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Am J Perinatol
DOI: 10.1055/s-0044-1785491
Original Article

Variability in Diagnosis and Management of Hypoglycemia in Neonatal Intensive Care Unit

Daniela Dinu
1   Department of Pediatrics, Baylor College of Medicine, Houston, Texas
,
Joseph L. Hagan
1   Department of Pediatrics, Baylor College of Medicine, Houston, Texas
,
Paul J. Rozance
2   Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado
› Author Affiliations Funding None.
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Abstract

Objective Hypoglycemia, the most common metabolic derangement in the newborn period remains a contentious issue, not only due to various numerical definitions, but also due to limited therapeutical options which either lack evidence to support their efficacy or are increasingly recognized to lead to adverse reactions in this population. This study aimed to investigate neonatologists' current attitudes in diagnosing and managing transient and persistent hypoglycemia in newborns admitted to the Neonatal Intensive Care Unit (NICU).

Methods A web-based electronic survey which included 34 questions and a clinical vignette was sent to U.S. neonatologists.

Results There were 246 survey responses with most respondents using local protocols to manage this condition. The median glucose value used as the numerical definition of hypoglycemia in first 48 hours of life (HOL) for symptomatic and asymptomatic term infants and preterm infants was 45 mg/dL (2.5 mmol/L; 25–60 mg/dL; 1.4–3.3 mmol/L), while after 48 HOL the median value was 50 mg/dL (2.8 mmol/L; 30–70 mg/dL; 1.7–3.9 mmol/L). There were various approaches used to manage transient and persistent hypoglycemia that included dextrose gel, increasing caloric content of the feeds using milk fortifiers, using continuous feedings, formula or complex carbohydrates, and use of various medications such as diazoxide, glucocorticoids, and glucagon.

Conclusion There is still large variability in current practices related to hypoglycemia. Further research is needed not only to provide evidence to support the values used as a numerical definition for hypoglycemia, but also on the efficacy of current strategies used to manage this condition.

Key Points

  • Numerical definition of glucose remains variable.

  • Strategies managing transient and persistent hypoglycemia are diverse.

  • There is a need for further research to investigate efficacy of various treatment options.

Keywords

hypoglycemia - hyperinsulinism - NICU - dextrose gel - diazoxide - complex carbohydrates - glucocorticoids

