Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73–1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

中文翻译：

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产后早期高剂量脂溶性肠内维生素 A 补充剂治疗极低出生体重婴儿中度或重度支气管肺发育不良或死亡 (NeoVitaA)：多中心、随机、平行组、双盲、安慰剂对照、研究者发起阶段3 试用


维生素 A 在肺部发育中发挥着关键作用，但对于极低出生体重 (ELBW) 婴儿的最佳维生素 A 剂量和给药途径尚未达成共识。我们的目的是评估在接受推荐的基本肠内维生素 A 补充剂的 ELBW 婴儿中，与安慰剂相比，产后早期额外补充高剂量脂溶性维生素 A 补充剂是否会降低中度或重度支气管肺发育不良或死亡率。这项前瞻性、多中心、随机、平行组、双盲、安慰剂对照、研究者发起的 3 期试验在奥地利和德国的 29 个新生儿重症监护病房进行，评估了早期高剂量肠内维生素 A 补充剂（5000 个国际单位）。对于 ELBW 婴儿，使用 28 天的安慰剂（花生油）。符合条件的婴儿出生体重大于400克且小于1000克；出生时的胎龄为月经后 32 周或更小；入院新生儿重症监护室后 72 小时内需要机械通气、无创呼吸支持或补充氧气。参与者通过不同块大小（两个和四个）的块随机化进行随机分配。所有参与者均接受基本维生素 A 补充剂（每天 1000 IU/kg）。复合主要终点是在意向治疗人群中分析的中度或重度支气管肺发育不良或月经后 36 周时死亡。该试验已在 EudraCT 注册，2013-001998-24。 2015年3月2日至2022年2月27日期间，参与中心对3066名婴儿进行了资格筛查。 915 名婴儿被纳入研究，并被随机分配到高剂量维生素 A 组 (n=449) 或对照组 (n=466)。 平均胎龄为 26·5 周 (SD 2·0)，平均出生体重为 765 g (162)。高剂量维生素 A 组 449 名婴儿中有 171 名（38%）发生中度或重度支气管肺发育不良或死亡，而对照组 466 名婴儿中有 178 名（38%）发生中度或重度支气管肺发育不良或死亡（调整比值比 0·99，95% CI 0 ·73–1·55）。各组之间发生至少一种不良事件的参与者人数相似（高剂量维生素 A 组 449 人中有 256 人 [57%]，对照组 466 人中有 281 人 [60%]）。两组的基线、干预结束时和月经后 36 周时的血清视黄醇浓度相似。 ELBW婴儿出生后早期肠内补充大剂量脂溶性维生素A是安全的，但不会改变中度或重度支气管肺发育不良或死亡的发生率，也不会显着增加血清视黄醇浓度。 Deutsche Forschungsgemeinschaft 和欧洲临床研究基础设施网络 (ECRIN)。