增补维生素A预防支气管肺发育不良的Meta分析
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摘要
目的:系统评价早产儿生后早期增补维生素A预防支气管肺发育不良(BPD)的有效性和安全性。方法:计算机检索PubMed、Embase、Cochrane Library、中国生物医学文献数据库、万方、中国知网、维普等数据库关于早产儿生后早期增补维生素A预防BPD的随机对照试验(RCT),检索时间均从建库至2018年7月1日,用RevMan5.3软件进行Meta分析,并根据不同给药途径进行亚组分析。结果:最终纳入9个RCT,含1 409例新生儿。结果显示:肌内注射增补维生素A时矫正胎龄(PMA)36周吸氧率更低(RR=0.85,95%CI:0.73～0.98,P=0.03);两组在PMA36周病死率、28 d吸氧率、28 d病死率、败血症发生率方面差异无统计学意义。口服时两组间PMA36周吸氧率、PMA36周病死率、28 d吸氧率、28 d病死率差异均无统计学意义。静脉注射时28 d吸氧率更低,差异无统计学意义。增补维生素A未增加不良反应的发生。结论:肌内注射增补维生素A可以降低PMA36周吸氧率,对28 d吸氧率无明显影响,口服及静脉注射增补维生素A预防BPD的疗效仍需更多高质量研究予以明确,常规剂量增补维生素A是安全的。
Objective:To systematically assess the efficacy and safety of early supplementation of vitamin A in preterm infants in the prevention agaiust bronchopulmonary dysplasia.Methods:Databases including PubMed, Embase, Cochrane Library, CBM, WanFang Data, CNKI and VIP were searched to collect randomized controlled trials(RCTs) about early supplementation of vitamin A in preterm infants in the prevention of bronchopulmonary dysplasia from inception to July 1, 2018. Then Meta analysis was conducted by RevMan 5.3 software.Results:A total of 9 RCTs, involving 1 409 neonates were included. The results showed that, when supplementation of vitamin A by intramuscular injection,the incidence of oxygen inhalation at 36 weeks' postmenstrual age was lower( RR = 0.85,95%CI:0.73 to 0.98,P = 0.03), and there were no statistically significant differences between the two groups on the incidence of mortality at 36 weeks' postmenstrual age, oxygen inhalation at 28 days, mortality at 28 days, sepsis. When supplementation of vitamin A orally, no significant differences between the two groups were detected on the incidence of oxygen inhalation at 36 weeks' postmenstrual age, mortality at 36 weeks' postmenstrual age, oxygen inhalation at 28 days, mortality at 28 days. Given by intravenous injection decreased the rate of oxygen inhalation at 28 days without statistically significant difference. Vitamin A supplementation didn't increase the occurrence of adverse reactions.Conclusions:Supplementation of vitamin A by intramuscular injection decreases the incidence of oxygen inhalation at 36 weeks' postmenstrual age, but there is no significant difference on the incidence of oxygen inhalation at 28 days. More high quality studies are needed to verify the efectiveness of supplementation of vitamin A orally and intravenously for prevention agaiust bronchopulmonary dysplasia. It is safe when vitamin A is supplementated by routine does.
