早产儿支气管肺发育不良危险因素前瞻性队列研究
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摘要
目的本研究应用前瞻性队列研究方法,调查早产儿支气管肺发育不良(BPD)的发病率、临床特征,筛查并确定早产儿BPD发病危险因素尤其是高危因素,为制定早产儿BPD综合干预措施提供依据。
方法应用单中心前瞻性队列研究的方法,对我院产科在2009年01月01日至2010年06月01日期间内出生的所有活产的早产儿进行研究。研究期间内对每一个早产新生儿进行调查,包括以下研究内容:(1)孕妇的产科及社会因素;(2)早产儿出生时的情况;(3)出生后到纠正胎龄40周期间早产儿患病及治疗情况。包括疾病的患病率、早产儿氧疗情况、抗生素使用情况、制酸药的应用、喂养情况、气道分泌物的培养结果、机械通气的呼吸力学参数、机械通气的时间、上机的次数、胸片的动态观察、实验室检查结果等。采用调查表形式收集数据资料。经单因素Pearson Chi-square检验或Fisher确切概率法及多因素Logistic回归分析筛选BPD发病的危险因素。
结果共有425个早产儿入组研究,其中男性266例(62.6%),女性159例(37.4%)。平均胎龄为33.9±2.4w(36w～26w)。出生体质量:3150g～770g,平均2038±660g,其中极低出生体重儿和超低出生体重儿共92例。发生BPD45例,发病率为10.59%,死亡(包括自动出院撤机后死亡)7例,BPD病死率15.56%。大多数BPD发生在胎龄32周及以下36/45(80.0%),以及出生体质量1500g以下的早产儿29/45(64.4%)。将各因素与BPD发病作单因素相关分析,筛选出BPD发生的22项可能危险因素,它们分别是:孕母非本市户口(OR值2.634)、异常生育史(OR值2.824)、试管婴儿(OR值17.239)、产道感染(OR值3.642)、胎膜早破(OR值4.056)、小于34w(OR值3.887)、<2000g(OR值6.518)、男(OR值2.258)、新生儿重度窒息(OR值2.783)、出生时动脉血PH值<7.20(OR值4.302)、NRDS(OR值13.905)、感染性肺炎(OR值7.347)、呼吸暂停(OR值5.151)、PDA开放(OR值42.452)、喂养不耐受(OR值6.377)、败血症(OR值4.302)、机械通气(OR值53.958)、H_2受体抑制剂(OR值17.281)、静脉营养≥20天(OR值8.894)、低白蛋白(OR值3.728)、输红细胞次数≥3次(OR值10.459)、应用碳青霉烯类抗生素(OR值15.122)。多因素Logistic回归分析发现8项为BPD发病的独立危险因素,它们分别是异常生育史(OR值1.57)、胎龄<30周(OR值3.10)、体质量<1500g(OR值2.29)、感染性肺炎(OR值2.74)、PDA开放(OR值2.12)、机械通气(OR值9.57)、H_2受体抑制剂(OR值1.36)、应用碳青霉烯类抗生素(OR值2.59)。并专门对接受机械通气的患儿进行BPD危险因素的多因素Logistic回归分析,发现8项为BPD发病的独立危险因素,分别是孕妇产道感染(OR值9.365)、胎龄<30周(OR值53.72)、性别(男婴)(OR值4.43)、感染性肺炎(OR值4.58)、PDA开放(OR值3.56)、机械通气≥2次(OR值9.86)、上机≥10天(OR值195.16)、H_2受体抑制剂(OR值9.56)。
结论早产儿BPD的发病率、病死率均较高。随着胎龄的减少和出生体质量的降低BPD发病率明显升高。多种因素导致BPD的发病率升高,其中,孕妇异常生育史、患儿胎龄<30周、出生体质量<1500g、感染性肺炎(包括呼吸机相关性肺炎)、动脉导管未闭、机械通气、应用碳青霉烯类抗生素和H_2受体抑制剂为早产儿BPD发生的独立危险因素。
Objective To investigate the incidence,clinical features and the risk factors for bronchopulmonary dysplasia (BPD) in premature infants with a prospective cohort study and provide a basis for the integrated intervention of the premature infants with BPD.
