Introduction

WHO has defined perinatal asphyxia as a 'failure to initiate and sustain breathing at birth.^[1] Hypoxic Ischemic Encephalopathy refers to the CNS dysfunction associated with perinatal asphyxia.^[2] Worldwide, hypoxic - ischemic encephalopathy is the leading cause of neonatal brain injury and neonatal mortality with neurodevelopmental impairment.^[3] 36.4% of neonatal seizures are due to hypoxic ischemic encephalopathy.^[4] According to Sarnat staging system newborn with HIE can be grouped into HIE stage 1, stage 2, stage 3.^[5] Of which convulsion is seen in stage 2 and stage 3 cases. In stage 1 seizures don't happen. Along with multi organ involvement electrolyte abnormalities are commonly seen in asphyxiated babies.^[6] SIADH is a very common complication resulting in hyponatremia and seizure.^[7] Hypocalcemia also promotes seizure activity. It is difficult to postulate seizure activity due to asphyxia or hyponatremia, hypocalcemia.^[8] There are previous studies suggesting strong correlation of severity of asphyxia with both hyponatremia and hypocalcemia.^[9] Rachna Pasi and others in a recent study to find out correlation of neonatal seizures and hyponatremia found significant hyponatremia among neonates with HIE.^[10] In a cohort study by Sakeer et al showed significant hypocalcemia among HIE babies prior to therapeutic hypothermia.^[11]

Subjects and Methods

Study design: Cross sectional observational study.

Study timeline: 6 months starting from August 2019 to January 2020.

Place of Study: Department of Pediatrics, Malda Medical College and Hospital.

Study Population: Asphyxiated inborn and outborn babies admitted to NICU.

Sample Size: 224

Inclusion Criteria: HIE stage 2 and stage 3 cases.

Exclusion criteria: HIE stage 1.

Laboratory investigations: Serum Sodium and Calcium levels. Hospital laboratory reference for hyponatremia was < 135 mEq/l (Mild: 125-134 mEq/l, Moderate: 110-124 mEq/l, Severe <110 mEq/l) and for hypocalcemia was < 9mg/dl (Severe < 7 mg/dl)

Ethical Clearance: Was taken from Institutional ethical committee.

Outcome measured: Data were analysed using SPSS Statistics 23.

Results

Correlation were also obtained between age on presentation and severity of birth asphyxia, serum sodium and calcium levels.

Among 224 cases taken 145 (64.7%) were boy and 79 (35.3%) were girl babies, 67 (29.9%) was inborn and 157 (70.1%) were outborn, 109 cases (48.7%) were delivered by LUCS and 115 (51.3%) were delivered by NVD. Mean gestational age of our sample size was 38.86 in weeks, mean birth weight was 2744 grams, mean age on presentation was 19.5 hours after birth. Of the 224 cases enrolled 114 (50.9%) were Sarnat HIE stage 2 and 110 (49.1%) were HIE stage 3.

Mean sodium level of total study population was 110.46±7.92 mEq/l. Of which HIE 2 cases had mean sodium of 115.36±6.5 mEq/l and HIE 3 cases had means sodium of 105.38±5.78 mEq/l. Mean calcium level of total study population was 8.32±0.59 mg/dl. Of which HIE 2 cases had mean calcium of 8.46±0.49 mg/dl and HIE 3 cases had 8.17±0.64 mg/dl. Significant difference was observed on comparing the mean values of sodium and calcium using ANOVA (p-value <0.001). To find correlation between severity of asphyxia and electrolytes level, bivariate analysis was done and pearson test was used to find correlation coefficient. Both calcium and sodium had negative correlation with severity of HIE but strength of association was more with sodium than with calcium level.

Discussion

Both Sodium and calcium are among the major electrolytes in the body. Alteration from their normal level contributes to convulsion and aggravate CNS injury in patients with HIE.^[12] Overall mean values for sodium and calcium was 110.46 ± 7.92 mEq/l and 8.32 ± 0.59 mg/dl. Now if we look at the mean values for HIE stage 2 and 3 separately then it is as follows: Mean sodium in HIE 2 was 115.36 ± 6.5 mEq/l and in HIE 3 it was 105.38±5.78 mEq/l. So when we compare the mean values of sodium among two stages of HIE using ANOVA there was significant difference between them (p- value <0.001). In a study conducted by Basu P et al the mean value for sodium was 122.1±.0 mEq/l.^[13] Reason for much lower mean sodium in our study may be due to timing of sample collection. Most (70.1%) cases were outborn babies, so mostly they presented late to us due to longer transportation time from rural areas of Bengal eventually worsening the severity. Presence of SIADH explains why so much hyponatremia in these newborns. Vijayalaxmi et al. in their study also showed presence of SIADH in HIE cases.^[14] Mean calcium in HIE 2 was 8.46±0.49 mg/dl and in HIE 3 it was 8.17±0.64 mg/dl. Again if we compare the mean values of calcium among different stages of HIE, there is statistically significant difference. So with worsening of HIE both hyponatremia and hypocalcemia worsened. In a study conducted in Tamil Nadu in 2018 by Satheesh et al showed similar findings.^[15] But ANOVA test showed mean decrease in sodium was statistically more significant than mean decrease in calcium. Now bivariate analysis was done between stages of HIE with sodium and calcium level. Sodium level had a negative correlation with severity of asphyxia (r = -.631) and also the calcium level had negative correlation(r = -.247). Now if we see at the strength of association definitely hyponatremia was more strongly correlated with severity of asphyxia than hypocalcemia. If we look at the correlation of HIE severity with age on presentation then there was obvious positive correlation as severity worsens with delay. Now if we look at the correlation of serum sodium with age on presentation significant negative correlation(r=-.165) was found but not that much with calcium(r=-.079). In perinatal asphyxia many other parameters like hypoglycemia, hypomagnesemia, acidosis comes into play when the baby is having seizures. ^[16] And it is also true that no single factor can be postulated to be the most important in causing seizures. Researches will be always there to evaluate different factors. But in view of this study we can definitely postulate that serum sodium, may it be cause or effect, is definitely of concern in worsening severity of hypoxic ischemic encephalopathy.

Conclusion

Biochemical disturbances are very common in newborn with perinatal asphyxia. Among those who are presenting with seizures, hyponatremia is possibly more detrimental than hypocalcemia.