Interventions for prevention of neonatal hyperglycemia in very low birth weight infants

 

Abstract

Background

Among very low birth weight (VLBW) infants, early neonatal hyperglycemia is common and is associated with increased risks for death and major morbidities. It is uncertain whether hyperglycemia per se is a cause of adverse clinical outcomes or whether outcomes can be improved by preventing hyperglycemia.

Objectives

To assess effects on clinical outcomes of interventions for preventing hyperglycemia in VLBW neonates receiving full or partial parenteral nutrition.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, issue 4 of 12, 2011; MEDLINE (1966 to April 2011); EMBASE (1980 to April 2011); CINAHL (1982 to Nov 2008); abstracts of Pediatric Academic Societies 2000 to 2011 and European Society for Pediatric Research 2005 to 2010.

Selection criteria

Randomized or quasi-randomized controlled trials of interventions for prevention of hyperglycemia in neonates with birth weight < 1500 g or gestational age < 32 wk.

Data collection and analysis

Two review authors independently selected studies for eligibility and extracted data on study design, methods, clinical features, and treatment outcomes. Included trials were assessed for blinding of randomization, intervention and outcome measurement, and completeness of follow-up. Treatment effect measures for categorical outcomes were relative risk and risk difference, and for continuous outcomes, mean difference, each with their 95% confidence intervals.

Main results

We detected four eligible trials. Two trials compared lower versus higher rates of glucose infusion in the early postnatal period. These trials were too small to assess effects on mortality or major morbidities. Two trials, one a moderately large multicentre trial (NIRTURE, Beardsall 2008), compared insulin infusion with standard care. Insulin infusion reduced hyperglycemia but increased death before 28 days and hypoglycemia. Reduction in hyperglycemia was not accompanied by significant effects on major morbidities; effects on neurodevelopment are awaited.

Authors' conclusions

Glucose infusion rate: There is insufficient evidence from trials comparing lower with higher glucose infusion rates to inform clinical practice. Large randomized trials are needed, powered on clinical outcomes including death, major morbidities and adverse neurodevelopment.

Insulin infusion: The evidence reviewed does not support the routine use of insulin infusions to prevent hyperglycemia in VLBW neonates. Further randomized trials of insulin infusion may be justified. They should enrol extremely low birth weight neonates at very high risk for hyperglycemia and neonatal death. They might use real time glucose monitors if these are validated for clinical use. Refinement of algorithms to guide insulin infusion is needed to enable tight control of glucose concentrations within the target range.

 

Plain language summary

Interventions for prevention of neonatal hyperglycemia in very low birth weight infants

Blood sugar levels higher than usually seen in full term infants are frequently seen in babies born very early (before 32 weeks gestation) or with very low birth weight (< 1500 grams) and who are fed totally or partially by vein. Several types of adverse outcomes have been associated with high blood sugar levels including increased risks for death, infections, vision problems, and bleeding into the brain. It is not known if prevention of high blood sugar levels improves those complications and, if so, which intervention is best. Possible options include restriction of the amount of sugar delivered by vein to nourish the baby or administration of insulin. Trials which compared lower with higher amounts of sugar delivered by vein were too small to determine effects on the health outcomes of the babies. Insulin was found to reduce the number of babies who developed high blood sugar levels, but the health outcomes of the babies were not improved. In fact, insulin infusion was associated with an increased risk of death before 28 days of age.

 

摘要

背景

極低體重嬰兒高血糖的預防措施

早期的高血糖在極低體重嬰兒是常見的,且會增加死亡和發病率的風險。 不管是高血糖是否為臨床不佳結果的原因,或者能否藉由預防高血糖來改善預後,這些都是不確知的。

目標

評估在極低出生體重新生兒接受全部或部分經靜脈營養來防止高血糖發生的處置措施對臨床療效的影響。

搜尋策略

我們搜尋了Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library資料庫, issue 4 2008; MEDLINE (1966  Nov 2008); EMBASE (1980  Nov 2008); CINAHL (1982  Nov 2008); Pediatric Academic Societies 2000 – 2008 摘要以及 European Society for Paediatric Research 2005 2008相關的文獻資料。

選擇標準

以隨機或半隨機對照試驗方法評估在出生體重小於1500公克或是出生週數小於32週的嬰兒預防高血糖發生的處置之試驗。

資料收集與分析

兩位回顧作者獨立選擇符合納入條件的試驗，並收集其研究設計、方法、臨床特點和治療結果的相關數據。納入的試驗其評估項目包括致盲隨機分配方法、處置和結果的評量和後續追蹤的完整性。治療效果的評估，在結果是項目者採相對風險和風險差異，在結果為連續數值和平均差採95％信賴區間。

主要結論

我們找到四個合格的試驗。其中有兩個試驗是比較較低與較高的葡萄糖輸液輸注率在新生兒早期的影響。但對於評估死亡率的影響或重大疾病發病率方面，這些試驗規模太小。另外兩個試驗，其中一個是中等大小的多中心試驗(NIRTURE，Beardsall 2008年)，比較給予胰島素輸注和標準照護之差異。結果顯示給予胰島素輸注能減少高血糖，但增加了28天內死亡以及低血糖的發生。減少高血糖的並沒有顯著影響主要疾病的發病率，對於神經發育的影響尚待結果。

作者結論

關於葡萄糖的輸注速率：在臨床照護方面，由目前的試驗沒有足夠的證據來建議要採用較低或較高的葡萄糖輸注率。還需要大型的隨機試驗，特別著重在包括死亡、主要疾病發病率和神經發育不良方面的臨床結果。關於胰島素的輸注方面：回顧的證據無法支持在極低體重的新生兒常規使用胰島素輸注來預防高血糖的發生。但進一步去設計關於給予胰島素的隨機試驗也許是合理的。試驗中應該包括具高血糖的高風險和新生兒死亡的極低出生體重兒。可使用經過驗證臨床可使用的即時血糖監測，需要經由換算來嚴格控制胰島素的輸注量而使得血糖濃度控制在目標範圍內。

翻譯人

本摘要由馬偕醫院林千裕翻譯。

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

總結

非常早期出生(妊娠32週之前)或極低出生體重(1500公克)的嬰兒和在完全使用或接受部分靜脈輸液的嬰兒，其血糖值常會較足月的嬰兒偏高。幾種不良後果都與高血糖值相關，包括增加死亡風險、感染、視力問題和腦內出血。目前還不清楚是否可藉著預防高血糖而減少併發症的發生，以及如果有幫助，哪些處置是最好的。納入試驗的可行項目包括限制經靜脈輸液的糖量或胰島素的給予量。設計分別給予較低與較高糖量的靜脈點滴試驗為太小的試驗設計，以至於不能確定對嬰兒健康預後的影響。胰島素的使用減少了嬰兒發生高血糖的情形，但是對於他們將來的健康情形並無改善。事實上，胰島素的輸注與出生28天內的死亡危險增加有關。