Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years

N Engl J Med. 2015 Oct 15;373(16):1507-18. doi: 10.1056/NEJMoa1504909.


Background: Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited.

Methods: We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function.

Results: Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome.

Conclusions: In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / analysis*
  • Child Development*
  • Child, Preschool
  • Developmental Disabilities / epidemiology*
  • Developmental Disabilities / etiology
  • Female
  • Glucose / therapeutic use*
  • Humans
  • Hypoglycemia / physiopathology*
  • Hypoglycemia / prevention & control
  • Hypoglycemia / psychology
  • Hypoglycemia / therapy
  • Infant, Newborn / blood*
  • Male
  • Prospective Studies
  • Risk


  • Blood Glucose
  • Glucose