligence, 4th edition). Mild neurodevelopmental disabilities, defined as mild cerebral palsy (GMFCS-1), or visual disability ≥3.2/10 and <5/10, or hearing loss <40 dB, or full scale intelligence quotient (minus two to minus one standard deviation) or developmental coordination disorders (Movement Assessment Battery for Children, 2nd edition, total score less than or equal to the fifth centile), or behavioural difficulties (strengths and difficulties questionnaire, total score greater than or equal to the 90th centile), school assistance (mainstream class with support or special school), complex developmental interventions, and parents' concerns about development. The distributions of the scores in contemporary term born children were used as reference. Results are given after multiple imputation as percentages of outcome measures with exact binomial 95% confidence intervals. RESULTS: Among 4441 participants, 3083 (69.4%) children were assessed. Rates of severe/moderate neurodevelopmental disabilities were 28% (95% confidence interval 23.4% to 32.2%), 19% (16.8% to 20.7%), and 12% (9.2% to 14.0%) and of mild disabilities were 38.5% (33.7% to 43.4%), 36% (33.4% to 38.1%), and 34% (30.2% to 37.4%) at 24-26, 27-31, and 32-34 weeks, respectively. Assistance at school was used by 27% (22.9% to 31.7%), 14% (12.1% to 15.9%), and 7% (4.4% to 9.0%) of children at 24-26, 27-31, and 32-34 weeks, respectively. About half of the children born at 24-26 weeks (52% (46.4% to 57.3%)) received at least one developmental intervention which decreased to 26% (21.8% to 29.4%) for those born at 32-34 weeks. Behaviour was the concern most commonly reported by parents. Rates of neurodevelopment disabilities increased as gestational age decreased and were higher in families with low socioeconomic status. CONCLUSIONS: In this large cohort of children born preterm, rates of severe/moderate neurodevelopmental disabilities remained high in each gestational age group. Proportions of children receiving school assistance or complex developmental interventions might have a significant impact on educational and health organisations. Parental concerns about behaviour warrant attention.

CONTEXT: Supplementation of breast milk is difficult once infants suckle the breast and is often discontinued at end of hospitalisation and after discharge. Thus, breastfed preterm infants are exposed to an increased risk of nutritional deficit with a possible consequence on neurodevelopmental outcome. OBJECTIVE: To assess the relationship between breast feeding at time of discharge, weight gain during hospitalisation and neurodevelopmental outcome. DESIGN: Observational cohort study. SETTING: Two large, independent population-based cohorts of very preterm infants: the Loire Infant Follow-up Team (LIFT) and the EPIPAGE cohorts. PATIENTS: 2925 very preterm infants alive at discharge. MAIN OUTCOME MEASURE: Suboptimal neurodevelopmental outcome, defined as a score in the lower tercile, using Age and Stages Questionnaire at 2 years in LIFT and Kaufman Assessment Battery for Children Test at 5 years in EPIPAGE. Two propensity scores for breast feeding at discharge, one for each cohort, were used to reduce bias. RESULTS: Breast feeding at time of discharge concerned only 278/1733 (16%) infants in LIFT and 409/2163 (19%) infants in EPIPAGE cohort. Breast feeding is significantly associated with an increased risk of losing one weight Z-score during hospitalisation (LIFT: n=1463, adjusted odd ratio (aOR)=2.51 (95% CI 1.87 to 3.36); EPIPAGE: n=1417, aOR=1.55 (95% CI 1.14 to 2.12)) and with a decreased risk for a suboptimal neurodevelopmental assessment (LIFT: n=1463, aOR=0.63 (95% CI 0.45 to 0.87); EPIPAGE: n=1441, aOR=0.65 (95% CI 0.47 to 0.89) and an increased chance of having a head circumference Z-score higher than 0.5 at 2 years in LIFT cohort (n=1276, aOR=1.43 (95% CI 1.02 to 2.02)) and at 5 years in EPIPAGE cohort (n=1412, aOR=1.47 (95% CI 1.10 to 1.95)). CONCLUSIONS: The observed better neurodevelopment in spite of suboptimal initial weight gain could be termed the 'apparent breastfeeding paradox' in very preterm infants. Regardless of the mechanisms involved, the current data provide encouragement for the use of breast feeding in preterm infants.