Supplementary Material



Publication History

Received: 18 January 2024

Accepted: 11 March 2024

Article published online:
02 April 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Mitchell NA, Grimbly C, Rosolowsky ET. et al. Incidence and risk factors for hypoglycemia during fetal-to-neonatal transition in premature infants. Front Pediatr 2020; 8: 34
    CrossrefPubMedGoogle Scholar
  • 2 Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161 (05) 787-791
    CrossrefPubMedGoogle Scholar
  • 3 Kaiser JR, Bai S, Gibson N. et al. Association between transient newborn hypoglycemia and fourth-grade achievement test proficiency: a population-based study. JAMA Pediatr 2015; 169 (10) 913-921
    CrossrefPubMedGoogle Scholar
  • 4 Special Care Nursery Admissions. Accessed January 15, 2024 at: https://www.marchofdimes.org/peristats/assets/s3/reports/archives/nicu_summary_final.pdf
    PubMed
  • 5 Thornton PS, Stanley CA, De Leon DD. et al; Pediatric Endocrine Society. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr 2015; 167 (02) 238-245
    CrossrefPubMedGoogle Scholar
  • 6 Adamkin DH. Committee on Fetus and Newborn. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 2011; 127 (03) 575-579
    CrossrefPubMedGoogle Scholar
  • 7 Narasimhan SR, Flaherman V, McLean M. et al. Practice variations in diagnosis and treatment of hypoglycemia in asymptomatic newborns. Hosp Pediatr 2021; 11 (06) 595-604
    CrossrefPubMedGoogle Scholar
  • 8 Harris DL, Weston PJ, Battin MR, Harding JE. A survey of the management of neonatal hypoglycaemia within the Australian and New Zealand Neonatal Network. J Paediatr Child Health 2014; 50 (10) E55-E62
    CrossrefPubMedGoogle Scholar
  • 9 Dixon KC, Ferris RL, Marikar D. et al. Definition and monitoring of neonatal hypoglycaemia: a nationwide survey of NHS England Neonatal Units. Arch Dis Child Fetal Neonatal Ed 2017; 102 (01) F92-F93
    CrossrefPubMedGoogle Scholar
  • 10 Rajay AB, Harding JE. hPOD Study Group. Variations in New Zealand and Australian guidelines for the management of neonatal hypoglycaemia: A secondary analysis from the hypoglycaemia Prevention with Oral Dextrose gel Trial (hPOD). J Paediatr Child Health 2022; 58 (05) 820-829
    CrossrefPubMedGoogle Scholar
  • 11 Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial. Lancet 2013; 382 (9910) 2077-2083
    CrossrefPubMedGoogle Scholar
  • 12 Gupta K, Amboiram P, Balakrishnan U, C A, Abiramalatha T, Devi U. Dextrose gel for neonates at risk with asymptomatic hypoglycemia: a randomized clinical trial. Pediatrics 2022; 149 (06) e2021050733
    CrossrefPubMedGoogle Scholar
  • 13 Rawat M, Chandrasekharan P, Turkovich S. et al. Oral dextrose gel reduces the need for intravenous dextrose therapy in neonatal hypoglycemia. Biomed Hub 2016; 1 (03) 1-9
    CrossrefPubMedGoogle Scholar
  • 14 Edwards T, Liu G, Battin M. et al. Oral dextrose gel for the treatment of hypoglycaemia in newborn infants. Cochrane Database Syst Rev 2022; 3 (03) CD011027
    PubMedGoogle Scholar
  • 15 Demirbilek H, Hussain K. Congenital hyperinsulinism: diagnosis and treatment update. J Clin Res Pediatr Endocrinol 2017; 9 (Suppl. 02) 69-87
    PubMedGoogle Scholar
  • 16 Snider KE, Becker S, Boyajian L. et al. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab 2013; 98 (02) E355-E363
    CrossrefPubMedGoogle Scholar
  • 17 Brar PC, Heksch R, Cossen K. et al. Management and appropriate use of diazoxide in infants and children with hyperinsulinism. J Clin Endocrinol Metab 2020; 105 (12) 105
    CrossrefPubMedGoogle Scholar
  • 18 Plummer EA, Ninkovic I, Rees A, Rao R, Bendel CM, Stepka EC. Neonatal hypoglycemia algorithms improve hospital outcomes. J Matern Fetal Neonatal Med 2022; 35 (12) 2278-2285
    CrossrefPubMedGoogle Scholar
  • 19 Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ 1988; 297 (6659) 1304-1308
    CrossrefPubMedGoogle Scholar
  • 20 Barrero-Castillero A, Mao W, Stark AR, Miedema D, Pursley DM, Burris HH. Glucose concentrations in enterally fed preterm infants. J Perinatol 2020; 40 (12) 1834-1840
    CrossrefPubMedGoogle Scholar
  • 21 Beardsall K, Thomson L, Guy C. et al; REACT collaborative. Real-time continuous glucose monitoring in preterm infants (REACT): an international, open-label, randomised controlled trial. Lancet Child Adolesc Health 2021; 5 (04) 265-273
    CrossrefPubMedGoogle Scholar
  • 22 Vajravelu ME, Congdon M, Mitteer L. et al. Continuous intragastric dextrose: a therapeutic option for refractory hypoglycemia in congenital hyperinsulinism. Horm Res Paediatr 2019; 91 (01) 62-68
    CrossrefPubMedGoogle Scholar
  • 23 Sigal WM, Alzahrani O, Guadalupe GM. et al. Natural history and neurodevelopmental outcomes in perinatal stress induced hyperinsulinism. Front Pediatr 2022; 10: 999274
    CrossrefPubMedGoogle Scholar
  • 24 Ross KM, Ferrecchia IA, Dahlberg KR, Dambska M, Ryan PT, Weinstein DA. Dietary management of the glycogen storage diseases: evolution of treatment and ongoing controversies. Adv Nutr 2020; 11 (02) 439-446
    CrossrefPubMedGoogle Scholar
  • 25 Ahmad N, Sharkia M, Stewart L. Long term medical treatment of congenital hyperinsulinaemic hypoglycemia. J Endocrinol Diabetes 2014; 1 (01) 4
