Lower on par with standard glucose treatment threshold for neonatal hypoglycaemia

In the management of infants born with moderate hypoglycaemia, a strategy of initiating treatment at a lower glucose concentration proves noninferior to a traditional threshold of 47 mg/dL in terms of preventing brain injury, according to the results of the HypoEXIT* trial.

“Our trial supports earlier expert opinion and current guidelines that recommend a treatment threshold value of 36 mg/dL and provides additional data for the development of guidelines for the large group of newborns—late-preterm infants, infants born small or large for gestational age, and infants of mothers with diabetes—who have a high incidence of neonatal hypoglycaemia,” the investigators said. [Pediatr Clin North Am 2015;62:385-409; Semin Fetal Neonatal Med 2014;19:27-32; J Pediatr 2012;161:787-791; https://www.nice.org.uk/guidance/ng3]

The analysis included 689 otherwise healthy neonates born at ≥35 weeks of gestation and had asymptomatic moderate hypoglycaemia between 3 and 24 hours after birth who had been randomized to a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg/dL; n=348) or a traditional threshold (treatment at a glucose concentration of <47 mg/dL; n=341).

Psychomotor development at 18 months was assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III-NL) in 287 of the 348 children (82.5 percent) in the lower-threshold group and in 295 of the 341 children (86.5 percent) in the traditional-threshold group. There were no significant between-group differences in cognitive (mean, 102.9 vs 102.2) and motor (mean, 104.6 vs 104.9) outcome scores, indicating noninferiority of the lower to the traditional threshold. [N Engl J Med 2020;382:534-544]

The mean glucose concentrations were 57 mg/dL in the lower-threshold group and 61 mg/dL in the traditional-threshold group. Hypoglycaemic episodes occurred less frequently and were less severe in the latter, but that group underwent more invasive diagnostic and treatment interventions. There were two serious adverse events documented in the lower-threshold group, one case of convulsions that occurred during normoglycaemia and another of death.

“[B]ecause the neonatal hypoglycaemia experience cannot be defined by a single numerical value, and long-term psychomotor development depends on multiple factors, a management strategy with a threshold value of 36 mg/dL should not be regarded as safe under all circumstances,” the investigators said.

They pointed out that while the frequency of hypoglycaemic episodes had no effect on the psychomotor outcome, the number of newborns with recurrent episodes was too small to exclude an effect with certainty. “[A]dditional investigations for underlying causes should be considered alongside adequate treatment for hypoglycaemia.

“Finally, our conclusions should not be extrapolated to hypoglycaemia that persists after the first 2 postnatal days or to newborns who are born at <35 weeks of gestation, have a birth weight of less than 2,000 g, or are sick. Such infants are already at an increased risk for impaired developmental outcome, which makes a lower treatment threshold less desirable,” the investigators explained.

Newborns with persistent hypoglycaemia due to endocrine or metabolic disorders may require a higher target glucose concentration, they added.

*Hypoglycemia–Expectant Monitoring versus Intensive Treatment