Objective:To systematically assess the efficacy and safety of early supplementation of vitamin A in preterm infants in the prevention agaiust bronchopulmonary dysplasia.Methods:Databases including PubMed, Embase, Cochrane Library, CBM, WanFang Data, CNKI and VIP were searched to collect randomized controlled trials(RCTs) about early supplementation of vitamin A in preterm infants in the prevention of bronchopulmonary dysplasia from inception to July 1, 2018. Then Meta analysis was conducted by RevMan 5.3 software.Results:A total of 9 RCTs, involving 1 409 neonates were included. The results showed that, when supplementation of vitamin A by intramuscular injection,the incidence of oxygen inhalation at 36 weeks' postmenstrual age was lower( RR = 0.85,95%CI:0.73 to 0.98,P = 0.03), and there were no statistically significant differences between the two groups on the incidence of mortality at 36 weeks' postmenstrual age, oxygen inhalation at 28 days, mortality at 28 days, sepsis. When supplementation of vitamin A orally, no significant differences between the two groups were detected on the incidence of oxygen inhalation at 36 weeks' postmenstrual age, mortality at 36 weeks' postmenstrual age, oxygen inhalation at 28 days, mortality at 28 days. Given by intravenous injection decreased the rate of oxygen inhalation at 28 days without statistically significant difference. Vitamin A supplementation didn't increase the occurrence of adverse reactions.Conclusions:Supplementation of vitamin A by intramuscular injection decreases the incidence of oxygen inhalation at 36 weeks' postmenstrual age, but there is no significant difference on the incidence of oxygen inhalation at 28 days. More high quality studies are needed to verify the efectiveness of supplementation of vitamin A orally and intravenously for prevention agaiust bronchopulmonary dysplasia. It is safe when vitamin A is supplementated by routine does.
引文
1.Stoll BJ,Hansen NI,Bell EF,et al.Trends in Care Practices,morbidity,and mortality of extremely preterm neonates,1993-2012[J].JAMA,2015,314(10):1 039-1 051.
2.Thébaud B,Kourembanas S.Can we cure bronchopulmonary dysplasia?[J].J Pediatr,2017,191:12-14.
3.Strueby L,Thébaud B.Novel therapeutics for bronchopulmonary dysplasia[J].Curr Opin Pediatr,2018,30(3):378-383.
4.杨雨晨,毛健,李娟.早产儿支气管肺发育不良的药物治疗研究进展[J].Zhongguo Dang Dai Er Ke Za Zhi,2018,20(01):67-71.
5.Shenai JP,Kennedy KA,Chytil F,et al.Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia[J].J Pediatr,1987,111(2):269-277.
6.Uberos J,Miras-Baldo M,Jerez-Calero A,et al.Effectiveness of vitamin A in the prevention of complications of prematurity[J].Pediatr Neonatol,2014,55(5):358-362.
7.Tolia VN,Murthy K,McKinley PS,et al.The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants[J].JAMA Pediatr,2014,168(11):1 039-1 044.
8.Couroucli XI,Placencia JL,Cates LA,et al.Should we still use vitamin A to prevent bronchopulmonary dysplasia?[J].J Perinatol,2016,36(8):581-585.
9.Higgins JPT GS.Higgins JPT,Green S(editors).Cochrane hand-book for systematic reviews of interventions version 5.1.0[updated March 2011].The Cochrane Collaboration,2011.Available from http://handbook.cochrane.org.
10.Kiatchoosakun P,Jirapradittha J,Panthongviriyakul MC,et al.Vitamin A supplementation for prevention of bronchopulmonary dysplasia in very-low-birth-weight premature thai infants:a randomized trial[J].J Med Assoc Thai,2014,97 Suppl 10:S82-88.
11.Mactier H,McCulloch DL,Hamilton R,et al.Vitamin Asupplementation improves retinal function in infants at risk of retinopathy of prematurity[J].J Pediatr,2012,160(6):954-959.e1.
12.Pearson E,Bose C,Snidow T,et al.Trial of vitamin Asupplementation in very low birth weight infants at risk for bronchopulmonary dysplasia[J].J Pediatr,1992,121(3):420-427.
13.Ravishankar C,Nafday S,Green RS,et al.A trial of vitamin A therapy to facilitate ductal closure in premature infants[J].J Pediatr,2003,143(5):644-648.
14.Tyson JE,Wright LL,Oh W,et al.Vitamin A supplementation for extremely-low-birth-weight infants.National Institute of Child Health and Human Development Neonatal Research Network[J].N Engl J Med,1999,340(25):1 962-1 968.
15.Wardle SP,Hughes A,Chen S,et al.Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease[J].Arch Dis Child Fetal Neonatal Ed,2001,84(1):F9-9F13.
16.Werkman SH,Peeples JM,Cooke RJ,et al.Effect of vitamin A supplementation of intravenous lipids on early vitamin A in-take and status of premature infants[J].Am JClin Nutr,1994,59(3):586-592.
