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二十二碳六烯酸和早产儿支气管肺发育不良
Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants


Carmel T. Collins ... 呼吸系统疾病 妇产科和儿科 • 2017.03.30
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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 • 长链多不饱和脂肪酸补剂未降低BPD发生风险

早产儿BPD发生率的增加与防治困惑

 

杜立中

浙江大学医学院附属儿童医院新生儿内科

 

传统支气管肺发育不良(BPD)是早产儿因呼吸窘迫用高浓度氧和机械通气后所致的慢性肺部疾病,该病于1967年由Northway首次描述,其特点是肺实质的纤维化、炎症、平滑肌增生导致的弥漫性气道损伤。但随着极低、超低体重儿存活率的提高,BPD的表现形式出现了变化,主要见于这些极不成熟的早产儿,其特点是炎症过程引起出生后肺泡和肺血管发育中止,形成所谓的“新BPD”1。关于BPD的防治,目前主要集中在肺保护性呼吸治疗策略,如无创通气与温和通气治疗的广泛使用。关于药物防治,近20年未有明显突破,主要问题为证据不足或伴随副作用发生。经典药物防治手段包括:利尿剂、血管扩张剂的全身或吸入应用,维生素A、咖啡因、糖皮质激素的全身或吸入应用,后期肺表面活性物质的应用。预防性措施包括:抗氧化剂、补充DHA等,但疗效存在争议。

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摘要 


背景

动物和人类研究均显示二十二碳六烯酸(docosahexaenoic acid,DHA),作为一种n-3长链多不饱和脂肪酸,可能降低支气管肺发育不良的发病风险。但目前缺少恰当设计的临床试验。

 

方法

我们将1,273名首次肠道喂养后不超过3日,且在29周胎龄前出生的婴儿(根据性别、胎龄[<27周或27~29周]和试验中心分层)随机分成DHA组和对照组,DHA组给予含有DHA 60 mg /(kg·d)的肠道乳剂,对照组给予无DHA的对照(大豆)乳剂,直至产妇停经后36周龄。主要结局为婴儿于停经后36周龄或出院时(以先发生者为准),发生生理基础定义的支气管肺发育不良(入选婴儿接受氧饱和度监测)。

 

结果

共计1,205名婴儿存活至主要结局评估阶段。DHA组592名婴儿中,291名(多重插补后49.1%)被分类为有生理性支气管肺发育不良;对照组613名婴儿中,269名(多重插补后43.9%)被分类为有生理性支气管肺发育不良(根据随机分层校正后,相对危险度为1.13;95%置信区间[CI]为1.02~1.25;P=0.02)。产妇停经后36周前,婴儿发生生理性支气管肺发育不良或死亡这一复合结局的比例如下:DHA组为52.3%,对照组为46.4%(校正后相对危险度为1.11;95% CI为1.00~1.23;P=0.045)。两组间死亡率和其他新生儿疾病的发生率无显著差异。基于临床定义的支气管肺发育不良发生于DHA组婴儿的53.2%,和对照组婴儿的49.7%中(P=0.06)。

 

结论

29周胎龄前出生的早产儿中,肠道补充DHA 60 mg/(kg·d),与对照乳剂相比未降低生理性支气管肺发育不良的发生风险,并可能导致更高的风险(该研究由澳大利亚国家卫生和医学研究委员会[Australian National Health and Medical Research Council]等资助;澳大利亚新西兰临床试验注册号[Australian New Zealand Clinical Trials Registry]为ACTRN12612000503820)。





作者信息

Carmel T. Collins, Ph.D., Maria Makrides, Ph.D., Andrew J. McPhee, M.B., B.S., Thomas R. Sullivan, B.Ma.&Comp.Sc., Peter G. Davis, M.D., Marta Thio, Ph.D., Karen Simmer, Ph.D., Victor S. Rajadurai, M.D., Javeed Travadi, D.M., Mary J. Berry, Ph.D., Helen G. Liley, M.B., Ch.B., Gillian F. Opie, M.B., B.S., Kenneth Tan, Ph.D., Kei Lui, M.D., Scott A. Morris, Ph.D., Jacqueline Stack, M.B., Ch.B., Michael J. Stark, Ph.D., Mei-Chien Chua, M.Med., Pooja A. Jayagobi, M.Med., James Holberton, M.B., B.S., Srinivas Bolisetty, M.D., Ian R. Callander, M.B., B.S., Deborah L. Harris, Ph.D., and Robert A. Gibson, Ph.D.
From Healthy Mothers, Babies, and Children, South Australian Health and Medical Research Institute (C.T.C., M.M., A.J.M., R.A.G.), the Schools of Medicine (C.T.C., M.M., A.J.M., M.J.S.), Public Health (T.R.S.), and Agriculture, Food, and Wine (R.A.G.) and the Robinson Research Institute (M.J.S.), University of Adelaide, the Department of Neonatal Medicine, Women’s and Children’s Hospital (A.J.M., M.J.S.), and the School of Medicine (S.A.M.), Flinders University, Adelaide, SA, the Newborn Research Centre, Royal Women’s Hospital (P.G.D., M.T.), University of Melbourne (P.G.D., M.T.), Murdoch Children’s Research Institute (M.T.), the Department of Paediatrics, Mercy Hospital for Women (G.F.O., J.H.), the Department of Paediatrics, Monash University and Monash Newborn, Monash Children’s Hospital (K.T.), Melbourne, VIC, the Clinical Trials Centre, University of Sydney (K.S.), School of Women’s and Children’s Health, University of New South Wales (K.L., J.S.), and Newborn Care, Royal Hospital for Women (S.B.), Sydney, the Neonatal Intensive Care Unit, John Hunter Children’s Hospital and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW (J.T.), the Neonatal Intensive Care Unit, Liverpool Hospital, Liverpool, NSW (J.S., I.R.C.), the Department of Newborn Medicine, Centre for Neonatal Research and Education, University of Western Australia, Perth (K.S.), and Newborn Services, Mater Misericordiae, and Mater Research Institute, University of Queensland, Brisbane (H.G.L.) — all in Australia; the Department of Paediatrics and Child Health, University of Otago, Wellington (M.J.B.), the Newborn Intensive Care Unit, Waikato Hospital, Hamilton (D.L.H.), and Liggins Institute, University of Auckland, Auckland (D.L.H.) — all in New Zealand; and the Department of Neonatology, KK Women’s and Children’s Hospital (V.S.R., M.-C.C., P.A.J.), Yong Loo Lin School of Medicine, National University of Singapore (V.S.R., M.-C.C.), and Duke–National University of Singapore Medical School (V.S.R., M.-C.C.) — all in Singapore. Address reprint requests to Dr. Collins at the South Australian Health and Medical Research Institute, Level 7 Reiger Bldg., 72 King William Rd., North Adelaide, SA 5006, Australia, or at carmel.collins@sahmri.com.

 

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