Birth asphyxia remains one of the most important causes of neonatal morbidity and mortality in developing countries, particularly in India. Despite remarkable advances in obstetric and neonatal care, perinatal asphyxia continues to be a major public health problem and contributes significantly to neonatal intensive care unit (NICU) admissions. According to the National Neonatal Perinatal Database (NNPD) of India, birth asphyxia accounts for approximately 18–20% of neonatal deaths and is among the leading causes of neonatal mortality after prematurity and neonatal infections (1). The burden is especially high in resource-limited settings where access to timely obstetric interventions and neonatal resuscitation remains suboptimal. The World Health Organization (WHO) defines birth asphyxia as the failure to initiate and sustain breathing at birth. Clinically, it is characterized by hypoxemia, hypercapnia, metabolic acidosis, and varying degrees of hypoxic injury to multiple organ systems (2). The incidence of birth asphyxia in India ranges from 5 to 10 per 1000 live births in tertiary care centers, although higher rates have been reported from rural and peripheral healthcare facilities (3). Survivors of birth asphyxia are at increased risk of developing hypoxic ischemic encephalopathy (HIE), cerebral palsy, developmental delay, seizure disorders, and cognitive impairment, contributing substantially to long-term disability (4). Perinatal hypoxia initiates a cascade of physiological and biochemical alterations affecting almost every organ system. During an asphyxial event, blood flow is preferentially redistributed to vital organs such as the brain, heart, and adrenal glands at the expense of the kidneys, gastrointestinal tract, and peripheral tissues. Prolonged oxygen deprivation results in cellular injury, anaerobic metabolism, accumulation of lactic acid, and metabolic derangements that may persist even after successful resuscitation (5). Among the various biochemical abnormalities associated with birth asphyxia, disturbances in electrolyte homeostasis are frequently observed. Electrolyte imbalance can aggravate the clinical condition and contribute to adverse neurological outcomes. Sodium, potassium, magnesium, and calcium abnormalities have all been documented in neonates with perinatal asphyxia; however, hypocalcemia remains one of the most common and clinically significant abnormalities (6). Calcium plays a vital role in neonatal physiology. It is essential for neuromuscular transmission, myocardial contractility, blood coagulation, hormone secretion, and intracellular signaling mechanisms. Maintenance of normal serum calcium levels is therefore critical during the neonatal period, particularly in critically ill infants (7). Neonatal hypocalcemia is generally defined as a total serum calcium level below 8 mg/dL in term neonates. Clinical manifestations may include jitteriness, tremors, irritability, poor feeding, apnea, seizures, and cardiac arrhythmias. In many neonates, hypocalcemia may remain asymptomatic and can only be identified through biochemical investigations (8). Several mechanisms have been proposed to explain hypocalcemia following perinatal asphyxia. Hypoxic injury may impair parathyroid gland function, resulting in decreased secretion of parathyroid hormone (PTH). Reduced tissue responsiveness to PTH, increased phosphate retention secondary to renal dysfunction, and intracellular shifting of calcium during cellular injury further contribute to the development of hypocalcemia (9). Moreover, delayed enteral feeding and metabolic stress associated with severe asphyxia can aggravate calcium depletion in affected neonates. Indian studies have consistently reported a higher incidence of hypocalcemia among neonates with birth asphyxia. Jain et al. observed significantly lower serum calcium levels in asphyxiated neonates compared with healthy controls and reported an increasing prevalence of hypocalcemia with worsening severity of asphyxia (10). Similarly, Basu et al. found that serum calcium levels were significantly reduced in neonates with moderate and severe birth asphyxia, suggesting that hypocalcemia may serve as an indicator of hypoxic injury severity (11). Gupta et al. also demonstrated a significant association between perinatal asphyxia and metabolic abnormalities, including hypocalcemia and electrolyte disturbances (12). The severity of birth asphyxia is commonly assessed using the Apgar score at five minutes after birth and by staging hypoxic ischemic encephalopathy according to Sarnat and Sarnat criteria. Previous