INTRODUCTION

Asphyxia is defined as the failure to breathe well within 1 minute after delivery.¹ Hypoxia may cause a baby to have a decreased heart rate, decreased blood flow out of the heart, and low blood pressure. This may limit the blood flow to organ and tissue, leading to improper cell function or damage.

The most frequent abnormalities involve kidneys (50%) followed by central nervous system (CNS; 28%), cardiovascular (25%), and pulmonary system (23%).² Thus, there is evidence of multiorgan system dysfunction in the immediate neonatal period, CNS, pulmonary, metabolic, gastrointestinal tract, hematologic, renal, and death.³ Perinatal mortality rate in India has remained almost static at appealingly high figure of around 65 per 1000 for nearly three decades.⁴

Calcium is an important second messenger in our body and also helps out muscle function and acts as a cofactor for several enzymatic activities. During pregnancy, calcium is transferred actively from the maternal circulation to the fetus by a transplacental calcium-pump regulated by the parathyroid hormone-related peptide. The majority of fetal calcium accretion occurs in the third trimester. This process results in higher plasma calcium concentration in fetus than in the mother and leads to fetal hypocalcemia with total and ionized calcium concentration of 10 to 11 and 6 mg/dL in umbilical cord blood at term. According to latest estimates by the World Health Organization,⁵ approximately 4 million babies die each year before they reach the age of 1 month. Actually, 98% of these neonatal deaths take place in developing countries. Perinatal asphyxia and birth injuries together contribute to almost 29% of these deaths.

After birth, due to the abrupt cessation of placental transfer, calcium levels start falling to 8 to 9 mg/dL and ionized calcium to 4.4 to 5.4 mg/dL at 24 hours of age. Serum calcium then starts rising to reach levels comparable to older children and adults by 2 weeks of age. Magnesium, the second most common intracellular cation, plays an important role in protein synthesis, bone formation, and regulation of potassium and calcium channels in the cell membrane. In addition, magnesium may play a role in neuroprotection for neonates with HIE. Magnesium also plays important roles in many physiologic functions, including protein synthesis, bone development, and cell membrane function.

With this background, it was deemed worthwhile to investigate the incidence of birth asphyxia in the hospital delivery, and biochemical changes especially serum calcium and serum magnesium during blood asphyxia.

MATERIALS AND METHODS

This study was carried out in neonatal intensive care unit of Department of Pediatrics, in collaboration with the Department of Biochemistry and Department of Obstetrics and Gynecology at a tertiary care center in Bhopal.

For the study, 75 newborns admitted to neonatal unit of the Department of Pediatrics were enrolled. The enrolled babies were further divided into group I (50 asphyxiated neonates) and group II (25 healthy neonates).

The study group comprised 50 asphyxiated term neonates. A baby was considered full term with complete gestational age of 37 weeks. The assessment of gestational age was done by the modified Dubowitz criteria and the staging of asphyxia was done by Sarnat and Sarnat staging.

RESULTS

Majority of babies were delivered by normal vaginal route (80%; n = 40); and 20% (n = 10) were delivered by LSCS route among the study group

Very significant (p ≤ 0.001) hypocalcemia was reported in hypoxic children from day of birth, which persisted up to the study period (p ≤ 0.01) on the first, third, and fifth day

The observation depicts that abnormal calcium metabolism percentage increases with severity of asphyxia (46.6% abnormal in stage I, while 71.4% abnormal in stage III) and this abnormality persists up to fifth day in stage III, but it gets improved in stages I and II by fifth day of life

No change in serum magnesium levels in both asphyxiated and nonasphyxiated neonates have been reported. Thus, there is no significant impact of asphyxia on magnesium metabolism

Abnormal magnesium metabolism percentage increases with severity of asphyxia (26.6% abnormal in stage I, while 71.4% abnormal in stage III) and this abnormality persists up to fifth day in stage III, but it gets improved in stages I and II by the fifth day of life

Abnormal calcium metabolism percentage increases with severity of asphyxia (46.6% abnormal in stage I, while 71.4% abnormal in stage III) and this abnormality persists up to fifth day in stage III, but it gets improved in stages I and II by fifth day of life

DISCUSSION

Birth asphyxia is very commonly seen in newborn babies. It has extremely serious immediate and long term adverse effects. The present study has been intended to evaluate the incidence and effect of birth asphyxia on certain biochemical parameters like serum calcium and serum magnesium among different categories of neonates. In India about one million babies suffer from birth asphyxia every year and it is the leading cause of neonatal mortality in our country, accounting for nearly 28.8% of the neonatal deaths and major subsequent squalid causing physical and mental handicap (1.5%).

In the present study, 40 (80%) were born by vaginal delivery and 10 (20%) were born by lower segment cesarean section (LSCS) (Table 1). Prasan et al⁸ have also reported male preponderance. Maximum number of cases (81.3%) were born by vaginal delivery. Similar observations were made by Finner et al,⁹ who have reported 65% vaginal delivery and 35% LSCS delivery in their study.

