Prevalence of electrolyte disturbances in perinatal asphyxia: a prospective study

In basic term birth asphyxia is delay in establishing spontaneous respiration upon delivery of a newborn [1]. More precisely, birth asphyxia is defined as the presence of hypoxia, hypercapnia, and acidosis leading to systemic disturbances in the newborn [2]. As per AAP (American Academy of Pediatrics) and ACOG (American College of Obstetrics and Gynecology), all the following must be present for designation of asphyxia such as, profound metabolic or mixed acidemia (pH < 7) in cord, Persistence of APGAR scores 0–3 for longer than 5 min, neonatal neurological sequel (eg: seizures, coma, hypotonia) and multiple organ involvement (kidney, lungs, liver, heart, intestine) [3]. It is a common problem with the incidence varying from 0.5–2% of live births [4]. Some report the incidence from 1 to 8 per 1000 live births [5].

Normally hypernatremia is expected in the early neonatal period as there is contraction of extracellular fluid due to excretion of water through kidney and high insensible water loss whereas in neonates with perinatal asphyxia there might be hyponatremia as there is increased secretion of anti-diuretic hormone (ADH) in neonates with HIE which leads to increased water retention and hence dilutional hyponatremia [6]. The other reason for hyponatremia is that the capacity of sodium reabsorption is limited and if the load of sodium reaching the Collecting Tubules (CT) increases significantly, reabsorption does not occur proportionately and the sodium load is excreted in the urine [7]. Other contributing factors to hyponatermia is partial resistance to aldosterone [8].

In newborns there is hyperkalemia in early neonatal period due to shift of potassium from the intracellular to extracellular space. The magnitude of this shift roughly correlates with the degree of immaturity i.e. the more premature the baby the more chance of hyperkalemia [9]. Serum potassium subsequently falls as this internal potassium “load” is excreted by the kidneys [10]. Whereas the rise in level of serum potassium can be explained from the fact that birth asphyxia is associated with acidosis, and in metabolic acidosis, more than one-half of the excess hydrogen ions are buffered in the cells. In this setting, electro neutrality is maintained in part by the movement of intracellular potassium into the extracellular fluid. It can also be due to acute renal failure secondary to birth asphyxia which leads to decreased excretion of potassium and hence hyperkalemia.

In normal newborn total calcium concentration in cord plasma increases with increasing gestational age and is significantly higher than paired maternal values [11, 12]. With the abrupt termination of calcium transport across the placenta at delivery, plasma calcium falls, reaching a nadir at age 24–48 h [11]. Serum parathyroid hormone (PTH) increases postnatally in response to this fall in plasma calcium concentration. This increase in PTH mobilizes calcium from bone, and plasma calcium concentration rises and subsequently stabilizes even in the absence of exogenous calcium intake. Clinically significant hypocalcaemia occurs in asphyxiated newborns [12]. The etiology behind this is a sluggish response in PTH secretion to the postnatal fall in plasma calcium concentration.

When a neonate suffers asphyxia, series of clinical [13] and biochemical [14] alterations occur which can adversely affect the outcome [15]. While treating hyponatremic seizures, correction of the electrolyte disturbance is more effective than using anticonvulsants [16]. Hyperkalemia is associated with cardiac dysfunction and death. Hypocalcaemia is associated with jitteriness, cardiac dysfunction and seizure. Further the degree of electrolyte imbalance may vary according to the severity of birth asphyxia.

In a case control study by Basu P et al. among asphyxiated newborn, hyponatremia and hypocalcaemia developed early and simultaneously and the decrease in their serum levels was directly proportional to each other and to the degree of asphyxia among cases [17]. Similarly in a prospective study done by Shah G S et al. among asphyxiated neonates, hyponatremia and hypocalcaemia was noted respectively as 23.3 and 11.7% [18]. But in a case control study by Varma V et al. among asphyxiated newborns, mean values of electrolytes showed no significant difference among cases and controls as well as in HIE stages [19]. So there is limited literature regarding electrolyte disturbance in asphyxiated newborn especially the correlation with severity of asphyxia. So this study was started with the aim to study electrolyte (sodium, potassium, calcium) disturbances in asphyxiated newborns of different severity in the early neonatal period and to find out correlation of levels of sodium, potassium, calcium with severity of perinatal asphyxia.