    CrossrefPubMedGoogle Scholar
  • 26 Gray KD, Dudash K, Escobar C. et al; Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Prevalence and safety of diazoxide in the neonatal intensive care unit. J Perinatol 2018; 38 (11) 1496-1502
    CrossrefPubMedGoogle Scholar
  • 27 Herrera A, Vajravelu ME, Givler S. et al. Prevalence of adverse events in children with congenital hyperinsulinism treated with diazoxide. J Clin Endocrinol Metab 2018; 103 (12) 4365-4372
    CrossrefPubMedGoogle Scholar
  • 28 Keyes ML, Healy H, Sparger KA. et al. Necrotizing enterocolitis in neonates with hyperinsulinemic hypoglycemia treated with diazoxide. Pediatrics 2021; 147 (02) e20193202
    CrossrefPubMedGoogle Scholar
  • 29 Chen SC, Dastamani A, Pintus D. et al. Diazoxide-induced pulmonary hypertension in hyperinsulinaemic hypoglycaemia: recommendations from a multicentre study in the United Kingdom. Clin Endocrinol (Oxf) 2019; 91 (06) 770-775
    CrossrefPubMedGoogle Scholar
  • 30 Thornton P, Truong L, Reynolds C, Hamby T, Nedrelow J. Rate of serious adverse events associated with diazoxide treatment of patients with hyperinsulinism. Horm Res Paediatr 2019; 91 (01) 25-32
    CrossrefPubMedGoogle Scholar
  • 31 Desai J, Key L, Swindall A, Gaston K, Talati AJ. The danger of diazoxide in the neonatal intensive care unit. Ther Adv Drug Saf 2021; 12: 20 420986211011338
    CrossrefPubMedGoogle Scholar
  • 32 Chandran S, R PR, Mei Chien C, Saffari SE, Rajadurai VS, Yap F. Safety and efficacy of low-dose diazoxide in small-for-gestational-age infants with hyperinsulinemic hypoglycemia. Arch Dis Child Fetal Neonatal Ed 2022; 107: 359-363
    CrossrefPubMedGoogle Scholar
  • 33 Aynsley-Green A, Hussain K, Hall J. et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal Ed 2000; 82 (02) F98-F107
    CrossrefPubMedGoogle Scholar
  • 34 Bhowmick SK, Lewandowski C. Prolonged hyperinsulinism and hypoglycemia. In an asphyxiated, small for gestation infant. Case management and literature review. Clin Pediatr (Phila) 1989; 28 (12) 575-578
    CrossrefPubMedGoogle Scholar
  • 35 Walsh EPG, Alsweiler JM, Ardern J, Hanning SM, Harding JE, McKinlay CJD. Glucagon for neonatal hypoglycaemia: systematic review and meta-analysis. Neonatology 2022; 119 (03) 285-294
    CrossrefPubMedGoogle Scholar
  • 36 McMahon AW, Wharton GT, Thornton P, De Leon DD. Octreotide use and safety in infants with hyperinsulinism. Pharmacoepidemiol Drug Saf 2017; 26 (01) 26-31
    CrossrefPubMedGoogle Scholar
  • 37 Chandran S, Agarwal A, Llanora GV, Chua MC. Necrotising enterocolitis in a newborn infant treated with octreotide for chylous effusion: is octreotide safe?. BMJ Case Rep 2020; 13 (02) e232062
    CrossrefPubMedGoogle Scholar
  • 38 Laje P, Halaby L, Adzick NS, Stanley CA. Necrotizing enterocolitis in neonates receiving octreotide for the management of congenital hyperinsulinism. Pediatr Diabetes 2010; 11 (02) 142-147
    CrossrefPubMedGoogle Scholar
  • 39 Yorifuji T, Horikawa R, Hasegawa T. et al; (on behalf of The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons). Clinical practice guidelines for congenital hyperinsulinism. Clin Pediatr Endocrinol 2017; 26 (03) 127-152
    CrossrefPubMedGoogle Scholar
  • 40 Karbalivand H, Iyare A, Aponte A, Xianhong X, Kim M, Havranek T. Hypoglycemia screening of asymptomatic newborns on the 2nd day of life. J Neonatal Perinatal Med 2022; 15 (02) 311-316
    CrossrefPubMedGoogle Scholar
  • 41 van Kempen AAMW, Eskes PF, Nuytemans DHGM. et al; HypoEXIT Study Group. Lower versus traditional treatment threshold for neonatal hypoglycemia. N Engl J Med 2020; 382 (06) 534-544
    CrossrefPubMedGoogle Scholar
  • 42 Shearer A, Boehmer M, Closs M. et al. Comparison of glucose point-of-care values with laboratory values in critically ill patients. Am J Crit Care 2009; 18 (03) 224-230
    CrossrefPubMedGoogle Scholar
  • 43 Cook A, Laughlin D, Moore M. et al. Differences in glucose values obtained from point-of-care glucose meters and laboratory analysis in critically ill patients. Am J Crit Care 2009; 18 (01) 65-71 , quiz 72
    CrossrefPubMedGoogle Scholar
  • 44 Glasgow MJ, Harding JE, Edlin R. for the CHYLD Study Team. Cost analysis of cot-side screening methods for neonatal hypoglycaemia. Neonatology 2018; 114 (02) 155-162
    CrossrefPubMedGoogle Scholar
  • 45 Raizman JE, Shea J, Daly CH. et al. Clinical impact of improved point-of-care glucose monitoring in neonatal intensive care using Nova StatStrip: evidence for improved accuracy, better sensitivity, and reduced test utilization. Clin Biochem 2016; 49 (12) 879-884
    CrossrefPubMedGoogle Scholar
  • 46 Makaya T, Memmott A, Bustani P. Point-of-care glucose monitoring on the neonatal unit. J Paediatr Child Health 2012; 48 (04) 342-346
    CrossrefPubMedGoogle Scholar
  • 47 Feltman DM, Du H, Leuthner SR. Survey of neonatologists' attitudes toward limiting life-sustaining treatments in the neonatal intensive care unit. J Perinatol 2012; 32 (11) 886-892
    CrossrefPubMedGoogle Scholar
  • 48 de Koning R, Egiz A, Kotecha J. et al. Survey fatigue during the COVID-19 pandemic: an analysis of neurosurgery survey response rates. Front Surg 2021; 8: 690680
    CrossrefPubMedGoogle Scholar