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OBJECTIVES The objectives were to describe mortality and causes of death in children with intraventricular hemorrhage (IVH) and to study neurodevelopmental outcomes. METHODS The study was a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. Children were recruited in 2011. A standardized assessment was conducted at age 5. Children born before 32 weeks’ gestation and admitted to a NICU were eligible. Exposure was IVH defined by the Papile classification. Main outcomes were mortality, causes of death, and neurodevelopmental outcomes at age 5. RESULTS Among the 3468 children included, 578 (16.7%) had grade 1 IVH, 424 (12.2%) grade 2 IVH, and 114 (3.3%) grade 3 IVH; 144 (4.1%) had intraparenchymal hemorrhage (IPH). Mortality was 29.7% (36 of 114) for children with grade 3 IVH and 74.4% (109 of 144) for those with IPH; 67.6% (21 of 31) and 88.7% (86 of 97) of deaths, respectively, were because of withholding and withdrawing of life-sustaining treatment. As compared with no IVH, low-grade IVH was not associated with measured neurodevelopmental disabilities at age 5. High-grade IVH was associated with moderate and severe neurodevelopmental disabilities, reduced full-scale IQ, and cerebral palsy. CONCLUSIONS Rates of neurodevelopmental disabilities at age 5 did not differ between children without IVH and those with low-grade IVH. For high-grade IVH, mortality rate was high, mostly because of withholding and withdrawal of life-sustaining treatment, and we found a strong association with overall neurodevelopmental disabilities in survivors.

OBJECTIVE: To determine whether mild and severe growth restriction at birth among preterm infants is associated with neonatal mortality and cerebral palsy and cognitive performance at 5 years of age and school performance at 8 years of age. METHODS: All 2846 live births between 24 and 32 weeks' gestation from 9 regions in France in 1997 were included in a prospective observational study (the EPIPAGE [Étude Epidémiologique sur les Petits Ages Gestationnels] study) and followed until 8 years of age. Infants were classified as “small-for-gestational-age” (SGA) if their birth weight for gestational age was at the RESULTS: Among the children born between 24 and 28 weeks' gestation, the mortality rate increased from 30% in the AGA group to 42% in the M-SGA group and to 62% in the SGA group (P < .01). Birth weight was not significantly associated with any cognitive, behavioral, or motor outcomes at the age of 5 or any school performance outcomes at 8 years. For the children born between 29 and 32 weeks' gestation, SGA children had a higher risk for mortality (adjusted odds ratio [aOR]: 2.79 [95% confidence interval (CI): 1.50–5.20]), minor cognitive difficulties (aOR: 1.73 [95% CI: 1.12–2.69]), inattention-hyperactivity symptoms (aOR: 1.78 [95% CI: 1.10–2.89]), and school difficulties (aOR: 1.74 [1.07–2.82]) compared with AGA children. Being born M-SGA was associated with an increased risk for minor cognitive difficulties (aOR: 1.87 [95% CI: 1.24–2.82]) and behavioral difficulties (aOR: 1.66 [95% CI: 1.04–2.62]). CONCLUSIONS: In preterm children, growth restriction was associated with mortality, cognitive and behavioral outcomes, as well as school difficulties.

