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
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.
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