==== Front Cureus Cureus 2168-8184 Cureus 2168-8184 Cureus Palo Alto (CA) 10.7759/cureus.11407 Neurology Pediatrics Public Health Clinico-Biochemical Correlation in Birth Asphyxia and Its Effects on Outcome Muacevic Alexander Adler John R Acharya Abhilipsa 1 Swain Banashree 2 Pradhan Sarbeswar 3 Jena Pradeep K 4 Mohakud Nirmal K 5 Swain Arakhita 4 Mohanty Niranjan 5 1 Pediatrics and Neonatology, Institute of Medical Sciences and Sum Hospital (IMS and Sum Hospital) Siksha 'O' Anusandhan (SOA) Deemed to be University (DU), Bhubaneshwar, IND 2 Biochemistry, Sriram Chandra Bhanj (SCB) Medical College, Cuttack, IND 3 Pediatrics, Kalinga Institute of Medical Sciences, Kalinga Institute of Industrial Technology (KIIT) Deemed to be University (DU), Bhubaneswar, IND 4 Pediatrics, Sriram Chandra Bhanj (SCB) Medical College, Cuttack, IND 5 Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, IND Nirmal K. Mohakud nirmal.mahakud@kims.ac.in 9 11 2020 11 2020 12 11 e114079 11 2020 Copyright © 2020, Acharya et al.2020Acharya et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/45021-clinico-biochemical-correlation-in-birth-asphyxia-and-its-effects-on-outcomeBackground Birth asphyxia is a major cause of early neonatal death and leads to severe consequences such as epilepsy, cerebral palsy, and developmental delay. This study aims to determine the correlation between dyselectrolytemia and the degree of hypoxic-ischemic encephalopathy (HIE) and to find out major risk factors contributing to the severity of HIE and neonatal death. Methods In this prospective cohort study (n=150), term babies weighing ≥ 2.5 kg at birth, with the diagnosis of birth asphyxia, admitted in a medical college in Odisha state from September 2014 to August 2016 were included. Clinical findings, biochemical parameters, treatment, and outcome of HIE babies were recorded. Result The majority of the asphyxiated babies were having moderate HIE (HIE II) (57.33%), whereas mild and severe stages were seen in 15.33%, and 27.34% of babies, respectively. Factors like prolonged labor (87.8%) and meconium-stained liquor (63.4%) were mostly attributed to the severe degree of birth asphyxia (p < 0.001). Apnea, lethargy, and hypothermia were the most remarkable feature of HIE III. The degree of hyponatremia, hypocalcemia, and hyperkalemia (124.4±4.4 mmol/l, 0.83±0.08 mmol/l, and 6.17± 0.89 mmol/l, respectively) were more severely affected in HIE III as compared to HIE l (137.5±3.8 mmol/l, 1.06±0.17 mmol/l, and 5.0±0.79 mmol/l, respectively). Serum urea and creatinine increased proportionately with an increase in the severity of HIE grade. The mildly asphyxiated neonates recovered completely, whereas all the cases who died (n=29,19.3%) belonged to the moderate or severe degree of birth asphyxia. Conclusion The asphyxiated neonates had hyponatremia, hypocalcemia, hyperkalemia, raised serum urea, and creatinine and correlated with the severity of birth asphyxia. Prolonged labor and meconium-stained liquor were the most attributable factor for the severe degree of birth asphyxia. Effective neonatal resuscitation and quick correction of electrolyte imbalances will help in the reduction of neonatal mortality and long-term neurological sequelae. hypoxic ischemic encephalopathybirth asphyxiaprolonged laborhyponatremiahyperkalemiahypothermiainstrumental deliveryThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. ==== Body Introduction Perinatal asphyxia/birth asphyxia is a major cause of neonatal morbidity and mortality in developing countries [1]. Effective neonatal resuscitation not only saves the life of newborns but prevents long-term neurological sequelae. Perinatal asphyxia constitutes 28.8% of neonatal mortality and 45.1% of