Automatic versus manual control of oxygen and neonatal clinical outcomes in extremely preterm infants: a multicentre, parallel-group, randomised, controlled, superiority trial

IF 15.5 1区医学 Q1 PEDIATRICS

Lancet Child & Adolescent Health Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI:10.1016/S2352-4642(25)00351-7

Axel R Franz MD , Christian A Maiwald , Hendrik J Niemarkt PhD , Prof Harald Ehrhardt MD , Marc R Mendler MD , Jochen Essers MD , Thilo Mohns MD , Prof Andreas W Flemmer MD , Adelheid Kley MD , Hans-Jörg Bittrich MD , Bettina Bohnhorst MD , Christoph Jacobi MD , RuiMiao Bai MD , Estelle E M Mulder MD , Patrick Neuberger MD , Matthias C Hütten PhD , Ralf Rauch MD , Thomas M K Völkl MD , Thomas Höhn MD , Britta Brenner MD , Amanda Forster

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Closed-loop automated control of the fractional concentration of oxygen in inspired air (FiO<sub>2</sub>-C) reduces the time below and above the target range for the pulse oximeter oxygen saturation (SpO<sub>2</sub>) and caregivers’ workload. We aimed to study whether FiO<sub>2</sub>-C during respiratory support versus routine manual control might also improve clinical outcomes.</div></div><div><h3>Methods</h3><div>This multicentre, parallel-group, randomised, controlled, superiority trial was done in 32 neonatal intensive care units in China, Germany, the Netherlands, and the UK. Infants born at 23<sup>+0</sup> weeks to 27<sup>+6</sup> weeks postmenstrual age were included and randomly assigned to FiO<sub>2</sub>-C or routine manual care stratified within centres by postmenstrual age at birth and sex. FiO<sub>2</sub>-C was provided in addition to routine manual control of FiO<sub>2</sub> using infant ventilators. 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引用次数: 0

Abstract

Background

Extremely preterm infants require respiratory support with supplemental oxygen and have frequent hypoxaemic episodes. These episodes, and exposure to inadequately high concentrations of oxygen, are associated with major complications and death. Closed-loop automated control of the fractional concentration of oxygen in inspired air (FiO₂-C) reduces the time below and above the target range for the pulse oximeter oxygen saturation (SpO₂) and caregivers’ workload. We aimed to study whether FiO₂-C during respiratory support versus routine manual control might also improve clinical outcomes.

Methods

This multicentre, parallel-group, randomised, controlled, superiority trial was done in 32 neonatal intensive care units in China, Germany, the Netherlands, and the UK. Infants born at 23⁺⁰ weeks to 27⁺⁶ weeks postmenstrual age were included and randomly assigned to FiO₂-C or routine manual care stratified within centres by postmenstrual age at birth and sex. FiO₂-C was provided in addition to routine manual control of FiO₂ using infant ventilators. The composite primary endpoint was death, necrotising enterocolitis, or bronchopulmonary dysplasia up to 36 weeks postmenstrual age, or severe retinopathy of prematurity by 44 weeks postmenstrual age. Secondary endpoints were the components of the primary endpoint and the maximum retinopathy of prematurity severity score in either eye on the International Neonatal Consortium Retinopathy of Prematurity Activity Scale. The trial was stopped early because of poor recruitment. The primary analysis included the intention-to-treat population with non-missing primary outcome data. This trial was registered with ClinicalTrials.gov (NCT03168516) and is closed.

Findings

Between July 1, 2018, and Oct 31, 2023, 1082 infants were enrolled and randomly assigned to the FiO₂-C group (n=539) or routine manual control group (n=543). Median postmenstrual age was 26⁺¹ weeks (IQR 24⁺⁶–27⁺¹). 557 (51%) of 1082 infants were male and 525 (49%) were female. The primary endpoint occurred in 206 (39%) of 534 infants in the FiO₂-C group versus 222 (41%) of 538 infants in the routine manual control group (adjusted odds ratio 0·90, 97·5% CI 0·65–1·24; p=0·47). Rates of death (48 [9%] of 536 infants vs 50 [9%] of 541 infants), necrotising enterocolitis (27 [5%] of 538 vs 36 [7%] of 542), bronchopulmonary dysplasia (104 [21%] of 486 vs 110 [23%] of 485), and severe retinopathy of prematurity (86 [18%] of 491 vs 95 [19%] of 496) were also similar between groups. The maximum retinopathy of prematurity severity score was similar between groups (median 7 [IQR 0–9]; p=0·24). Overall, 197 serious adverse events were reported in the FiO₂-C group and 192 in the routine manual control group, with no evidence of harm related to the intervention. Postnatal age at death and primary causes of death were similar in both groups. Four serious incidents related to software function without apparent harm to affected infants were reported.

