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Hypoglycemia in preterm babies

By Dr. Namrata Todurkar

Why do NICU staff fuss so much about blood sugars?

Glucose, like oxygen, is of existential importance for any living being and it is the major energy source for the newborn infant. The placenta ensures a steady supply of glucose to the fetus, while birth marks a sudden change in glucose delivery and a major change in metabolism. This makes the vulnerable infant prone to low sugars, especially if he or she cannot feed immediately. The symptoms of neonatal hypoglycemia are nonspecific and overlap with symptoms of other conditions, including sepsis, birth asphyxia and electrolyte imbalance. Therefore, one may never know that a vulnerable infant is hypoglycemic unless a blood glucose check is performed.


In medical jargon, low sugar level is known as hypoglycemia, and high sugar level is known as hyperglycemia. Both hypo and hyperglycemia occur in sick infants, but hypoglycemia is by far the most common metabolic abnormality encountered in the neonatal intensive care unit and affects a large number of neonates. Before the first 72 hours of life a blood glucose level of < 2.6 mmol/L is considered as low and after that time, a blood glucose level of > 3.3 mmol/L is considered as hypoglycemia.


Who are at risk of hypoglycemia?

Certain group of infants such as those born preterm, small for gestational age (SGA) and with intra-uterine growth restriction (IUGR) are especially vulnerable to hypoglycemia due to their lack of metabolic reserves and associated co-morbidities; and therefore, are considered as high risk. Nearly 30–60% of these high-risk infants are hypoglycemic and require immediate intervention. Among them, preterm neonates are uniquely predisposed to developing hypoglycemia due to their limited glycogen and fat stores, inability to generate new glucose using existing pathways, having higher metabolic demands due to a relatively larger brain size, and inability to mount a counter-regulatory response to hypoglycemia.

Infants at high risk of hypoglycemia:

  • Birth weight <10th percentile (Small for gestational age)

  • Birth weight >90th percentile (Large for gestational age)

  • Intrauterine growth restriction

  • Infants of diabetic mother

  • Preterm infants (born at <37 weeks gestation)

  • Inborn errors of metabolism (e.g: CPT-1 deficiency)

  • Syndromes associated with hypoglycemia (e.g: Beckwith-Wiedemann syndrome)

What will happen if a baby develops hypoglycemia?

Normal brain obtains more than 50% of its energy needs from glucose oxidation. Nervous tissue can survive short periods of low blood glucose levels by utilizing alternative energy substrates (ketones, amino acids, lactate) to fuel its metabolic demands. Ultimately, a glucose supply must be re-established. A number of studies of at-risk term, preterm, and small-for-gestational-age (SGA) infants have associated blood glucose levels of <2.6 mmol/L with abnormal short- and long-term neurological changes. Current evidence suggests that the therapeutic goal for glucose levels in infants with persistent hypoglycemia should be ≥3.3 mmol/L after 72 hours post-birth.

In preterm infants, the situation is more complicated as the brain is still developing and is therefore highly prone to injury. A significant amount of brain cell multiplication takes place during the third trimester of fetal life. Hypoglycemia delays this cell multiplication in preterm infants. Hypoglycemic brain injury is associated with a smaller head circumference measured at 12 months, 18 months, and 5 years corrected age and poor cognitive abilities. The duration, severity as well as the number of hypoglycemia events closely correlate with adverse outcomes. This may manifest as early as a few hours of life in the form of seizures, apnea, irritability, lethargy, or coma; or may manifest later in childhood with delayed milestones, developmental delays, poor Bayley scores, or poor test proficiency by 4th or 5th grade.

Special risk factors causing hypoglycemia in preterm infants in NICU:

  • Co-morbidities like feed intolerance, necrotizing enterocolitis may result in dependance on IV fluids for glucose supply.

  • IV lines may be disrupted without warning leading to unrecognized hypoglycemia.

  • Fluid intake restriction in kidney failure or fluid overload state may decrease glucose supply.

  • Incompatibility of IV fluid with medication may force the treating team to give lower concentration of dextrose in IV fluid in order to preserve the vein.

  • Certain medications which cause high blood sugars e.g: Steroids may be discontinued without adjustment to IV/oral glucose intake. This may lead to sudden onset hypoglycemia.

  • Preterm infants are prone to temperature fluctuations and both high or low temperature will increase the utilization of glucose in the body.

  • Frequently suffer from infection which increases glucose utilization.

  • May not develop hypoglycemia symptoms like lethargy or seizures due to neurological immaturity and thus may be unrecognized for a long time.

Why bigger is not better:

While we spoke about small size babies being prone to low sugar levels, bigger babies are not safe either. Infants of diabetic mothers (IDM) and large for gestational age infants (birth weight >90th percentile) experience fetal hyperinsulinism and increased glucose utilization, putting them at risk for hypoglycemia immediately after birth. Prolonged elevations in maternal glucose concentrations result in increased fetal insulin production. These elevated levels of insulin persist after birth and, in the absence of a continuous glucose source, result in hypoglycemia.


The Canadian Paediatric Society has the following recommendations regarding screening infants for hypoglycemia:

  • Infants of diabetic (gestational or type 1 or 2) mothers, asphyxiated infants, preterm infants, SGA and LGA infants should be routinely screened for hypoglycemia at 2 hours of age and every 3 to 6 hours after that. Symptomatic and unwell infants require immediate glucose testing.

  • Before discharge from hospital, infants with persistent hypoglycemia should have a 5 to 6 hour fast, while maintaining blood glucose levels ≥3.3 mmol/L, to ensure safety at home.


Thoughts for the future:

It is difficult to see a baby getting multiple heel pokes for blood glucose check in NICU. Having an arterial line for frequent blood testing is desirable, but it may damage the tiny artery leading to decreased blood supply to the area beyond. Future research in biomedical engineering is needed to develop techniques to measure blood glucose non-invasively. Adapting the continuous glucose monitors like Dexcom to extremely preterm infants by research and product development will be a boon to such infants in NICU.


RECOMMENDED RESOURCE FOR PARENTS

https://caringforkids.cps.ca/handouts/blood_glucose_in_newborn_babies


Dr. Namrata Todurkar, MBBS, MD (Pediatrics), DNB (Pediatrics). Fellowship in Neonatology from National Neonatology Forum India. Fellow in Neonatal-Perinatal Medicine at the University of British Columbia. Areas of interest: Neonatal nutrition, Fluid and Electrolyte Management, Inborn Errors, Neurodevelopmental follow-up of preterm infants. Dr. Todurkar is a volunteer blogger at CPBF.

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