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Variation in very preterm extrauterine growth in a European multicountry cohort
  1. Rym El Rafei1,2,
  2. Pierre-Henri Jarreau1,3,
  3. Mikael Norman4,5,
  4. Rolf Felix Maier6,
  5. Henrique Barros7,8,
  6. Patrick Van Reempts9,
  7. Pernille Pedersen10,
  8. Marina Cuttini11,
  9. Jennifer Zeitlin1
  10. EPICE Research Group
  1. 1 Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team,EPOPé, INSERM, INRA, F-75004, Paris, France
  2. 2 Sorbonne Université, Collège Doctoral, F-75005, Paris, France
  3. 3 Université Paris Descartes and Assistance Publique Hôpitaux de Paris, Hôpitaux Universitaire Paris Centre Site Cochin, DHU Risks in pregnancy, Service de Médecine et Réanimation néonatales de Port-Royal, Paris, France
  4. 4 Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  5. 5 Department of Neonatal Medicine, Karolinska Institute, Stockholm, Sweden
  6. 6 Children’s Hospital, Philipps-Universitat Marburg, Marburg, Hessen, Germany
  7. 7 EPIUnit-Institute of Public Health, University of Porto, Porto, Portugal
  8. 8 Department of Clinical Epidemiology, Predictive Medicine and Public Health, University of Porto, Porto, Portugal
  9. 9 Neonatology, Laboratory of Experimental Medicine and Pediatrics, Division of Neonatology, University of Antwerp, Antwerp. Study Centre for Perinatal Epidemiology Flanders, Brussels, Belgium
  10. 10 Department of Paediatrics, Hvidovre Hospital, Hvidovre, Denmark
  11. 11 Clinical Care and Management Innovation Research Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
  1. Correspondence to Rym El Rafei, Obstetrical Perinatal and Pediatric Epidemiology Research Team (EPOPé), INSERM UMR 1153, 75014 Paris, France; rym.el-rafei{at}


Objective Extrauterine growth restriction (EUGR) among very preterm infants is related to poor neurodevelopment, but lack of consensus on EUGR measurement constrains international research. Our aim was to compare EUGR prevalence in a European very preterm cohort using commonly used measures.

Design Population-based observational study.

Setting 19 regions in 11 European countries.

Patients 6792 very preterm infants born before 32 weeks’ gestational age (GA) surviving to discharge.

Main outcome measures We investigated two measures based on discharge-weight percentiles with (1) Fenton and (2) Intergrowth (IG) charts and two based on growth velocity (1) birth weight and discharge-weight Z-score differences using Fenton charts and (2) weight-gain velocity using Patel’s model. We estimated country-level relative risks of EUGR adjusting for maternal and neonatal characteristics and associations with population differences in healthy newborn size, measured by mean national birth weight at 40 weeks’ GA.

Results About twofold differences in EUGR prevalence were observed between countries for all indicators and these persisted after case-mix adjustment. Discharge weight <10th percentile using Fenton charts varied from 24% (Sweden) to 60% (Portugal) and using IG from 13% (Sweden) to 43% (Portugal), while low weight-gain velocity ranged from 35% (Germany) to 62% (UK). Mean term birth weight strongly correlated with both percentile-based measures (Spearman’s rho=−0.90 Fenton, −0.84 IG, p<0.01), but not Patel’s weight-gain velocity (rho: −0.38, p=0.25).

Conclusions Very preterm infants have a high prevalence of EUGR, with wide variations between countries in Europe. Variability associated with mean term birth weight when using common postnatal growth charts complicates international benchmarking.

  • epidemiology
  • growth
  • neonatology
  • statistics

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  • Collaborators EPICE Research Group: Belgium: Flanders (Evelyne Martens, Guy Martens, Patrick Van Reempts); Denmark: Eastern Region (Klaus Boerch, Asbjoern Hasselager, Lene Huusom, Ole Pryds, Tom Weber); Estonia (Liis Toome, Heili Varendi); France: Burgundy, Ile-de France and Northern Region (Pierre Yves Ancel, Beatrice Blondel, Antoine Burguet, Pierre Henri Jarreau, Patrick Truffert); Germany: Hesse (Rolf Felix Maier, Bjorn Misselwitz, Stephan Schmidt), Saarland (Ludwig Gortner); Italy: Emilia Romagna (Dante Baronciani, Giancarlo Gargano), Lazio (Rocco Agostino, Ileana Croci, Francesco Franco), Marche (Virgilio Carnielli), Marina Cuttini, Domenico DiLallo; The Netherlands: Eastern and Central (Corine Koopman-Esseboom, Arno van Heijst, Joppe Nijman); Poland: Wielkopolska (Janusz Gadzinowski, Jan Mazela); Portugal: Lisbon and Tagus Valley (Luis Mendes Graça, Maria do Ceu Machado), Northern region (Carina Rodrigues, Teresa Rodrigues), Henriques Barros; Sweden: Stockholm (Anna Karin Bonamy, Mikael Norman, Emilija Wilson); UK: East Midlands and Yorkshire and Humber (Elaine Boyle, Elizabeth Draper, Brad Manktelow), Northern Region (Alan Fenton, David WA Milligan); INSERM, Paris (Jennifer Zeitlin, Mercedes Bonet, Aurelie Piedvache).

  • Funding This work was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013 under grant agreement n°259882) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 733280. RER has a doctoral contract funded by Sorbonne Université Collège Doctoral, Paris, France.

  • Competing interests None declared.

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

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