Methods Single-center prospective cohort study. Between January 1,2009 and June 01,2010, we paid regular visits to the maternity wards,and neonatal intensive care unit (NICU) for an in-depth study and investigation of all the live births of premature infants. The investigation was conducted in three stages: (1) For those pregnant women whose pregnancy was less than 37 weeks and who showed premature signs, surveys were launched right after their admission to the Obstetrics Wards concerning their history of pregnancy as well as social factors; (2) Surveys were conducted in the maternity wards on the premature infants; ( 3) Investigations were done on the infants between their birth and their corrected gestational age of 40 weeks, including the collection of following information: the morbidity incidence of such major diseases as respiratory problems, infection, brain injury, ROP,and deformity; the premature infants’use of oxygen, antibiotics; the cultured results of their airway secretion; the respiratory parameters of mechanical ventilation; the duration of mechanical ventilation; the number of times of mechanical ventilation; the dynamic observation of chest radiograph; the data of hemoglobin, platelet, serum albumin; the infants’feeding conditions; the application of acid drugs and so on. With the final clinical diagnosis of BPD, we also recorded the prognosis of the disease, the growth and development status and the nutritional status of the BPD group and the non-BPD group between birth and the corrected gestational age of full-term pregnancy. Questionnaire forms have been used to collect the above data. BPD risk factors are screened through Univariate Pearson Chi-square tests or Fisher exact test and multivariate Logistic regression analysis.
Results Among 425 cases of premature infants, 266(62.6%) cases male, and 159(37.4%) cases female, with average gestational age -- 33.9±2.4w, and birth weight -- 2800g ~ 750g, with an average of 1820±462g, of which 97 cases were of very low birth weight infants. Among these infants there were 45 BPD cases with the incidence of 10.59%, 7 of them being death cases (including the deaths after automatic discharge from hospital and weaning mechanical ventilation) with the crude mortality of 15.56%. The potential risk factors of BPD in univariate pearson Chi-Square test were mother not local people (OR 2.634, 95%CI 1.409~4.921; P=0.002) , abnormal generation history (OR 2.824 , 95%CI 1.456～5.480; P=0.002),test-tube baby (OR17.239, 95%CI 6.275～47.361; P=0.000) , birthcanal infection(OR3.642, 95%CI 1.682～7.888; P=0.001), prematurerupture of menbranes (0R4.056,95%CI 1.675～9.817;P=0.001), gestational age<32w (OR3.887, 95%CI 1.217～12.416; P=0.025) , < 2000g (OR6.518 , 95%CI 2.198～19.328; P=0.02501), male(OR2.258,95%CI 1.085～4.696; P=0.026),severe neonatal asphyxia (OR2.783, 95%CI 1.211～6.398; P=0.026), baby’s PH<7.20(0R4.302,95%CI 2.189～8.454; P=0.000), NRDS(OR13.905,95%CI 7.002～27.615;P=0.000) , infectious pneumonia (OR7.347 , 95%CI 3.742～14.425;P=0.000),premature apnea(OR 5.151, 95%CI 2.713～9.780;P=0.000),PDA(OR42.452,95%CI 13.176～136.778; P=0.000),feed intolerance(OR6.377,95%CI3.32～12.240; P=0.000),sepsis(OR4.302,95%CI 2.189～8.454; P=0.000), mechanical ventilation(OR53.958,95%CI 23.055～126.283;P=0.000),administration of histamine(H-2)antagonists(OR17.281,95%CI 8.144～36.672; P=0.000) , parenteral Nutrition≥20 days(OR8.894,95%CI4.339～18.230; P=0.000) , albumin<25g/L(OR3.728,95%CI 1.795～7.744;P=0.000), frequencies of blood transfusion exceed three(OR10.459 , 95%CI 5.311～20.596;P=0.000) , administration of advanced broad-spectrum antibiotics (OR15.122,95%CI 6.793～33.663;P=0.000). Multivariate Logistic regression analysis with backward (Likehood ratio) method found that abnormal generation history(0R1.57,95%CI0.90～3.32; P=0.066) , gestational age<30w(OR3.1,95%CI 1.58～5.47; P=0.001) , < 1500g(OR2.29 , 95%CI 1.32～4.55; P=0.010), infectious pneumonia(OR2.74,95%CI 1.45～4.71;P=0.001) , PDA(OR2.12 , 95%CI 1.12～4.41;P=0.010) , mechanical ventilation(OR9.57,95%CI 4.78～22.26; P=0.000), antacids (OR1.36,95%CI 1.00～3.57; P=0.047),advanced broad-spectrum antibiotics (OR2.59,95%CI 1.23～4.12; P=0.030) were independent risk factors of BPD in premature infants.
