Hypoglycemia In Newborn Infants Research Articles

New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia.

For the past 70 years, controversy about hypoglycemia in newborn infants has focused on a numerical "definition of neonatal hypoglycemia", without regard to its mechanism. This ignores the purpose of screening newborns for hypoglycemia, which is to identify those with pathological forms of hypoglycemia and to prevent hypoglycemic brain injury. Recent clinical and basic research indicates that the three major forms of neonatal hypoglycemia are caused by hyperinsulinism (recognizing also that other rare hormonal or metabolic conditions may also present during this time frame). These include transitional hypoglycemia, which affects all normal newborns in the first few days after birth; perinatal stress-induced hypoglycemia in high-risk newborns, which afflicts ∼1 in 1,200 newborns; and genetic forms of congenital hyperinsulinism which afflict ∼1 in 10,000-40,000 newborns. (1) Transitional hyperinsulinism in normal newborns reflects persistence of the low glucose threshold for insulin secretion during fetal life into the first few postnatal days. Recent data indicate that the underlying mechanism is decreased trafficking of ATP-sensitive potassium channels to the beta-cell plasma membrane, likely a result of the hypoxemic state of fetal life. (2) Perinatal stress-induced hyperinsulinism in high-risk infants appears to reflect an exaggeration of this normal low fetal glucose threshold for insulin release due to more severe and prolonged exposure to perinatal hypoxemia. (3) Genetic hyperinsulinism, in contrast, reflects permanent genetic defects in various steps controlling beta-cell insulin release, such as inactivating mutations of the K ATP-channel genes. The purpose of this report is to review our current knowledge of these three major forms of neonatal hyperinsulinism as a foundation for the diagnosis and management of hypoglycemia in newborn infants. This includes selection of appropriate interventions based on underlying disease mechanism; combined monitoring of both plasma glucose and ketone levels to improve screening for infants with persistent forms of hypoglycemia; and ultimately to ensure that infants at risk of persistent hyperinsulinemic hypoglycemia are recognized prior to discharge from the nursery.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants

How effective and safe is oral dextrose gel in correcting hypoglycemia in newborn infants?

How effective and safe is oral dextrose gel in correcting hypoglycemia in newborn infants?

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

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.

A Novel HNF4A Mutation Causing Three Phenotypic Forms of Glucose Dysregulation in a Family

Maturity-onset diabetes of the young (MODY) classically describes dominantly inherited forms of monogenic diabetes diagnosed before 25 years of age due to pancreatic β-cell dysfunction. In contrast, mutations in certain MODY genes can also present with transient or persistent hyperinsulinemic hypoglycemia in newborn infants, reflecting instead β-cell dysregulation. Of the MODY genes described to date, only hepatocyte nuclear factor-4-alpha (HNF4A; MODY1) and hepatocyte nuclear factor-1-alpha (HNF1A; MODY3) mutations may result in a biphasic phenotype of hypoglycemia in early life and hyperglycemia in later life. We report a family with a novel HNF4A mutation with diverse phenotypic presentations of glucose dysregulation. The proband was a term, appropriate-for-gestational age male infant with symptomatic hypoglycemia on day 3 of life needing high glucose infusion rate to maintain normoglycemia. He was born to a non-obese and non-diabetic mother. Glucose regulation was optimized using diazoxide upon confirmation of hyperinsulinism. Cascade genetic screening identified the same mutation in his father and elder sister, but mother was negative. Father was diagnosed with Type 1 diabetes at 15 years of age that required insulin therapy. Proband's elder sister, born at term appropriate for gestational age, presented with transient neonatal hypoglycemia needing parenteral glucose infusion for a week followed by spontaneous resolution. The paternal grandparents were negative for this mutation, confirming a paternal de novo mutation and autosomal dominant inheritance in this family. This pedigree suggests that the presence of early-onset paternal diabetes should prompt molecular testing in infants presenting in the newborn period with diazoxide-responsive hyperinsulinemic hypoglycemia, even in the absence of maternal diabetes and macrosomia.

Swedish national guideline for prevention and treatment of neonatal hypoglycaemia in newborn infants with gestational age ≥35weeks.

