Pierre-Yves Ancel

Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

BACKGROUND The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

Cerebral Palsy Among Very Preterm Children in Relation to Gestational Age and Neonatal Ultrasound Abnormalities: The EPIPAGE Cohort Study

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.

White matter damage and intraventricular hemorrhage in very preterm infants: the EPIPAGE study☆

OBJECTIVE To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge. STUDY DESIGN A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available. RESULTS The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL. CONCLUSION The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

The relationship between intrauterine growth restriction and preterm delivery: an empirical approach using data from a European case-control study.

Objective To test whether being small for gestational age, defined as having a birthweight less than the 10th centile of intrauterine growth references, is a risk factor for preterm delivery for singleton live births.

Women's health after childbirth: a longitudinal study in France and Italy.

Objective To describe the prevalence of various symptoms five months and twelve months after childbirth in two European countries, according to employment, financial difficulties and relationship with partner.

Neonatal and 5-year outcomes after birth at 30-34 weeks of gestation

OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30–34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30–34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30–34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment. LEVEL OF EVIDENCE: II

Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study.

Aim  The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population‐based cohort of very preterm infants.

The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT

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.

Obstetric patients treated in intensive care units and maternal mortality

OBJECTIVE To ascertain the frequency of serious diseases in pregnant women. STUDY DESIGN A population based survey was performed in France. The cases were all the women admitted for treatment in intensive care unit (ICU). The severity of the cases was measured with the simplified acute physiology score (SAPS) the lethality and the rate of still birth. RESULTS 435 obstetric patients were included. The estimated frequency of severe diseases was 310 S.D.36 per 100,000 live births. The most frequent diagnose that motived admission in ICU was hypertensive diseases. The lethality rates differed greatly between specific disorders. The lethality rate was lower when scheduled maternity was located in a teaching hospital. CONCLUSION Regarding these results it appears that the majority of obstetric patients with severe diseases are referred to suitable care, but a small proportion of women who had to change their type of care registered a significant higher lethality.

Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants.

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.