英国医学会：早期胎儿生长受限的新生儿结局：EVERREST研究的亚组分析

Neonatal outcomes following early fetal growth restriction: a subgroup analysis of the EVERREST study

1. http://orcid.org/0000-0001-6621-1896 Ingran Lingam1,2, Jade Okell1, Katarzyna Maksym1, Rebecca Spencer1,3, Donald Peebles4,5, Gina Buquis1, Gareth Ambler6, Eva Morsing7, David Ley7, Dominique Singer8, Violeta Tenorio9, Jade Dyer1, Yuval Ginsberg1,10,  http://orcid.org/0000-0001-5558-7871 Tal Weissbach1,11, Angela Huertas-Ceballos4,  http://orcid.org/0000-0001-5890-2953 Neil Marlow1, Anna David1 on behalf of the EVERREST consortium
2. Correspondence to Dr Ingran Lingam, Institute for Women's Health, University College London, London WC1E 6BT, UK; ingranlingam@nhs.net

Abstract

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.