Perinatal asphyxia occurs when the fetus experiences inadequate oxygen supply before, during, or immediately after delivery, leading to serious systemic and neurological complications3.

Hypoxia and hypercapnia trigger anaerobic metabolism, resulting in lactic acidosis and damage to vital organs, such as the liver, kidneys, and lungs. Birth asphyxia (BA) affects 2 per 1,000 births in developed countries, but its incidence is ten times higher in developing nations with limited neonatal care4. Of the affected neonates, 15% die, and 25% suffer lasting complications5.

Diagnosing acute kidney injury (AKI) in neonates is difficult due to fluctuations in serum creatinine and urine output, which can complicate accurate assessment. AKI occurs in approximately 56% of neonates with asphyxia, presenting as either oliguric or non-oliguric renal dysfunction6,7. This study, conducted at GSL Medical College, Rajahmundry, aimed to address the high mortality rate and diagnostic challenges in neonates with BA, with approximately 5 cases seen weekly at the tertiary care center.

STUDY DESIGN: This was a prospective observational study.

SAMPLE SIZE: According to V Babu’s study8, the incidence of asphyxia in India is 6.6%. Using Epi Info Software, the sample size was calculated based on the population survey model as follows:

N = Z²PQ / E²

Where:

• N = sample size
• P = population proportion (6.6%)
• Q = 1 - P
• E = margin of error (6%)
• Confidence level: 95%

The calculated sample size was 62, which was the minimum required. Therefore, 62 neonates were included in the current study.

INCLUSION CRITERIA:   

1. Term neonates with birth asphyxia
2. APGAR score ≤7 at 1 and 5 minutes
3. Umbilical cord arterial pH <7 at birth

EXCLUSION CRITERIA: 

1. Neonates with incomplete data
2. Neonates with septicemia or respiratory distress syndrome (RDS)
3. Neonates who have received aminoglycoside antibiotics or aminophylline

Septicemia was excluded based on blood reports, including leukocyte count and CRP levels.

RDS was excluded using the Silverman Anderson’s score.

Medication usage was excluded based on parental history and medications provided.

METHODOLOGY:

The study was approved by the institutional ethics committee, ensuring confidentiality. A detailed history, including personal and family medical histories, was obtained from each parent. Demographic details (e.g., gender) and clinical examination findings were recorded, and data were entered into a case record form for statistical analysis.

Parameters Assessed:

• Neonate's gender
• APGAR score at 1 and 5 minutes
• Asphyxia severity
• Birth weight
• Prolonged labor and meconium-stained liquor
• Serum calcium, bicarbonate, sodium, potassium, urea, and creatinine
• Urine output (low or normal), sodium, analysis, and creatinine
• Renal dysfunction incidence
• Biochemical Parameters Measured at 24, 48, and 72 hours:
• Blood urea, serum calcium, sodium, potassium, bicarbonate, creatinine
• Urine output: Low if <1 ml/kg/hr
• Asphyxia severity: Severe (APGAR 3-4), Moderate (APGAR 5-6), Mild (APGAR 7)

A complete clinical workup was performed, including history, physical examination, vital signs, systemic examination, and study parameters.

STATISTICAL ANALYSIS: The collected data was entered into MS Excel 2019, and analysis was performed using Microsoft Excel and Epi Info version 7.2.5 (free version). A p-value of <0.05 was considered statistically significant.Frequencies and percentages were also calculated.A Chi-square test was used to identify factors associated with birth asphyxia. Pearson correlation was used to assess the relationship between serum calcium, bicarbonate, sodium, potassium, and asphyxia severity.Additionally, a Chi-square test was used to correlate urine sodium and urine creatinine levels with asphyxia severity.

The following assumptions were made for the data: Dependent variables are normally distributed.                                           Skewed variables were log-transformed to achieve normal distribution

Table 1: Gender of neonates

In the current study, 58% of the neonates were boys and 41.9% were girls.

