Pathogenesis, screening, and diagnosis of neonatal hypoglycemia
- Paul J Rozance, MD
Paul J Rozance, MD
- Associate Professor of Pediatrics, Neonatal Medicine
- University of Colorado Denver
- Section Editors
- Joseph A Garcia-Prats, MD
Joseph A Garcia-Prats, MD
- Section Editor — Neonatology
- Professor of Pediatrics
- Baylor College of Medicine
- Joseph I Wolfsdorf, MB, BCh
Joseph I Wolfsdorf, MB, BCh
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Harvard Medical School
During the normal transition to extrauterine life, blood glucose concentration in the healthy term newborn falls during the first two hours after delivery, reaching a nadir that usually is no lower than 40 mg/dL. It is important to differentiate this normal physiologic transitional response from disorders that result in persistent or recurrent hypoglycemia, which may lead to neurologic sequelae.
This topic will discuss the normal transient neonatal low glucose levels, causes of persistent or pathologic neonatal hypoglycemia, and the clinical manifestations and diagnosis of neonatal hypoglycemia. The management of neonatal hypoglycemia, including evaluation of persistent hypoglycemia and outcome of neonatal hypoglycemia, is discussed separately. (See "Management and outcome of neonatal hypoglycemia".)
CHALLENGE OF DEFINING NEONATAL HYPOGLYCEMIA
Clinically significant neonatal hypoglycemia requiring intervention cannot be defined by a precise numerical blood glucose concentration because of the following:
●Normal low neonatal blood glucose levels − Low blood glucose concentrations normally occur in the first hours after birth and may persist for up to several days. Although most newborns remain asymptomatic despite very low blood glucose concentrations, some newborns become symptomatic at the same or even higher blood glucose concentrations than are observed in asymptomatic infants. This variability in the clinical response in neonates to low blood glucose concentrations is due to a number of factors that include the infant's gestational age and postnatal age, the presence of other sources of energy (eg, lactate and ketone bodies), and circumstances that affect glucose metabolism and cerebral glucose uptake and utilization.
●Lack of outcome data − Ideally, clinically significant neonatal hypoglycemia would be defined as the blood glucose concentration at which intervention should be initiated to avoid significant morbidity, especially neurologic sequelae. However, this definition remains elusive because the blood glucose concentration and duration of hypoglycemia associated with poor neurodevelopmental outcome has not been established [1,2].
- Cornblath M, Hawdon JM, Williams AF, et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics 2000; 105:1141.
- Hay WW Jr, Raju TN, Higgins RD, et al. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr 2009; 155:612.
- McKinlay CJ, Alsweiler JM, Ansell JM, et al. Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years. N Engl J Med 2015; 373:1507.
- Screening guidelines for newborns at risk for low blood glucose. Paediatr Child Health 2004; 9:723.
- Tin W, Brunskill G, Kelly T, Fritz S. 15-year follow-up of recurrent "hypoglycemia" in preterm infants. Pediatrics 2012; 130:e1497.
- Stanley CA, Rozance PJ, Thornton PS, et al. Re-evaluating "transitional neonatal hypoglycemia": mechanism and implications for management. J Pediatr 2015; 166:1520.
- Committee on Fetus and Newborn, Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127:575.
- Stanley CA, Baker L. The causes of neonatal hypoglycemia. N Engl J Med 1999; 340:1200.
- Lubchenco LO, Bard H. Incidence of hypoglycemia in newborn infants classified by birth weight and gestational age. Pediatrics 1971; 47:831.
- Hawdon JM, Weddell A, Aynsley-Green A, Ward Platt MP. Hormonal and metabolic response to hypoglycaemia in small for gestational age infants. Arch Dis Child 1993; 68:269.
- Worthen HG, al Ashwal A, Ozand PT, et al. Comparative frequency and severity of hypoglycemia in selected organic acidemias, branched chain amino acidemia, and disorders of fructose metabolism. Brain Dev 1994; 16 Suppl:81.
- Bateman BT, Patorno E, Desai RJ, et al. Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia. Pediatrics 2016; 138.
- Miralles RE, Lodha A, Perlman M, Moore AM. Experience with intravenous glucagon infusions as a treatment for resistant neonatal hypoglycemia. Arch Pediatr Adolesc Med 2002; 156:999.
- Collins JE, Leonard JV. Hyperinsulinism in asphyxiated and small-for-dates infants with hypoglycaemia. Lancet 1984; 2:311.
- Hoe FM, Thornton PS, Wanner LA, et al. Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism. J Pediatr 2006; 148:207.
- Sinclair JC, Bottino M, Cowett RM. Interventions for prevention of neonatal hyperglycemia in very low birth weight infants. Cochrane Database Syst Rev 2009; :CD007615.
- Sue CM, Hirano M, DiMauro S, De Vivo DC. Neonatal presentations of mitochondrial metabolic disorders. Semin Perinatol 1999; 23:113.
- Seidner G, Alvarez MG, Yeh JI, et al. GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier. Nat Genet 1998; 18:188.
- Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161:787.
- Pertierra-Cortada A, Ramon-Krauel M, Iriondo-Sanz M, Iglesias-Platas I. Instability of glucose values in very preterm babies at term postmenstrual age. J Pediatr 2014; 165:1146.
- Mizumoto H, Honda Y, Ueda K, et al. Glycemic variability in preterm infants receiving intermittent gastric tube feeding: report of three cases. Pediatr Int 2013; 55:e25.
- Rozance PJ, Hay WW. Hypoglycemia in newborn infants: Features associated with adverse outcomes. Biol Neonate 2006; 90:74.
- Balion C, Grey V, Ismaila A, et al. Screening for hypoglycemia at the bedside in the neonatal intensive care unit (NICU) with the Abbott PCx glucose meter. BMC Pediatr 2006; 6:28.
- Rosenthal M, Ugele B, Lipowsky G, Küster H. The Accutrend sensor glucose analyzer may not be adequate in bedside testing for neonatal hypoglycemia. Eur J Pediatr 2006; 165:99.
- Harris DL, Battin MR, Weston PJ, Harding JE. Continuous glucose monitoring in newborn babies at risk of hypoglycemia. J Pediatr 2010; 157:198.
- Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, et al. Validation of the continuous glucose monitoring sensor in preterm infants. Arch Dis Child Fetal Neonatal Ed 2013; 98:F136.
- Wackernagel D, Dube M, Blennow M, Tindberg Y. Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia. Acta Paediatr 2016; 105:917.
- Hay WW Jr, Rozance PJ. Continuous glucose monitoring for diagnosis and treatment of neonatal hypoglycemia. J Pediatr 2010; 157:180.
- CHALLENGE OF DEFINING NEONATAL HYPOGLYCEMIA
- NORMAL TRANSITIONAL LOW GLUCOSE LEVELS
- PATHOLOGIC AND/OR PERSISTENT HYPOGLYCEMIA
- Diminished glucose supply
- - Inadequate glycogen stores
- - Impaired glucose production
- Inborn errors of metabolism
- Endocrine disorders
- Other causes
- Increased glucose utilization
- - Hyperinsulinism
- - Without hyperinsulinism
- CLINICAL MANIFESTATIONS
- Who should be evaluated?
- Timing and frequency of glucose screening
- How glucose testing is performed
- DIFFERENTIAL DIAGNOSIS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS