Taygen Edwards1, Gordon Liu1, Joanne E Hegarty1,2, Caroline A Crowther1,3, Jane Alsweiler2,4, Jane E Harding1. 1. Liggins Institute, University of Auckland, Auckland, New Zealand. 2. Neonatal Intensive Care Unit, Auckland Hospital, Auckland, New Zealand. 3. ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, Australia. 4. Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
Abstract
BACKGROUND: Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures usually involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive and effective for treatment of neonatal hypoglycaemia. Prophylactic dextrose gel can reduce the incidence of neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury. This is an update of a previous Cochrane Review published in 2017. OBJECTIVES: To assess the effectiveness and safety of oral dextrose gel given to newborn infants at risk of hypoglycaemia in preventing hypoglycaemia and reducing long-term neurodevelopmental impairment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 10) in the Cochrane Library; and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) on 19 October 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no intervention, or other therapies for the prevention of neonatal hypoglycaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We contacted investigators to obtain additional information. We used fixed-effect meta-analyses. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included two studies conducted in high-income countries comparing oral dextrose gel versus placebo in 2548 infants at risk of neonatal hypoglycaemia. Of these, one study was included in the previous version of this review. We judged these two studies to be at low risk of bias, and that the evidence for most outcomes was of moderate certainty. Meta-analysis of the two studies showed that oral dextrose gel reduces the risk of hypoglycaemia (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95; risk difference (RD) -0.06, 95% CI -0.10 to -0.02; 2548 infants; high certainty evidence). One study reported that oral dextrose gel probably reduces the risk of major neurological disability at two years' corrected age (RR 0.21, 95% CI 0.05 to 0.78; RD -0.05, 95% CI -0.09 to 0.00; 360 infants; moderate certainty evidence). Meta-analysis of the two studies showed that oral dextrose gel probably reduces the risk of receipt of treatment for hypoglycaemia during initial hospital stay (RR 0.89, 95% CI 0.79 to 1.00; 2548 infants; moderate certainty evidence) but makes little or no difference to the risk of receipt of intravenous treatment for hypoglycaemia (RR 1.01, 0.68 to 1.49; 2548 infants; moderate certainty evidence). Oral dextrose gel may have little or no effect on the risk of separation from the mother for treatment of hypoglycaemia (RR 1.12, 95% CI 0.81 to 1.55; two studies, 2548 infants; low certainty evidence). There is probably little or no difference in the risk of adverse events in infants who receive oral dextrose gel compared to placebo gel (RR 1.22, 95% CI 0.64 to 2.33; two studies, 2510 infants; moderate certainty evidence), but there are no studies comparing oral dextrose with other comparators such as no treatment, standard care or other therapies. No data were available on exclusive breastfeeding after discharge. AUTHORS' CONCLUSIONS: Oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of major neurological disability at two years of age or greater without increasing the risk of adverse events compared to placebo gel. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in low- and middle-income countries, preterm infants, using other dextrose gel preparations, and using comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when published.
