Aim To analyse biochemical markers as possible predictors of death before discharge in cooled newborns following perinatal asphyxia. Methods A total of 91 infants that underwent therapeutic hypothermia after perinatal asphyxia were included. Inclusion criteria for therapeutic hypothermia were Sarnat stage 2 or 3. Data were collected from medical histories regarding gender, gestational age, birth weight, Apgar and Sarnat score; additionally, gas analyses, liver and cardiac enzymes before, and in the first 12 hours after starting therapeutic hypothermia, were evaluated. The patients’ characteristics were compared between two groups, survivors and non-survivors. Results Statistical difference was not found between groups regarding gender, gestational age, birth weight, delivery type, 1st and 5th minute Apgar score, seizures, alanine aminotransferase (ALT), creatine kinase (CK), troponin and fibrinogen level. Groups were significantly different regarding acid-base balance (p=0.012), base excess (BE) (p=0.025), lactate (p=0.002), aspartate aminotransferaze (AST), (p=0.011), lactate dehydrogenase (LDH) (p=0.006), activated partial thromboplastin clotting time (aPTT) (p=0.001) and international normalized ratio (INR) (p=0.001). Conclusion Acid-base balance, BE, lactate, AST, LDH, aPTT and INR were significantly higher in the group of cooled newborns after perinatal asphyxia (non-survivors), and can serve as predictors of death before discharge. Combining diagnostic modalities raises a chance for accurate prediction of outcomes of asphyxiated infants.
Tariqul I, Seikh A, Matin M, Nazrul I. Alteration of hepatic function: helpful to diagnose and assess severity of perinatal asphyxia. Bangladesh J Child Health. 2010;7–1016.
2.
Gano D, Orbach S, Bonifacio S, Glass H. Neonatal seizures and therapeutic hypothermia for hypoxic-ischemic encephalopathy. Mol Cell Epilepsy. 2014;88.
3.
Bennet L, Dean J, Wassink G, Gunn A. Differential effects of hypothermia on early and late epileptiform events after severe hypoxia in preterm fetal sheep. J Neurophysiol. 2007;572–8.
4.
Tooley J, Satas S, Porter H, Silver I, Thoresen M. Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective. Ann Neurol. 2003;65–72.
5.
Wang Y, Liu P, Li L, Zhang H, Li T. Hypothermia reduces brain edema, spontaneous recurrent seizure attack, and learning memory deficits in the kainic acid treated rats. CNS Neurosci Ther. 2011;271–80.
6.
Jacobs S, Berg M, Hunt R, Tarnow-Mordi W, Inder T, Davis P. Cooling for newborns with hypoxic-ischemic encephalopathy. Cochrane Database Syst Rev. 2013;
7.
Shah P. Hypothermia: a systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med. 2010;238–46.
8.
Chandrasekaran M, Chaban B, Montaldo P, Thayyil S. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a metaanalysis. J Perinatol. 2017;684–9.
9.
Chhavi N, Zutshi K, Kumar Singh N, Awasthi A, Goel A. Serum Liver Enzyme Pattern in Birth Asphyxia Associated Liver Injury. Pediatr Gastroenterol Hepatol Nutr. 2014;162–9.
10.
Escobedo M, Aziz K, Kapadia V, Lee H, Niermeyer S, Schmölzer G, et al. American Heart Association focused update on neonatal resuscitation: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Pediatrics. 2019;
11.
Nakajima J, Tsutsumi N, Nara S, Ishii H, Suganami Y, Sunohara D, et al. Correlations of enzyme levels at birth in stressed neonates with short-term outcomes. Fetal Pediatr Pathol. 2018;157–65.
12.
Choudhary M, Sharma D, Dabi D, Lamba M, Pandita A, Shastri S. Hepatic dysfunction in asphyxiated neonates: prospective case-controlled study. Clin Med Insights Pediatr. 2015;1–6.
13.
Sweetman D, Kelly L, Zareen Z, Nolan B, Murphy J, Boylan G, et al. Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy. Front Pediatr. 2019;399.
14.
Shah S, Tracy M, Smyth J. Postnatal lactate as an early predictor of short-term outcome after intrapartum asphyxia. J Perinatol. 2004;16–20.
