Notes

Hypoglycemia of the Newborn

Types:
1. Transitional (<72 hours)
2. Persistent

Definitions of a safe range:
1. Normative ranges (What the majority of neonates have reached by any given age)
2. Symptoms (jitters/tremors, cyanosis, convulsions, apneic spells, tachypnea, lethargy)
- These symptoms overlap with other conditions such as meningitis, or seizures unrelated to hypoglycemia
- While Whipple's triad (signs/symptoms, low serum glucose and resolution w/ glucose administration) is not used diagnostically, it can help to establish hypoglycemia as a cause for the symptoms and should be documented
3. Sequelae (some studies have used neurological changes or consequences of low glucose to determine a safe range)
- this has been challenging as there is a great deal of variability even in normal glucose levels, so hard to find correlations between levels and sequelae
4. physiologic changes (rise in ketones, growth hormone, decrease in insulin etc)

Based on this, the generally accepted numbers are:
Transitional: 2.6mmol
Persistent: 2.8mmol (threshold for investigation); 3.3mmol (treatment target)

Screening

Note on screening:
- treatment can be initiated on the basis of point-of-care assessments, but findings should be confirmed by laboratory assays as POC tools are inaccurate at very low glucose levels
Risk factors: SGA, LGA, IUGR, Infant of diabetic mother, preterm, maternal Labetalol use, late preterm exposure to antenatal steroids, perinatal asphyxia, metabolic conditions (e.g. CPT-1 deficiency, particularly in Inuit children, syndromes (e.g. Beckwith-Wiedmann)
Who should be screened:
1. No study which gives optimal timing and schedule for screening
2. No evidence to support routine screening of asymptomatic, low risk children

Therefore:
1. Symptomatic children should have assessment right away
- levels should be maintained >2.6mmol
2. Asymptomatic children during the transitional period
- studies have shown that low glucose (as low as 2.0mmol) doesn't necessarily have consequences 
3. Persistent glucose levels below 3.3mmol should be treated

Screening Recommendation:

1. Asymptomatic children with no risk factors: no routine screening
2. At risk children
- 2 hours of life
- every 3-6 hours after that

- LGA and IDM can stop glucose assessment if they remain >2.6 for 12 hours
- SGA and preterm can stop if feeding has been established and they remain >2.6 for 24 hours

Treatment:

1. Asymptomatic hypoglycemia
- increasing breastfeeding frequency
- supplementation of feeds
- intrabuccal dextrose gel
- IV glucose

-- Studies are unclear on which of these is best long term, or if they're better than frequent breastfeeding on demand. As such, frequent breastfeeding on demand should be encouraged in at-risk children.

2. Symptomatic hypoglycemia
- Immediate IV glucose
- response should be checked every 30 minutes, and if no response to the first dose, doses should be increased in a stepwise manner

Further investigation

1. Transitional: Not necessary to investigate further unless there is suspicion of a condition that will result in persistent or recurrent hypoglycemia
2. Persistent: Should be investigated further
- The workup should include a confirmatory plasma glucose, beta-hydroxybutyrate, bicarbonate, lactate, free fatty acids, insulin, growth hormone, cortisol, carnitine, and acylcarnitine profiling.
- Further workup should be conducted in collaboration with specialists in endocrinology and inborn errors of metabolism.