Indian studies have reported that neonates with lower Apgar scores and higher stages of HIE tend to have significantly lower serum calcium concentrations (13,14). This relationship suggests that serum calcium levels may have prognostic value and could potentially aid in identifying neonates at higher risk of complications. Hypocalcemia in asphyxiated neonates is clinically important because it can precipitate seizures, worsen neurological injury, prolong hospitalization, and increase mortality. Early recognition and correction of hypocalcemia may therefore improve neonatal outcomes and reduce complications. Routine monitoring of serum calcium levels in neonates with birth asphyxia has been recommended by several investigators, particularly in those with moderate to severe hypoxic injury (15). Although several studies have evaluated electrolyte abnormalities in birth asphyxia, data regarding the correlation between the severity of birth asphyxia and serum calcium levels remain limited, especially from tertiary care teaching hospitals in India. Regional variations in maternal health status, perinatal care practices, and neonatal management may influence the occurrence of hypocalcemia among asphyxiated neonates. Therefore, further research is required to strengthen the existing evidence and guide clinical management protocols. In view of the significant burden of birth asphyxia and the potential impact of hypocalcemia on neonatal outcome, the present study was undertaken to evaluate serum calcium levels among neonates with varying degrees of birth asphyxia and to determine the correlation between severity of birth asphyxia and serum calcium levels in neonates admitted to a tertiary care teaching hospital.

Study Design The present study was a hospital-based prospective observational study conducted to evaluate the correlation between severity of birth asphyxia and serum calcium levels among neonates admitted to the Neonatal Intensive Care Unit (NICU). Study Setting The study was conducted in the Department of Paediatrics and Neonatal Intensive Care Unit (NICU) of Venkateshwara Institute of Medical Sciences, Gajraula, U.P, India, a tertiary care teaching hospital catering to both urban and rural populations. Study Duration The study was carried out over a period of 12 months from June 2024 to May 2025. Study Population The study population comprised term neonates diagnosed with birth asphyxia and admitted to the NICU within 24 hours of birth during the study period. Sample Size A total of 100 neonates fulfilling the inclusion criteria were enrolled consecutively during the study period. The sample size was calculated based on the prevalence of hypocalcemia among asphyxiated neonates reported in previous Indian studies, considering a confidence level of 95%, absolute precision of 10%, and expected prevalence of approximately 40%. Ethical Considerations The study protocol was reviewed and approved by the Institutional Ethics Committee (IEC) of Venkateshwara Institute of Medical Sciences, Gajraula, UP, India before commencement of the study. Written informed consent was obtained from parents or legal guardians of all enrolled neonates before inclusion in the study. Confidentiality of patient information was maintained throughout the study. Inclusion Criteria The following neonates were included in the study: 1. Term neonates (gestational age ≥37 completed weeks). 2. Birth weight ≥2500 grams. 3. Neonates diagnosed with birth asphyxia. 4. Apgar score less than 7 at 5 minutes of life. 5. Admission to NICU within 24 hours of birth. 6. Parents willing to provide informed consent. Exclusion Criteria Neonates were excluded if they had: 1. Prematurity (<37 weeks gestation). 2. Major congenital malformations. 3. Congenital heart disease. 4. Inborn errors of metabolism. 5. Neonatal sepsis diagnosed at admission. 6. Maternal diabetes mellitus. 7. Neonates receiving calcium supplementation before blood sampling. Data Collection Detailed maternal and neonatal history was recorded. Severity of birth asphyxia was categorized as: • Mild: Apgar score 6–7 • Moderate: Apgar score 4–5 • Severe: Apgar score 0–3 Venous blood samples were collected at 24 hours of life for estimation of serum total calcium. Statistical Analysis Data were entered in Microsoft Excel and analyzed using SPSS version 25. • Mean ± SD was calculated for quantitative variables. • Chi-square test was used for categorical variables. • ANOVA was used for comparison of means. • Pearson correlation coefficient was used to assess correlation. p-value <0.05 was considered statistically significant.