stillbirths in India [2]. Perinatal asphyxia causes hypoxia (lack of oxygen) or inadequate perfusion (ischemia) to various organs of the fetus or newborn. Birth asphyxia is defined as a combination of hypoxia, hypercarbia, and metabolic acidosis due to the blockage of umbilical vessels, placental insufficiency in utero, or ineffective breathing after delivery [3-4]. It is an insult to the fetus or newborn either in the antepartum or intrapartum period or both, leading to various functional and/or biochemical changes. Birth asphyxia is the most common preventable cause of central nervous system (CNS) injury in neonates and thereby protects from long-term neurological abnormality and disability [5]. Around 3.6 million neonates suffer from moderate to severe birth asphyxia in developing countries. Nearly 840,000 babies (23%) die or may develop serious neurological sequelae [6]. Prevention is more important than treatment for perinatal asphyxia. Maternal factors like prolonged labor, gestational diabetes, antepartum hemorrhage, preeclampsia, and multiple pregnancies have a significant role in the development of neonatal asphyxia [1]. The prolonged second stage of labor underlies around 60% of HIE and could be prevented by institutional setup and the availability of skilled medical personnel and facilities for operative deliveries, where required [7-8]. Neonatal factors for birth asphyxia (HIE) are post-dated, cord around the neck, oligohydramnios, meconium-stained amniotic fluid (MSAF), malpresentation, etc. [8]. The serum level of electrolytes plays a pivotal role in the outcome of these HIE babies. Any deviation from the normal levels of electrolytes (sodium, potassium, and calcium) may lead to convulsions, shock, and other types of metabolic abnormalities. Perinatal asphyxia results in anaerobic metabolism, decreased adenosine triphosphate (ATP) production, impairment of the function of ion pump, and the accumulation of intracellular sodium, chloride, water, calcium, and extracellular potassium leading to an electrolyte imbalance, which adversely affects the outcome of asphyxiated babies [9-10]. Besides CNS, the kidney is the most sensitive organ to hypoxia [10]. Birth asphyxia results in ischemia to the proximal tubule, thereby developing acute tubular necrosis and acute renal failure. This leads to an increase in serum urea and creatinine [10]. So the meticulous management of body temperature, electrolytes, and blood sugar and providing appropriate oxygen may reduce the severity of the ischemic insult. The objective of the present study is to identify the risk factors and biochemical derangements associated with increased morbidity and mortality. Materials and methods This prospective observational study was conducted at the department of pediatrics, Sriram Chandra Bhanj (SCB) Medical College, Cuttack, in the state of Odisha in the eastern part of India over a period of two years, from September 2014 to September 2016. The study cohort (n=150) consisted of hospitalized term neonates of birth weight ≥ 2.5 kg with the diagnosis of birth asphyxia as per the following criteria [11-12]: metabolic acidosis (cord or infant blood in 1st hour); APGAR (appearance, pulse, grimace, activity, and respiration) score < 7 at five minutes of birth; apnea at birth; base deficit > 16 mmol/l; and clinical evidence of encephalopathy (altered consciousness, seizure, hypotonia, or absence of suck). Newborn babies with congenital anomalies, suspected inborn errors of metabolism, congenital infection, septic shock, intrauterine growth restriction (IUGR), received diuretics prior to the evaluation, and < 37 weeks of postmenstrual age were excluded. Data of neonates presenting with perinatal