Conclusion Among premature infants there is a high BPD incidence and mortality rate. The independent risk factors for the BPD in premature infants are as follows: the abnormal pregnancy and birth history of pregnant women, the infants’gestational age less than 30 weeks, the birth weight less than 1500g, infectious pneumonia (including ventilator-related pneumonia), patent ductus arteriosus, mechanical ventilation, and the use of advanced broad-spectrum antibiotics and antacids.
方法应用单中心前瞻性队列研究的方法,对我院产科在2009年01月01日至2010年06月01日期间内出生的所有活产的早产儿进行研究。研究期间内对每一个早产新生儿进行调查,包括以下研究内容:(1)孕妇的产科及社会因素;(2)早产儿出生时的情况;(3)出生后到纠正胎龄40周期间早产儿患病及治疗情况。包括疾病的患病率、早产儿氧疗情况、抗生素使用情况、制酸药的应用、喂养情况、气道分泌物的培养结果、机械通气的呼吸力学参数、机械通气的时间、上机的次数、胸片的动态观察、实验室检查结果等。采用调查表形式收集数据资料。经单因素Pearson Chi-square检验或Fisher确切概率法及多因素Logistic回归分析筛选BPD发病的危险因素。
结果共有425个早产儿入组研究,其中男性266例(62.6%),女性159例(37.4%)。平均胎龄为33.9±2.4w(36w～26w)。出生体质量:3150g～770g,平均2038±660g,其中极低出生体重儿和超低出生体重儿共92例。发生BPD45例,发病率为10.59%,死亡(包括自动出院撤机后死亡)7例,BPD病死率15.56%。大多数BPD发生在胎龄32周及以下36/45(80.0%),以及出生体质量1500g以下的早产儿29/45(64.4%)。将各因素与BPD发病作单因素相关分析,筛选出BPD发生的22项可能危险因素,它们分别是:孕母非本市户口(OR值2.634)、异常生育史(OR值2.824)、试管婴儿(OR值17.239)、产道感染(OR值3.642)、胎膜早破(OR值4.056)、小于34w(OR值3.887)、<2000g(OR值6.518)、男(OR值2.258)、新生儿重度窒息(OR值2.783)、出生时动脉血PH值<7.20(OR值4.302)、NRDS(OR值13.905)、感染性肺炎(OR值7.347)、呼吸暂停(OR值5.151)、PDA开放(OR值42.452)、喂养不耐受(OR值6.377)、败血症(OR值4.302)、机械通气(OR值53.958)、H_2受体抑制剂(OR值17.281)、静脉营养≥20天(OR值8.894)、低白蛋白(OR值3.728)、输红细胞次数≥3次(OR值10.459)、应用碳青霉烯类抗生素(OR值15.122)。多因素Logistic回归分析发现8项为BPD发病的独立危险因素,它们分别是异常生育史(OR值1.57)、胎龄<30周(OR值3.10)、体质量<1500g(OR值2.29)、感染性肺炎(OR值2.74)、PDA开放(OR值2.12)、机械通气(OR值9.57)、H_2受体抑制剂(OR值1.36)、应用碳青霉烯类抗生素(OR值2.59)。并专门对接受机械通气的患儿进行BPD危险因素的多因素Logistic回归分析,发现8项为BPD发病的独立危险因素,分别是孕妇产道感染(OR值9.365)、胎龄<30周(OR值53.72)、性别(男婴)(OR值4.43)、感染性肺炎(OR值4.58)、PDA开放(OR值3.56)、机械通气≥2次(OR值9.86)、上机≥10天(OR值195.16)、H_2受体抑制剂(OR值9.56)。
结论早产儿BPD的发病率、病死率均较高。随着胎龄的减少和出生体质量的降低BPD发病率明显升高。多种因素导致BPD的发病率升高,其中,孕妇异常生育史、患儿胎龄<30周、出生体质量<1500g、感染性肺炎(包括呼吸机相关性肺炎)、动脉导管未闭、机械通气、应用碳青霉烯类抗生素和H_2受体抑制剂为早产儿BPD发生的独立危险因素。
Objective To investigate the incidence,clinical features and the risk factors for bronchopulmonary dysplasia (BPD) in premature infants with a prospective cohort study and provide a basis for the integrated intervention of the premature infants with BPD.
