Hyperammonemia and perinatal asphyxia association in newborns

Abstract

Neonatal hyperammonemia is a life-threatening condition, caused by inherited metabolic disorders or perinatal complications. Neonatal asphyxia is one of the factors leading to transient hyperammonemia in newborns that can cause the hypoxic or toxic-metabolic central nervous system damage.

Objective. To determine the hyperammonemia in newborns with birth asphyxia frequency and to identify the clinically significant outcomes of this condition.

Material and methods. The study included 78 children with moderate or severe birth asphyxia. Newborns were divided into groups depending on the hypoxic-ischemic encephalopathy severity and the hyperammonemia presence. Children had complex clinical, laboratory and instrumental examinations, and had neurological follow-up after discharge.

Results. Hyperammonemia was detected in 28 (35.8%) patients. The frequency was comparable in children with various hypoxic-ischemic encephalopathy degrees (p>0.05), however no correlation between the level of ammonia, gender, gestational age, birth weight and Apgar score was observed (p>0.05). In the first three days of life, patients with hyperammonemia did not show specific changes in the neurological status (p>0.05). With a later manifestation, hyperammonemia led to a deterioration in the child’s condition as neurological symptoms. In the long-term period, the presence of hyperammonemia did not affect the cerebral palsy, epilepsy, and psychomotor retardation incidence. However, a significantly higher incidence of neurological disorders, such as dyspraxia and delayed expressive speech development of varying severity signs, was revealed (p<0.05).

Conclusion. Ammonia blood test in newborns with birth asphyxia can determine the neurological prognosis of such children and thus, it is of great clinical importance.

Keywords:transient hyperammonemia; ammonia; neonatal asphyxia; hypoxic-ischemic encephalopathy; inborn error of metabolism

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

Contribution. Collection of information, development of a statistical model, data processing – Sokolova E.V.; general management, development of a statistical model, data processing – Degtyareva A.V.; general management, information collection, data processing – Ushakova L.V.; general management – Ivanets T.Yu., Kirtbaya A.R., Lenyushkina A.A., Burov A.A., Podurovskaya Yu.L.; collection of information, data processing – Degtyareva N.D., Ippolitov A.L.

For citation: Sokolova E.V., Degtyareva A.V., Ushakova L.V., Ivanets T.Yu., Kirtbaya A.R., Lenyushkina A.A., Burov A.A., Podurovskaya Yu.L., Degtyareva N.D., Ippolitov A.L. Hyperammonemia and perinatal asphyxia association in newborns. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2023; 11 (1): 10–8. DOI: https://doi.org/10.33029/2308-2402-2023-11-1-10-18 (in Russian)

Received 21.02.2022. Accepted 06.03.2023.

REFERENCES

1.Mayatepek E. Inborn errors of metabolism – early detection, key symptoms and therapeutic options. 2nd ed. Bremen, Germany: UNI-MED Science, 2017; 109 p.

2. Walker V. Ammonia toxicity and its prevention in inherited defects of the urea cycle. Diabetes Obes Metab. 2009; 11 (9): 823–35. DOI: https://doi.org/10.1111/j.1463-1326.2009.01054.x; PMID: 19531057.

3. Usmani S.S., Cavaliere T., Casatelli J., Harper R.G. Plasma ammonia levels in very low birth weight preterm infants. J Pediatr. 1993; 123 (5): 797–800. DOI: https://doi.org/10.1016/s0022-3476(05)80864-9

4. Degtyareva A.V., Sokolova E.V., Zakharova E.Yu., Isaeva M.Kh., Vysokikh M.Yu., Ivanets T.Yu., et al. Hyperammonemia in neonatologist practice. Rossiyskiy vestnik perinatologii i pediatrii [Russian Bulletin of Perinatology and Pediatrics]. 2020; 65: (6): 98–107. DOI: https://doi.org/10.21508/1027-4065-2020-65-6-98-107 (in Russian)

5. Brar G., Thomas R., Bawle E.V., Delaney-Black V. Transient hyperammonemia in preterm infants with hypoxia. Pediatr Res. 2004; 56: 671.

6. Joseph M., Hageman J.R. Neonatal transport: a 3-day-old neonate with hypothermia, respiratory distress, lethargy and poor feeding. J Perinatol. 2002; 22 (6): 506–9. DOI: https://doi.org/10.1038/sj.jp.7210755; PMID: 12168133.

7. Enns G.M. Inborn errors of metabolism masquerading as hypoxic-ischemic encephalopathy. Neo Rev. 2005; 6 (12): 549–58.

8. Haüssinger D. Nitrogen metabolism in liver: structural and functional organization and physiological relevance. Biochem J. 1990; 267 (2): 281–90. DOI: https://doi.org/10.1042/bj2670281; PMID: 2185740.

9. Weiner I.D., Verlander J.W. Recent advances in understanding renal ammonia metabolism and transport. Curr Opin Nephrol Hypertens. 2016; 25 (5): 436–43. DOI: https://doi.org/10.1097/MNH.0000000000000255; PMID: 27367914.

10. Dasarathy S., Mookerjee R.P., Rackayova V., Rangroo Thrane V., Vairappan B., Ott P., et al. Ammonia toxicity: from head to toe? Metab Brain Dis. 2017; 32 (2): 529–38. DOI: https://doi.org/10.1007/s11011-016-9938-3; PMID: 28012068.

11. Braissant O., McLin V.A., Cudalbu C. Ammonia toxicity to the brain. J Inherit Metab Dis. 2013; 36 (4): 595–612. DOI: https://doi.org/10.1007/s10545-012-9546-2; PMID: 23109059.