asphyxia were evaluated using a prestructured proforma. Classification of mild (HIE I), moderate (HIE II), and severe (HIE III) stage was based on the modified Sarnat staging for neonatal encephalopathy [13]. Detailed history regarding type and place of delivery, type of resuscitation required, any complication before/during delivery, onset and duration of seizure, and findings of clinical examination, with special reference to the central nervous system, were noted. Various risk factors like prolonged labor, preeclampsia, antepartum hemorrhage (APH), multiple pregnancies, gestational diabetes (GDM), cord around the neck, meconium-stained amniotic fluid (MSAF), oligohydramnios, and malpresentation were recorded. Biochemical parameters like sodium (Na+), potassium (K+), calcium (Ca+2), serum urea, and creatinine, quantitative C-reactive protein (CRP), and complete blood count were estimated. Clinical findings during the treatment in the hospital until discharge or death were recorded. Neurological findings like abnormal movements, feeding problems, subtle/frank seizures, or neurological deficits were evaluated. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20 (IBM Corp., Armonk, NY). A p-value of < 0.05 was considered statistically significant. Association of risk factors and biochemical parameters with respect to the severity of HIE were evaluated using the chi-square test. Furthermore, univariate analysis was used to find out the significance of various parameters in the outcome of the present study. Institutional ethical clearance was taken prior to the study. Results Male babies (n=116, 77.3%) outnumbered female babies and the ratio was 3.4: 1. Term and post-term babies constituted 86 (57.3%) and 64 (42.7%) cases, respectively. The majority of babies (57.33%) were having moderate HIE, whereas 15.33% and 27.34% of babies were mild and severe HIE, respectively. Post-term babies were more likely to be affected by HIE I or HIE II as compared to HIE III (p < 0.01). Normal and assisted delivery (122/137, 89%) cases were mostly having HIE II/HIE III, whereas it was less in lower segment cesarian section (LSCS) delivery (5/13, 38.4%). Among the risk factors, prolonged second stage of labor (n=95, 63.3%) and meconium-stained liquor (n= 63,42%) were more common. The association of these two factors increased the severity of birth asphyxia (p< 0.001) (Table 1). Table 1 Correlation of risk factors with the severity of hypoxic-ischemic encephalopathy HIE, hypoxic-ischemic encephalopathy; vs, versus; GDM, gestational diabetes; MSAF, meconium-stained amniotic fluid; APH, antepartum hemorrhage Risk Factors Mild cases (%) (HIE I) Moderate cases (%) (HIE II) Severe cases (%) (HIE III) Total cases (%) HIE I vs HIE II P-value HIE I vs HIE III P-value HIE II vs HIE III P-value Prolonged labor 12 (52.2) 47 (54.7) 36 (87.8) 95 (63.3) 0.832 0.001 0.0002 Preeclampsia 1 (4.3) 2 (2.3) 3 (7.3) 6 (4) 0.598 0.637 0.387 GDM 1 (4.3) 3 (3.5) 2 (4.9) 6 (4) 0.845 0.637 0.706 Multiple Pregnancy 1 (4.3) 2 (2.3) 2 (4.9) 5 (3.3) 0.598 0.923 0.820 MSAF 1 (4.3) 36 (41.9) 26 (63.4)  63 (42) 0.001 0.0001 0.023 Cord around neck 1 (4.3) 10 (11.6) 9 (22) 20 (13.3) 0.522 0.133 0.127 Oligohydramnios 2 (8.7) 7 (8.1) 8 (19.5) 17 (11.3) 0.931 0.432 0.063 Malpresentation 3 (13) 23 (26.7) 5 (12.2) 31 (20.7) 0.273 0.921 0.064 APH 1 (4.3) 6 (7) 7 (17.1) 14 (9.3) 0.647 0.278 0.079 No-Risk Factors 8 (34.8) 11 (12.8) 0 19 (12.7) 0.013 0.0003 0.039 Other maternal factors like antepartum hemorrhage, gestational diabetes, and preeclampsia had less contribution to the development of HIE (17.3%). Babies delivered outside the hospital (n=42, 28%) had more chance of developing severe birth asphyxia ( p < 0.003). Hypothermia (n=55, 36.7%), lethargy (n= 128, 85.3%), respiratory distress (n=71, 47.3%), convulsion (n=100, 66.7%), and apnea (n=48, 32%) were associated with HIE, but apnea, lethargy, and hypothermia were the most remarkable features of HIE III. Hyponatremia (62, 41.3%) was predominately found in HIE II/III as compared to HIE l (p<0.0001). The incidence of hypocalcemia (n=118, 78.7%) observed in HIE II/III was significant compared to HIE I (p<0.0001) (Table 2). Table 2 Electrolyte levels and their correlation within various grades of birth asphyxia HIE, hypoxic-ischemic encephalopathy; vs, versus; Na+, sodium; K+, potassium; Ca+2, calcium Parameters Mild cases (%) (HIE I) Moderate cases (%) (HIE II) Severe cases (%) (HIE III) Total cases (%) HIE I vs HIE II P-value HIE I vs HIE III P-value HIE II vs HIE III P-value Serum Na+               Normal (130-150 mmol/l) 23(100) 51(59.3) 7(17.1)  81(54) 0.0005 <0.0001 <0.0001 Hypernatremia 0 7(8.1) 0 7 (4.7) 0.3495  _ 0.1433 Hyponatremia 0 28(32.6) 34(82.9) 62(41.3) 0.0037 <0.0001 <0.0001 Serum K+               Normal(3.5- 5.5 mmol/l) 12(52.2) 27(31.4) 1(2.4) 40(26.7) 0.0648 <0.0001 0.0006 Hyperkalemia 11 (47.8) 58(67.4) 39(95.2) 108(72) 0.080 <0.0001 0.0013 Hypokalemia 0 1(1.2) 1(2.4) 2(1.3) 0.6034 0.4503 0.5891 Serum Ca2+               Normal 13(56.5) 19(22.1) 0 32(21.3) < 0.0001 < 0.0001 0.0027 Hypocalcemia 10(43.5) 67(77.9) 41(100) 118(78.7) Serum urea               Normal 20(86.9) 38(44.2) 4(9.8)  62(41.3) 0.0006 < 0.0001 0.0003 High 3(13.1) 48(55.8) 37(90.2)  88(58.7) Serum Creatinine               Normal 23(100) 60(69.8) 4(9.8) 87(58)  0.006 < 0.0001  <0.0001 High 0 26(30.2) 37(90.2) 63(42) The degree of hyponatremia, hypocalcemia, and hyperkalemia (124.4±4.4 mmol/l, 0.83±0.09 mmol/l, 6.17± 0.89 mmol/l respectively) were significantly different between HIE III and HIE I (137.5±3.8 mmol/l, 1.05±0.19 mmol/l, 5±0.79 mmol/l, respectively). Similarly, serum urea and creatinine levels were significantly different between HIE I and HIE III (Table 3). Table 3 Mean values of biochemical parameters in different stages of hypoxic-ischemic encephalopathy Statistical analysis, ANOVA, and post hoc test. HIE, hypoxic-ischemic encephalopathy; vs, versus; Na+, sodium; K+, potassium; Ca+2, calcium; mmol, millimole; mg, milligram; dl, decilitre; SD, standard deviation Parameters HIE-l  HIE-ll HIE lll HIE l vs HIE ll P-value HIE l vs HIE lll P-value HIE ll vs HIE ll P-value Serum Na+ (mmol/l) ± SD 137.5±3.8 132.7±6.8 124.4±4.4 < 0.01 < 0.01 < 0.01 Serum K+ (mmol/l) ± SD 5.00±0.79 5.55±0.77 6.17±0.89 < 0.05 < 0.01 < 0.01 Serum Ca+2 (mmol/l) ± SD 1.06+ 0.17 0.86 + 0.15 0.83+ 0.09 <0.01 <0.001 >0.05 Serum urea (mg/dl) ± SD 26.75± 8.8 47.98± 24.7 89.38± 28.6 <0.01 <0.001 < 0.01 Serum creatinine (mg/dl) ± SD 0.70±0.16 0.94±0.54 2.41±0.89 >0.05 (NS) < 0.01 < 0.01 Of 150 cases, 29 (19.3%) had died. Mortality among mild, moderate, and severe stages were zero, two (2.3%), and 27 (65.9%), respectively. It was found that mortality in HIE III was significant compared to HIE I and HIE II (p<0.01). Recovery with no abnormal movement/focal neurological deficit was seen in all HIE I (n=66, 76.7%), whereas neurological sequelae were observed in HIE II (n=18, 21%) and HIE III (n=14, 34.1%) cases.  