Gupta Samir, O'Connor Heather, Juszczak Edmund, Subhedar Nimish V, Bowler Ursula, Clarke Charlotte, Field David, Hutchison Elizabeth, Kelsall Wilf, Pepperell Justine, Roberts Tracy, Sinha Sunil, Stanbury Kayleigh, Wyllie Jonathan, Hardy Pollyanna, Johnson Samantha
Division of Neonatology, Sidra Medicine, Doha, Qatar.
Department of Engineering, Durham University, UK.
EClinicalMedicine. 2025 Aug 20;87:103424. doi: 10.1016/j.eclinm.2025.103424. eCollection 2025 Sep.
Children born extremely preterm are at increased risk of developmental problems and respiratory morbidity due to patent ductus arteriosus (PDA). The objective of this study was to evaluate whether early treatment of a PDA ≥1.5 mm with ibuprofen improved neurodevelopmental and respiratory outcomes at 24 months of age, corrected for prematurity.
Baby-OSCAR was a UK multi-center placebo-controlled masked randomized clinical trial in infants born 23-28 weeks' gestation. The main long-term outcome was survival without moderate or severe neurodevelopmental impairment at 24 months' corrected age, assessed using parent report primarily or classified by blinded end-point review committee where parent-reported data were not available. Other secondary outcomes included survival without respiratory morbidity and duration of oxygen supplementation. (ISRCTN Registry number ISRCTN84264977).
From July 2015 through December 2020, 653 infants underwent randomization. At 24 months' corrected age, outcome data were available for 537 children: 263 in the ibuprofen group and 274 in the placebo group. Survival without moderate to severe neurodevelopmental impairment in the ibuprofen and placebo groups was 131/248 (53.0%) and 134/259 (51.9%) respectively; adjusted risk ratio 1.01 (95% confidence interval [CI] 0.86-1.18); p = 0.901. Survival without respiratory morbidity was 66/220 (30%) and 74/225 (32.9%) respectively; adjusted risk ratio 0.89 (95% CI 0.68-1.18). Median duration of oxygen supplementation from randomization was 76.0 and 78.0 days, respectively; adjusted median difference -1.5 (-13.8 to 10.9).
We found no evidence of an improvement in neurodevelopmental and respiratory outcomes at 24 months' corrected age, after selective early treatment of a PDA ≥1.5 mm with ibuprofen in children born extremely preterm.
This study was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (11/92/15).
由于动脉导管未闭（PDA），极早产儿患发育问题和呼吸系统疾病的风险增加。本研究的目的是评估用布洛芬早期治疗直径≥1.5 mm的PDA是否能改善24个月龄（矫正胎龄）时的神经发育和呼吸结局。
Baby-OSCAR是一项在英国多中心开展的安慰剂对照双盲随机临床试验，研究对象为妊娠23-28周出生的婴儿。主要长期结局是在矫正年龄24个月时存活且无中度或重度神经发育障碍，主要通过家长报告进行评估，若无法获取家长报告的数据，则由盲法终点审查委员会进行分类。其他次要结局包括存活且无呼吸系统疾病以及吸氧持续时间。（国际标准随机对照试验编号：ISRCTN84264977）。
2015年7月至2020年12月，653名婴儿接受了随机分组。在矫正年龄24个月时，537名儿童有结局数据：布洛芬组263名，安慰剂组274名。布洛芬组和安慰剂组存活且无中度至重度神经发育障碍的比例分别为131/248（53.0%）和134/259（51.9%）；调整后风险比为1.01（95%置信区间[CI] 0.86-1.18）；p = 0.901。存活且无呼吸系统疾病的比例分别为66/220（30%）和74/225（32.9%）；调整后风险比为0.89（95% CI 0.68-1.18）。从随机分组开始的吸氧持续时间中位数分别为76.0天和78.0天；调整后中位数差值为-1.5（-13.8至10.9）。
我们发现，对于极早产儿，在用布洛芬选择性早期治疗直径≥1.5 mm的PDA后，未发现矫正年龄24个月时神经发育和呼吸结局有改善的证据。
本研究由英国国家卫生研究院（NIHR）卫生技术评估项目（11/92/15）资助。