Methods Single-center prospective cohort study. Between January 1,2009 and June 01,2010, we paid regular visits to the maternity wards,and neonatal intensive care unit (NICU) for an in-depth study and investigation of all the live births of premature infants. The investigation was conducted in three stages: (1) For those pregnant women whose pregnancy was less than 37 weeks and who showed premature signs, surveys were launched right after their admission to the Obstetrics Wards concerning their history of pregnancy as well as social factors; (2) Surveys were conducted in the maternity wards on the premature infants; ( 3) Investigations were done on the infants between their birth and their corrected gestational age of 40 weeks, including the collection of following information: the morbidity incidence of such major diseases as respiratory problems, infection, brain injury, ROP,and deformity; the premature infants’use of oxygen, antibiotics; the cultured results of their airway secretion; the respiratory parameters of mechanical ventilation; the duration of mechanical ventilation; the number of times of mechanical ventilation; the dynamic observation of chest radiograph; the data of hemoglobin, platelet, serum albumin; the infants’feeding conditions; the application of acid drugs and so on. With the final clinical diagnosis of BPD, we also recorded the prognosis of the disease, the growth and development status and the nutritional status of the BPD group and the non-BPD group between birth and the corrected gestational age of full-term pregnancy. Questionnaire forms have been used to collect the above data. BPD risk factors are screened through Univariate Pearson Chi-square tests or Fisher exact test and multivariate Logistic regression analysis.
Results Among 425 cases of premature infants, 266(62.6%) cases male, and 159(37.4%) cases female, with average gestational age -- 33.9±2.4w, and birth weight -- 2800g ~ 750g, with an average of 1820±462g, of which 97 cases were of very low birth weight infants. Among these infants there were 45 BPD cases with the incidence of 10.59%, 7 of them being death cases (including the deaths after automatic discharge from hospital and weaning mechanical ventilation) with the crude mortality of 15.56%. The potential risk factors of BPD in univariate pearson Chi-Square test were mother not local people (OR 2.634, 95%CI 1.409~4.921; P=0.002) , abnormal generation history (OR 2.824 , 95%CI 1.456～5.480; P=0.002),test-tube baby (OR17.239, 95%CI 6.275～47.361; P=0.000) , birthcanal infection(OR3.642, 95%CI 1.682～7.888; P=0.001), prematurerupture of menbranes (0R4.056,95%CI 1.675～9.817;P=0.001), gestational age<32w (OR3.887, 95%CI 1.217～12.416; P=0.025) , < 2000g (OR6.518 , 95%CI 2.198～19.328; P=0.02501), male(OR2.258,95%CI 1.085～4.696; P=0.026),severe neonatal asphyxia (OR2.783, 95%CI 1.211～6.398; P=0.026), baby’s PH<7.20(0R4.302,95%CI 2.189～8.454; P=0.000), NRDS(OR13.905,95%CI 7.002～27.615;P=0.000) , infectious pneumonia (OR7.347 , 95%CI 3.742～14.425;P=0.000),premature apnea(OR 5.151, 95%CI 2.713～9.780;P=0.000),PDA(OR42.452,95%CI 13.176～136.778; P=0.000),feed intolerance(OR6.377,95%CI3.32～12.240; P=0.000),sepsis(OR4.302,95%CI 2.189～8.454; P=0.000), mechanical ventilation(OR53.958,95%CI 23.055～126.283;P=0.000),administration of histamine(H-2)antagonists(OR17.281,95%CI 8.144～36.672; P=0.000) , parenteral Nutrition≥20 days(OR8.894,95%CI4.339～18.230; P=0.000) , albumin<25g/L(OR3.728,95%CI 1.795～7.744;P=0.000), frequencies of blood transfusion exceed three(OR10.459 , 95%CI 5.311～20.596;P=0.000) , administration of advanced broad-spectrum antibiotics (OR15.122,95%CI 6.793～33.663;P=0.000). Multivariate Logistic regression analysis with backward (Likehood ratio) method found that abnormal generation history(0R1.57,95%CI0.90～3.32; P=0.066) , gestational age<30w(OR3.1,95%CI 1.58～5.47; P=0.001) , < 1500g(OR2.29 , 95%CI 1.32～4.55; P=0.010), infectious pneumonia(OR2.74,95%CI 1.45～4.71;P=0.001) , PDA(OR2.12 , 95%CI 1.12～4.41;P=0.010) , mechanical ventilation(OR9.57,95%CI 4.78～22.26; P=0.000), antacids (OR1.36,95%CI 1.00～3.57; P=0.047),advanced broad-spectrum antibiotics (OR2.59,95%CI 1.23～4.12; P=0.030) were independent risk factors of BPD in premature infants.