Discussion Among the all asphyxiated babies, HIE II constituted the major portion (57.33%). So prompt identification of risk factors and biochemical derangements with timely intervention may prevent progression to severe grade and reasonably better neurological outcomes. The serum Na+, K+, and Ca+2 levels in the first 24 hours of life are between 134 and 146 mEq/L, 3.0 and 7.0 mEq/L, and 2 and 2.25 mmol/L, respectively [10]. Any change of sodium, potassium, and calcium levels in the blood beyond the normal range might cause seizures and metabolic abnormalities [14]. Calcium being the second messenger acts on various cofactors for many enzymatic activities and muscle contraction [14]. In this study, the degree of hyponatremia, hypocalcemia, and hyperkalemia was directly proportional to the degree of severity of HIE (Figure 1). Figure 1 Line diagram showing the mean serum sodium (Na+) and potassium (K+) levels with the severity of birth asphyxia There is a progressive decrease in serum sodium (Na+) with increasing severity of birth asphyxia Hypoxia and ischemia cause neuronal injury and worsen cerebral edema due to maladaptation to the hyponatremic effect. So the quick and appropriate management of dyselectrolytemia reduces ischemic penumbra, seizure, and further CNS injury [14]. It was found that post-dated neonates are more likely to develop HIE II and HIE III (HIE II: 45.3%, HIE III: 53.7%) compared to HIE I (p<0.01). This is due to postdated pregnancy associated with meconium aspiration, respiratory distress syndrome, sepsis neonatorum, oligohydramnios, macrosomia, and fetal birth injury [15]. In this study, the largest number of birth asphyxia babies were from normal vaginal delivery but mostly with a mild (47.8%) to moderate (52.2%) degree. It may be assumed that vaginal delivery is a difficult process and may cause a prolonged second stage of labor. Other associated factors like breech presentation, macrosomia, and large size baby increase the severity of birth asphyxia. Previous studies in other parts of India and developing countries had similar findings [11,16]. Our study revealed that forceps/ventouse delivery may lead to severe birth asphyxia (p < 0.01), whereas LSCS is better and associated with HIE I (p < 0.001). Findings reported by Benedetto C et al. in Italy found that instrumental deliveries have the highest rate of short-term maternal and neonatal complications [17]. Usually, vacuum extraction is one of the safe practices to shorten the second stage of labor and the prevention of prolonged labor-related complications. A study from Japan proved successful vacuum‐assisted deliveries, as it shortened the duration of extraction and no complication for neonates [18]. That’s true for delivery in normal cases but babies delivered by forceps at a late stage, leading to HIE had unfavorable outcomes. Prolonged labor was the commonest risk factor in all three stages of asphyxia. The prolonged labor leads to dehydration and exhaustion, and the fetus becomes distressed [19]. It also contributes to maternal infection, neonatal infection, and intracranial hemorrhage ultimately develops birth asphyxia [7,20]. Hypothermia was associated with the majority (61%) of cases of HIE III. Very recently, therapeutic hypothermia is a very successful modality to improve the outcome for infants with hypoxic-ischemic encephalopathy by neuroprotective effects [21]. The kidney is the most common organ to be affected by HIE in the first 24 hours of life, and if hypoxia is not corrected later, irreversible cortical necrosis may occur [22]. So early diagnosis and appropriate fluid and electrolyte management is required for better outcomes for these newborns. Our study found serum urea and creatinine values proportionately increasing with stages of birth asphyxia (Figure 2). Figure 2 Line diagram showing the mean serum urea and creatinine levels with severity of birth asphyxia There is a progressive increase in serum urea and creatinine with increasing severity of birth asphyxia, but it is more marked in urea levels. These findings are comparable with other studies from India and Nepal [22-23]. Perinatal hypoxia causes acute tubular necrosis, renal vein