Delivery room glucose to reduce the risk of admission hypoglycemia in preterm infants: a systematic literature review

In order to mitigate early hypoglycemia in preterm infants, some clinicians have recently explored interventions such as delivery room commencement of dextrose infusions or delivery room administration of buccal dextrose gel. This review aimed to systematically investigate the literature regarding the provision of delivery room (prior to admission) parenteral glucose as a method to reduce the risk of initial hypoglycemia (measured at the time of NICU admission blood testing) in preterm infants. Using PRISMA guidelines a literature search (May 2022) was conducted using PubMed, Embase, Scopus, Cochrane Library, OpenGrey, and Prospero databases. The clinicaltrials.gov database was searched for possible completed/ongoing clinical trials. Studies that included moderate preterm (≤33⁺⁶ weeks) or younger birth gestations or very low birth weight (or smaller) infants, and that administered parenteral glucose in the delivery room were included. The literature was appraised via data extraction, narrative synthesis, and critical review of the study data. A total of five studies (published 2014–2022) were eligible for inclusion (three before-after “quasi-experimental” studies, one retrospective cohort study, and one case-control study). Most included studies used intravenous dextrose as the intervention. Individual study effects (odds ratios) favored the intervention in all included studies. It was felt that the low number of studies, the variability in study design, and the nonadjustment for confounding co-interventions (co-exposures) precluded a meta-analysis. Quality assessment of the studies revealed a spectrum of bias from low to high risk, however, most studies had moderate to high risk of bias, and their direction of bias favored the intervention. This extensive search and systematic appraisal of the literature indicates that there exists few studies (these are low grade and at moderate to high risk of bias) for the interventions of either intravenous or buccal dextrose given in the delivery room. It is not clear if these interventions impact on rates of early (NICU admission) hypoglycemia in these preterm infants. Obtaining intravenous access in the delivery room is not guaranteed and can be difficult in these small infants. Future research should consider various routes for commencing delivery room glucose in these preterm infants and should take the form of randomized controlled trials.

为降低早产儿早期低血糖症的发生风险，近年来部分临床医师探索了产房起始葡萄糖输注、产房给予颊部葡萄糖凝胶等干预措施。本系统评价旨在系统探究有关产房（入院前）给予肠外葡萄糖，以降低早产儿初始低血糖症（于新生儿重症监护病房[Neonatal Intensive Care Unit, NICU]入院采血时检测）发生风险的相关文献。
本研究遵循PRISMA指南，于2022年5月利用PubMed、Embase、Scopus、考克兰图书馆（Cochrane Library）、开放灰色文献数据库（OpenGrey）及国际前瞻性系统评价注册库（PROSPERO）开展文献检索，并通过美国临床试验注册平台（clinicaltrials.gov）检索已完成或正在进行的相关临床试验。
纳入标准为：胎龄≤33+6周的中度早产儿或胎龄更小的早产儿，或极低出生体重及更低出生体重的婴儿，且在产房给予肠外葡萄糖的研究。
通过数据提取、描述性综合及研究数据批判性评价对纳入文献进行质量评估。最终共有5项2014—2022年发表的研究符合纳入标准，其中3项为前后对照类实验研究、1项为回顾性队列研究、1项为病例对照研究。纳入研究大多采用静脉葡萄糖作为干预手段。所有纳入研究的效应量（比值比[Odds Ratios, OR]）均支持干预措施有效。
由于纳入研究数量较少、研究设计存在异质性，且未针对混杂协同干预（协同暴露因素）进行校正，因此无法开展荟萃分析（Meta-Analysis）。对研究的偏倚风险（Risk of Bias）评估结果显示，偏倚风险分布范围从低到高，但多数研究存在中度至高度偏倚风险，且此类偏倚方向倾向于支持干预措施。
本次全面检索及系统评价结果显示，针对产房给予静脉或颊部葡萄糖的干预措施，相关研究数量较少（证据等级较低且存在中度至高度偏倚风险）。目前尚不清楚此类干预是否可降低早产儿早期（NICU入院时）低血糖症的发生风险。此外，在产房建立静脉通路并非易事，对于此类低体重婴儿而言操作难度较大。
未来研究应探索早产儿产房起始葡萄糖输注的多种给药途径，并采用随机对照试验（Randomized Controlled Trials, RCT）的研究设计。