极早产儿早期氨基酸摄入与 2 岁时神经发育障碍。

Early Amino Acids in Extremely Preterm Infants and Neurodisability at 2 Years.

机构信息

From the Liggins Institute (F.H.B., Y.J., J.E.H., C.A.C., B.E.C.) and the Department of Statistics, (Y.J.), University of Auckland, and Newborn Services, Auckland City Hospital (F.H.B., B.E.C.) - all in Auckland, New Zealand.

出版信息

N Engl J Med. 2022 Nov 3;387(18):1661-1672. doi: 10.1056/NEJMoa2204886.

DOI:10.1056/NEJMoa2204886

PMID:36322845

Abstract

BACKGROUND

Whether higher parenteral amino acid intake improves outcomes in infants with extremely low birth weight is unclear.

METHODS

In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned infants with birth weights of less than 1000 g at 8 neonatal intensive care units to receive amino acids at a dose of 1 g per day (intervention group) or placebo in addition to usual nutrition for the first 5 days after birth. The primary outcome was survival free from neurodisability as assessed with the Bayley Scales of Infant and Toddler Development and neurologic examination at 2 years, corrected for gestational age at birth. Secondary outcomes were the components of the primary outcome as well as the presence or absence of neonatal disorders, the rate of growth, and nutritional intake.

RESULTS

We enrolled 434 infants (217 per group) in this trial. Survival free from neurodisability was observed in 97 of 203 children (47.8%) in the intervention group and in 102 of 205 (49.8%) in the placebo group (adjusted relative risk, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P = 0.56). Death before the age of 2 years occurred in 39 of 217 children (18.0%) in the intervention group and 42 of 217 (19.4%) in the placebo group (adjusted relative risk, 0.93; 95% CI, 0.63 to 1.36); neurodisability occurred in 67 of 164 children (40.9%) in the intervention group and 61 of 163 (37.4%) in the placebo group (adjusted relative risk, 1.16; 95% CI, 0.90 to 1.50). Neurodisability was moderate to severe in 27 children (16.5%) in the intervention group and 14 (8.6%) in the placebo group (adjusted relative risk, 1.95; 95% CI, 1.09 to 3.48). More children in the intervention group than in the placebo group had patent ductus arteriosus (adjusted relative risk, 1.65; 95% CI, 1.11 to 2.46). In a post hoc analysis, refeeding syndrome occurred in 42 of 172 children in the intervention group and 26 of 166 in the placebo group (adjusted relative risk, 1.64; 95% CI, 1.09 to 2.47). Eight serious adverse events occurred.

CONCLUSIONS

In infants with extremely low birth weight, extra parenteral amino acids at a dose of 1 g per day for 5 days after birth did not increase the number who survived free from neurodisability at 2 years. (Funded by the New Zealand Health Research Council and others; ProVIDe Australian New Zealand Clinical Trials Registry number, ACTRN12612001084875.).

摘要

背景

极高出生体重儿额外补充外源性氨基酸能否改善预后尚不明确。

方法

在这项多中心、平行分组、双盲、随机、安慰剂对照试验中，我们将 8 个新生儿重症监护病房出生体重不足 1000g 的婴儿随机分配至干预组（每天接受 1g 氨基酸）或安慰剂组（除了标准营养支持之外），两组均在出生后 5 天内接受治疗。主要结局是校正胎龄后 2 岁时使用贝利婴幼儿发育量表（Bayley Scales of Infant and Toddler Development）和神经检查评估的无神经发育障碍存活率。次要结局包括主要结局的组成部分以及有无新生儿疾病、生长速度和营养摄入。

结果

本试验共纳入了 434 名婴儿（每组 217 名）。干预组 203 名婴儿中有 97 名（47.8%）和安慰剂组 205 名婴儿中有 102 名（49.8%）在 2 岁时存活且无神经发育障碍（校正后相对风险为 0.95；95%置信区间为 0.79 至 1.14；P=0.56）。干预组 217 名婴儿中有 39 名（18.0%）和安慰剂组 217 名婴儿中有 42 名（19.4%）在 2 岁前死亡（校正后相对风险为 0.93；95%置信区间为 0.63 至 1.36）；干预组 164 名婴儿中有 67 名（40.9%）和安慰剂组 163 名婴儿中有 61 名（37.4%）出现神经发育障碍（校正后相对风险为 1.16；95%置信区间为 0.90 至 1.50）。干预组 27 名（16.5%）婴儿和安慰剂组 14 名（8.6%）婴儿的神经发育障碍为中重度（校正后相对风险为 1.95；95%置信区间为 1.09 至 3.48）。干预组发生动脉导管未闭的婴儿多于安慰剂组（校正后相对风险为 1.65；95%置信区间为 1.11 至 2.46）。在事后分析中，干预组 172 名婴儿中有 42 名（24.4%）和安慰剂组 166 名婴儿中有 26 名（16.1%）发生再喂养综合征（校正后相对风险为 1.64；95%置信区间为 1.09 至 2.47）。共发生 8 例严重不良事件。