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Neonatal outcomes following early fetal growth restriction: a subgroup analysis of the EVERREST study
  1. Ingran Lingam1,2,
  2. Jade Okell1,
  3. Katarzyna Maksym1,
  4. Rebecca Spencer1,3,
  5. Donald Peebles4,5,
  6. Gina Buquis1,
  7. Gareth Ambler6,
  8. Eva Morsing7,
  9. David Ley7,
  10. Dominique Singer8,
  11. Violeta Tenorio9,
  12. Jade Dyer1,
  13. Yuval Ginsberg1,10,
  14. Tal Weissbach1,11,
  15. Angela Huertas-Ceballos4,
  16. Neil Marlow1,
  17. Anna David1
  18. on behalf of the EVERREST consortium
    1. 1 EGA Institute for Women's Health, University College London, London, UK
    2. 2 Woodland Neonatal Unit, West Hertfordshire Teaching Hospitals NHS Trust, Watford, UK
    3. 3 Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
    4. 4 Neonatal Intensive Care Unit, University College London Hospitals NHS Foundation Trust, London, UK
    5. 5 National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London, London, UK
    6. 6 Department of Statistical Science, University College London, London, UK
    7. 7 Department of Paediatrics, Lund University, Lund, Sweden
    8. 8 Division of Neonatology and Pediatric Critical Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    9. 9 Institut D’Investigacions Biomèdiques August Pi í Sunyer, University of Barcelona, Barcelona, Spain
    10. 10 Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel
    11. 11 Institute of Obstetrical and Gynecological Imaging, Diagnostic Ultrasound Unit, Sheba Medical Center, Tel-Hashomer, Israel
    1. Correspondence to Dr Ingran Lingam, Institute for Women's Health, University College London, London WC1E 6BT, UK; ingranlingam{at}


    Objective To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR).

    Design The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women diagnosed with EP-FGR (singleton, estimated fetal weight (EFW) <3rd percentile, <600 g, 20+0–26+6 weeks of gestation). The UK subgroup of EP-FGR infants (<36 weeks) were sex-matched and gestation-matched to appropriate for age (AGA) infants born in University College London Hospital (1:2 design, EFW 25th−75th percentile).

    Setting Four tertiary perinatal units (UK, Germany, Spain, Sweden).

    Main outcomes Antenatal and postnatal mortality, bronchopulmonary dysplasia (BPD), sepsis, surgically treated necrotising enterocolitis (NEC), treated retinopathy of prematurity (ROP).

    Results Of 135 mothers recruited with EP-FGR, 42 had a stillbirth or termination of pregnancy (31%) and 93 had live births (69%). Postnatal genetic abnormalities were identified in 7/93 (8%) live births. Mean gestational age at birth was 31.4 weeks (SD 4.6). 54 UK-born preterm EP-FGR infants (<36 weeks) were matched to AGA controls. EP-FGR was associated with increased BPD (43% vs 26%, OR 3.6, 95% CI 1.4 to 9.4, p=0.01), surgical NEC (6% vs 0%, p=0.036) and ROP treatment (11% vs 0%, p=0.001). Mortality was probably higher among FGR infants (9% vs 2%, OR 5.0, 95% CI 1.0 to 25.8, p=0.054). FGR infants more frequently received invasive ventilation (65% vs 50%, OR 2.6, 95% CI 1.1 to 6.1, p=0.03), took longer to achieve full feeds and had longer neonatal stays (median difference 6.1 days, 95% CI 3.8 to 8.9 and 19 days, 95% CI 9 to 30 days, respectively, p<0.0001).

    Conclusions Mortality following diagnosis of EP-FGR is high. Survivors experience increased neonatal morbidity compared with AGA preterm infants.

    Trial registration number NCT02097667.

    • intensive care units, neonatal
    • neonatology
    • paediatrics

    Data availability statement

    Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    Data availability statement

    Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.

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    • Collaborators On behalf of the EVERREST consortium: Professor Stefan R. Hansson, Professor Karel Marsal, Dr Jana Brodszki, Professor Kurt Hecher, Professor Anke Diemert, Dr Fatima Crispi, Dr Albert Batista, Professor Francesc Figueras, Professor Eduard Gratacos, Professor Neil Sebire, Professor Ian Zachary and Anna Morka

    • Contributors UK data collection was undertaken by IL, JO, GB, RS, KM (European data collection led by EM, DL, DS, VT, YG, TW). Analysis was performed by IL, RS, GA. The manuscript was drafted by IL and reviewed by JO, RS, KM, GA, DP, AH-C, NM, AD. AD is responsible for the overall content as the guarantor. All coauthors approved the final manuscript.

    • Funding This study received funding from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement no. 305823), the Rosetrees Trust and Mitchell Charitable Trust.

    • Competing interests None declared.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.