15.
Neacsu A, Herghelegiu C, Voinea S, Dimitriu M, Ples L, Bohiltea R, et al. Umbilical cord lactate compared with pH as predictors of intrapartum asphyxia. Exp Ther Med. 2021;80.
16.
Abiramalatha T, Kumar M, Chandran S, Sudhakar Y, Thenmozhi M, Thomas N. Troponin-T as a biomarker in neonates with perinatal asphyxia. J Neonatal Perinatal Med. 2017;275–80.
17.
Ouwehand S, Smidt L, Dudink J, Benders M, De Vries L, Groenendaal F, et al. Predictors of outcomes in hypoxic-ischemic encephalopathy following hypothermia: a meta-analysis. Neonatology. 2020;411–27.
18.
Reddy S, Dutta S, Narang A. Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among sick neonates. Indian Pediatr. 2008;144–7.
19.
Boskabadi H, Zakerihamidi M, Sadeghian M, Avan A, Ghayour-Mobarhan M, Ferns G. Nucleated red blood cells count as a prognostic biomarker in predicting the complications of asphyxia in neonates. J Matern Fetal Neonatal Med. 2017;2551–6.
20.
Boskabadi H, Ashrafzadeh F, Doosti H, Zakerihamidi M. Assessment of risk factors and prognosis in asphyxiated infants. Iran J Pediatr. 2015;
21.
Boskabadi H, Afshari J, Ghayour-Mobarhan M, Maamouri G, Shakeri M, Sahebkar A, et al. Association between serum interleukin-6 levels and severity of perinatal asphyxia. Asian Biomedicine. 2010;79–85.
22.
Edwards A, Brocklehurst P, Gunn A, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010;363.
23.
Odd D, Heep A, Luyt K, Draycott T. Hypoxic-ischemic brain injury: planned delivery before intrapartum events. J Neonatal Perinatal Med. 2017;347–53.
24.
Galvao T, Silva M, Marques M, De Oliveira N, Pereira M. Hypothermia for perinatal brain hypoxia-ischemia in different resource settings: a systematic review. J Trop Pediatr. 2013;453–9.
25.
Abate B, Bimerew M, Gebremichael B, Kassie M, Kassaw A, Gebremeskel M, et al. Effects of therapeutic hypothermia on death among asphyxiated neonates with hypoxic-ischemic encephalopathy: A systematic review and meta-analysis of randomized control trials. PLoS One. 2021;247229.
26.
Verco L, Hockings L. Therapeutic hypothermia for brain injury. Anaesthesia & Intensive Care Medicine. 2013;371–4.
27.
Mcguire W. Perinatal asphyxia. BMJ Clin Evid. 2007;320.
28.
Paliwal P, Varma M, Shaikh M, Mulye S, Paliwal M. Study of hepatic function in neonatal asphyxia. J Evol Med Dent Sci. 2013;5764–7.
29.
Patra C, Sarkar S, Dasgupta M. Study of hepatic enzyme activity as a predictor of perinatal asphyxia and its severity and outcome. Indian J Health Sci Biomed Res. 2016;297–302.
30.
Prashantha Y, Rao S, Nesargi P, Chandrakala S, Balla B, Shashidhar K, et al. Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy in newborns using low-cost devices -ice packs and phase changing material. Paediatr Int Child Health. 2019;234–9.
31.
Natarajan G, Pappas A, Shankaran S. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). Semin Perinatol. 2016;549–55.
32.
Pfister R, Bingham P, Edwards E, Horbar J, Kenny M, Inder T, et al. The Vermont Oxford Neonatal Encephalopathy Registry: rationale, methods, and initial results. BMC Pediatr. 2012;84.
33.
Fairchild K, Sokora D, Scott J, S. Zanelli Therapeutic hypothermia on neonatal transport: 4-year experience in a single NICU. J Perinatol. 2010;324–9.
34.
Kapadia V, Chalak L, Dupont T, Rollins N, Brion L, Wyckoff M. Perinatal asphyxia with hyperoxemia within the first hour of life is associated with moderate to severe hypoxic-ischemic encephalopathy. J Pediatr. 2013;949–54.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
