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Postnatal growth restriction and neurodevelopment at 5 years of age: a European extremely preterm birth cohort study
  1. Rym El Rafei1,2,
  2. Rolf Felix Maier3,
  3. Pierre Henri Jarreau1,
  4. Mikael Norman4,5,
  5. Henrique Barros6,7,
  6. Patrick Van Reempts8,
  7. Arno Van Heijst9,
  8. Pernille Pedersen10,
  9. Marina Cuttini11,
  10. Samantha Johnson12,
  11. Raquel Costa6,
  12. Michael Zemlin13,
  13. Elizabeth S Draper12,
  14. Jennifer Zeitlin1
  15. for the SHIPS Research Group
    1. 1 Université Paris Cité, Inserm, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS), Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, F-75004 Paris, France
    2. 2 Sorbonne Université, Collège Doctoral, F-75005 Paris, France
    3. 3 Children's Hospital, University Hospital, Philipps University Marburg, Marburg, Germany
    4. 4 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
    5. 5 Department of Neonatal Medicine, Karolinska University Hospital, Stockholm, Sweden
    6. 6 EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
    7. 7 Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto Medical School, Porto, Portugal
    8. 8 Laboratory of Experimental Medicine and Pediatrics, Division of Neonatology, Study Centre for Perinatal Epidemiology Flanders, University of Antwerp, Flanders, Brussels, Belgium
    9. 9 Department of Neonatology, Radboud University Medical Center, Nijmegen,the Netherlands/Erasmusmc, Rotterdam, The Netherlands
    10. 10 Department of Paediatrics, Hvidovre Hospital, Hvidovre, Denmark
    11. 11 Clinical Care and Management Innovation Research Area, Bambino Gesù Children’s Hospital, Rome, Italy
    12. 12 Department of Health Sciences, University of Leicester, Leicester, UK
    13. 13 Department of General Paediatrics and Neonatology, Saarland University, Saarland University Medical School, Homburg, Germany
    1. Correspondence to Dr Rym El Rafei, Obstetrical Perinatal and Pediatric Epidemiology Research Team, Paris 75004, France; rym.elrafei{at}


    Objective To investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age.

    Study design Population-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age.

    Setting 11 European countries.

    Patients 957 EPT infants born in 2011–2012.

    Main outcomes EUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <−2 SD as severe, −2 to −1 SD as moderate using Fenton’s growth charts (Fenton) and (2) average weight-gain velocity using Patel’s formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2–12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition.

    Results 40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (−3.9 points, 95% Confidence Interval (CI)=−7.2 to −0.6 for Fenton and −5.0 points, 95% CI=−8.2 to −1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP.

    Conclusions Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age.

    • child development
    • epidemiology
    • growth
    • paediatrics

    Data availability statement

    No data are available. Data are not available. Only aggregated data are available apart from the RECAP Platform (

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    Data availability statement

    No data are available. Data are not available. Only aggregated data are available apart from the RECAP Platform (

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    • Presented at The authors disclose that some results from this study were presented as a poster at the 9th e-conference on Nutrition & Growth held in march 2022 and at the society for pediatric and perinatal epidemiologic research (SPER) 34rd annual meeting held in June 2022 in Chicago, USA.

    • Collaborators SHIPS Research Group Belgium (J Lebeer, P Van Reempts, E Bruneel, E Cloet, A Oostra, E Ortibus, I Sarrechia); Denmark (K Boerch, L Huusom, P Pedersen, T Weber); Estonia (L Toome, H Varendi, M Männamaa); France (PY Ancel, A Burguet, PH Jarreau, V Pierrat, P Truffert); Germany (RF Maier, M Zemlin, B Misselwitz, S Schmidt, L Wohlers,) Italy (M Cuttini, D Di Lallo, G Ancora, D Baronciani, V Carnielli, I Croci, G Faldella, F Ferrari, F Franco, G Gargano); The Netherlands (A van Heijst, C Koopman-Esseboom); Poland (J Gadzinowski, J Mazela, A Montgomery, T Pikuła) Portugal (H Barros, R Costa, L Mendes Graça, M do Céu Machado, C Rodrigues, T Rodrigues); Sweden (U Aden, AK Edstedt Bonamy, M Norman); UK (ES Draper, EM Boyle, A Fenton, SJ Johnson, BN Manktelow, DWA Milligan) EFCNI (S Mader, N Thiele, JM Walz); Health Economics team (S Petrou); Inserm Coordination (J Zeitlin, AM Aubert, M Bonet, C Bonnet, R El Rafei, A Piedvache, AV Seppanen).

    • Contributors All authors contributed to this manuscript with different profiles including neonatologists and epidemiologists from the 11 study countries. All authors contributed to the research design, acquisition or management of data and participated in its interpretation. Authors also read and revised the manuscript and accepted the final version for publication. RER, JZ, RFM, PHJ and MN had a larger role in the conceptualisation of the study and the drafting of the manuscript. RER 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 study was funded by the European Union’s Horizon 2020 Research and Innovation Programme (grant no. 633724). Additional funding was received in the following regions: France: French National Institute of Public Health Research (IRESP TGIR 2009-01 programme)/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 for the future (grant no. ANR-11-EQPX-0038) and the PremUp Foundation; Poland: 2016–2019 allocation of funds for international projects from the Polish Ministry of Science and Higher Education; Sweden: Swedish Medical Research Council (grant no. 2017-03043) and the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet (grant no. ALF SLL 20170243).

    • Competing interests None declared.

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

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