Conclusion Among premature infants there is a high BPD incidence and mortality rate. The independent risk factors for the BPD in premature infants are as follows: the abnormal pregnancy and birth history of pregnant women, the infants’gestational age less than 30 weeks, the birth weight less than 1500g, infectious pneumonia (including ventilator-related pneumonia), patent ductus arteriosus, mechanical ventilation, and the use of advanced broad-spectrum antibiotics and antacids.
引文
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[34]王晓蕾,薛辛东.促红细胞生成素与支气管肺发育不良[J].实用儿科临床杂志,2006,21(24):1734-1735.
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[41]吕芳.妊高征严重并发症对围生儿结局的影响[J].现代医院,2007,7(4):31-34.
[42]王伟.早产主要因素及对早产儿的影响[J].中国实用妇科与产科杂志,2003,2(19):93—94.
[43] Kitaw Demissie, George G Rhoads, Cande V Ananth,et al. Trends in Preterm Birth and Neonatal Mortality among Blacks and Whites in the United States from 1989 to 1997[J]. Am J Epidemiol,2001,154(4):307-315.
[44]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社.1999 :878,333,339.
[45]杨杰,杨默,霍泰辉等.高氧性肺损伤大鼠骨髓巨核细胞集落形成能力与肺组织巨核细胞数目[J].中华儿科杂志.1998,36(7):398-400.
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[1] Michele C. Walsh, Stanley Szefler, Jonathan Davis, et al.Summary Proceedings From the Bronchopulmonary Dysplasia Group [J]. Pediatrics, 2006,117(3):S52-S56.
[2] Short EJ, Klein NK, Lewis BA, et al. Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes[J]. Pediatrics, 2003,112:e359-e359.
[3] Aly H. Is there strategy for preventing bronchopulmonary dysplasia? Absence of evidence is not evidence of absence[J]. Pediatrics, 2007,119:818-820.
[4] Speer CP. Pulmonary inflammation and bronchopulmonary dysplasia[J]. J Perinatol, 2006,26:Suppl:S57-S62.
[5] Askie LM, Henderson-Smart DJ, Irwig L,et al. Oxygen-saturation targets and outcomes in extremely preterm infants[J]. N Engl J Med, 2003,349:959-967.
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[7] Aly H, Massaro AN, Patel K, et al. Is it safer to intubate premature infants in the delivery room? [J]. Pediatrics, 2005,115:1660-1665.
[8] Booth C, Premkumar MH, Yannoulis A, et al. Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery[J]. Arch Dis Child Fetal Neonatal Ed, 2006,91:F398-F402.
[9] Miller JD, Carlo WA. Safety and effectiveness of permissive hypercapnia in the preterm infant[J]. Curr Opin Pediatr, 2007,19:142-144.
[10] Thome UH, Carlo WA, Pohlandt F. Ventilation strategies and outcome in randomised trials of high frequency ventilation[J]. Arch Dis Child Fetal Neonatal Ed ,2005,90:F466-F473.
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[32] Nagatak H,Iwasaki Y,Yamada T,et al.Over expression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury[J].Respir Med,2006,101(4):800-807.
[33] Wang X , Wang Y , Kin HP , et al.Carbon monoxide protects against hyperoxia-induced endothelial cell apoptosis by inhibiting reactive oxygen species formation[J].J Biol Chem,2006,29(2):321-329.
[34]王晓蕾,薛辛东.促红细胞生成素与支气管肺发育不良[J].实用儿科临床杂志,2006,21(24):1734-1735.
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[41]吕芳.妊高征严重并发症对围生儿结局的影响[J].现代医院,2007,7(4):31-34.
[42]王伟.早产主要因素及对早产儿的影响[J].中国实用妇科与产科杂志,2003,2(19):93—94.
[43] Kitaw Demissie, George G Rhoads, Cande V Ananth,et al. Trends in Preterm Birth and Neonatal Mortality among Blacks and Whites in the United States from 1989 to 1997[J]. Am J Epidemiol,2001,154(4):307-315.
