Department of Neonatology, Academic Medical Center, Amsterdam, the Netherlands.
Department of Academic Neonatology, Institute for Women's Health, University College London, London, UK.
BJOG. 2017 Jun;124(7):1072-1078. doi: 10.1111/1471-0528.14511. Epub 2017 Feb 3.
To study the relationship between neonatal morbidity (NNM) and two-year neurodevelopmental impairment (NDI) in surviving children after early fetal growth restriction (FGR).
Secondary analysis of a European randomised trial (TRUFFLE) of delivery for very preterm fetuses dependent on venous Doppler or cardiotocographic criteria.
Tertiary perinatal centres, participants in TRUFFLE.
402 surviving children after early FGR.
Prospective data were collection from the recognition of FGR until the corrected age of two years. We studied the association between NNM and NDI, retaining trial allocation in all statistical models. NNM included any of bronchopulmonary dysplasia, brain injury, sepsis or necrotising enterocolitis. NDI was a composite of Bayley cognitive score < 85, cerebral palsy or severe sensory impairment.
NDI in relation to NNM.
NNM occurred in 104 cases (26%) and was more frequent in 17 of 39 infants with NDI (44%) than in the 87 of 363 infants with normal outcome (24%) [odds ratio 2.5 (95% CI, 1.3-4.8); P = 0.01]. In 22 of 39 NDI cases (56%) there was no preceding NNM. NNM was inversely related to gestational age, but NDI did not vary by gestational age. In multivariable analyses, cerebral ultrasound abnormalities were most strongly associated with NDI, together with trial group allocation, birthweight ratio, infant sex and Apgar score.
With the exception of cerebral ultrasound abnormalities, commonly used NNMs are poor markers of later NDI and should not be used as surrogate outcomes for NDI.
Neonatal morbidities cannot be used as surrogate outcomes for neurodevelopmental impairment.
研究早期胎儿生长受限（FGR）后存活儿新生儿发病率（NNM）与两年神经发育障碍（NDI）之间的关系。
对依赖静脉多普勒或胎心监护标准的极早产儿分娩的欧洲随机试验（TRUFFLE）进行二次分析。
三级围产中心，TRUFFLE 参与者。
402 例早期 FGR 后存活儿。
从 FGR 发现到校正年龄 2 岁前瞻性收集数据。我们研究了 NNM 与 NDI 之间的关联，在所有统计模型中保留试验分配。NNM 包括任何支气管肺发育不良、脑损伤、败血症或坏死性小肠结肠炎。NDI 是贝利认知评分<85、脑瘫或严重感觉障碍的综合指标。
NNM 与 NDI 的关系。
104 例（26%）发生 NNM，17 例（44%）NDI 患儿中 NNM 发生率高于 363 例（24%）无异常结局患儿[比值比 2.5（95%可信区间，1.3-4.8）；P=0.01]。39 例 NDI 中有 22 例（56%）无先前 NNM。NNM 与胎龄呈负相关，但 NDI 与胎龄无关。多变量分析显示，脑超声异常与 NDI 最密切相关，同时与试验组分配、出生体重比、婴儿性别和 Apgar 评分有关。
除脑超声异常外，常用的 NNM 是 NDI 的不良标志物，不能作为 NDI 的替代结局。
新生儿发病率不能作为神经发育障碍的替代结局。