Interpretation

FiO₂-C did not improve neonatal clinical outcomes. The long-term application of FiO₂-C to reduce caregivers’ workload might be considered safe. FiO₂-C algorithms should be tested before routine application.

Funding

German Federal Ministry of Education and Research.

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自动与手动控制氧气与极早产儿新生儿临床结局：一项多中心、平行组、随机、对照、优势试验

极度早产儿需要呼吸支持和补充氧气，并有频繁的低氧血症发作。这些发作以及暴露于浓度不充分的氧气中，与主要并发症和死亡有关。吸入空气中氧气分数浓度（FiO2-C）的闭环自动控制减少了脉搏血氧仪氧饱和度（SpO2）低于和高于目标范围的时间和护理人员的工作量。我们的目的是研究在呼吸支持和常规手动控制期间，FiO2-C是否也可以改善临床结果。方法该多中心、平行组、随机、对照、优势试验在中国、德国、荷兰和英国的32个新生儿重症监护病房进行。研究纳入经后23+0周至27+6周出生的婴儿，并按出生后年龄和性别在中心内随机分配FiO2-C或常规人工护理。除了使用婴儿呼吸机常规手动控制FiO2外，还提供FiO2- c。复合主要终点为死亡、坏死性小肠结肠炎或支气管肺发育不良，直至经后36周，或经后44周早产儿严重视网膜病变。次要终点是主要终点的组成部分，以及国际新生儿联盟早产儿视网膜病变活动量表中任意一只眼睛的最大早产儿视网膜病变严重程度评分。由于招募不足，试验提前停止了。主要分析包括意向治疗人群，主要结局数据未缺失。该试验已在ClinicalTrials.gov注册（NCT03168516），目前已结束。在2018年7月1日至2023年10月31日期间，1082名婴儿被纳入研究，并随机分配到FiO2-C组（n=539）或常规手动对照组（n=543）。中位经后年龄为26+1周（IQR 24+ 6-27 +1）。1082例婴儿中，男557例（51%），女525例（49%）。主要终点发生在FiO2-C组534例婴儿中的206例（39%），而常规手工对照组538例婴儿中的222例（41%）（校正优势比0.90,97.5% CI 0.65 - 1.24; p= 0.47）。死亡率（536例中48例[9%]vs 541例中50例[9%]）、坏死性小肠结肠炎（538例中27例[5%]vs 542例中36例[7%]）、支气管肺发育不良（486例中104例[21%]vs 485例中110例[23%]）和早产儿严重视网膜病变（491例中86例[18%]vs 496例中95例[19%]）在两组之间也相似。早产儿视网膜病变严重程度评分中位数为7 [IQR 0 - 9]， p= 0.24]，组间差异无统计学意义。总体而言，FiO2-C组报告了197例严重不良事件，常规手工对照组报告了192例，没有证据表明与干预有关的危害。两组的出生后死亡年龄和主要死亡原因相似。报告了四起与软件功能有关的严重事件，但对受影响的婴儿没有明显的伤害。fio2 - c并没有改善新生儿的临床结果。长期应用o2 - c来减少护理人员的工作量可能被认为是安全的。FiO2-C算法应在常规应用前进行测试。资助德国联邦教育和研究部。

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来源期刊

Lancet Child & Adolescent Health Psychology-Developmental and Educational Psychology

CiteScore

40.90

自引率

0.80%

发文量

381

期刊介绍： The Lancet Child & Adolescent Health, an independent journal with a global perspective and strong clinical focus, presents influential original research, authoritative reviews, and insightful opinion pieces to promote the health of children from fetal development through young adulthood. This journal invite submissions that will directly impact clinical practice or child health across the disciplines of general paediatrics, adolescent medicine, or child development, and across all paediatric subspecialties including (but not limited to) allergy and immunology, cardiology, critical care, endocrinology, fetal and neonatal medicine, gastroenterology, haematology, hepatology and nutrition, infectious diseases, neurology, oncology, psychiatry, respiratory medicine, and surgery. Content includes articles, reviews, viewpoints, clinical pictures, comments, and correspondence, along with series and commissions aimed at driving positive change in clinical practice and health policy in child and adolescent health.