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吸入型布地奈德治疗支气管肺发育不良的远期疗效
Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia


Dirk Bassler ... 其他 • 2018.01.11
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• 二十二碳六烯酸和早产儿支气管肺发育不良

摘要


背景

应用吸入型糖皮质激素预防或治疗极早产儿支气管肺发育不良对神经发育的远期影响尚未确定。

 

方法

我们将863例新生儿(胎龄:23周0日到27周6日)随机分组,分别给予早期(出生后24小时内)吸入布地奈德或安慰剂。预设的次要远期结局为幸存患儿出现神经发育障碍,其定义为矫正月龄18~22个月时出现脑瘫、认知发育延迟(第2版贝利婴儿发育量表智力发育指数评分<85分[均值100减1个SD],得分较高说明表现较佳)、耳聋或失明等复合症状。

 

结果

629例极早产儿有充分的预设复合远期结局数据可供分析。这629例患儿中,308例接受了布地奈德吸入治疗,其中148例(48.1%)出现神经发育障碍,安慰剂组的321例患儿中则有165例(51.4%)出现神经发育障碍 (校正胎龄后的相对危险度,0.93;95%置信区间[CI],0.80~1.09;P=0.40),任一独立的预设结局指标在两组间均无显著差异。布地奈德组死亡例数多于安慰剂组(对可用生命状态资料的患儿数据进行分析,得到的两组死亡率为82/413 [19.9%] vs. 58/400 [14.5%];相对危险度,1.37;95% CI,1.01~1.86;P=0.04)。

 

结论

存活的极早产儿中,2岁时神经发育障碍的发病率在接受早期布地奈德吸入以预防或治疗支气管肺发育不良和接受安慰剂的两组之间无显著性差异,但前组死亡率高于后组(本研究由欧盟和意大利凯西制药公司[Chiesi Farmaceutici]资助;在ClinicalTrials.gov注册号为NCT01035190)。





作者信息

Dirk Bassler, M.D., Eric S. Shinwell, M.D., Mikko Hallman, M.D., Ph.D., Pierre-Henri Jarreau, M.D., Ph.D., Richard Plavka, M.D., Ph.D., Virgilio Carnielli, M.D., Christoph Meisner, Ph.D., Corinna Engel, Ph.D., Alexander Koch, M.D., Karen Kreutzer, M.D., Johannes N. van den Anker, M.D., Ph.D., Matthias Schwab, M.D., Henry L. Halliday, M.D., and Christian F. Poets, M.D. for the Neonatal European Study of Inhaled Steroids Trial Group*
From the Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich (D.B.), and the Division of Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital, Basel (J.N.A.) — both in Switzerland; Ziv Medical Center, Faculty of Medicine in the Galilee, Bar-Ilan University, Ramat Gan, Israel (E.S.S.); the Department of Children and Adolescents, Oulu University Hospital, and PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu, Oulu, Finland (M.H.); Assistance Publique–Hôpitaux de Paris, Département Hospitalo-Universitaire Risques et Grossesse, Université Paris Descartes, Hôpital Cochin, Service de Médecine et Réanimation Néonatales de Port-Royal, Paris (P.-H.J.); Charles University, General Faculty Hospital and 1st Faculty of Medicine in Prague, Prague, Czech Republic (R.P.); Polytechnical University of Marche, Salesi Children’s Hospital, Ancona, Italy (V.C.); Institute for Clinical Epidemiology and Applied Biometry (C.M.), University Children’s Hospital Tübingen, Center for Pediatric Clinical Studies (C.E.), Department of Neonatology, University Children’s Hospital (A.K., K.K., C.F.P.), and Department of Clinical Pharmacology and Department of Pharmacy and Biochemistry, University Hospital and University of Tübingen (M.S.), Tübingen, and Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart (M.S.) — all in Germany; Intensive Care and Department of Pediatric Surgery, Erasmus Medical Center–Sophia Children’s Hospital, Rotterdam, the Netherlands (J.N.A.); the Division of Clinical Pharmacology, Children’s National Health System, Washington, DC (J.N.A.); and the Department of Child Health at Queen’s University Belfast, Institute of Clinical Science, Belfast, United Kingdom (H.L.H.). Address reprint requests to Dr. Bassler at the Department of Neonatology, University Hospital Zurich, University of Zurich, Frauenklinikstr., 10 8091 Zurich, Switzerland, or at dirk.bassler@usz.ch. *A list of members of the Neonatal European Study of Inhaled Steroids Trial Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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