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Screening & Management of Hypoglycemia in Late Preterm and Term Infants (Greater than or Equal to 34 weeks GA)

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UCSF NCNC (Northern California Neonatology Consortium) 

Table of Contents

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PART I: Background

  • Risk factors for neonatal hypoglycemia
    • Inadequate glycogen stores
          • Small for gestational age (SGA)
          • Intrauterine growth restriction (IUGR)
          • Prematurity (< 37 weeks gestational age)
          • Post-term gestation (greater than or equal to 42 weeks gestational age)
    • Increased glucose utilization
          • Large for gestational age (LGA)
          • Infant of a diabetic mother (IDM)
            • Includes mothers with pre-existing diabetes (DM1 or 2) or gestational diabetes (GDMA1 = diet-controlled or GDMA2 = medication-controlled)
          • Conditions which increase metabolic demand: sepsis, encephalopathy, HIE, perinatal stroke, seizures, hypothermia, prematurity, polycythemia, hemolytic disease, metabolic disease, respiratory distress, endocrine abnormalities, congenital heart disease, maternal substance use
    • Hyperinsulinemia
          • LGA
          • IUGR
          • IDM
          • Certain genetic/metabolic conditions (e.g. Beckwith-Weidemann Syndrome)
  • Sequelae of neonatal hypoglycemia
    • Neurodevelopmental Sequelae
      • Association with worse cognitive and motor performance on developmental testing at 18 months, 3 years, 5 years; lower school achievement in children at 4th grade
      • NOTE: recurrent episodes of hypoglycemia are more predictive of long-term sequelae
      • CAVEAT: causality has not been determined for these associations, nor effectiveness / safety of screening and intervention to raise glucose levels

 

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PART II: Definition of hypoglycemia

  • Definition of hypoglycemia
    • “Plasma glucose concentration below which normal brain function cannot occur”
    • Published thresholds for diagnosing hypoglycemia:
      • NOTE: difficult to define a single blood glucose concentration that warrants intervention in every neonate. Published literature and guidelines primarily rely on normative values since defining hypoglycemia based on presence/absence of sequelae or performing prospective clinical trials is impossible.
      • NOTE: units for all glucose values are in mg/dL
      • Alkalay, et al. (2006) - estimate of 5th percentile (breast and formula fed infants):
        • 1-2hrs:     27 mg/dl
        • 3-23hrs:   40 mg/dl
        • 24-47hrs: 41 mg/dl
        • 48-72hrs: 48 mg/dl
      • Cornblath & Ichord (2000) - formula fed infants:
        • All infants: < 20-25 mg/dl
        • First 24hrs:< 30-35 mg/dl (sick < 45-50 mg/dl)
        • > 24hrs:      < 40-50 mg/dl
      • Canadian Pediatric Society (2004):
        • < 32 mg/dl 2hrs post-feed
        • < 36 mg/dl post-subsequent feed
      •  American Academy of Pediatrics (AAP) (2011):
        • Birth-4hrs:< 25 mg/dl (target >40 mg/dl)
        • 4-24hrs: < 35 mg/dl (target >45 mg/dl)
      • Academy of Breastfeeding Medicine (ABM) (2014):
        • < 20-25 mg/dl requires intervention (goal >40 mg/dl)
  • UCSF NCNC consensus thresholds for hypoglycemia:
    • NOTE: values based primarily on 2011 AAP Clinical Report
    • Target/goal neonatal glucose:
      • greater than or equal to 45 mg/dl prior to routine feeds @ 0-24 hours after birth
      • greater than or equal to 50 mg/dl prior to routine feeds @ > 24 hours after birth

 

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PART III: Screening of asymptomatic, at risk infants

  • Screening criteria for asymptomatic, well-appearing, at risk infants
    • IDM (pre-existing maternal diabetes, GDMA1, GDMA2)
    • Growth Restricted or Macrosomic (defined by average of male & female weights on Fenton 2013 intrauterine growth curves):
      • Growth Restricted (<5th%)
      • Macrosomic (>97.5th%)  
      • NOTE: use of a strict birthweight criteria for all term infants is no longer recommended (e.g. <2500, >4000)

 

37-37+6/7 weeks

38-38+6/7 weeks

39-39+6/7 weeks

40-40+6/7 weeks

>41 weeks

Growth restricted (<5th%)

2280 g

2470 g

2650 g

2820 g

3000 g

Macrosomic (>97.5th%)

