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Objective: To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children., Methods: We included all live births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models., Results: A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84-3.45]) or isolated LOS (OR: 1.71 [95% CI: 1.14-2.56]) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02-5.33]). There was no association between neonatal infection and cognitive impairment., Conclusions: Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS.

Background: Altered palatal morphology has been observed among some preterm children, with possible consequences on chewing, speaking and esthetics, but determinants remain unknown., Aim: To explore the role of neonatal characteristics and neuromotor dysfunction in alteration of palatal morphology at 5 years of age in very preterm children., Study Design: Prospective population-based cohort study., Subjects: 1711 children born between 22 and 32 weeks of gestation in 1997 or born between 22 and 26 weeks of gestation in 1998 were included in the study. They all had a medical examination at 5 years of age., Outcome Measures: Alteration of palatal morphology., Results: The prevalence of altered palatal morphology was 3.7% in the overall sample, 5.1% among boys and 2.2% among girls (adj OR: 2.52; 95%CI: 1.44-4.42). The risk for altered palatal morphology was higher for lower gestational age (adj OR: 0.85; 95%CI: 0.74-0.97 per week), small-for-gestational age children (adj OR: 2.11; 95%CI: 1.20-3.72) or children intubated for more than 28 days (adj OR: 3.16; 95%CI: 1.11-8.98). Altered palatal morphology was more common in case of cerebral palsy or moderate neuromotor dysfunction assessed at 5 years. Results were basically the same when neuromotor dysfunction was taken into account, except for intubation., Conclusion: Male sex, low gestational age, small-for-gestational age and long intubation have been identified as probable neonatal risk factors for alteration of palatal morphology at 5 years of age in very preterm children. Further studies are needed to confirm these results., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: Low-dose aspirin (LDA) given during pregnancy may alter brain development in very preterm infants. We report the short- and long-term outcomes of very preterm infants according to LDA treatment., Patients and Methods: Data were from the Etude Epidemiologique des Petites Ages Gestationnels (EPIPAGE) cohort study, which included all infants born before 33 weeks of gestation in 9 French regions in 1997. This study was restricted to 656 children who were born to 584 women with an obstetric history of placental vascular disease or with chronic hypertension or renal or autoimmune diseases. The main outcome measures were mortality, cerebral lesions, and outcome at 5 years of age, which were measured by a diagnosis of cerebral palsy; behavioral difficulties, which were assessed with the Strength and Difficulties Questionnaire; and cognitive impairment, which was measured by the mental processing composite scale of the Kaufman Assessment Battery for Children (an IQ-equivalent measure of cognitive ability in 2 dimensions: sequential and simultaneous processing scores)., Results: LDA treatment was administered to 125 of 584 (21%) mothers and was not significantly associated with mortality, cerebral lesions, cerebral palsy, or global cognitive impairment of the children at 5 years of age. The proportion of low simultaneous processing scores (<70) was lower in the group with LDA (7% vs 19% without LDA; P = .04). This association was not significant after adjustment for propensity score, prognostic factors, and social class (adjusted odds ratio [aOR]: 0.59 [95% confidence interval (CI): 0.17-2.06]). LDA treatment was associated with a reduction, at the limit of significance, in total behavioral difficulties (aOR: 0.44 [95% CI: 0.19-1.02]) and hyperactivity (aOR: 0.43 [95% CI: 0.17-1.05])., Conclusions: LDA was not associated with adverse neonatal or long-term outcomes. Moreover, the results suggest that LDA may be associated with a reduction in neurobehavioral difficulties. More research is needed to assess the effects of aspirin alone or combined with other neuroprotective agents.

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.

The objective was to determine whether the temperament of very preterm singleton infants born before 29 weeks' gestation differs from their full-term counterparts at 9 months and to examine the influence of neurological sequelae on temperament in very preterm infants. The parents of very preterm infants from nine French regions and a group of full-term infants were sent the Infant Characteristics Questionnaire when the infants were 9 months old. The analysis included 266 singleton very preterm infants from the same regions born before 29 weeks' gestation and 546 full-term singleton infants. There were no significant differences for the Difficult, Unadaptable, and Unpredictable scales between very premature and term infants. Very preterm infants had a slightly higher Dull scale score than term infants. After taking into account mother's age, duration of hospitalization, and cerebral lesions found on neonatal ultrasound scans, this difference was no longer significant. Among very premature infants, those with cerebral lesions as diagnosed by neonatal ultrasound scan were rated higher on the Dull and Unadaptable scales. Delays in development at 9 months were also related to higher Dull and Unpredictable scales. These data suggest that prematurity does not affect temperament ratings at 9 months as assessed by the mother. However, very preterm infants with neurological insults, documented by the neonatal cerebral ultrasound or by a delay in development, are rated higher by their mothers on the Dull, Unadaptable, and Unpredictable scales.

Objective: This study was undertaken to explore the association between fetal sex, mode of onset of labor, and principal cause of very preterm birth. Study design The analysis uses data on 2624 very preterm singleton births less than 33 weeks' gestation from a prospective study of all very preterm births in 9 French regions in 1997., Results: Fifty-seven percent of the spontaneous births were male versus 50.8% of births after medical decision (P=.005). This pattern was explained by sex differences in causes of preterm birth. Male infants had a greater incidence of very preterm birth after spontaneous labor (relative risk [RR]=1.42 [1.21-1.66]), but one third less risk of indicated preterm birth associated with hypertension both with and without growth restriction (RR=0.73 [0.55-0.97] and 0.77 [0.60-0.97])., Conclusion: These results support previous reports of greater male susceptibility to preterm labor. The finding that pregnancies carrying female infants have a greater predisposition to indicated very preterm birth associated with hypertension has not been reported previously and merits further study.

Objectives: To compare the use of health and social services between children born before 33 weeks (very preterm), children born at 33 or 34 weeks (moderately preterm) and children born at 39 or 40 weeks (full term)., Population and Methods: All very preterm children born in 1997 in nine French regions and a representative sample of the two other groups were followed up since birth. Data on the use of services between discharge from initial neonatal hospitalisation and the 9 months after birth were obtained by mail questionnaire filled in by parents., Results: 38.2% of very preterm children, 24.3% of moderately preterm children and 10.3% of full term children were admitted to hospital at least once. Respiratory tract disorder was the main reason for rehospitalisation of very preterm children. The total number of visits, visits to specialists, and chest therapy were more frequent among very preterm children than among the two other groups., Conclusion: Medical care of very preterm children is intensive after discharge from initial neonatal hospitalisation. Need of services are also substantial for moderately preterm children.