Liggins Institute, University of Auckland, Auckland, New Zealand.
Neonatal Intensive Care Unit, Auckland Hospital, Auckland, New Zealand.
Cochrane Database Syst Rev. 2022 Mar 18;3(3):CD011027. doi: 10.1002/14651858.CD011027.pub3.
Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, often given enterally with milk-feeding or intravenously with dextrose solution, which may decrease breastfeeding success. Intravenous dextrose also often requires that mother and baby are cared for in separate environments. Oral dextrose gel is simple and inexpensive, and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breastfeeding and maternal care. This is an update of a previous review published in 2016.
To assess the effectiveness of oral dextrose gel in correcting hypoglycaemia in newborn infants from birth to discharge home and reducing long-term neurodevelopmental impairment.
We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase from database inception to October 2021. We also searched international clinical trials networks, the reference lists of included trials, and relevant systematic reviews identified in the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no treatment, or other therapies for the treatment of neonatal hypoglycaemia in newborn infants from birth to discharge home.
Two review authors independently assessed study quality and extracted data; they did not assess publications for which they were study authors. We contacted investigators to obtain additional information. We used fixed-effect models and the GRADE approach to assess the certainty of evidence.
We included two studies conducted in high-income countries, involving 312 late preterm and at-risk term infants and comparing oral dextrose gel (40% concentration) to placebo gel. One study was at low risk of bias, and the other (an abstract) was at unclear to high risk of bias. Oral dextrose gel compared with placebo gel probably increases correction of hypoglycaemic events (rate ratio 1.08, 95% confidence interval (CI) 0.98 to 1.20; rate difference 66 more per 1000, 95% CI 17 fewer to 166 more; 1 study; 237 infants; moderate-certainty evidence), and may result in a slight reduction in the risk of major neurological disability at age two years or older, but the evidence is uncertain (risk ratio (RR) 0.46, 95% CI 0.09 to 2.47; risk difference (RD) 24 fewer per 1000, 95% CI 41 fewer to 66 more; 1 study, 185 children; low-certainty evidence). The evidence is very uncertain about the effect of oral dextrose gel compared with placebo gel or no gel on the need for intravenous treatment for hypoglycaemia (RR 0.78, 95% CI 0.46 to 1.32; RD 37 fewer per 1000, 95% CI 91 fewer to 54 more; 2 studies, 312 infants; very low-certainty evidence). Investigators in one study of 237 infants reported no adverse events (e.g. choking or vomiting at the time of administration) in the oral dextrose gel or placebo gel group (low-certainty evidence). Oral dextrose gel compared with placebo gel probably reduces the incidence of separation from the mother for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; RD 116 fewer per 1000, 95% CI 174 fewer to 18 fewer; 1 study, 237 infants; moderate-certainty evidence), and increases the likelihood of exclusive breastfeeding after discharge (RR 1.10, 95% CI 1.01 to 1.18; RD 87 more per 1000, 95% CI 9 more to 157 more; 1 study, 237 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Oral dextrose gel (specifically 40% dextrose concentration) used to treat hypoglycaemia in newborn infants (specifically at-risk late preterm and term infants) probably increases correction of hypoglycaemic events, and may result in a slight reduction in the risk of major neurological disability at age two years or older. Oral dextrose gel treatment probably reduces the incidence of separation from the mother for treatment and increases the likelihood of exclusive breastfeeding after discharge. No adverse events have been reported. Oral dextrose gel is probably an effective and safe first-line treatment for infants with neonatal hypoglycaemia in high-income settings. More evidence is needed about the effects of oral dextrose gel treatment on later neurological disability and the need for other treatments for hypoglycaemia. Future studies should be conducted in low-and middle-income settings, in extremely and moderately preterm infants, and compare oral dextrose gel with other therapies such as intravenous dextrose. There are two ongoing studies that may alter the conclusions of this review when published.