The mean value of serum calcium (Table 2) on days 1, 3, and 5 (groups I—II) were 7.004 ± 0.691, 8.788 ± 0.399, 7.482 ± 0.760, 9.476 ± 0.250, 8.184 ± 0.811, 9.992 ± 0.277 respectively.

It shows a very significant (p ≤ 0.001) hypocalcemia in hypoxic children from day of birth, which persisted up to the study period (p ≤ 0.01): First, third, and fifth day.

When the serum calcium was compared according to stages of HIE, abnormal calcium metabolism percentage increases with severity of asphyxia (46.6% abnormal in stage I, while 71.4% abnormal in stage III), and this abnormality persists up to fifth day in stage III, but it gets improved in stages I and II by fifth day of life (Table 3). Ilves et al¹⁰ studied 46 asphyxiated and 35 healthy term infants. Between 24 and 48 hours, hypocalcemia was discovered in 23% of asphyxiated infants.

The pathogenetic mechanism by which birth asphyxia causes hypocalcemia is poorly understood. However, it has been speculated that delayed introduction of feeds, increased calcitonin production, increased endogenous phosphate load, transient functional hypoparathyroidism, target organ unresponsiveness, and sodium bicarbonate therapy may play a role. Of the total serum calcium, 40% is protein-bound, 10% is complexed with anions, such as citrate, sulfate, bicarbonate, phosphate, and lactate, and 50% is in the free or ionized physiologically active form.

In the present study, it was found that there was a significant decrease in the extracellular calcium levels in the asphyxiated babies, and the decrease was directly proportional to the degree of asphyxia.

Jajoo et al¹¹ studied 35 term infants with asphyxia. Asphyxiated infants had significantly lower serum calcium levels than control infant during each of the time period studied.

Schultz and Soltész¹² in their study on serum calcium levels in birth anoxic neonates found 26.76% incidence of hypocalcemia in full-term infants and 58.3% in premature infants. Hypocalcemia was associated with acidosis in the first 24 hours of life.

Tsang et al¹³ in their study found that 37.6% of premature infants had serum calcium of <7 mg% and they also found that Apgar score was associated with low serum calcium values from 12 to 72 hours of age (p < 0.01). Birth asphyxia therefore, appears to play a separate role in neonatal calcium homeostasis apart from role of gestational age.

The mean values of serum magnesium (Table 4) on days 1, 3, and 5 (groups I and II) were 1.545 ± 0.045, 1.518 ± 0.053, 1.496 ± 0.067, 1.597 ± 0.049, 1.556 ± 0.057, 1.66 ± 0.065 respectively. There was no change in serum magnesium level in both asphyxiated and nonasphyxiated neonates. Thus, there is no significant impact of asphyxia on magnesium metabolism.

Abnormal magnesium metabolism percentage increases with severity of asphyxia (26.6% abnormal in stage I, while 71.4% abnormal in stage III) and this abnormality persists up to fifth day in stage III, but it gets improved in stages I and II by fifth day of life (Table 5). The mean value of serum magnesium in the cases were slightly lower in days 1, 3, and 5 in full-term babies < 2.5 kg as compared with full-term babies ≥ 2.5 kg, but this observation was not statistically significant (Table 6).

Asphyxiated infants whose serum magnesium level dipped only slightly at 12 hours and then rose to normal by 24 hours were compared with asphyxiated infants whose hypoxemia (starting at 12 hours) persisted through 48 to 72 hours.¹⁴ Such infants, however, often exhibit hypomagnesemia within 12 hours after birth,¹⁴ possibly reflecting inadequacy of tissue stores or the shift of extracellular magnesium to the intracellular phase with normal oxygenation. Serum calcium concentration should be determined in all neonates with encephalopathy.

Birth asphyxia is the most common and important cause of preventable cerebral injury occurring in the neonatal period. In India, about one million babies suffer from birth asphyxia every year, and it is the leading cause of neonatal mortality in our country, accounting for nearly 28.8% of the neonatal deaths and major subsequent sequelae causing physical and mental handicap (1.5%).¹⁵

In infants with HIE, hypomagnesemia may be the result of increased magnesium consumption during the ischemic insult or ongoing losses caused by ischemic damage to renal glomeruli and tubules. Glutamate is an important neurotransmitter that plays a major role in the development of the CNS. Magnesium plays some important roles in many physiologic functions, including protein synthesis, bone development, and cell membrane function. There is some evidence to suggest a role for magnesium sulfate as a therapeutic neuroprotective agent along with therapeutic hypothermia in infants with HIE, but studies are inconclusive. Both ischemic insult and hypothermia may play a role in altered magnesium levels in this population. Therapeutic hypothermia likely involved in normal brain functions, including cognition, learning, and memory.⁸ However, the release of excessive quantities of glutamate in HIE results in overstimulation of glutamate receptors, 2-aminomethylphenylacetic acid, kainite, and N-methyl-D-aspartate, located on the postsynaptic membrane of nerve cells, resulting in excitotoxicity.