Table 2: Birth weight of neonates

In the current study, the birth weight of all neonates ranged between 2.5 and 3.5 kg.

Table 3: APGAR scores at 1min

The APGAR score at 1 minute was 3 in 20.9% of neonates, 4 in 16.1%, 5 in 14.5%, and 6 in 9.68%. The majority of neonates (38.71%) had an APGAR score of 7 at 1 minute.

Table 4: APGAR scores at 5 min.

In some neonates, the APGAR score improved, while in those with a score of 7 at 1 minute, it remained unchanged. No neonate had a score of 3 at 5 minutes, and a score of 7 was the most commonly observed at this time.

Table 5: Severity of asphyxia

Asphyxia severity was determined based on the APGAR scores at 1 minute. It was severe in 38% of neonates, moderate in 24%, and mild in 38%.

Table 6: Renal dysfunction among neonates

Renal dysfunction developed in 67.7% of neonates, while renal function remained normal in 32.2%. Urine analysis was normal for all neonates at 24, 48, and 72 hours.

Table 7: Renal dysfunction and severity of asphyxia

A highly significant association was found between the severity of asphyxia and renal dysfunction in the current study, as indicated by chi-square analysis (P=0.000). Among the 23 neonates with severe birth asphyxia, renal dysfunction was observed in 21.

Table 8: Correlation between blood urea at 24 hours and asphyxia  severity

A significant association was found between blood urea levels at 24 hours and the severity of asphyxia, according to chi-square analysis (P=0.00). Blood urea levels were higher in neonates with severe asphyxia compared to those with mild and moderate asphyxia.

Table 9: Correlation between blood urea at 48 hours and asphyxia  severity

Chi-square analysis (p=0.00) indicates a significant association between blood urea levels at 48 hours and the severity of asphyxia.

Table 10: Correlation between blood urea at 72 hours and asphyxia severity

Chi-square analysis (p=0.00) shows a significant association between blood urea levels at 72 hours and the severity of asphyxia.

• Serum sodium correlation increased from 24 to 72 hours. At 24 hours, no correlation was found, but significant correlation appeared at 48 and 72 hours, indicating hyponatremia in neonates with asphyxia.
• A small positive correlation at 24 hours, medium correlation at 48 hours, and large correlation at 72 hours were observed between potassium and asphyxia severity, indicating hyperkalemia in severe cases.
• Urine creatinine levels showed a non-significant positive correlation at 24 hours, becoming significantly positive by 72 hours, suggesting increased levels in severe asphyxia neonates.
• Serum calcium showed a non-significant negative correlation at 24 and 48 hours, becoming significantly negative at 72 hours, indicating hypocalcemia in severe asphyxia.
• Significant associations were found between blood urea and urine sodium levels at all time points (24, 48, and 72 hours) and asphyxia severity.
• Serum bicarbonate levels had a significant negative correlation with asphyxia severity, indicating acidosis in severe cases.

Both bicarbonate and potassium levels indicated renal dysfunction from 24 hours

The present study aimed to correlate perinatal asphyxia with renal injury using biochemical parameters in neonates. The findings indicate that renal dysfunction was observed in 67.7% of neonates with birth asphyxia, highlighting the significant impact of hypoxic-ischemic injury on renal function. These results are consistent with previous research showing that acute kidney injury (AKI) occurs in a substantial proportion of neonates with perinatal asphyxia, often manifesting as oliguric or non-oliguric renal dysfunction9,10. The study further emphasizes the importance of early biochemical assessments to predict renal dysfunction and facilitate timely intervention. 

Analysis of APGAR scores revealed that 38% of neonates had severe asphyxia, 24% had moderate asphyxia, and 38% had mild asphyxia. A strong correlation was observed between the severity of asphyxia and renal dysfunction, as indicated by a highly significant chi-square test result (p=0.000). Among neonates with severe birth asphyxia, 91.3% developed renal dysfunction, compared to 80% in moderate cases and 33.3% in mild cases. These findings align with previous studies demonstrating a dose-dependent relationship between hypoxia severity and renal impairment, where prolonged hypoxic episodes lead to significant renal tubular damage due to ischemic injury11,12. 