新生儿低血糖是一种常见病症，可能导致脑损伤。通常通过为婴儿提供替代葡萄糖源来进行管理，这种替代源通常通过母乳喂养或静脉输注葡萄糖溶液（可能会降低母乳喂养的成功率）来提供。静脉输注葡萄糖溶液还常常需要母亲和婴儿在不同的环境中接受治疗。口服葡萄糖凝胶简单且廉价，可以直接施用于颊黏膜，以快速纠正低血糖，同时继续母乳喂养和母婴护理。这是对 2016 年发表的一篇综述的更新。
评估口服葡萄糖凝胶在纠正新生儿从出生到出院期间低血糖症和降低长期神经发育障碍方面的效果。
我们检索了 Cochrane 对照试验中心注册库、MEDLINE 和 Embase，检索时间从数据库建立到 2021 年 10 月。我们还检索了国际临床试验网络、纳入试验的参考文献列表以及检索中确定的相关系统评价。
我们纳入了比较口服葡萄糖凝胶与安慰剂、无治疗或其他治疗新生儿低血糖症的随机对照试验（RCT）和准随机对照试验，这些试验的纳入对象为出生至出院回家的新生儿。
两名综述作者独立评估了研究质量并提取了数据；他们没有评估自己为作者的出版物。我们联系了研究人员以获取更多信息。我们使用固定效应模型和 GRADE 方法来评估证据的确定性。
我们纳入了两项在高收入国家进行的研究，涉及 312 名晚期早产儿和高危足月婴儿，比较了口服 40%葡萄糖凝胶与安慰剂凝胶。其中一项研究的偏倚风险较低，另一项（摘要）的偏倚风险为不明确至高。与安慰剂凝胶相比，口服葡萄糖凝胶可能更能纠正低血糖事件（率比 1.08，95%置信区间[CI]为 0.98 至 1.20；差值为每 1000 次治疗中多 66 次，95%CI 为 17 次治疗中少至 166 次治疗中多；1 项研究；237 名婴儿；中等确定性证据），并且可能降低 2 岁及以上儿童发生主要神经发育障碍的风险，但证据不确定（风险比[RR]0.46，95%CI 为 0.09 至 2.47；差值为每 1000 次治疗中少 24 次，95%CI 为 41 次治疗中少至 66 次治疗中多；1 项研究，185 名儿童；低确定性证据）。与安慰剂凝胶或无凝胶相比，口服葡萄糖凝胶对低血糖症需要静脉治疗的影响的证据非常不确定（RR 0.78，95%CI 为 0.46 至 1.32；差值为每 1000 次治疗中少 37 次，95%CI 为 91 次治疗中少至 54 次治疗中多；2 项研究，312 名婴儿；非常低确定性证据）。一项涉及 237 名婴儿的研究报告称，口服葡萄糖凝胶或安慰剂凝胶组均未发生不良事件（如治疗时呛咳或呕吐；低确定性证据）。与安慰剂凝胶相比，口服葡萄糖凝胶可能减少因治疗低血糖而与母亲分离的发生率（RR 0.54，95%CI 为 0.31 至 0.93；差值为每 1000 次治疗中少 116 次，95%CI 为 174 次治疗中少至 18 次治疗中多；1 项研究；237 名婴儿；中等确定性证据），并增加出院后纯母乳喂养的可能性（RR 1.10，95%CI 为 1.01 至 1.18；差值为每 1000 次治疗中多 87 次，95%CI 为 9 次治疗中多至 157 次治疗中多；1 项研究；237 名婴儿；中等确定性证据）。
口服葡萄糖凝胶（特别是 40%葡萄糖浓度）用于治疗新生儿低血糖症（特别是有风险的晚期早产儿和足月婴儿）可能增加低血糖症纠正的可能性，并可能降低 2 岁及以上儿童发生主要神经发育障碍的风险。口服葡萄糖凝胶治疗可能减少因治疗而与母亲分离的发生率，并增加出院后纯母乳喂养的可能性。尚未报告不良事件。口服葡萄糖凝胶可能是高收入环境中新生儿低血糖症的有效且安全的一线治疗方法。需要更多的证据来评估口服葡萄糖凝胶治疗对以后神经发育障碍和低血糖症其他治疗方法的需求。未来的研究应在中低收入国家、极早产儿和中度早产儿中进行，并比较口服葡萄糖凝胶与静脉葡萄糖等其他治疗方法。有两项正在进行的研究可能会在发表时改变本综述的结论。
