Neonatal hypoglycemia

Neonatal hypoglycemia cannot be defined by a single value of glucose applicable to all clinical situations and to all infants.

Neonatal hypoglycemia is common, occurring in up to 15% of babies born at or near term.The brain utilizes 95% of body’s available glucose. Long term follow up studies of hypoglycemic infants suggests, there is an association between hypoglycemia and adverse neurologic sequelae, even if asymptomatic.Early and frequent feeds provide nutrient substrates to support gluconeogenesis to possibly prevent hypoglycemia in at-risk infants.Because these clinical manifestations may result from various causes, it is critical to measure serum glucose levels and to determine whether they disappear with the administration of sufficient glucose to raise the blood sugar to normal levels; if they do not, other diagnoses must be considered.

So-called ‘normal ranges’ are presumably dependent on the infant’s size, gestation and clinical condition, as well as the availability of energy sources and ongoing energy demands.Baby may have jitteriness or tremors, apathy, episodes of cyanosis, convulsions, intermittent apneic spells or tachypnea, weak or high-pitched cry, limpness or lethargy, difficulty in feeding, and eye rolling. Episodes of sweating, sudden pallor, hypothermia, and cardiac arrest and failure also occur.

In exclusively breastfed, appropriate-for-gestational-age, term babies, blood glucose falls immediately after birth from two-thirds of maternal levels to the 5th percentile of approximately 1.8 mmol/L at 1 hr of age.

There is a subsequent rise to levels over 2.0 mmol/L that is maintained for 72 hr (based on individual cohort study, level 2B evidence).

 It is important to note that 12% to 14% of normal, appropriate-for-gestational- age, breastfed newborns have a blood glucose level of less than 2.6 mmol/L in the first three days of life (based on systematic review of cohort studies, level 2a evidence). 

Neonatal hypoglycemia most commonly occurs in infants with impaired gluconeogenesis, brought about by excess insulin production, altered counter-regulatory hormone production or an inadequate substrate supply. Classically, these states occur in SGA (weight at less than the 10th percentile) infants, large-for-gestational-age (LGA; weight at more than the 90th percentile) infants, IDMs and preterm infants. Neonatal glucose levels fall during the first hour or two after birth, reaching a natural trough before rising to stable neonatal levels.

It is recommended that infants at risk be screened at 4 hr to 6 hr of age. IDMs frequently experience asymptomatic hypoglycemia by 1 hr of age, supporting earlier screening in this population.Hypoglycemia usually occurs in LGA infants and IDMs within 12 hr of birth, and screening beyond this period is not required if blood glucose is maintained at 2.6 mmol/L or higher. However, preterm and SGA infants may be vulnerable up to 36 hr of age and perhaps later, particularly if regular feeds or intravenous infusions are not yet established.The inference is that screening of preterm and SGA infants can be  discontinued at 36 hr of age if feeding is established and blood  glucose is maintained at 2.6 mmol/L or higher.

Brief periods of asymptomatic hypoglycemia are benign, it is recommended that screening be initiated in at-risk babies at 2 hr of age (after an initial feed) and should be continued until the period of risk is considered over.

‘Symptomatic infants’ should have a blood glucose assessment without delay as part of the workup for diagnostic and therapeutic purposes. Feeding raises blood glucose and stimulates ketosis , it seems rational to feed at-risk infants at regular intervals, while screening before feeds. IDMs & LGA infants) were most likely to develop hypoglycemia in the first few hours of life – as a consequence, screening is not required in this population after 12 hr of age if levels remain at 2.6 mmol/L or greater.

  SGA and preterm infants may become hypoglycemic as late as the second day. It would be reasonable to screen once or twice on the second day  of life, to ensure levels remain at 2.6 mmol/L or higher in this group. If there are no feeding concerns and the infant is well, screening may be discontinued at 36 h of age. 

Blood glucose is measured on capillary samples using chemical strips or portable, bedside glucose meters as a substitute for formal laboratory analysis. Sometimes many of these ‘point-of-care’ methods are not reliable at the low glucose levels  and are prone to sample or observer error. If ‘point-of-care’ methods are used, a formal process for assuring quality control at the bedside should be in place and rapid laboratory testing should be available to verify glucose levels that may require intervention.