[44]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社.1999 :878,333,339.
[45]杨杰,杨默,霍泰辉等.高氧性肺损伤大鼠骨髓巨核细胞集落形成能力与肺组织巨核细胞数目[J].中华儿科杂志.1998,36(7):398-400.
[46] Lisa G Smithers,Robert A Gibson,Andrew Mcphee,Maria Makrides.Effect of long-chain polyunsaturated fatty acid supplementation of preterm infants on disease risk and neurodevelopment:a systematic review of randomized controlledtrials[J]. American Journal of Clinical Nutrition,2008,87( 4): 912-920.
[47]连朝辉,杨传忠,朱小瑜.支气管肺发育不良的早期诊治及预后研究[J].小儿急救医学2004,11(1):39-40.
[48] Nathaniel R Payne MDa,Meena La Corte MDb, Shyan Sun MDc.Evaluation and Development of Potentially Better Practices to Reduce Bronchopulmonary Dysplasia in Very Low Birth Weight Infants[J]. Pediatrics,2006,118:S65-S72.
[1] Michele C. Walsh, Stanley Szefler, Jonathan Davis, et al.Summary Proceedings From the Bronchopulmonary Dysplasia Group [J]. Pediatrics, 2006,117(3):S52-S56.
[2] Short EJ, Klein NK, Lewis BA, et al. Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes[J]. Pediatrics, 2003,112:e359-e359.
[3] Aly H. Is there strategy for preventing bronchopulmonary dysplasia? Absence of evidence is not evidence of absence[J]. Pediatrics, 2007,119:818-820.
[4] Speer CP. Pulmonary inflammation and bronchopulmonary dysplasia[J]. J Perinatol, 2006,26:Suppl:S57-S62.
[5] Askie LM, Henderson-Smart DJ, Irwig L,et al. Oxygen-saturation targets and outcomes in extremely preterm infants[J]. N Engl J Med, 2003,349:959-967.
[6] Van Marter LJ, Allred EN, Pagano M, et al. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? [J]. Pediatrics, 2000,105:1194-1201.
[7] Aly H, Massaro AN, Patel K, et al. Is it safer to intubate premature infants in the delivery room? [J]. Pediatrics, 2005,115:1660-1665.
[8] Booth C, Premkumar MH, Yannoulis A, et al. Sustainable use of continuous positive airway pressure in extremely preterm infants during the first week after delivery[J]. Arch Dis Child Fetal Neonatal Ed, 2006,91:F398-F402.
[9] Miller JD, Carlo WA. Safety and effectiveness of permissive hypercapnia in the preterm infant[J]. Curr Opin Pediatr, 2007,19:142-144.
[10] Thome UH, Carlo WA, Pohlandt F. Ventilation strategies and outcome in randomised trials of high frequency ventilation[J]. Arch Dis Child Fetal Neonatal Ed ,2005,90:F466-F473.
[11] Keszler M, Abubakar K. Volume guarantee ventilation[J]. Clin Perinatol, 2007,34:107-116.
[12] Eichenwald EC, Stark AR. Are postnatal steroids ever justified to treat severebronchopulmonary dysplasia? [J]. Arch Dis Child Fetal Neonatal Ed, 2007,92:F334-F337.
[13] Walsh MC, Yao Q, Horbar JD, Carpenter JH, et al. Changes in the use of postnatal steroids for bronchopulmonary dysplasia in 3 large neonatal networks[J]. Pediatrics, 2006,118:e1328-e1335.
[14] Watterberg KL, Gerdes JS, Cole CH, et al. Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial[J]. Pediatrics, 2004,114:1649-1657.
[15]Rademaker KJ, Uiterwaal CS, Groenendaal F, et al. Neonatal hydrocortisone treatment: neurodevelopmental outcome and MRI at school age in preterm-born children[J]. J Pediatr, 2007,150:351-357.
[16]Watterberg KL , Shaffer ML , Mishefske MJ , et al. Growth and neurodevelopmental outcome after early low-dose hydrocortisone treatment in extremely low birth weight infants[J]. Pediatrics, 2007,120:40-48.
[17] Ballard PL, Gonzales LW, Godinez RI, et al. Surfactant composition and function in a primate model of infant chronic lung disease: effects of inhaled nitric oxide[J]. Pediatr Res, 2006,59:157-162.
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