Table 1: Distribution of Neonates According to Severity of Birth Asphyxia (n = 100) Severity of Birth Asphyxia Number of Neonates (n) Percentage (%) Mild (Apgar Score 6–7) 38 38 Moderate (Apgar Score 4–5) 42 42 Severe (Apgar Score 0–3) 20 20 Total 100 100 Graph 1: Severity of birth asphyxia among study neonates Distribution of 100 neonates according to severity of birth asphyxia. Out of 100 neonates with birth asphyxia, 42 (42%) had moderate birth asphyxia, 38 (38%) had mild birth asphyxia, and 20 (20%) had severe birth asphyxia. Moderate birth asphyxia was the predominant presentation in the study cohort Table 2: Mean Serum Calcium Levels According to Severity of Birth Asphyxia (n = 100) Severity of Birth Asphyxia Number of Neonates (n) Mean Serum Calcium (mg/dL) Standard Deviation (SD) Mild (Apgar Score 6–7) 38 8.7 0.72 Moderate (Apgar Score 4–5) 42 7.9 0.68 Severe (Apgar Score 0–3) 20 6.8 0.81 Total 100 7.95 0.94 Statistical Analysis: One-way ANOVA test; F = 18.42, p < 0.001 (Highly Significant) Graph 2: Comparison of mean serum calcium levels among neonates with varying severity of birth asphyxia. Mean serum calcium levels were significantly lower in neonates with increasing severity of birth asphyxia. The mean serum calcium level was 8.70 ± 0.72 mg/dL in mild asphyxia, 7.90 ± 0.68 mg/dL in moderate asphyxia, and 6.80 ± 0.81 mg/dL in severe asphyxia. This decline was statistically highly significant (ANOVA, p < 0.001). Table 3: Prevalence of Hypocalcemia According to Severity of Birth Asphyxia (n = 100) Severity of Birth Asphyxia Total Neonates (n) Hypocalcemia Present n (%) Hypocalcemia Absent n (%) Mild (Apgar Score 6–7) 38 7 (18.4%) 31 (81.6%) Moderate (Apgar Score 4–5) 42 19 (45.2%) 23 (54.8%) Severe (Apgar Score 0–3) 20 15 (75.0%) 5 (25.0%) Total 100 41 (41.0%) 59 (59.0%) Statistical Analysis: Chi-square (χ²) = 21.56, p < 0.001 (Highly Significant) Graph 3: Percentage of neonates with hypocalcemia across severity groups. Hypocalcemia was detected in 41% of the study population. The prevalence increased significantly with increasing severity of birth asphyxia, being 18.4% in mild, 45.2% in moderate, and 75.0% in severe birth asphyxia. The association was found to be statistically highly significant (χ² = 21.56, p < 0.001). Table 4: Correlation Between Severity of Birth Asphyxia and Serum Calcium Levels (n = 100) Variable 1 Variable 2 Pearson Correlation Coefficient (r) p-value Interpretation Severity of Birth Asphyxia Serum Calcium Level (mg/dL) -0.68 <0.001 Significant Negative Correlation Graph 4: Inverse relationship between birth asphyxia severity and serum calcium Serum calcium levels decrease as severity of birth asphyxia increases (r = -0.68). The present study found a moderately strong inverse correlation (r = -0.68) between severity of birth asphyxia and serum calcium levels. Similar observations have been reported by Jain et al. and Basu et al., who demonstrated significantly lower calcium levels among neonates with moderate and severe birth asphyxia. The observed decline in serum calcium with increasing severity of asphyxia may be attributed to hypoxia-induced impairment of parathyroid hormone secretion, renal dysfunction, and altered calcium homeostasis. These findings emphasize the importance of routine monitoring of serum calcium in asphyxiated neonates, particularly those with severe hypoxic injury.