Few neuroprotective agents have been identified for the population of very preterm infants at high risk of long-term neurosensory, cognitive, and behavioral disabilities. Treatment of mothers who have high-risk pregnancies with low-dose aspirin (LDA) appears to be well tolerated by the fetus and may produce a moderate reduction in several different risks including preeclampsia, delivery before 37 weeks' gestation, and fetal growth restriction. Little data exist on the long-term effects of aspirin on children born preterm. This observational population-based study investigated the effects of antenatal LDA treatment of high-risk pregnancies on the neurodevelopmental and behavioral abilities of 5-year-olds born before 33 weeks of gestation. Data were obtained from a large cohort study for all infants born before 33 weeks of gestation in 9 regions of France in 1997. The participants were 584 mothers (656 children) with an obstetric history of preeclampsia, fetal growth restriction, or fetal death, or with chronic hypertension, renal, or autoimmune disease. A total of 125 of the 584 mothers (21 %) were treated with LDA (LDA group) and 447 were not (no-LDA group). The primary outcome measures were mortality, cerebral damage, and outcome at 5 years of age. Outcomes were measured by a diagnosis of cerebral palsy; assessment of behavioral difficulties using the Strength and Difficulties Questionnaire; and assessment of cognitive outcome using the mental processing composite scale of the Kaufman Assessment Battery for Children, a global IQ-equivalent measure of cognitive ability in 2 dimensions: a sequential score and a simultaneous processing score. LDA had no significant adverse effects on outcomes of fetal/neonatal mortality, cerebral damage, cerebral palsy, or global cognitive impairment at 5 years of age. The rate of simultaneous processing scores of

OBJECTIVES. Our goal was to compare the prevalence of behavioral problems between very preterm children and term children at 3 years of age and examine the factors associated with behavioral problems in very preterm children.METHODS. We conducted a prospective population-based cohort study: the EPIPAGE (Étude Epidémiologique sur les Petits Ages Gestationnels) study. All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included and compared with a control group of infants born at term. Sociodemographic status, obstetric, and neonatal data were collected at birth and in the neonatal units. At 3 years of age, the behavioral problems of 1228 very preterm singleton children without major neurodisabilities, and 447 term children were studied using the Strengths and Difficulties Questionnaire completed by the parents.RESULTS. Very preterm children were more likely than controls to have behavioral difficulties. Among very preterm children, several medical conditions were associated with a high total difficulty score: major neonatal cerebral lesions diagnosed by cranial ultrasonographic studies, hospitalization within the last year, poor health, and psychomotor delay. A high birth order and sociodemographic factors such as young maternal age and low educational level of the mother were also identified as risk factors for behavioral difficulties. The differences between very preterm children and controls remained significant after adjustment for sociodemographic characteristics, neonatal complications, and neurodevelopmental status, for a high total difficulties score, hyperactivity, conduct problems, and for peer problems. For emotional problems, the difference was at the limit of significance.CONCLUSIONS. Very preterm children have a higher risk of behavioral problems at 3 years of age compared with term-born children. Health and neurodevelopmental status of the child were significantly associated with behavioral difficulties.

OBJECTIVE. To estimate the prevalence of cerebral palsy at 2 years of age among children born very preterm, according to gestational age, infant gender, plurality, and neonatal cranial ultrasound abnormalities. METHODS. All infants born between 22 and 32 weeks of gestation in 9 regions of France in 1997 were included in this prospective, population-based, cohort study. The main outcome measure was cerebral palsy prevalence at 2 years. Of the 2364 survivors eligible for follow-up evaluation, 1954 (83%) were assessed at 2 years of age. RESULTS. Among the 1954 children assessed at 2 years, 8.2% had cerebral palsy. Bilateral spastic cerebral palsy, hemiplegia, and monoplegia accounted for 72%, 9%, and 10% of cases, respectively. Fifty percent of the children with cerebral palsy walked independently at the age of 2, 31% were unable to walk but could sit independently, and 19% could not sit (unable to maintain head and trunk control). The prevalence of cerebral palsy was 20% at 24 to 26 weeks of gestation, compared with 4% at 32 weeks. On the basis of ultrasound findings in the neonatal period, we found that 17% of children with isolated grade III intraventricular hemorrhage and 25% of children with white matter damage (ie, ventricular dilation, persistent echodensities, or cystic periventricular leukomalacia) had cerebral palsy, compared with 4% of children with normal ultrasound scans. CONCLUSIONS. Despite recent improvements in survival rates, cerebral palsy remains highly prevalent among very preterm children. Severe cranial ultrasound abnormalities predict motor disability strongly, but one third of infants with cerebral palsy had no ultrasound abnormalities.