Postnatal hypoglycaemia in newborn infants remains an important clinical problem where prolonged periods of hypoglycaemia are associated with poor neurodevelopmental outcome. The aim was to develop an evidence-based national guideline with the purpose to optimise prevention, diagnosis and treatment of hypoglycaemia in newborn infants with a gestational age ≥35+0weeks. A PubMed search-based literature review was used to find actual and applicable evidence for all incorporated recommendations. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used for grading the evidence of the recommendations. Recommendations for the prevention of neonatal hypoglycaemia were extended and updated, focusing on promotion of breastfeeding as one prevention strategy. Oral dextrose gel as a novel supplemental therapy was incorporated in the treatment protocol. A new threshold-based screening and treatment protocol presented as a flow chart was developed. An updated and evidence-based national guideline for screening and treatment of neonatal hypoglycaemia will support standardised regimes, which may prevent hypoglycaemia and the risk for hypoglycaemia-related long-term sequelae.

Incidence of hypoglycemia in newborn infants identified as at risk

Background: Temporary low plasma glucose concentrations are common in healthy newborns. Although there is no uniform definition of neonatal hypoglycemia, there is a consensus in the current literature that plasma glucose concentrations should be measured in infants at risk. Known risk groups for transient neonatal hypoglycemia include infants of diabetic mothers (IDM), large (LGA) or small (SGA) for gestational age and late preterm (LPT) infants.Objectives: The aim of this retrospective trial was to determine the incidence of hypoglycemia and the impact of the application of a 2011 revised guideline in respect of additional feeding or i.v. glucose administration, admission to a neonatal ward and the number of blood samples taken.Methods: During the period 1 January 2015 to 31 January 2016, the plasma glucose concentrations of all infants at risk were determined. They were screened over a period of 24 hours or until plasma glucose concentration was >45 mg/dL on three occasions. Hypoglycemia was defined as a plasma glucose concentration <40 mg/dL, regardless of the age of the infant.Results: One hundred and thirty-six (13.6%) out of 1017 newborns were identified as at-risk patients, 119 (87.5%) of whom were included in the final data evaluation. Ten study participants had more than one risk factor and 32 (26.9%) newborns (male:female = 1.1:1) had a total of 40 hypoglycemic episodes. Three (9.4%) out of these 32 newborns had to be transferred to the neonatal ward for i.v. glucose treatment. The mean number of blood samples taken was 7.6 ± 2.4.Conclusions: The incidence of hypoglycemia in the studied infants at risk was 27%, and 19.7 blood samples had to be taken to detect one episode of low glucose concentration. Neonatal hypoglycemia can be recognized and avoided in time, which justifies the establishment of a standardized plasma glucose measurement protocol in newborn infants at risk.Brief RationaleFollowing a considerable number of sources, it is recommended that infants at risk be identified, low plasma glucose concentrations prevented and, if necessary, the affected neonates cared for. Our data show that the risk group for neonatal hypoglycemia comprised about one-tenth of all infants at our nursery and hypoglycemia occurred in one-fourth. These results are in accordance with the recommendations to implement this protocol as a screening tool in neonates.

Incidence of hypoglycemia in newborns at risk and an audit of the 2011 American academy of pediatrics guideline for hypoglycemia

BackgroundHypoglycemia is low blood glucose level that may negatively affect neurological and developmental prognosis. The American Academy of Pediatrics (AAP), Committee on Fetus and Newborn defined the safe glucose concentrations in the 2011 guideline for newborns at risk for hypoglycemia. This study aimed to investigate the incidence and associated risk factors for hypoglycemia in newborn infants having risk and to assess compliance with the AAP guideline. MethodsAccording to 2011 AAP guideline for hypoglycemia, the newborns at risk for hypoglycemia included in this study were divided to four groups [infant of diabetic mother (IDM), large-for-gestational-age (LGA) infants, small-for-gestational-age (SGA) infants, and late preterm infants (LPI)]. ResultsOf the 207 newborn infants, there were 12 cases in IDM group (5.7%), 79 cases in LGA group (38.1%), 66 cases in SGA group (31.8%) and 50 cases in LPI group (24.1%). The incidences of hypoglycemia in these four groups were 2 (16.6%), 10 (12.7%), 8 (12.2%) and 17 (34%), respectively. Although the gender, delivery method, birth weight and 5-min Apgar score at 5-min were not found to be associated with hypoglycemia (P > 0.05), lower gestational age was determined to be associated with higher incidence of hypoglycemia (P = 0.02). Median first feeding time was 55 min and time between first nutrition and blood glucose measurement was 30 min in all cases. ConclusionHighest risk for hypoglycemia in early postnatal period was present especially in LPI group. Our compliance levels with the AAP guideline was found to be satisfactory.

Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia.