thrombosis, and damage to nephrons. Thus, the sodium reabsorption capacity of the direct Coombs test (DCT) and more sodium loss in the urine causes hyponatremia. Further, birth asphyxia causes a syndrome of inappropriate antidiuretic hormone secretion (SIADH) and partial aldosterone resistance, leading to hyponatremia [16]. Hyponatremia leads to hypovolemia and further compromise of renal functions. The abnormal neurological finding is more prominent in HIE neonates (9/12;75%) having renal failure. The average duration of hospital stay among mild, moderate, and severe stages of HIE babies were 3.9±0.7 days, 9.0±1.9 days, 17.6±3.5 days, respectively, indicating neonates with HIE III had longer hospitalization as compared to HIE I neonates (p < 0.05). Neonates with antiepileptic drug use or having focal neurological deficits were likely to have adverse outcomes and later may develop seizure disorder [24]. All the mildly asphyxiated neonates recovered uneventfully, whereas all the 29 (19.3%) cases who died belonged to the moderate and severe stages of birth asphyxia. There is a proportionate increase in mortality with the severity of HIE owing to the involvement of multiple systems [11]. The majority (59.3%) of HIE babies were discharged without focal neurological deficits. Similar reports were observed in other studies [11,25]. The present study has a few limitations. A large number of referral cases were coming from peripheral hospitals and the long duration of the journey may be responsible for the delay in receiving institutional treatment. These factors were responsible for prolonged labor, out-of-hospital deliveries, and more complications. Therapeutic hypothermia for infants ≥36 weeks gestational age (GA), with moderate-to-severe HIE, had not been used as a treatment modality for all, which might have an influence on the neurological outcome. Our findings may not be generalized to the community, however, due to the long duration of the study and a good number of cases, the findings of risk factors for HIE and correlation dyselectrolytemia can be used for planning the interventional strategy. Conclusions Hypoxic-ischemic babies with dyselectrolytemia were found to have severe disease in our study group. The risk factors for birth asphyxia can be prevented by proper antenatal care and active and timely management during labor. Effective neonatal resuscitation and quick correction of electrolyte imbalances will help in the reduction of neonatal mortality and long-term neurological sequelae. The authors have declared that no competing interests exist. Human Ethics Consent was obtained by all participants in this study. Sriram Chandra Bhanj (SCB) Medical College/IEC issued approval Appln. No-49 Animal Ethics Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. We are obliged to Professor S.K. Satpathy for his guidance in writing the manuscript. We thank Dr. Mirabai Das for her help in grammatical correction and typing the manuscript. ==== Refs References 1 Stillbirths: rates, risk factors, and acceleration towards 2030 Lancet Lawn JE Blencowe H Waiswa P 587 603 387 2016 26794078 2 NNPD Network, Indian Council of Medical Research, National Neonatology Forum NNPD Network 8 10 2005 https://www.newbornwhocc.org/pdf/nnpd_report_2002-03.PDF 3 Low Apgar scores and the definition of birth asphyxia Pediatr Clin North Am Leuthner SR Das UG 737 745 51 2004 15157595 4 Perinatal asphyxia from the obstetric standpoint: diagnosis and Interventions Clin Perinatol Herrera CA Silver RM 423 438 43 2016 27524445 5 Outcome of very severe birth asphyxia Arch Dis Child Scott H 712 716 51 1976 1033733 6 The state of the world's children 2009: maternal health is the key to achieve MDGs 4 and 5 