Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates

 

Abstract

Background

Cysteine is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity and acidifies the solution, thereby increasing calcium and phosphate solubility and potentially improving bone mineralization.

Objectives

To determine the effects of supplementing PN with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes.

Search methods

The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (The Cochrane Library) and recent abstracts from the Society for Pediatric Research/ American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were originally searched in 2005. In August 2009 updated searches were done of The Cochrane Library, MEDLINE (search via PubMed), CINAHL and EMBASE from 2006 to 2009.

Selection criteria

All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed.

Data collection and analysis

The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD).

Main results

Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (≤ 1000 grams).

Growth was not significantly affected by cysteine supplementation (1 trial) or by N-acetylcysteine supplementation (1 trial). Nitrogen retention was significantly increased by cysteine supplementation (4 trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants).

Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH.

Authors' conclusions

Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance. However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants.

 

Plain language summary

Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates

Sick or preterm newborn infants may require intravenous nutrition, including intravenous administration of solutions containing amino acids. Newborn infants need cysteine (an amino acid) for growth under certain conditions. Cysteine may decrease the chance of liver disease and brittle bones. This systemic review was done to analyze whether adding cysteine (or related compounds) to intravenous nutrition affects growth and other outcomes in newborn infants. Five trials studied the effects of adding cysteine to intravenous nutrition that did not contain cysteine. Addition of cysteine significantly improved the babies' ability to build body proteins (analyzed in four studies); however, it did not improve growth (analyzed in one study); no other outcomes were available. One large randomized trial studied the effect of adding another chemical, N-acetyl-cysteine, to intravenous nutrition that already contained cysteine. This study showed no benefit and no toxicity of this intervention. We conclude that present data are insufficient to justify routine addition of cysteine to the intravenous nutrition of newborn infants that does not contain cysteine. Available evidence does not support routine addition of N-acetylcysteine to intravenous nutrition of newborn infants containing cysteine.

 

摘要

背景

給予非腸道餵食的新生兒半胱氨酸(Cysteine), cystine或 Nacetylcysteine補給

Cysteine是glutathione的前驅物質，為一種抗氧化劑，可減少氧化造成的損傷。在腸外營養(PN)中添加cysteine，可以減少因腸外營養得到的methionine的量，進而減少肝毒性和溶液酸化，提高鈣和磷的溶解度，並可能改善骨骼礦化。

目標

決定腸外營養補充品(cysteine, cystine 或 其前驅物 Nacetylcysteine)在新生兒成長、短期與長期之效果。

搜尋策略

採用Cochrane Neonatal Review Group標準的搜尋方式。搜尋MEDLINE, EMBASE, Cochrane中心註冊的對照試驗(The Cochrane Library)和來自以下研究單位的近期(2005)摘要(the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition)。2009年八月完成以下資料庫的更新搜尋：The Cochrane Library, MEDLINE (search via PubMed), CINAHL and EMBASE from 2006 to 2009.

選擇標準

隨機或半隨機對照試驗檢驗新生兒腸外營養給予cysteine, cystine or Nacetylcysteine的效果。

資料收集與分析

採用Cochrane Collaboration和Neonatal Review Group的標準方法。統計分析包含相對危險比、相對危險差和加權均數差(WMD)。

主要結論

6個試驗符合收案標準。在這些試驗中大多數患者都是早產。五個小的試驗評估短期在不含cysteine腸外營養中補充cysteine。一個大型的多中心隨機對照試驗，評估極低出生體重嬰兒(≦1000克)短期給予含有cysteine的腸外營養中補充Nacetylcysteine之效果。補充cysteine(1個試驗)和補充Nacetylcysteine(1個試驗)嬰兒的生長無明顯影響。在給予cysteine補充組的氮滯留有顯著增加(4個試驗)(WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, 包含73名早產兒)。血漿中cysteine的量在給予cysteine補充組有顯著的增加，而補充Nacetylcysteine組則沒有。補充Nacetylcysteine組對於胎齡36周後的死亡風險，肺支氣管發育不良(BPD)，死亡或支氣管肺發育不良，早產兒視網膜病變(ROP)，嚴重的早產兒視網膜病變，需要手術的壞死性腸炎，腦室周圍白質軟化，腦室內出血(IVH)，或嚴重腦室出血則皆沒有顯著影響。

作者結論

目前來自隨機對照試驗的證據顯示，給予早產兒不含cysteine的腸道外營養時，常規短期補充cysteine chloride有助於改善氮平衡。但沒有足夠的證據來評估補充cysteine的風險，特別是在給予cysteine頭兩個星期(目前已有報告指出會產生代謝性酸中毒)。一個大型隨機對照試驗提供的證據顯示，目前尚並不支持在極低出生體重嬰兒含有cysteine的腸外營養中，常規補充Nacetylcysteine。

翻譯人

本摘要由臺中榮民總醫院薛榮華翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

給予非腸道營養的新生兒半胱氨酸(Cysteine), cystine或 Nacetylcysteine補給：病嬰或早產新生兒可能需要靜脈營養，包括靜脈注射含有胺基酸的溶液。新生兒在一些情況下需要cysteine(一種胺基酸)幫助成長。cysteine可降低肝臟疾病和骨質易碎的機會。這種系統性的回溯研究分析在靜脈營養中添加cysteine(或相關化合物)，是否影響新生兒的生長和造成其他結果。有五個試驗研究在分析不含cysteine的靜脈營養中添加cysteine的效果。添加cysteine有意義的提高了嬰兒製造體內蛋白質的能力(有四份研究分析)，但卻沒有改善成長(有一份研究分析)。一個大型隨機試驗研究在已含有cysteine的靜脈營養中添加Nacetylcysteine。研究顯示此舉無益也無害。我們的結論是現有的數據還不足以判斷給予新生兒不含cysteine的靜脈營養中常規添加cysteine的影響。現有的證據並不支持常規添加Nacetylcysteine到已含有cysteine的靜脈營養中。