Vitamin D and Its Role in Neonatal Hypoxic-Ischemic Brain Injury

Stessman & Peeples, Neonatology 2018


Emerging evidence has demonstrated that vitamin D plays an important role in many adult neurologic disorders, but is also critical in neuronal development and pruning in the neonatal and pediatric populations. Neonates are at a particularly high risk of vitamin D deficiency, in part due to the high prevalence of maternal deficiency during pregnancy. Several preclinical studies have demonstrated that infants born to vitamin D-deficient mothers are at a high risk of developing neonatal brain injury, and recent clinical studies have shown that neonates with hypoxic-ischemic encephalopathy (HIE) tend to be vitamin D-deficient. There are limited data, however, on whether additional prenatal or postnatal supplementation may alter the prevalence or severity of neonatal HIE. This review examines the current data supporting the neuroprotective role of vitamin D, with a focus on how these findings may be translated to neonates with HIE.


Vitamin D is a vital component of normal neuronal development, but may also play an important role in the brain’s response to injury in the neonatal period. Vitamin D deficiency has been linked to both abnormal brain development and increased vulnerability to neurologic injury. Treatment with vitamin D has resulted in the reduced size and severity of brain infarcts, but many of the studies on its role in the central nervous system are either performed on animal models or adult humans. To better understand the efficacy of vitamin D in altering HIE outcomes, it is necessary to conduct further clinical research in the neonatal population. Important questions to address include establishing the role of maternal vitamin D supplementation in the prevention of HIE and the dosing required for adequate neuroprotection, although both questions will face the issue of obtaining adequate sample sizes in clinical studies due to the relative rarity of neonatal HIE. Multicenter trials will therefore be critical, as vitamin D has significant (though still mostly theoretical) potential for preventing or reducing long-term neurologic injury due to neonatal HIE.

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