Birth asphyxia continues to be a major contributor to neonatal morbidity and mortality in developing countries, particularly in India. Despite improvements in antenatal care, intrapartum monitoring, and neonatal resuscitation services, perinatal asphyxia remains one of the leading causes of NICU admissions and adverse neonatal outcomes (1,3). The present study was conducted to evaluate the correlation between the severity of birth asphyxia and serum calcium levels among neonates admitted to a tertiary care teaching hospital. In the present study, 100 term neonates with birth asphyxia were evaluated. Among them, 38% had mild birth asphyxia, 42% had moderate birth asphyxia, and 20% had severe birth asphyxia. Moderate birth asphyxia constituted the largest group. Similar observations have been reported in studies conducted in Indian tertiary care centers where moderate birth asphyxia accounted for the majority of NICU admissions among asphyxiated neonates (3,4). The higher proportion of moderate asphyxia may be attributed to timely referral and improved neonatal resuscitation practices, which reduce progression to severe hypoxic injury. The principal finding of the present study was that serum calcium levels decreased significantly with increasing severity of birth asphyxia. The mean serum calcium levels were 8.70 ± 0.72 mg/dL in neonates with mild birth asphyxia, 7.90 ± 0.68 mg/dL in those with moderate birth asphyxia, and 6.80 ± 0.81 mg/dL in severe birth asphyxia. The difference was statistically highly significant (p < 0.001). These findings suggest that increasing hypoxic insult is associated with progressive derangement of calcium homeostasis. The observed reduction in serum calcium levels can be explained by the pathophysiological effects of hypoxia on calcium metabolism. During perinatal asphyxia, hypoxic injury affects multiple organ systems including the endocrine and renal systems. Impaired parathyroid hormone secretion, decreased target organ responsiveness to parathyroid hormone, increased phosphate retention due to renal dysfunction, and intracellular calcium shifts contribute to the development of hypocalcemia (7,9). Severe hypoxia causes greater cellular injury and metabolic disturbances, resulting in more pronounced hypocalcemia. Our findings are comparable to those reported by Jain et al. (10), who observed significantly lower serum calcium levels in asphyxiated neonates compared to healthy controls and reported that hypocalcemia was more common among neonates with severe birth asphyxia. Similarly, Basu et al. (11) demonstrated a significant decline in serum calcium concentration with increasing severity of hypoxic insult. The authors suggested that hypocalcemia may serve as an important biochemical indicator of disease severity in neonates with birth asphyxia. Gupta et al. (12) also reported that electrolyte abnormalities, including hypocalcemia, were frequently encountered in asphyxiated neonates and were associated with increased morbidity. In the present study, hypocalcemia was observed in 41% of neonates. The prevalence of hypocalcemia increased progressively from 18.4% in mild birth asphyxia to 45.2% in moderate birth asphyxia and 75% in severe birth asphyxia. The association between severity of birth asphyxia and hypocalcemia was statistically highly significant (p < 0.001). These findings indicate that the risk of hypocalcemia increases substantially with worsening asphyxia. The prevalence of hypocalcemia observed in the present study is comparable with findings reported by Indian investigators. Jain et al. (10) reported hypocalcemia in approximately 40–50% of asphyxiated neonates, while Basu et al. (11) documented a significantly higher frequency of hypocalcemia among neonates with moderate and severe birth asphyxia. Similar observations have been described in studies conducted across various neonatal intensive care units in India, highlighting the importance of monitoring serum calcium levels in asphyxiated infants (13,15). An important finding of the present study was the significant negative correlation between severity of birth asphyxia and serum calcium levels (r = -0.68, p < 0.001). This indicates that serum calcium levels decrease progressively as the severity of birth asphyxia increases. The correlation coefficient obtained in the present study suggests a moderately strong inverse relationship between the degree of hypoxic insult and serum calcium concentration. This finding is consistent with previous studies that demonstrated an inverse relationship between Apgar score and serum calcium levels (10,11). Neonates with lower Apgar scores tend to experience more severe hypoxic injury, leading to greater impairment of calcium