3950 g

4180 g

4400 g

4630 g

4880 g
    • Late preterm (34-37 weeks)
    • Post term (greater than or equal to 42 weeks)
    • Additional consideration: neonates with conditions known to be associated with secondary hypoglycemia (i.e., polycythemia, sepsis) should also be considered for hypoglycemia screening
  • Method of screening
    • Glucometer
        • NOTE: accuracy in low range can depend on make/model of glucometer.
        • ** Thresholds for repeating low point-of-care-testing (POCT) glucose may differ depending on the device and laboratory; follow your local institutions guidelines for repeating low POCT glucose tests.
          • Consider repeating for POCT values < /= 40 
          • NOTE: sample should be drawn from warmed heel stick
        • NOTE: Consider initiating treatment for hypoglycemia prior to confirmatory testing if waiting for laboratory result will delay treatment excessively
  • Timing of screening
    • General principles:
          • Initial screen after first (breast)feeding (by ~1 hour after birth)
          • More frequent screening in first 2-4 hours of life, then pre-prandial screening that is roughly linked to feeding schedule
          • Stop screening at 12 hours for macrosomic, IDM infants (very low risk of late hypoglycemia)
          • Continue screening until 24 hours for growth restricted, late preterm infants (greater risk of late hypoglycemia)
          • Consider 36 hour screening for growth restricted, late preterm infants if glucoses consistently < 45 mg/dl in first 24 hours after birth
    • Time points for Glucose Screening: ~1, 2, 4, 6, 9, 12, 24 hours unless intervention is required
    • “Early exit”: consider discontinuing glucose screening prior to completion of all time points in asymptomatic infants with “stable”, “normal” glucoses in the first 24 hours after birth:
          • Glucoses > 45 mg/dl on 3 occasions
          • Repeat one pre-prandial glucose measurement at 24 hours after birth for growth restricted, late pre-term infants
          • NOTE: these recommendations are consensus-based; no specific evidence is currently available to support these recommendations

 

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PART IV: Management of asymptomatic infants

  • See APPENDIX 2 for summary clinical pathway / decision tree (ASYMPTOMATIC)
  • Intervention thresholds (see PART II above for details):
    • NOTE: treatment thresholds vary at 0-4 hours and 4-24 hours after birth to reflect changing physiology / normal values during transition to postnatal life
  • Treatment:
    • See algorithm for full work flow and indications for treatment
    • Oral feeding (breast or formula):
      • Method:
        • Breastfeeding
          • Re-check glucose 1 hour after initiation of feeding
          • Repeat breastfeeding if glucose remains below threshold; if glucose remains below threshold after >2 breastfeeding attempts, then consider oral formula supplementation
          • Oral administration of expressed maternal breastmilk (MBM) is also an acceptable form of treatment
        • Formula
          • Use protein hydrolysate formula (i.e., Alimentum, Nutramigen, Pregestimil) preferentially if available to reduce exposure to cow milk protein
            • 1-4 hours -> 10-20 mL
            • 4-24 hours -> 15-30 mL
          • Re-check glucose 1 hour after initiation of feeding
          • If glucose remains below threshold after > 2 oral feedings, then consider IV treatment
    • Oral glucose gel
      • Method:
        • Glucose (Dextrose) 40% gel
        • Administer 0.5 ml/kg with max of 2.5 mL
        • Dry newborn’s mouth with 2x2 gauze
        • Massage the ordered amount of glucose gel using gloved fingertips into the buccal mucosa, instilling no more than 0.5ml into each cheek at a time
      • Important considerations
        • MAXIMUM of THREE doses per 24 hours of oral glucose gel before proceeding to IV treatment.
        • Consider IV treatment prior to 3rd dose of oral glucose if infant is not having sequentially rising glucoses in response to oral therapy.
    • IV treatment:
      • Indications for IV treatments:
        • Glucose levels not responding to oral glucose and feeding therapy
        • Persistent hypoglycemia after 3 doses of oral glucose gel
        • Any glucose < 35 mg/dl after 5 HOL
      • Method:
        • D10W 2-3 ml/kg IV bolus, followed by:
        • D10W @ 80 ml/kg/day (3.5 ml/kg/hr or GIR=5.5 mg/kg/min)
            • Note: Glucose Infusion Rate (GIR) calculated in mg/kg/min
              • IV Rate (mL/hr) x Dextrose% (g/dL)

                                                Wt(kg) x 6

            • Increase D10W in increments of 20 ml/kg/day (0.8 ml/kg/hr or GIR 1.4mg/kg/min) for persistent hypoglycemia
            • Peripheral IV (PIV) may use up to 12.5% dextrose solutions (D12.5W). Increasing IV rate will increase GIR, but if approaching 150 ml/kg/day (6.25 ml/kg/hr) consider using higher dextrose% to avoid fluid overload.
            • For persistent hypoglycemia requiring increasing GIR, consider obtaining central venous access early (e.g., UVC, PICC) to administer high-dextrose fluids (> D12.5).
        • Continue IV treatment until glucose levels are stable > 50 mg/dl, then wean IV gradually
        • If persistently hypoglycemic, consider further evaluation for underlying etiology in parallel with treatment.  Strongly consider involving neonatology, obtaining central venous access, and consulting endocrinology prior to starting glucagon, octreotide, or other therapies.