Biochemical parameters such as blood urea, serum sodium, potassium, calcium, bicarbonate, and urine creatinine were assessed at 24, 48, and 72 hours. Blood urea levels showed a strong positive correlation with asphyxia severity at all time points, with significantly higher values in neonates with severe asphyxia (p=0.00). This finding supports prior studies indicating that elevated blood urea serves as a key biomarker of renal dysfunction following perinatal asphyxia13,14. 

Serum sodium levels exhibited a progressive correlation with asphyxia severity from 24 to 72 hours, suggesting that hyponatremia is a common electrolyte disturbance in asphyxiated neonates. Similar trends were observed for serum potassium, with increasing hyperkalemia severity in neonates with more severe asphyxia. These alterations in electrolyte balance may be attributed to impaired renal tubular function and reduced glomerular filtration rate (GFR) due to hypoxic-ischemic injury, as previously reported in neonatal AKI studies 15,16. Urine creatinine levels were not significantly correlated at 24 hours but showed a strong positive correlation at 72 hours, indicating progressive renal dysfunction. The delayed increase in urine creatinine levels suggests a time-dependent manifestation of renal injury, where initial hypoxia-induced tubular dysfunction leads to a gradual decline in creatinine clearance. Similar findings have been reported in studies assessing renal function markers in asphyxiated neonates, emphasizing the need for continued monitoring beyond the first 24 hours17. 

Serum calcium levels demonstrated a significant negative correlation with asphyxia severity at 72 hours, indicating hypocalcemia in neonates with severe asphyxia. This is consistent with prior reports suggesting that hypocalcemia may result from renal dysfunction-related phosphate retention and altered parathyroid hormone regulation in neonates with birth asphyxia 12. Likewise, serum bicarbonate levels showed a significant negative correlation with asphyxia severity, reflecting metabolic acidosis due to impaired renal compensation. The development of acidosis in severely asphyxiated neonates further supports the role of hypoxia-induced renal dysfunction in acid-base disturbances10. 

Overall, the study reinforces the strong association between perinatal asphyxia and renal dysfunction, with the severity of asphyxia serving as a key determinant of renal injury risk. The findings underscore the importance of early biochemical assessments in asphyxiated neonates, as parameters such as blood urea, serum sodium, potassium, calcium, bicarbonate, and urine creatinine can serve as valuable markers for predicting renal dysfunction. Timely identification of at-risk neonates allows for appropriate therapeutic interventions, reducing the likelihood of long-term renal complications and improving neonatal outcomes. 

The study found a 67.8% prevalence of renal dysfunction in neonates with perinatal asphyxia. Biochemical parameters, including serum sodium, potassium, calcium, bicarbonate, urine creatinine, blood urea, and urine sodium, were assessed at 24, 48, and 72 hours after birth. Asphyxia severity, determined by the APGAR score, was classified as severe in 38% of neonates.Significant correlations between serum sodium, potassium, calcium, bicarbonate, blood urea, and urine sodium levels with asphyxia severity allowed for early prediction of renal dysfunction within 72 hours. This facilitated timely clinical intervention, preventing permanent renal damage and reducing mortality. No neonates in the study died due to the prompt actions taken.

