Gérard Thiriez

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

BACKGROUNDnThe 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.nnnMETHODSnWe 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).nnnFINDINGSnIn 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.nnnINTERPRETATIONnIn 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.

Survival and Morbidity of Preterm Children Born at 22 Through 34 Weeks' Gestation in France in 2011 Results of the EPIPAGE-2 Cohort Study

IMPORTANCEnUp-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.nnnOBJECTIVESnTo 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.nnnDESIGN, SETTING, AND PARTICIPANTSnThe 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.nnnMAIN OUTCOMES AND MEASURESnSurvival 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).nnnRESULTSnA 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 <u2009.001) at 25 through 29 weeks and 6% (P <u2009.001) 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.nnnCONCLUSIONS AND RELEVANCEnThe 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.

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

Behavioral Outcome at 3 Years of Age in Very Preterm Infants: The EPIPAGE Study

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.

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

Aimu2002 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.

Previous induced abortions and the risk of very preterm delivery: results of the EPIPAGE study

Objectivesu2003 To evaluate the risk of very preterm birth (22–32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons.

Prolonged Sedation and/or Analgesia and 5-Year Neurodevelopment Outcome in Very Preterm Infants: Results From the EPIPAGE Cohort

OBJECTIVEnTo describe the long-term outcome of very preterm infants receiving prolonged sedation and/or analgesia and examine the relationship between prolonged sedation and/or analgesia and this long-term outcome.nnnDESIGNnA prospective population-based study (Etude EPIdémiologique sur les Petits Ages GEstationnels [EPIPAGE]). To reduce bias, the propensity score method was used.nnnSETTINGnNine regions of France.nnnPARTICIPANTSnThe study population included very preterm infants of fewer than 33 weeks gestational age, born in 1997, who received mechanical ventilation and/or surgery. Main Exposure Prolonged exposure to sedative and/or analgesic drugs in the neonatal period, defined as exposure of more than 7 days to sedative and/or opioid drugs.nnnMAIN OUTCOME MEASUREnPresence of moderate or severe disability at 5 years of age.nnnRESULTSnThe analysis concerns 1572 premature infants who received mechanical ventilation for whom information about exposure to prolonged sedation and/or analgesia in the neonatal period was available. A total of 115 were exposed and 1457 were not exposed. There was no significant difference between the number of patients lost to follow-up from the group of very preterm infants who were exposed to prolonged sedation and/or analgesia and the group who were not. Exposed very preterm infants had severe or moderate disability at 5 years (41/97; 42%) more often than those who were not exposed (324/1248; 26%). After adjustment for gestational age and propensity score, this association was no longer statistically significant (adjusted relative risk, 1.0; 95% confidence interval, 0.8-1.2).nnnCONCLUSIONnProlonged sedation and/or analgesia is not associated with a poor 5-year neurological outcome after adjustment for the propensity score.

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.

Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort

Aim:u2002 To assess cerebral lesions and other medical as well as social characteristics as predictors of risk of mild and severe cognitive deficiencies in very preterm infants.