Physiology and diagnostic potential of beta-hydroxybutyrate in neonatal glycemia - a prospective cohort study

Neonatal hypoglycemia is the most common metabolic disorder in newborns and may lead to adverse neurodevelopment. The role of alternative substrates such as beta-hydroxybutyrate (BOHB) during neonatal hypoglycemia is poorly understood.

To examine BOHB in neonates with and without hypoglycemia risk factors across different feeding regimens, and to estimate the potential to guide discontinuation of blood glucose (BG) screening.

Prospective cohort study (05/2020-09/2022). Standardized BG and BOHB measurements.

Single-center tertiary hospital.

895 neonates with (n = 752) and without (n = 143, controls) hypoglycemia risk factors.

None.

Comparison of BG and combined BG + BOHB values and percentiles across different risk factors and feeding regimens. Ketonemia was defined as BOHB >0.5 mmol/L.

Of 516 neonates with BOHB measurements at ≥24 hours of age, 107 (20.7%) had ketonemia. Ketonemia was more frequent in controls than in at-risk neonates (28.2% (33/117) vs. 18.6% (74/399), P = .023), and in neonates receiving exclusively breastmilk than in exclusively formula-fed neonates (34% (16/47) vs. 3% (1/39), P < .001). BG and BG + BOHB percentile trajectories diverged more over time in controls, large-for-gestational-age neonates, and infants of diabetic mothers than in small-for-gestational and/or fetal-growth-restricted, preterm, or perinatally stressed neonates.

Neonates with hypoglycemia risk factors and those receiving formula developed less ketonemia. The low overall incidence of ketonemia and its dependence on feeding regimen - particularly among at-risk neonates - limit the utility of BOHB, alone or in combination with BG, as a broadly applicable marker for determining when hypoglycemia screening can be safely discontinued.