1. Roberts, D.S., Haycock, G.B., Dalton, R.N., et al. "Prediction of Acute Renal Failure After Birth Asphyxia." Archives of Disease in Childhood, vol. 65, 1990, pp. 1021-1028.
2. Durkan, A.M., and Alexander, R.T. "Acute Kidney Injury Post Neonatal Asphyxia." The Journal of Pediatrics, vol. 158, no. 2, 2011, pp. e29-e33, https://doi.org/10.1016/j.jpeds.2010.11.010.
3. Perlman, J.M., Tack, E.D., Martin, T., Shackelford, G., and Amon, E. "Acute Systemic Organ Injury in Term Infants After Asphyxia." American Journal of Diseases of Children, vol. 143, 1989, pp. 617–620.
4. Misra, P.K., Kumar, A., Natu, S.M., Kapoor, R.K., Srivastava, K.L., and Das, K. "Renal Failure in Symptomatic Perinatal Asphyxia." Indian Pediatrics, vol. 28, 1991, pp. 1147–1151.
5. Agras, P.I., Tarcan, A., Baskin, E., Cengiz, N., Gürakan, B., and Saatci, U. "Acute Renal Failure in the Neonatal Period." Renal Failure, vol. 26, 2004, pp. 305–309.
6. Saini, R., Sehra, R.N., Verma, S., Pansari, V.K., Nagaraj, N., and Yadav, R. "A Study of Renal Functions in Asphyxiated Term Newborns." Journal of Pediatric Research, vol. 4, no. 6, 2017, pp. 363-369, doi:10.17511/ijpr.2017.06.03.
7. Rainaldi, M.A., and Perlman, J.M. "Pathophysiology of Birth Asphyxia." Clinical Perinatology, vol. 43, no. 3, 2016, pp. 409-422, doi:10.1016/j.clp.2016.04.002.
8. Babu, V.A., Shyamala Devi, S., and Kishore Kumar, B. "Birth Asphyxia – Incidence and Immediate Outcome in Relation to Risk Factors and Complications." International Journal of Research in Health Sciences, vol. 2, no. 4, 2014, pp. 1064-1071.
9. Babu, V.A., Shyamala Devi, S., and Kishore Kumar, B. "Birth Asphyxia – Incidence and Immediate Outcome in Relation to Risk Factors and Complications." International Journal of Research in Health Sciences, vol. 2, no. 4, 2014, pp. 1064-1071.
10. Roberts, D.S., Haycock, G.B., Dalton, R.N., et al. "Prediction of Acute Renal Failure After Birth Asphyxia." Archives of Disease in Childhood, vol. 65, 1990, pp. 1021-1028.
11. Durkan, A.M., and Alexander, R.T. "Acute Kidney Injury Post Neonatal Asphyxia." The Journal of Pediatrics, vol. 158, no. 2, 2011, pp. e29-e33, https://doi.org/10.1016/j.jpeds.2010.11.010.
12. Perlman, J.M., Tack, E.D., Martin, T., Shackelford, G., and Amon, E. "Acute Systemic Organ Injury in Term Infants After Asphyxia." American Journal of Diseases of Children, vol. 143, 1989, pp. 617–620.
13. Misra, P.K., Kumar, A., Natu, S.M., Kapoor, R.K., Srivastava, K.L., and Das, K. "Renal Failure in Symptomatic Perinatal Asphyxia." Indian Pediatrics, vol. 28, 1991, pp. 1147–1151.
14. Agras, P.I., Tarcan, A., Baskin, E., Cengiz, N., Gürakan, B., and Saatci, U. "Acute Renal Failure in the Neonatal Period." Renal Failure, vol. 26, 2004, pp. 305–309.
15. Saini, R., Sehra, R.N., Verma, S., Pansari, V.K., Nagaraj, N., and Yadav, R. "A Study of Renal Functions in Asphyxiated Term Newborns." Journal of Pediatric Research, vol. 4, no. 6, 2017, pp. 363-369, doi:10.17511/ijpr.2017.06.03.
16. Rainaldi, M.A., and Perlman, J.M. "Pathophysiology of Birth Asphyxia." Clinical Perinatology, vol. 43, no. 3, 2016, pp. 409-422, doi:10.1016/j.clp.2016.04.002.
17. Babu, V.A., Shyamala Devi, S., and Kishore Kumar, B. "Birth Asphyxia – Incidence and Immediate Outcome in Relation to Risk Factors and Complications." International Journal of Research in Health Sciences, vol. 2, no. 4, 2014, pp. 1064-1071.