Symptomatic hypoglycemia results in neuronal injury, making urgent intervention desirable in sick infants. Because there is no absolute level at which intervention is mandated, the proposed cut-off (repeated levels of less than 2.6 mmol/L in an at-risk infant) is recommended.There are, essentially, two approaches.

The first supports increased energy intake (orally or intravenously), while the second supports increased mobilization of energy stores (using counter-regulatory hormones, such as glucagon or corticosteroids).

The urgency and nature of interventions depend on the presence of symptoms and the severity of the hypoglycemia.Blood glucose levels as low as 2.0 mmol/L (or even 1.8 mmol/L at 1 hr of age) are not uncommon in healthy newborns.

Asymptomatic, at-risk babies should receive at least one effective feed before a blood glucose check at 2 hr of age and should be encouraged to feed regularly thereafter.

At-risk babies who have a blood glucose of less than 1.8 mmol/L at 2 hr of age despite one feed (breastfeed or approximately 5 mL/kg to 10 mL/kg of formula or glucose water), or less than 2.0 mmol/L after subsequent feeding, should receive an intravenous dextrose infusion.At-risk babies who repeatedly have blood glucose levels of less than 2.6 mmol/L despite subsequent feeding should also be considered for intravenous therapy.For both the prevention and treatment of asymptomatic hypoglycemia, include increased breastfeeding frequency, supplementation with breastmilk or a breast milk substitute, or intravenous glucose therapy. Frequent breastfeeding on demand should be encouraged in at-risk babies, and, if formula fed or supplemented, the volume of enteral intake should be adjusted according to the size, age and gestation of the infant.

When feeding interventions are offered for low blood glucose, levels should be rechecked in 60 min to ensure that there has been a response.Sick, hypoglycemic infants, particularly those with neurological signs, should be treated immediately with an intravenous infusion of glucose.The effect of intravenous interventions may be rechecked after 30 min. The target level should be 2.6 mmol/L or higher. An initial failure to respond to intravenous glucose requires a stepwise increase in glucose supply, with a review of blood glucose 30 min after each increment.

Changing from 10% to 12.5% dextrose will increase intravenous intake by 25%, as would a rate increase from 80 mL/kg/day to 100 mL/kg/day. An increase from 100 mL/kg/day to 120 mL/kg/day of 12.5% dextrose raises the glucose supply from 8.7 mg/kg/min to 10.4 mg/kg/min.uIf this infusion rate fails to keep blood glucose levels at 2.6 mmol/L or higher, further investigation, specialist referral and/or pharmacological intervention (e.g., intravenous glucagon) should be considered. Investigations should be aimed at identifying endocrine pathology (particularly hyperinsulinism) and inborn errors of metabolism.

Glucagon by intravenous bolus (0.1 mg/kg to 0.3 mg/kg) or infusion (10 μg/kg/h to 20 μg/kg/h) has been observed to raise blood glucose and prevent recurrent episodes of hypoglycemia in both term and preterm infants. Severe hyponatremia with the use of glucagon is a potential risks associated with this therapy. Monitoring of serum sodium should be conducted while receiving glucagon therapy.

Alternative therapies include hydrocortisone, diazoxide and octreotide.u? Dextrose gel 40% (Insta-Glucose?) is available in a single use tube containing a pink, cherry flavored gel. In neonates, it is appropriate to use the same tube for the same baby if further doses are required within 24 hours. Breastfeeding may be continued without risk of over hydration because the volume of colostrum is small.

To avoid overhydration and hyponatremia in supplemented infants, oral and intravenous intake should not exceed 100 mL/kg/day without careful monitoring for dilutional hyponatremia. Blood glucose levels should be checked frequently until interventions result in stable glucose levels of 2.6 mmol/L or higher; failure to achieve this level requires re-evaluation and consultation. Intravenous dextrose can be weaned when levels have been stable for 12 hr.

Both parents and health care providers require education regarding screening. Parents should be aware that their child is symptomatic or at risk, and therefore, requires blood testing at regular intervals.

An informed explanation, possibly with the aid of a parent handout will help ensure appropriate parental participation in monitoring and allay fears if further interventions are required.