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Neurodevelopment at age 5.5 years according to Ages & Stages Questionnaire at 2 years’ corrected age in children born preterm: the EPIPAGE-2 cohort study
  1. Marie-Laure Charkaluk1,2,
  2. Gildas Delavoix Kana1,
  3. Valérie Benhammou1,
  4. Isabelle Guellec1,3,
  5. Mathilde Letouzey1,4,
  6. Andrei Scott Morgan1,5,
  7. Alexandra Nuytten2,
  8. Héloïse Torchin1,6,
  9. Sabrina Twilhaar7,
  10. Gilles Cambonie8,
  11. Stéphane Marret9,10,
  12. Pierre Yves Ancel1,11,
  13. Véronique Pierrat1,12
  14. Neurodevelopmental writing group of EPIPAGE-2
    1. 1 Université Paris Cité, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRAE, F-75004 Paris, France
    2. 2 Department of Neonatology, Saint Vincent de Paul Hospital, GHICL, F -59800 Lille, France
    3. 3 Neonatal Intensive Care Unit, Nice Côte d’Azur, Archet University Hospital, Nice, France
    4. 4 Department of Neonatal Pediatrics, Poissy Saint Germain Hospital, Poissy, France
    5. 5 Elizabeth Garrett Anderson Institute for Women’s Health London, University College London, London, UK
    6. 6 Department of Neonatal Medicine, Cochin-Port Royal Hospital, FHU PREMA, AP-HP Centre, 75014 Paris, France
    7. 7 Department of Psychology, University of Warwick, Coventry, UK
    8. 8 Department of Neonatal Medicine, Montpellier University Hospital, Montpellier, France
    9. 9 Department of Neonatal Medicine - Intensive Care - Neuropediatrics, Rouen University Hospital, Rouen, France
    10. 10 INSERM U1245 - Neovasc team - Perinatal handicap, Institute of Biomedical Research and Innovation, Normandy University, Rouen, France
    11. 11 Clinical Investigation Center P1419, Assistance Publique-Hôpitaux de Paris, Paris, France
    12. 12 Department of Neonatalogy, CHI Créteil, F-94028 Créteil, France
    1. Correspondence to Dr Marie-Laure Charkaluk, Hôpital Saint Vincent de Paul, Service de Néonatologie, Boulevard de Belfort, 59020 Lille cedex, France; charkaluk.marie-laure{at}


    Objective To report neurodevelopment at age 5.5 years according to developmental delay screening with the Ages & Stages Questionnaire (ASQ) in late infancy in preterm-born children.

    Design Population-based cohort study, EPIPAGE-2.

    Setting France, 2011–2017.

    Participants 2504 children born at 24–26, 27–31 and 32–34 weeks, free of cerebral palsy, deafness or blindness at 2 years’ corrected age.

    Main outcome measures Moderate/severe, mild or no disability at age 5.5 years using gross and fine motor, sensory, cognitive and behavioural evaluations. Results of the ASQ completed between 22 and 26 months’ corrected age described as positive screening or not.

    Results Among 2504 participants, 38.3% had ASQ positive screening. The probability of having moderate/severe or mild disability was higher for children with ASQ positive versus negative screening: 14.2% vs 7.0%, adjusted OR 2.5 (95% CI 1.8 to 3.4), and 37.6% vs 29.7%, adjusted OR 1.5 (1.2 to 1.9). For children with ASQ positive screening, the probability of having neurodevelopmental disabilities at age 5.5 years was associated with the number of domain scores below threshold, very low gestational age and severe neonatal morbidities. For children with ASQ negative screening, this probability was increased for boys and children born small-for-gestational age. For both groups, maternal level of education was strongly associated with outcomes.

    Conclusion In preterm-born children, ASQ screening at 2 years’ corrected age was associated with neurodevelopmental disabilities at age 5.5 years. However, other factors should be considered when interpreting the ASQ data to draw further follow-up.

    Trial registration number 2016-A00333-48.

    • Infant Development
    • Epidemiology
    • Neonatology
    • Child Health Services

    Data availability statement

    Data are available upon reasonable request. Data are available upon reasonable request and will be shared in accordance with the European regulation.

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    Data availability statement

    Data are available upon reasonable request. Data are available upon reasonable request and will be shared in accordance with the European regulation.

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    • Correction notice This article has been corrected since it was first published. Professor Stéphane Marret's affiliation has been corrected.

    • Collaborators Neurodevelopmental writing group of EPIPAGE-2: Eliane Basson (Réseau AURORE-ECLAUR, Hôpital de la Croix-Rousse, Lyon, France); Marie Chevallier (TIMC-IMMAG research department, Grenoble Alps University, Grenoble, France; Department of Neonatal Intensive Care Unit, CHU Grenoble, Grenoble, France); Valérie Datin-Dorrière (CHU Caen, Néonatologie-Réanimation, Caen, France. Université de Paris, CNRS UMR 8240 «LaPsyDE», Paris, France); Cécile Lebeaux (Department of Neonatology, Centre Hospitalier Intercommunal de Créteil, Créteil, France; Reseau perinatal RPVM, Créteil, France); Jean-Baptiste Muller (Department of Neonatal Medicine, University Hospital, Nantes, France).

    • Contributors M-LC, GDK and VP had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. M-LC, VP, ST, ASM, HT and SM conceptualised the study and wrote the manuscript. GDK performed the statistical analysis. VB coordinated data collection and had responsibility for technical support. PYA obtained funding and supervised the study. All authors contributed to the analysis plan and interpretation of the results and reviewed and approved the final manuscript. All members of the writing group were involved in the regional organisation for data collection, reviewed and/or approved the final manuscript. M-LC accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.

    • Funding This project has been funded with support from the French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer and the National Solidarity Fund for Autonomy (CNSA); the National Research Agency through the French EQUIPEX programme of investments in the future (reference ANR-11-EQPX-0038); the PREMUP Foundation; Fondation de France (reference 11779); Fondation pour la Recherche Médicale (SPF20160936356); and Programme Hospitalier de Recherche Clinique Epinutri (DGOS13-040).

    • Disclaimer The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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