Postnatal hypoglycaemia increases the risk of adverse neurological outcomes in newborn infants, and adequate glucose control requires repetitive and painful blood sampling. This study evaluated a continuous glucose monitoring system (CGMS) that aims to improve glucose control and decrease the frequency of blood samples taken from neonates. CGMS sensors, which measure glucose values every five minutes and require calibration twice a day, were placed on 20 infants at risk of hypoglycaemia. The infants also underwent blood glucose sampling, and the blood glucose values were compared with CGMS values six times during the first 30 minutes after sampling. We used 97/264 (37%) of the blood glucose values taken for the CGMS calibration. The highest accuracy, a mean of 0.22 (95% confidence interval 0.13-0.30 mmol/L), was found 15-19 minutes after sampling, due to the calibration process. No significant subcutaneous glucose time lag was detectable. The CGMS system was an accurate and feasible method for glucose control, provided earlier detection of hypoglycaemia in newborn infants and reduced their exposure to procedural pain. The delay in calibration in infants was a new finding and needs to be taken into account when comparing CGMS readings to blood glucose values.

Oral dextrose gel for the treatment of hypoglycaemia in newborn infants.

Neonatal hypoglycaemia, a common condition, can be associated with brain injury. It is frequently managed by providing infants with an alternative source of glucose, given enterally with formula or intravenously with dextrose solution. This often requires that mother and baby are cared for in separate environments and may inhibit breast feeding. Dextrose gel is simple and inexpensive and can be administered directly to the buccal mucosa for rapid correction of hypoglycaemia, in association with continued breast feeding and maternal care. To assess the effectiveness of dextrose gel in correcting hypoglycaemia and in reducing long-term neurodevelopmental impairment. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science from inception of the database to February 2016. We also searched international clinical trials networks and handsearched proceedings of specific scientific meetings. Randomised and quasi-randomised studies comparing dextrose gel versus placebo, no treatment or other therapies for treatment of neonatal hypoglycaemia. Two review authors independently assessed trial quality and extracted data and did not assess publications for which they themselves were study authors. We included two trials involving 312 infants. No data were available for correction of hypoglycaemia for each hypoglycaemic event. We found no evidence of a difference between dextrose gel and placebo gel for major neurosensory disability at two-year follow-up (risk ratio (RR) 6.27, 95% confidence interval (CI) 0.77 to 51.03; one trial, n = 184; quality of evidence very low). Dextrose gel compared with placebo gel or no gel did not alter the need for intravenous treatment for hypoglycaemia (typical RR 0.78, 95% CI 0.46 to 1.32; two trials, 312 infants; quality of evidence very low). Infants treated with dextrose gel were less likely to be separated from their mothers for treatment of hypoglycaemia (RR 0.54, 95% CI 0.31 to 0.93; one trial, 237 infants; quality of evidence moderate) and were more likely to be exclusively breast fed after discharge (RR 1.10, 95% CI 1.01 to 1.18; one trial, 237 infants; quality of evidence moderate). Estimated rise in blood glucose concentration following dextrose gel was 0.4 mmol/L (95% CI -0.14 to 0.94; one trial, 75 infants). Investigators in one trial reported no adverse outcomes (n = 237 infants). Treatment of infants with neonatal hypoglycaemia with 40% dextrose gel reduces the incidence of mother-infant separation for treatment and increases the likelihood of full breast feeding after discharge compared with placebo gel. No evidence suggests occurrence of adverse effects during the neonatal period or at two years' corrected age. Oral dextrose gel should be considered first-line treatment for infants with neonatal hypoglycaemia.

Correction: Hypoglycemia in Newborn Infants at Risk.

Correction: Hypoglycemia in Newborn Infants at Risk.

Hypoglycemia in newborn infants at risk.

Infants of diabetic mothers (IDM), large (LGA) or small (SGA) for gestational age and late preterm (LPT) infants are at risk for hypoglycemia. We report the incidence, the consequences and the impact of a recently implemented guideline. From 1 January to 31 December 2012 we screened infants at risk. The first blood glucose was done within 90 min after birth, 30 min after the first feeding and had to be repeated before each feeding. Hypoglycemia was defined as blood glucose below 40 mg/dL independent of age; all babies remained in the study for at least 24 h or until at least 3 glucose measurements were >40 mg/dL. We identified 259 out 1 074 (24.1%) infants and included 145 (56.0%) of these infants in a retrospective analysis. 17 (11.7%) infants (male:female=1:1.1) showed 19 episodes of hypoglycemia. 3 of them had more than one risk factor, 2 were LGA at term. 6 (35%) out of 17 infants had to be transferred, one due to clinical signs and 5 according to the protocol. Mean number of blood glucose measurement was 6.9±1.9. The number of procedures performed to detect one episode of hypoglycemia was 54. The incidence of hypoglycemia in infants at risk is low and does not justify screening such a large risk group, which may harm them by requiring a disproportionately large number of blood withdrawals.

Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting

Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (Elite™ XL, Ascensia™ Contour™ and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance.

Hyperinsulinaemic hypoglycaemia in preterm neonates

Hyperinsulinism in infancy (HI) is an important cause of severe and recurrent hypoglycaemia in newborn infants. It usually appears in infants born at term, and only one case of its...

Hypoglycemic brain injury

Hypoglycemia frequently occurs in newborn infants who previously have suffered asphyxia, who are offspring of diabetic mothers, or who are low birthweight for gestational age (IUGR). Many infants who are hypoglycemic do not exhibit clinical manifestations, while others are symptomatic and at risk for the occurrence of permanent brain damage. This review emphasizes the clinical, neuropathologic, and neuro-imaging features of hypoglycemia in newborn infants, especially those who are symptomatic. Neurologic morbidity occurs particularly in those infants who have suffered severe, protracted, or recurrent symptomatic hypoglycemia. Experimental observations emphasize the resistance of the immature brain to the damaging effect of hypoglycemia; such resistance occurs as a consequence of compensatory increases in cerebral blood flow, lower energy requirements, higher endogenous carbohydrate stores, and an ability to incorporate and consume alternative organic substrates to spare glucose for energy production. Hypoglycemia combined with hypoxia-ischemia (asphyxia) is more deleterious to the immature brain than either condition alone.

Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial

Objective: To compare perinatal outcome and glycaemic control in two groups of pregnant diabetic patients receiving two insulin regimens.Design: Randomised controlled open label study.Setting: University affiliated hospital, Israel.Participants: 138 patients...

Glucose metabolism in a term infant with transient hyperinsulinism and high carbohydrate intake

Transient hyperinsulinaemia is a well-known cause of hypoglycaemia in newborn infants. The hypoglycaemia may be caused by a decreased glucose production and/or an increased glucose uptake. Whether the increased uptake is caused by increased glucose oxidation or increased non-oxidative disposal is not known. The aim of this study was to investigate the fate of the large amount of glucose infused in a term infant who developed hypoglycaemia due to transient hyperinsulinaemia shortly after birth and was treated with high glucose infusions. On day 6 an indirect calorimetry study was performed, together with a glucose turnover study. Carbohydrate intake was 13.6 mg/kg per minute (19.6 g/kg per day). Both studies were repeated on day 11, when carbohydrate intake was normalised to 7.8 mg/kg per minute (11.2 g/kg per day). Glucose oxidation was 28% higher and non-oxidative glucose disposal was 257% higher on day 6 as compared to day 11. Our results indicate that hypoglycaemia during hyperinsulinism is the result of increased non-oxidative disposal of glucose and not increased glucose oxidation. The results indicate a remarkable capacity of the newborn for lipogenesis during high carbohydrate intake.

SYMPTOMATIC AND ASYMPTOMATIC HYPOGLYCEMIA IN NEWBORN INFANTS PROVOKED BY THE INTRAPARTUM ADMINISTRATION OF THE FLUIDS THAT CONTAIN GLUCOSE

Article SYMPTOMATIC AND ASYMPTOMATIC HYPOGLYCEMIA IN NEWBORN INFANTS PROVOKED BY THE INTRAPARTUM ADMINISTRATION OF THE FLUIDS THAT CONTAIN GLUCOSE was published on January 1, 1990 in the journal Journal of Perinatal Medicine (volume 18, issue s1).

Hypoglycemia in newborn infants.

Hypoglycemia in newborn infants.

Growth Hormone Response to Insulin–Induced Hypoglycemia in Newborn Infants

In the article by J. R. Humbert and R. W. Gotlin,1 the authors state that previous reports in which hypoglycemia was induced artificially with insulin demonstrated a variable growth hormone response. They then refer to the paper by Cornblath, et al.2 as reporting a failure to obtain a rise in growth hormone levels. This is incorrect as we found that insulin-induced hypoglycemia actually resulted in a very marked rise in growth hormone levels in both the full-term and premature infants tested.