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Hypoglycemia in Infants and Children - Approach to the Patient

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General Information

Definitions

  • hypoglycemia1,2
    • clinically defined as plasma glucose sufficiently low to cause signs and/or symptoms of impaired brain function
    • plasma glucose thresholds for specific manifestations of hypoglycemia cannot be defined by a single plasma glucose level which can be influenced by
      • degree and duration of hypoglycemia
      • presence of alternative fuels such ketones
    • additionally, artifacts and inaccuracies in glucose level measurements can complicate interpretation of a single plasma glucose
    • Whipples triad (commonly used to define hypoglycemia in adults)
      • has limited utility in infants and young children who cannot communicate symptoms
      • can be used in older children and adults; triad includes
        • presence of symptoms consistent with hypoglycemia
        • low plasma glucose level
        • resolution of symptoms when normal plasma glucose is restored
  • persistent hypoglycemia – low plasma glucose due to congenital defect in regulation of insulin secretion, hormonal deficiency (cortisol and/or growth hormone), or inborn error of metabolism1
  • hyperinsulinemic hypoglycemia – hypoglycemia caused by hyperinsulinism due to genetic defect or tumor or as seen among infants born to mothers with diabetes3
  • congenital hyperinsulinism – mutation in insulin secretion pathway causes dysregulated insulin secretion that results in hypoglycemia that increases risk of developmental disability (reported in 25%-50% of children with congenital hyperinsulinism)1
  • factitious hypoglycemia – hypoglycemia that is voluntarily self-induced or induced by parent or caretaker3
  • transitional neonatal hypoglycemia – hypoketonemic hypoglycemia with inappropriately large glycemic response to glucagon that occurs in healthy newborns during first 72 hours after birth before maturation of glucose stimulated-insulin secretion mechanism 1
  • ketotic hypoglycemia – low blood glucose accompanied by ketosis characterized by elevated beta-hydroxybutyrate and acetoacetate in blood and urine

Incidence and prevalence

  • 34 children diagnosed with nondiabetic hypoglycemia per 100,000 patients treated at emergency department
    studySummary
    • based on retrospective cohort study Cohort Study
    • 276,313 patients treated at tertiary children's hospital between 1994 and 1999 had medical records reviewed
    • 94 children with complete medical record identified with nondiabetic hypoglycemia
    • 11 children diagnosed with idiopathic ketotic hypoglycemia
    • PubMed12865107The Journal of emergency medicine20030701J Emerg Med2513939 Reference - 12865107J Emerg Med 2003 Jul;25(1):39OpenInNew
  • incidence and relative prevalence of specific types and causes of hypoglycemia
    • idiopathic ketotic hypoglycemia (no underlying endocrine or metabolic defect) is most common nondiabetic hypoglycemia in children4
    • congenital hyperinsulinism
    • although rare overall, insulinomas are more commonly found in older children than in younger children4

References

General references used

  1. Thornton PS, Stanley CA, De Leon DD, et al. Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children. J Pediatr. 2015 Aug;167(2):238-45OpenInNewfull-textOpenInNew
  2. Gandhi K. Approach to hypoglycemia in infants and children. Transl Pediatr. 2017 Oct;6(4):408-420OpenInNewfull-textOpenInNew
  3. Shah P, Rahman SA, Demirbilek H, Güemes M, Hussain K. Hyperinsulinaemic hypoglycaemia in children and adults. Lancet Diabetes Endocrinol. 2017 Sep;5(9):729-742OpenInNew
  4. Ghosh A, Banerjee I, Morris AA. Recognition, assessment and management of hypoglycaemia in childhood. Arch Dis Child. 2016 Jun;101(6):575-80OpenInNew

Recommendation grading systems used

  • Pediatric Endocrine Society (PES) uses Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Working Group framework for recommendations
    • strength of recommendation
      • Strong recommendation - recommend (Grade 1)
      • Weak recommendation - suggest (Grade 2)
    • level of evidence
      • High - further research is unlikely to change confidence in the estimate of effect (++++)
      • Moderate - further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate (+++0)
      • Low - further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate (++00)
      • Very low - any estimate of effect is very uncertain (+000)
    • Reference - PES recommendation on evaluation and management of persistent hypoglycemia in neonates, infants, and children (25957977J Pediatr 2015 Aug;167(2):238OpenInNewfull-textOpenInNew)
  • Endocrine Society uses Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification system for recommendations
    • strength of recommendation
      • Strong recommendation - guideline panel members have high confidence that desirable effects of recommendation outweigh undesirable effects (or vice versa)
      • Weak recommendation - guideline panel members conclude with less confidence that desirable effects of recommendation probably outweigh undesirable effects, or benefits and harms are finely balanced, or appreciable uncertainty
    • quality of evidence
      • High-quality evidence - consistent evidence from well-performed randomized controlled trials, or exceptionally strong evidence from unbiased observational studies
      • Moderate-quality evidence - randomized controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise evidence), or unusually strong evidence from unbiased observational studies
      • Low-quality evidence - ≥ 1 critical outcome from observational studies, randomized controlled trials with serious flaws, or indirect evidence
      • Very low-quality evidence - ≥ 1 of the critical outcomes from unsystematic clinical observations or very indirect evidence

Synthesized Recommendation Grading System for DynaMed

  • DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based MethodologyOpenInNew).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed (DM), we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE)OpenInNew to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed (DM) synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

Special acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of DynaMed Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors are employees of DynaMed and oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T922336, Hypoglycemia in Infants and Children - Approach to the Patient; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T922336. Registration and login required.

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