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      Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks’ gestation in France in 2011: EPIPAGE-2 cohort study

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          Abstract

          Objectives To describe neurodevelopmental outcomes at 2 years corrected age for children born alive at 22-26, 27-31, and 32-34 weeks’ gestation in 2011, and to evaluate changes since 1997.

          Design Population based cohort studies, EPIPAGE and EPIPAGE-2.

          Setting France.

          Participants 5567 neonates born alive in 2011 at 22-34 completed weeks’ gestation, with 4199 survivors at 2 years corrected age included in follow-up. Comparison of outcomes reported for 3334 (1997) and 2418 (2011) neonates born alive in the nine regions participating in both studies.

          Main outcome measures Survival; cerebral palsy (2000 European consensus definition); scores below threshold on the neurodevelopmental Ages and Stages Questionnaire (ASQ; at least one of five domains below threshold) if completed between 22 and 26 months corrected age, in children without cerebral palsy, blindness, or deafness; and survival without severe or moderate neuromotor or sensory disabilities (cerebral palsy with Gross Motor Function Classification System levels 2-5, unilateral or bilateral blindness or deafness). Results are given as percentage of outcome measures with 95% confidence intervals.

          Results Among 5170 liveborn neonates with parental consent, survival at 2 years corrected age was 51.7% (95% confidence interval 48.6% to 54.7%) at 22-26 weeks’ gestation, 93.1% (92.1% to 94.0%) at 27-31 weeks’ gestation, and 98.6% (97.8% to 99.2%) at 32-34 weeks’ gestation. Only one infant born at 22-23 weeks survived. Data on cerebral palsy were available for 3599 infants (81.0% of the eligible population). The overall rate of cerebral palsy at 24-26, 27-31, and 32-34 weeks’ gestation was 6.9% (4.7% to 9.6%), 4.3% (3.5% to 5.2%), and 1.0% (0.5% to 1.9%), respectively. Responses to the ASQ were analysed for 2506 children (56.4% of the eligible population). The proportion of children with an ASQ result below threshold at 24-26, 27-31, and 32-34 weeks’ gestation were 50.2% (44.5% to 55.8%), 40.7% (38.3% to 43.2%), and 36.2% (32.4% to 40.1%), respectively. Survival without severe or moderate neuromotor or sensory disabilities among live births increased between 1997 and 2011, from 45.5% (39.2% to 51.8%) to 62.3% (57.1% to 67.5%) at 25-26 weeks’ gestation, but no change was observed at 22-24 weeks’ gestation. At 32-34 weeks’ gestation, there was a non-statistically significant increase in survival without severe or moderate neuromotor or sensory disabilities (P=0.61), but the proportion of survivors with cerebral palsy declined (P=0.01).

          Conclusions In this large cohort of preterm infants, rates of survival and survival without severe or moderate neuromotor or sensory disabilities have increased during the past two decades, but these children remain at high risk of developmental delay.

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          Most cited references37

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          Surveillance of cerebral palsy in Europe: a collaboration of cerebral palsy surveys and registers. Surveillance of Cerebral Palsy in Europe (SCPE).

          (2000)
          Although cerebral palsy (CP) is the most common cause of motor deficiency in young children, it occurs in only 2 to 3 per 1000 live births. In order to monitor prevalence rates, especially within subgroups (birthweight, clinical type), it is necessary to study large populations. A network of CP surveys and registers was formed in 14 centres in eight countries across Europe. Differences in prevalence rates of CP in the centres prior to any work on harmonization of data are reported. The subsequent process to standardize the definition of CP, inclusion/exclusion criteria, classification, and description of children with CP is outlined. The consensus that was reached on these issues will make it possible to monitor trends in CP rate, to provide a framework for collaborative research, and a basis for services planning among European countries.
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            Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.

            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. 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). 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. 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.
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              Neurodevelopmental outcomes following late and moderate prematurity: a population-based cohort study

              Objective There is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm (LMPT; 32+0–36+6 weeks). This paper present the results of a prospective, population-based study of 2-year outcomes following LMPT birth. Design 1130 LMPT and 1255 term-born children were recruited at birth. At 2 years corrected age, parents completed a questionnaire to assess neurosensory (vision, hearing, motor) impairments and the Parent Report of Children's Abilities-Revised to identify cognitive impairment. Relative risks for adverse outcomes were adjusted for sex, socio-economic status and small for gestational age, and weighted to account for over-sampling of term-born multiples. Risk factors for cognitive impairment were explored using multivariable analyses. Results Parents of 638 (57%) LMPT infants and 765 (62%) controls completed questionnaires. Among LMPT infants, 1.6% had neurosensory impairment compared with 0.3% of controls (RR 4.89, 95% CI 1.07 to 22.25). Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). LMPT infants were at twice the risk for neurodevelopmental disability (RR 2.19, 95% CI 1.27 to 3.75). Independent risk factors for cognitive impairment in LMPT infants were male sex, socio-economic disadvantage, non-white ethnicity, preeclampsia and not receiving breast milk at discharge. Conclusions Compared with term-born peers, LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age, with the majority of impairments observed in the cognitive domain. Male sex, socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth.
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                Author and article information

                Contributors
                Role: neonatologist and researcher
                Role: statistician
                Role: associate professor of public health
                Role: director of research
                Role: professor in biostatistics
                Role: medical doctor
                Role: associate professor of epidemiology
                Role: postdoctoral research fellow and neonatologist
                Role: professor of obstetrics and gynecology
                Role: professor of paediatrics
                Role: professor of public health
                Journal
                BMJ
                BMJ
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2017
                16 August 2017
                : 358
                : j3448
                Affiliations
                [1 ]Obstetrical, Perinatal, and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Center (U1153), INSERM, Paris, France; Paris Descartes University, Paris, France
                [2 ]CHU Lille, Department of Neonatal Medicine, Jeanne de Flandre Hospital, F-59000 Lille, France
                [3 ]INSERM UMR 1027, Université Toulouse III Paul Sabatier, Toulouse, France
                [4 ]Biostatistics and Medical Information Department, AP-HP Saint-Louis Hospital, Paris, France
                [5 ]École des Hautes Études en Santé Publique (EHESP), Rennes, France
                [6 ]Maternité Port-Royal, Université Paris Descartes, Groupe Hospitalier Cochin Broca Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, DHU Risques et Grossesse, Paris, France
                [7 ]Department of Neonatal Pediatrics, Intensive care, and Neuropediatrics, Rouen University Hospital, Rouen, France
                [8 ]Research Unit U1245, Institute for Research and Innovation in Biomedicine, Rouen, France
                [9 ]Clinical Research Unit, Center for Clinical Investigation P1419, Cochin Broca Hôtel-Dieu Hospital, Paris, France
                [10]Accepted: 13 July 2017
                Author notes
                Correspondence to: V Pierrat Obstetrical, Perinatal, and Pediatric Epidemiology Team (EPOPé), INSERM U 1153, Bâtiment Recherche, Hôpital Tenon, 4 Rue de la Chine, 75020 Paris, France veronique.pierrat@ 123456inserm.fr
                Article
                piev037914
                10.1136/bmj.j3448
                5558213
                28814566
                b2145a9f-3b34-4230-ab96-80df4949723b
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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