17.汤晶晶,李志飞,邹英杰,等.大剂量维生素A预防新生儿支气管肺发育不良的临床研究[J].健康研究,2016,36(05):533-535.
18.Bancalari E,Jain D.Bronchopulmonary Dysplasia:Can We Agree on a Definition?[J].Am J Perinatol,2018,35(6):537-540.
19.Walsh MC,Yao Q,Gettner P,et al.Impact of a physiologic definition on bronchopulmonary dysplasia rates[J].Pediatrics,2004,114(5):1 305-1 311.
20.梁穗新,王一飞,何少茹.早产儿生理性支气管肺发育不良研究进展[J].中华实用儿科临床杂志,2016,(2):158-160.
21.Jobe AH,Bancalari E.Bronchopulmonary dysplasia[J].Am J Respir Crit Care Med,2001,163(7):1 723-1 729.
22.Stevens GA,Bennett JE,Hennocq Q,et al.Trends and mortality effects of vitamin A deficiency in children in138 low-income and middle-income countries between1991 and 2013:a pooled analysis of population-based surveys[J].Lancet Glob Health,2015,3(9):e528-536.
23.刘登礼,何必子.不同胎龄和不同出生体重新生儿出生时血清维生素A水平测定[J].中国新生儿科杂志,2015,30(05):358-360.
24.McDonald SL,Savy M,Fulford AJ,et al.A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses:the gambia protocol[J].BMC Pediatr,2014,14:92.
25.James ML,Ross AC,Nicola T,et al.VARA attenuates hyperox-ia-induced impaired alveolar development and lung function in newborn mice[J].Am J Physiol Lung Cell Mol Physiol.2013.304(11):L803-812.
26.陈丹丹,朱雪萍.早产儿生后补充维生素A可预防支气管肺发育不良:基于6篇随机对照试验的Meta分析[J].中国循证儿科杂志,2017,12(06):429-433.
27.Deep GB,Bansal A,Kabra NS.Role of vitamin A supplementation in prevention of Bronchopulmonary dysplasia in ex-tremely low birth weight neonates:A systematic review of randomized trials[J].J Matern Fetal Neonatal Med,2018.DOI:10.1080/14767058.2018.1441282.
28.Schwartz E,Zelig R,Parker A,et al.Vitamin A Supplementation for the Prevention of Bronchopulmonary Dysplasia in Pre-term Infants:An Update[J].Nutr Clin Pract,2017,32(3):346-353.
2.Thébaud B,Kourembanas S.Can we cure bronchopulmonary dysplasia?[J].J Pediatr,2017,191:12-14.
3.Strueby L,Thébaud B.Novel therapeutics for bronchopulmonary dysplasia[J].Curr Opin Pediatr,2018,30(3):378-383.
4.杨雨晨,毛健,李娟.早产儿支气管肺发育不良的药物治疗研究进展[J].Zhongguo Dang Dai Er Ke Za Zhi,2018,20(01):67-71.
5.Shenai JP,Kennedy KA,Chytil F,et al.Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia[J].J Pediatr,1987,111(2):269-277.
6.Uberos J,Miras-Baldo M,Jerez-Calero A,et al.Effectiveness of vitamin A in the prevention of complications of prematurity[J].Pediatr Neonatol,2014,55(5):358-362.
7.Tolia VN,Murthy K,McKinley PS,et al.The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants[J].JAMA Pediatr,2014,168(11):1 039-1 044.
8.Couroucli XI,Placencia JL,Cates LA,et al.Should we still use vitamin A to prevent bronchopulmonary dysplasia?[J].J Perinatol,2016,36(8):581-585.
9.Higgins JPT GS.Higgins JPT,Green S(editors).Cochrane hand-book for systematic reviews of interventions version 5.1.0[updated March 2011].The Cochrane Collaboration,2011.Available from http://handbook.cochrane.org.
