Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review

BMC Pediatrics

Abhay K Lodha⁴  Helen Lee Robertson²  Huma Shaireen¹  Harish Amin¹  Alexander Lyttle³  Kevin Mitchell³ 

[1] Section of Neonatology, Department of Paediatrics, University of Calgary, Foothills Medical Centre, Calgary, AB, Canada;Health Sciences Library, Health Sciences Centre, University of Calgary, Calgary, Canada;Department of Paediatrics, University of Calgary, Alberta Children’s Hospital, Calgary T2N2T9, AB, Canada;Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada

关键词: Premature infant;    L-arginine;    Necrotizing enterocolitis;   

Others  :  1137294
DOI  :  10.1186/1471-2431-14-226

 received in 2014-07-23, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

Background

Hypoxic-ischemic injury is thought to play a significant role in necrotizing enterocolitis (NEC). Nitric Oxide (NO) is the principal inhibitory neurotransmitter in the gut and is involved in regulation of mucosal blood flow and maintenance of mucosal integrity. NO is synthesized from L-arginine by NO synthases. Our primary objective was to determine the effectiveness of supplemental L-arginine versus placebo in prevention of NEC in preterm infants ≤ 34 weeks gestational age by systematic review of published randomized controlled trials (RCTs).

Methods

This review included RCTs in which L-arginine was administered as a supplement to neonates to prevent NEC. Searches were conducted in OVID MEDLINE, EMBASE, PubMed, and CINAHL from their dates of inception to July, 2014. Inclusion criteria were informed parental consent, neonates born at ≤ 34 weeks gestation, and birth weight ≤ 1500 g. Exclusion criteria included neonates with severe congenital anomalies and inborn errors of metabolism. Incidence of NEC was the primary outcome measure. Whole data were analyzed by RevMan 5.1 (Update Software, Oxford, UK). Outcome data were analyzed to determine risk ratios, number needed to treat, confidence intervals, and test for overall effect.

Results

Two trials including 425 neonates were eligible for this review. Of these, 235 neonates were included in the study. L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02). A similar finding was identified for all stages of NEC (60% reduction, RR 0.40, 95% CI 0.23 to 0.69, NNT = 5) (P = 0.001). At age 3 yrs, there was no significant difference between the 2 groups in terms of any neurodevelopmental disability (RR 0.65; 95% CI 0.23-1.83, P = 0.41).

Conclusions

L-arginine supplementation appears to be protective in prevention of NEC in preterm infants and without any significant impact on neurodevelopmental outcomes at 36 months of corrected age. With the addition of the results of one more study to the literature, an intriguing role for L-arginine supplementation continues to gain support. However, large multi-centre RCTs are needed before this can become common practice.

【 授权许可】

   
2014 Mitchell et al.; licensee BioMed Central Ltd.

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