Serum Calcium Derangements in Neonates with Hypoxic Ischemic Encephalopathy (HIE) With and Without Therapeutic Hypothermia

Abstract

Abstract BACKGROUND: Perinatal hypoxia is a recognized cause of hypocalcemia in neonates in the first 3 days of age. However, therapeutic hypothermia (TH), the standard care for moderate to severe HIE, promotes neuropro-tection by decreasing calcium (Ca) influx into the cells during reperfusion phase. So TH can increase serum Ca levels and may even negate the hypo-calcemic effects in HIE. OBJECTIVES: To examine the trends in serum Ca levels in neonates with HIE with and without TH. DESIGN/METHODS: A retrospective cohort study of neonates with moderate to severe HIE admitted to a level III NICU between September 2011 and October 2015. HIE staging was done as per modified Sarnat’s scoring system. Hypercalcemia was defined as serum ionised Ca (iCa) >1.35 mmol/L and hypocalcemia was defined as serum iCa <0.9 mmol/L. Acidosis was considered if pH <7.2. Serum Ca and pH were followed in the first 3 days of age (Day 1-3). The relation of serum Ca levels with acidosis,seizures, intracranial hemorrhage, and MRI changes in neonates with and without TH was examined. Categorical variables were analysed using chi-square test. Logistic regression analysis was done to explore the association of hypo/hypercalcemia with various variables, adjusting for TH, HIE staging, and acidosis. RESULTS: Total number of neonates with moderate-severe HIE= 113; 89 neonates (79%) underwent TH. Incidence of hypercalcemia was 57/89 (88%) in the TH group whereas only one-third in the no TH group, whereas for hypocalcemia, it was 11/89(12%) and 5/24(21%) for the TH and no TH groups respectively. Hypercalcemia on Day 1 was significantly higher with TH(p 0.007) and acidosis(p 0.015). Hypocalcemia did not have any such association. Hypo/hypercarbia did not seem to alter the serum Ca levels. There was no increase in intracranial hemorrhage, clinical/EEG seizures, antiepileptic drug use or hypoxic MRI changes with Ca derangements. CONCLUSION: Incidence of hypocalcemia was reduced by almost half in TH group. Hypercalcemia on day 1 was significantly associated with TH and acidosis. On days 2 and 3, hypercalcemia occurred in TH even in the absence of acidosis, but the association was not statistically significant. Less hypocalcemia and more hypercalcemia in TH may be attributed to the neuroprotective effect of TH by inhibiting Ca influx into the cells. However, there was no correlation between Ca derangements and seizures or severity of hypoxic changes in MRI.