 

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PART V: Management of symptomatic infants

  • See APPENDIX 3 for summary clinical pathway / decision tree (SYMPTOMATIC)
  • Symptoms of hypoglycemia may include:
    • General symptoms:
      • Abnormal cry, poor feeding, hypothermia, diaphoresis
    • Neurologic symptoms:
      • Tremors, jitteriness, hypotonia, irritability, high-pitched cry, lethargy, seizures
    • Cardiorespiratory disturbances:
      • Cyanosis, pallor, tachypnea, apnea, cardiac arrest
  • Differentiation of “concerning” (“definite”) versus “possible” symptoms of hypoglycemia:
    • “CONCERNING”: seizure, lethargy/poorly responsive, hypotonia, apnea, cyanosis
    • “POSSIBLE”: jitteriness, tremors, irritability, exaggerated Moro reflex, high-pitched cry, poor feeding, excessive sleepiness/drowsiness
  • Thresholds for intervention & treatment:
    • “CONCERNING” (regardless of age)
      • < 45 mg/dl -> IV treatment
        • Use IV treatment method from PART IV above
      • Recheck glucose 30 min after intervention
      • If a baby remains hypoglycemic, remember that GIR can be temporarily raised by increasing the IV infusion rate. Watch for signs of fluid overload.
      • Ok to give small aliquots of oral glucose gel (0.5 mL at a time) while obtaining IV access.
      • If symptoms do not resolve after glucose >50 mg/dl, pursue work-up of other potential causes of symptoms.  Involve neonatology, obtain central venous access and consider an endocrine consult.
      • Glucagon:
        • Option if inadequate glucose response after at least 2 x D10 boluses
        • If considering Glucagon- consult Neonatology and administer in consultation with subspecialist
        • If giving IV bolus of glucagon recheck glucose after 30min.
        • Recommended empiric (unambiguously therapeutic) dose:
          • 1.0 mg glucagon -> if AGA infant >/= 3kg
          • 0.5 mg glucagon -> if infant <3kg
        • Clinical response to glucagon suggests adequate glycogen stores in liver and is consistent with a dx of hyperinsulinemia.
    • “POSSIBLE” (regardless of age)
      • 35-45 mg/dl -> oral treatment (breastfeeding or formula) + oral glucose gel
      • IV treatment after one attempt at oral feeding
      • Use IV or oral treatment method from PART IV above
      • If symptoms do not resolve after glucose > 50, pursue work-up of other potential causes of symptoms

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PART VI: NICU and Special Care / Transitional Care Nursery

  • Treatment thresholds and treatment methods are different for infants in these higher level care settings; consult neonatology for recommendations

 

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References

Adamkin DH & AAP COFN. 2011. Clinical Report – Postnatal Glucose Homeostasis in Late-Preterm and Term Infants. Pediatrics. 127,3: 575-579.

Alkalay, et al. 2006. Population meta-analysis of low plasma glucose thresholds in full-term normal newborns. Am J Perinatol. 23: 115-119.

Canadian Pediatric Society. 2004. Screening guidelines for newborns at risk for low blood glucose. Pediatr Child Health. 9: 723-729.

Cornblath, M & Ichord, R. 2000. Hypoglycemia in the neonate. Sem Perinatol. 24: 136-

Harris, et al. 2012. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 161: 787-791.

Kaiser JR, et al. 2015. Association between Transient Newborn Hypoglycemia and Fourth Grade Achievement Test Proficiency. JAMA. E1-9.

McKinlay C & J Harding. 2015. Revisiting Transitional Hypoglycemia: only time will tell (opinion). JAMA. E1-2.

Rozance, PJ & Hay, WW. 2006. Hypoglycemia in newborn infants: Features associated with adverse outcomes. Biol Neonate. 90: 74-86.

Rozance, PJ. 2014. Update on neonatal hypoglycemia. Curr Opin Endocrinol Diabetes Obes. 21: 45-50.

Stanley, et al. 2015. Re-evaluating “transitional neonatal hypoglycemia”: mechanism and implications for management. J Pediatr. 166,6: 1520-5.

Stieren, Emily & Fernando Gonzalez. Clinical Consensus Conference: Neonatal Hypoglycemia. UCSF. May 26, 2015.

Thornton, et al. 2015. Recommendations from the Pediatric Endocrine Society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr. 167,2: 238-45.

Wight, et al. 2014. ABM Clinical Protocol #1: Guidelines for blood glucose monitoring and treatment of hypoglycemia in term and late-preterm neonates. Breastfeeding Med. 9: 173-179.

 

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APPENDIX 1: Fenton Neonatal Growth Curves (2013).

 

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APPENDIX 2: Screening & Management of Neonatal Hypoglycemia in ASYMPTOMATIC infants Greater than or Equal to 34wks GA

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APPENDIX 3: Screening & Management of Neonatal Hypoglycemia in SYMPTOMATIC infants Greater than or Equal to 34wks GA

 

UCSF NC2 (Northern CA Neonatology Consortium). Originated 5/2014. Edited 9/2015, 5/2018. Revised: 12/2022

Approved by UCSF ICN Patient Safety Committee: 2/3/2023

Approved by UCSF Pharmacy and Therapeutics Committee: 2/8/2023

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