Neonatal Intensive Care Unit, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Acta Paediatr. 2011 May;100(5):641-6. doi: 10.1111/j.1651-2227.2011.02189.x. Epub 2011 Mar 2.
Important short-term intermediate outcomes such as patent ductus arteriosus (PDA), severe intraventricular haemorrhage, surgical ligation of PDA and serious pulmonary haemorrhage correlate with worse neurosensory outcomes in extreme low birth weight infants. Indomethacin prophylaxis has been shown to significantly prevent such outcomes. However, this positive effect did not translate into neither prevention of bronchopulmonary dysplasia nor long-term neurosensory outcome. The indomethacin prophylaxis story is indeed a puzzling one to neonatal practitioners. We present a summary of evidence and possible explanations to the lack of appreciated long-term effect of indomethacin prophylaxis. As the trial of indomethacin prophylaxis for preterms trial is a major contributor to current evidence, a detailed critical analysis of its methodology is presented. Methodological concerns such as the use of a composite outcome, statistical power, anticipated side effects of indomethacin prophylaxis and lack of predictive validity of cognitive delay measurements are presented.
Conclusive evidence of indomethacin prophylaxis use in extreme low birth weight infants is still lacking. Future research should put more emphasis on parental preferences, synergistic effect of indomethacin prophylaxis and fluid restriction and early targeted approach to PDA management.
极早产儿的动脉导管未闭（PDA）、重度脑室出血、PDA 手术结扎和严重肺出血等重要短期中期结局与较差的神经感觉预后相关。吲哚美辛预防已被证明能显著预防这些结局。然而，这种积极效果并没有转化为支气管肺发育不良或长期神经感觉结局的预防。吲哚美辛预防的故事确实让新生儿科医生感到困惑。我们总结了证据和可能的解释，以说明吲哚美辛预防缺乏被认可的长期效果。由于吲哚美辛预防早产儿试验是当前证据的主要贡献者，因此对其方法学进行了详细的批判性分析。提出了一些方法学问题，如复合结局的使用、统计效力、吲哚美辛预防的预期副作用以及认知延迟测量的预测效度缺乏。
极早产儿使用吲哚美辛预防的结论性证据仍然缺乏。未来的研究应更加重视父母的偏好、吲哚美辛预防和液体限制的协同作用以及对 PDA 管理的早期靶向方法。
