Vitamin D insufficiency in neonatal hypoxic–ischemic encephalopathy

Abstract

BackgroundVitamin D has neuroprotective and immunomodulatory properties, and deficiency is associated with worse stroke outcomes. Little is known about effects of hypoxia-ischemia or hypothermia treatment on vitamin D status in neonates with hypoxic-ischemic encephalopathy (HIE). We hypothesized vitamin D metabolism would be dysregulated in neonatal HIE altering specific cytokines involved in Th17 activation, which might be mitigated by hypothermia.MethodsWe analyzed short term relationships between 25(OH) and 1,25(OH)2 vitamin D, vitamin D binding protein, and cytokines related to Th17 function in serum samples from a multicenter randomized controlled trial of hypothermia 33°C for 48h after HIE birth versus normothermia in 50 infants with moderate to severe HIE.ResultsInsufficiency of 25(OH) vitamin D was observed after birth in 70% of infants, with further decline over the first 72h, regardless of treatment. 25(OH) vitamin D positively correlated with antiinflammatory cytokine IL-17E in all HIE infants. However, Th17 cytokine suppressor IL-27 was significantly increased by hypothermia, negating the IL-27 correlation with vitamin D observed in normothermic HIE infants.ConclusionsSerum 25(OH) vitamin D insufficiency is present in the majority of term HIE neonates and is related to lower circulating anti-inflammatory IL-17E. Hypothermia does not mitigate vitamin D deficiency in HIE.

Neonatal Vitamin D Status Is Associated with the Severity of Brain Injury in Neonatal Hypoxic–Ischemic Encephalopathy: A Pilot Study

“…[6][7][8] Recent studies have demonstrated that the majority of infants who have suffered from HIE have vitamin D deficiency. 9 The resulting neuronal injury in HIE is primarily driven by hypoxia and inflammation, and vitamin D appears to be protective against both. 10 Vitamin D reduces differentiation and proliferation of lymphocytes that produce the proinflammatory cytokine interleukin (IL)-17, 11,12 and vitamin D insufficiency is associated with low levels of the anti-inflammatory cytokines IL-10, IL-17E (IL-25), and IL-27.…”

“…10 Vitamin D reduces differentiation and proliferation of lymphocytes that produce the proinflammatory cytokine interleukin (IL)-17, 11,12 and vitamin D insufficiency is associated with low levels of the anti-inflammatory cytokines IL-10, IL-17E (IL-25), and IL-27. 9,[11][12][13] As such, insufficient levels of 25-hydroxyvitamin D (25OHD) could be an aggravating factor after neonatal HIE; however, there is minimal published data assessing the effects of vitamin D levels on outcomes in human neonates with HIE. 9 Although vitamin D deficiency has been associated with HIE, there has historically been considerable controversy in the literature in defining deficiency.…”

The alterations effects in phosphorus of erythropoietin and U-74389G

“…31 P-MRS may provide quantitative parameters for evaluating graft viability ex vivo and is a promising tool for objective non-invasive assessment of the quality of human pancreas grafts prior to transplantation or islet isolation. Lowe, et al positively correlated [23] anti-in lammatory cytokine IL-17E with serum 25(OH) vitamin D insuf iciency present in the majority of term HIE neonates. Layec, et al assessed muscle metabolism and peripheral hemodynamics in healthy, untrained, elderly individuals subjected [24] to dynamic plantar lexion exercise and other imaging examinations including phosphorus magnetic resonance spectroscopy (31P-MRS).…”

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

“…In infants with HIE, both the infants and their mothers have been found to have decreased levels of vitamin D [18]. One study demonstrated that at the time of NICU admission, 70% of infants with hypoxic-ischemic brain injury were considered to be vitamin D-deficient, and many of these infants continued to have declining levels for 72 h after the injury despite the administration of parenteral nutrition containing vitamin D 2 supplementation of about 400 IU/day.…”

“…Given the data supporting the role of vitamin D as a protective neurohormone, investigators have begun to assess if vitamin D could play role in the prevention or therapy of neonatal HIE. Early results have demonstrated low levels of vitamin D in infants and the mothers of infants who have suffered from HIE [18], and the neonates’ serum vitamin D levels often continue to decline for 72 h after the injury despite supplementation [19]. The story of the interaction between vitamin D and neonatal HIE has just begun to unfold, and many questions remain unanswered.…”