This prospective observational study was conducted in the Department of Paediatrics and Adolescent medicine, Bishweshwar Prasad koirala Institute of Health Sciences (BPKIHS), Dharan, Nepal during a study period of one year from June 2015 to May 2016 in asphyxiated new-borns born at this institute and a total of 88 cases were enrolled in the study.

Out of 88 enrolled cases 60 (68%) were male and 28 were (32%) female and mean weight being 2975.45 ± 349.53 g. (Tables 2 and 3).

On comparing the means of sodium, potassium and ionized calcium between different stages of HIE using ANOVA, there was significant difference between them with p-value < 0.001 (Table 4).

Bivariate analysis was used to find the correlation between Apgar score and serum electrolyte level and Pearson test was used to find correlation coefficient. Box plot was used to show median and quartiles of serum electrolyte with respect to Apgar at 5 min.

Significant correlation was present between serum sodium and Apgar score at 5 min with p-value < 0.001 i.e. as Apgar score at 5 min increased serum sodium also increased with Pearson correlation co-efficient of 0.448 (Fig. 1).

There was significant negative correlation between serum potassium and Apgar at 5 min with p-value < 0.001 i.e. as Apgar score at 5 min increased serum potassium decreased with Pearson correlation coefficient of − 0.422 (Fig. 2).

No significant correlation was present between Apgar at 5 min and serum ionized calcium level with p-value< 0.077 i.e. change in the value of Apgar score at 5 min had no relation with change in serum ionized calcium level and Pearson correlation coefficient of 0.479 (Fig. 3).

The overall mean of sodium, potassium and ionized calcium was 130.73 ± 4.60 meq/l, 5.98 ± 1.03 meq/l and ionized calcium 1.05 ± 0.14 mmol/l respectively. In a case control study done by Basu P et al., the mean value of sodium, potassium and calcium was 122.1 ± 6.0 meq/l, 5.05 ± 0.63 meq/l and calcium 6.85 ± 0.95 respectively [17]. Similarly in another case control study done by Varma V et al., the means of sodium and potassium among cases were 136.5 ± 8.7 meq/l and 3.78 ± 0.36 meq/l respectively [19]. The difference between the results were probably because of difference in the timing of collection of samples, as we collected blood sample as early as possible no later than one hour of life, so chance of correction of electrolyte by body’s internal milieu was less.

Basu et al. [17] found increased severity of hyponatremia, hyperkalemia and hypocalcaemia with increased severity of birth asphyxia. The pattern of hyponatremia and hyperkalemia was similar to our study. Similarly in case control study by Jajoo et al. [22], Rai [23] et al. and Schedewie et al. [24], showed that asphyxiated newborns had lower serum calcium level compared to their controls.

The treatment of hyponatremia in such condition is by fluid restriction rather increasing sodium load for reasons mentioned in background section. So fluid should be restricted in cases of birth asphyxia till normalization of serum sodium with close monitoring of weight and serum sodium. Serum potassium and Electrocardiography (ECG) monitoring should be done to avoid the deadly complications of hyperkalemia. Apart from other treatment measures, correction of acidosis and use of potassium free fluid are the most useful measures to correct hyperkalemia. Our study however did not find significant hypocalcaemia with increasing severity of HIE but there was hypocalcaemia associated with birth asphyxia, so regular supplementation and monitoring of serum calcium should be done.

Our study had various limitations:

Hyponatremia, hyperkalemia and hypocalcaemia occur in neonates with birth asphyxia which may cause increased morbidity and mortality. More severe hyponatremia should be suspected if there is severe birth asphyxia and vice versa. Hence its level should be more regularly monitored to prevent the problems associated with it. Severe hyperkalemia is associated with severe birth asphyxia and vice versa; so regular potassium monitoring and ECG monitoring is required to detect cardiac changes associated with it so that prompt management can be instituted.