10.Kiatchoosakun P,Jirapradittha J,Panthongviriyakul MC,et al.Vitamin A supplementation for prevention of bronchopulmonary dysplasia in very-low-birth-weight premature thai infants:a randomized trial[J].J Med Assoc Thai,2014,97 Suppl 10:S82-88.
11.Mactier H,McCulloch DL,Hamilton R,et al.Vitamin Asupplementation improves retinal function in infants at risk of retinopathy of prematurity[J].J Pediatr,2012,160(6):954-959.e1.
12.Pearson E,Bose C,Snidow T,et al.Trial of vitamin Asupplementation in very low birth weight infants at risk for bronchopulmonary dysplasia[J].J Pediatr,1992,121(3):420-427.
13.Ravishankar C,Nafday S,Green RS,et al.A trial of vitamin A therapy to facilitate ductal closure in premature infants[J].J Pediatr,2003,143(5):644-648.
14.Tyson JE,Wright LL,Oh W,et al.Vitamin A supplementation for extremely-low-birth-weight infants.National Institute of Child Health and Human Development Neonatal Research Network[J].N Engl J Med,1999,340(25):1 962-1 968.
15.Wardle SP,Hughes A,Chen S,et al.Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease[J].Arch Dis Child Fetal Neonatal Ed,2001,84(1):F9-9F13.
16.Werkman SH,Peeples JM,Cooke RJ,et al.Effect of vitamin A supplementation of intravenous lipids on early vitamin A in-take and status of premature infants[J].Am JClin Nutr,1994,59(3):586-592.
17.汤晶晶,李志飞,邹英杰,等.大剂量维生素A预防新生儿支气管肺发育不良的临床研究[J].健康研究,2016,36(05):533-535.
18.Bancalari E,Jain D.Bronchopulmonary Dysplasia:Can We Agree on a Definition?[J].Am J Perinatol,2018,35(6):537-540.
19.Walsh MC,Yao Q,Gettner P,et al.Impact of a physiologic definition on bronchopulmonary dysplasia rates[J].Pediatrics,2004,114(5):1 305-1 311.
20.梁穗新,王一飞,何少茹.早产儿生理性支气管肺发育不良研究进展[J].中华实用儿科临床杂志,2016,(2):158-160.
21.Jobe AH,Bancalari E.Bronchopulmonary dysplasia[J].Am J Respir Crit Care Med,2001,163(7):1 723-1 729.
22.Stevens GA,Bennett JE,Hennocq Q,et al.Trends and mortality effects of vitamin A deficiency in children in138 low-income and middle-income countries between1991 and 2013:a pooled analysis of population-based surveys[J].Lancet Glob Health,2015,3(9):e528-536.
23.刘登礼,何必子.不同胎龄和不同出生体重新生儿出生时血清维生素A水平测定[J].中国新生儿科杂志,2015,30(05):358-360.
24.McDonald SL,Savy M,Fulford AJ,et al.A double blind randomized controlled trial in neonates to determine the effect of vitamin A supplementation on immune responses:the gambia protocol[J].BMC Pediatr,2014,14:92.
25.James ML,Ross AC,Nicola T,et al.VARA attenuates hyperox-ia-induced impaired alveolar development and lung function in newborn mice[J].Am J Physiol Lung Cell Mol Physiol.2013.304(11):L803-812.
26.陈丹丹,朱雪萍.早产儿生后补充维生素A可预防支气管肺发育不良:基于6篇随机对照试验的Meta分析[J].中国循证儿科杂志,2017,12(06):429-433.
27.Deep GB,Bansal A,Kabra NS.Role of vitamin A supplementation in prevention of Bronchopulmonary dysplasia in ex-tremely low birth weight neonates:A systematic review of randomized trials[J].J Matern Fetal Neonatal Med,2018.DOI:10.1080/14767058.2018.1441282.
28.Schwartz E,Zelig R,Parker A,et al.Vitamin A Supplementation for the Prevention of Bronchopulmonary Dysplasia in Pre-term Infants:An Update[J].Nutr Clin Pract,2017,32(3):346-353.