BACKGROUND: Neonatal hypoglycaemia is a common condition that can be associated with brain injury. Current practice usually includes early identification of at-risk infants (e.g. infants of diabetic mothers; preterm, small- or large-for-gestational-age infants), and prophylactic measures are advised. However, these measures usually involve use of formula milk or admission to the neonatal unit. Dextrose gel is non-invasive, inexpensive and effective for treatment of neonatal hypoglycaemia. Prophylactic dextrose gel can reduce the incidence of neonatal hypoglycaemia, thus potentially reducing separation of mother and baby and supporting breastfeeding, as well as preventing brain injury. This is an update of a previous Cochrane Review published in 2017. OBJECTIVES: To assess the effectiveness and safety of oral dextrose gel given to newborn infants at risk of hypoglycaemia in preventing hypoglycaemia and reducing long-term neurodevelopmental impairment. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 10) in the Cochrane Library; and Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) on 19 October 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing oral dextrose gel versus placebo, no intervention, or other therapies for the prevention of neonatal hypoglycaemia. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias. We contacted investigators to obtain additional information. We used fixed-effect meta-analyses. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included two studies conducted in high-income countries comparing oral dextrose gel versus placebo in 2548 infants at risk of neonatal hypoglycaemia. Of these, one study was included in the previous version of this review. We judged these two studies to be at low risk of bias, and that the evidence for most outcomes was of moderate certainty. Meta-analysis of the two studies showed that oral dextrose gel reduces the risk of hypoglycaemia (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95; risk difference (RD) -0.06, 95% CI -0.10 to -0.02; 2548 infants; high certainty evidence). One study reported that oral dextrose gel probably reduces the risk of major neurological disability at two years' corrected age (RR 0.21, 95% CI 0.05 to 0.78; RD -0.05, 95% CI -0.09 to 0.00; 360 infants; moderate certainty evidence). Meta-analysis of the two studies showed that oral dextrose gel probably reduces the risk of receipt of treatment for hypoglycaemia during initial hospital stay (RR 0.89, 95% CI 0.79 to 1.00; 2548 infants; moderate certainty evidence) but makes little or no difference to the risk of receipt of intravenous treatment for hypoglycaemia (RR 1.01, 0.68 to 1.49; 2548 infants; moderate certainty evidence). Oral dextrose gel may have little or no effect on the risk of separation from the mother for treatment of hypoglycaemia (RR 1.12, 95% CI 0.81 to 1.55; two studies, 2548 infants; low certainty evidence). There is probably little or no difference in the risk of adverse events in infants who receive oral dextrose gel compared to placebo gel (RR 1.22, 95% CI 0.64 to 2.33; two studies, 2510 infants; moderate certainty evidence), but there are no studies comparing oral dextrose with other comparators such as no treatment, standard care or other therapies. No data were available on exclusive breastfeeding after discharge. AUTHORS' CONCLUSIONS: Oral dextrose gel reduces the risk of neonatal hypoglycaemia in at-risk infants and probably reduces the risk of major neurological disability at two years of age or greater without increasing the risk of adverse events compared to placebo gel. Additional large follow-up studies at two years of age or older are required. Future research should also be undertaken in low- and middle-income countries, preterm infants, using other dextrose gel preparations, and using comparators other than placebo gel. There are three studies awaiting classification and one ongoing study which may alter the conclusions of the review when published.
Authors: Della A Forster; Anita M Moorhead; Susan E Jacobs; Peter G Davis; Susan P Walker; Kerri M McEgan; Gillian F Opie; Susan M Donath; Lisa Gold; Catharine McNamara; Amanda Aylward; Christine East; Rachael Ford; Lisa H Amir Journal: Lancet Date: 2017-06-03 Impact factor: 79.321
Authors: Jane E Harding; Joanne E Hegarty; Caroline A Crowther; Richard Edlin; Greg Gamble; Jane M Alsweiler Journal: BMC Pediatr Date: 2015-09-16 Impact factor: 2.125
Authors: Joanne Elizabeth Hegarty; Jane Elizabeth Harding; Gregory David Gamble; Caroline Anne Crowther; Richard Edlin; Jane Marie Alsweiler Journal: PLoS Med Date: 2016-10-25 Impact factor: 11.069
Authors: Taygen Edwards; Gordon Liu; Joanne E Hegarty; Caroline A Crowther; Jane Alsweiler; Jane E Harding Journal: Cochrane Database Syst Rev Date: 2021-05-17
Authors: Amy Keir; Alice Rumbold; Carmel T Collins; Andrew J McPhee; Jojy Varghese; Scott Morris; Thomas R Sullivan; Shalem Leemaqz; Philippa Middleton; Maria Makrides; Karen P Best Journal: PLoS One Date: 2022-08-15 Impact factor: 3.752