Indian Pediatr Vashishtha VM 233 234 46 2009 https://www.indianpediatrics.net/mar2009/233.pdf 19346571 7 Determinants of birth asphyxia among live birth newborns in University of Gondar referral hospital, northwest Ethiopia: a case-control study PLoS One Wosenu L Worku AG Teshome DF Gelagay AA 203763 7 2018 8 Perinatal asphyxia: multivariate analysis of risk factors in hospital births Indian Pediatr Chandra S Ramji S Thirupuram S 206 212 34 1997 https://indianpediatrics.net/mar1997/206.pdf 9282487 9 Electrolyte status in birth asphyxia Indian J Pediatr Basu P Som S Das H Choudhuri N 259 262 77 2010 20177828 10 Perinatal asphyxia and hypoxic-ischemic encephalopathy Manual of Neonatal Care Hansen AR Soul JS 711 728 Philadelphia, PA Lippincott Williams & Wilkins 2012 http://www.ypeda.com/attachments/article/150/manual%20of%20neonatal%20care%207th.pdf 11 Postasphyxial hypoxic-ischemic encephalopathy in neonates: outcome prediction rule within 4 hours of birth Arch Pediatr Adolesc Med Shah PS Beyene J To T Ohlsson A Perlman M 729 736 160 2006 16818839 12 Diagnosis of birth asphyxia on the basis of fetal pH, Apgar score, and newborn cerebral dysfunction Am J Obstet Gynecol Iii LCG Leveno KJ Burris J Williams ML Little BB 825 830 161 1989 2782367 13 Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study Arch Neurol Sarnat HB Sarnat MS 696 705 33 1976 987769 14 Electrolytes disturbances and seizures Epilepsia Castilla-Guerra L del Carmen Fernández-Moreno M López-Chozas JM Fernández-Bolaños R 1990 1998 47 2006 https://pubmed.ncbi.nlm.nih.gov/17201695/ 17201695 15 Meconium-stained amniotic fluid as a potential risk factor for perinatal asphyxia: a single-center experience J Clin Neonatol Mehar V Agarwal N Agarwal A Agarwal S Dubey N Kumawat H 157 161 24 2016 https://www.jcnonweb.com/article.asp?issn=2249-4847;year=2016;volume=5;issue=3;spage=157;epage=161;aulast=Mehar 16 Prevalence of electrolyte disturbances in perinatal asphyxia: a prospective study Ital J Pediatr Thakur J Bhatta NK Singh RR Poudel P Lamsal M Shakya A 56 44 2018 29784025 17 Short-term maternal and neonatal outcomes by mode of delivery. A case-controlled study Eur J Obstet Gynecol Reprod Biol Benedetto C Marozio L Prandi G Roccia A Blefari S Fabris C 35 40 135 2007 17126475 18 Impact of clinical practice guidelines for vacuum-assisted delivery on maternal and neonatal outcomes in Japan: a single-center observational study J Obstet Gynaecol Res Egami N Muta R Anami A Koga H [Epub ahead of print] 2020 19 Neonatal and maternal outcomes with a prolonged second stage of labor Obstet Gynecol Laughon SK Berghella V Reddy UM Rajeshwari S Zhaohui L Hoffman MK 57 67 124 2014 24901265 20 Prolonged second stage of labor is associated with low Apgar score Eur J Epidemiol Altman M Sandström A Petersson G Frisell T Cnattingius S Stephansson O 1209 1215 30 2015 26008749 21 Hypoxic ischemic encephalopathy and hypothermia: a critical look Obstet Gynecol Higgins RD 1385 1387 106 2005 16319267 22 Renal failure in asphyxiated neonates Indian Pediatr Gupta BD Sharma P Bagla J Parakh M Soni JP 928 934 42 2005 https://pubmed.ncbi.nlm.nih.gov/16208054/ 16208054 23 Clinico-biochemical profile of neonates with birth asphyxia in Eastern Nepal J Nepal Paediatr Soc Shah G Agrawal J Mishra O Chalise O 206 209 32 2013 https://doi.org/10.3126/jnps.v32i3.7626 24 Clinical feature and outcome of childhood status epilepticus in a teaching hospital, Odisha, India Cureus Das K Das SK Pradhan S Sahoo PI Mohakud NK Swain A Satpathy S 0 12 2020 25 When do newborns die? A systematic review of timing of overall and cause-specific neonatal deaths in developing countries J Perinatol Sankar MJ Natarajan CK Das RR Agarwal R Chandrasekaran A Paul VK 0 36 2016