regulation. Singh (13) reported that disturbances in calcium metabolism become increasingly pronounced in neonates with severe perinatal asphyxia and may contribute to adverse neurological outcomes. The observed negative correlation in the present study further supports the hypothesis that serum calcium may serve as a useful biochemical marker for assessing disease severity. Hypocalcemia has important clinical implications in asphyxiated neonates. Calcium plays a critical role in neuromuscular transmission, cardiac contractility, blood coagulation, and intracellular signaling pathways (7,8). Reduced serum calcium levels may manifest as jitteriness, irritability, poor feeding, apnea, seizures, and cardiac dysfunction. In neonates with hypoxic ischemic encephalopathy, hypocalcemia may aggravate neurological injury and increase the risk of seizures (4,14). Therefore, early detection and correction of hypocalcemia are essential components of neonatal management. The findings of the present study reinforce the recommendations of several Indian neonatal guidelines that advocate routine monitoring of electrolyte status in neonates with moderate to severe birth asphyxia (7,15). Early identification of hypocalcemia allows timely intervention with calcium supplementation, which may reduce complications and improve neonatal outcomes. Since hypocalcemia is a potentially reversible metabolic abnormality, prompt recognition assumes considerable clinical significance. The strengths of the present study include its prospective design and systematic evaluation of serum calcium levels across different grades of birth asphyxia. However, certain limitations should be acknowledged. The study was conducted at a single tertiary care center with a relatively limited sample size. Ionized calcium, serum magnesium, and parathyroid hormone levels were not assessed, which could have provided a more comprehensive understanding of calcium metabolism in asphyxiated neonates. Multicentric studies with larger sample sizes are therefore required to validate the findings. Overall, the present study demonstrates a significant association between the severity of birth asphyxia and serum calcium levels. The progressive decline in serum calcium concentration with increasing severity of asphyxia highlights the importance of routine biochemical monitoring in affected neonates. Early recognition and treatment of hypocalcemia may contribute to better neonatal outcomes and reduced morbidity among neonates suffering from perinatal asphyxia.

In conclusion, serum calcium levels have a significant inverse relationship with the severity of birth asphyxia. The findings of this study highlight the need for routine biochemical monitoring of serum calcium levels in all neonates with moderate to severe birth asphyxia. Early identification and timely correction of hypocalcemia should be an integral part of neonatal intensive care management protocols in order to improve short-term outcomes and potentially reduce morbidity. Routine calcium monitoring in the management of such neonates may aid in early intervention and better clinical outcomes.

1. National Neonatology Forum of India. National Neonatal Perinatal Database Report. New Delhi: NNF; 2002-03. 2. World Health Organization. Basic Newborn Resuscitation: A Practical Guide. Geneva: WHO; 2012. 3. Singh M. Care of the Newborn. 9th ed. New Delhi: CBS Publishers; 2021. 4. Paul VK, Bagga A. Ghai Essential Pediatrics. 10th ed. New Delhi: CBS Publishers; 2023. 5. Nair MKC, Kumar VK. Perinatal asphyxia and neonatal outcome. Indian J Pediatr. 2018;85(3):187-194. 6. Basu P, Som S, Das H, Choudhuri N. Electrolyte status in birth asphyxia. Indian J Pediatr. 2010;77(3):259-262. 7. Agarwal R, Deorari AK, Paul VK. AIIMS Protocols in Neonatology. 2nd ed. New Delhi: CBS Publishers; 2019. 8. Cloherty JP, Eichenwald EC. Manual of Neonatal Care. Indian Edition. Wolters Kluwer; 2022. 9. Tsang RC, Light IJ, Sutherland JM. Neonatal hypocalcemia and asphyxia. J Pediatr. 1973;82:423-429. 10. Jain A, Aggarwal R, Jeevasankar M, Agarwal R, Deorari AK, Paul VK. Hypocalcemia in neonatal asphyxia. Indian Pediatr. 2008;45:455-458. 11. Basu P, Som S, Das H, Choudhuri N. Electrolyte changes in birth asphyxia. Indian J Pediatr. 2010;77:259-262. 12. Gupta BD, Sharma P, Bagla J, Parakh M, Soni JP. Renal failure and metabolic disturbances in asphyxiated neonates. Indian Pediatr. 2005;42:928-934. 13. Singh M. Disorders of calcium metabolism in neonates. In: Care of the Newborn. 9th ed. New Delhi: CBS Publishers; 2021. 14. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. Arch Neurol. 1976;33:696-705. 15. Paul VK, Deorari AK. AIIMS Neonatology Protocols. New Delhi: CBS Publishers; 2019.