12. Barkovich A.J. Pediatric Neuroimaging. 4th Еd. Philadelphia: Lippincott Williams & Wilkins, 2005: 206 p.

13. Häberle J. Clinical and biochemical aspects of primary and secondary hyperammonemic disorders. Arch Biochem Bioph. 2013; 536 (2): 101–8. DOI: https://doi.org/10.1016/j.abb.2013.04.009

14. Robinson M.B., Batshaw M.L. Neurotransmitter alterations in congenital hyperammonemia. Ment Retard Dev Disabil Res Rev. 1995; 1: 201–7.

15. Butterworth R.F. Effects of hyperammonaemia onbrain function. J Inherit Metab Dis. 1998; 21: 6–20. DOI: https://doi.org/10.1023/a:1005393104494

16. Marcaida G., Felipo V., Hermenegildo C., Minana M.D., Grisolía S. Acute ammonia toxicity is mediated by the NMDA type of glutamate receptors. FEBS Lett. 1992; 296: 67–8. DOI: https://doi.org/10.1016 / 0014-5793 (92) 80404-5

17. Kosenko E., Kaminsky Y., Grau E., Miñana M.D., Marcaida G., Grisolía S., et al. Brain ATP depletion induced by acute ammonia intoxication in rats is mediated by activation of the NMDA receptor and Na+, K(+)-ATPase. J Neurochem. 1994; 63 (6): 2172–8. DOI: https://doi.org/10.1046/j.1471-4159.1994.63062172.x; PMID: 7964737.

18. Duffy T., Plum F. Seizures and comatose states. In: Siegel G.J., Albers R.W., Katzman R. (eds). Basic Neurochemistry. Boston: Little Brown, 1981; 857.

19. Hindfelt B., Siesjo B.K. Cerebral effects of acute ammonia intoxication. II. The effect upon energy metabolism. Scand J Clin Lab Invest. 1971; 28: 365–74. DOI: https://doi.org/10.3109/00365517109095711

20. Keiding S., Sorensen M., Bender D., et al. Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography. Hepatology. 2006; 43: 42–50.

21. Ballard R.A., Vinocur B., Reynolds J.W., Wennberg R.P., Merritt A., Sweetman L., et al. Transient hyperammonemia of the preterm infant. N Engl Med J. 1978; 299: 920–5.

22. Goldberg R.N., Cabal L.A., Sinatra F.R., Plajstek C.E., Hodgman J.E. Hyperammonemia associated with perinatal asphyxia. Pediatrics. 1979; 64 (3): 336–41. PMID: 481980.

23. Chung M.Y., Chen C.C., Huang L.T., Ko T.Y., Lin Y.J. Transient hyperammonemia in a neonate. Acta Pediatr Taiwan 2005; 46 (2): 94–6.

24. Degtyareva A.V., Kirtbaya A.R., Sokolova E.V., Balashova E.N., Ionov O.V., Vysokikh M.Yu., et al. Neonatal hyperammonemia transient condition or marker of inborn errors of metabolism? Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2018; 7 (1): 96–102. DOI: https://doi.org/10.24411/2308-2402-2018-00013] (in Russian)

25. Konecki U.L., Batshaw M.L. Inborn errors of urea synthesis. In : Swaiman K.F., Ashwal S., Ferrio D.M., Schor N.F., eds. Swaiman’s Pediatric Neurology Principle and Practice. 5th ed. Philadelphia: Elsevier/Saunders; 2012: 362–3.

26. Russian Association of Perinatal Medicine Specialists & Russian Society of Neonatologists. Therapeutic hypothermia in newborn. Approved clinical guidelines. February 2019. (in Russian)

27. Sarnat H.B., Sarnat M.S. Neonatal encephalopathy following fetal distress: a clinical and electroencephalographic study. Arch Neur. 1976; 33: 696–705.

28. B.J. Stoll R.M.K. Nervous System Discorders. Nelson Text book of Pediatrics. 17th ed. Philadelphia: Saunders, 2004: 561–9.

29. Khalessi N., Khosravi N., Mirjafari M., Afsharkhas L. Plasma ammonia levels in newborns with asphyxia. Iran J Child Neurol. 2016; 10 (1): 42–6.

30. Haberle J., Chakrapani A., Ah Mew N., et al. Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories. Orphanet J Rare Dis. 2018; 13: 219.

31. Ozanne B., Nelson J., Cousineau J., et al. Threshold for toxicity from hyperammonemia in critically ill children. J Hepatol. 2012; 56: 123–8.

32. Nguyen K.Q.N., Jones P.M., Patel K. A newborn with hypothermia and hyperammonemia. Clinical Chemistry. 2018; 64 (2): 411–20.

33. Yoshino M., Sakaguchi Y., Kuriya N., Ohtani Y., Yamashita F., Hashimoto T., et al. A nationwide survey on transient hyperammonemia in newborn infants in Japan: prognosis of life and neurological outcome. Neuropediatrics. 1991; 22 (4): 198–202. DOI: https://doi.org/10.1055/s-2008-1071441; PMID: 1775216.

34. Kim J.Y., Lee Y., Cho H. Optimal prescriptions of continuous renal replacement therapy in neonates with hyperammonemia. Blood Purif. 2019; 47: 16–22.

35. Ninković D., Mustapić Ž., Bartoniček D., Benjak V., Ćuk M., Buljević A.D., et al. The therapeutic hypothermia in treatment of hyperammonemic encephalopathy due to urea cycle disorders and organic acidemias. Klin Padiatr. 2019; 231 (2): 74–9. DOI: https://doi.org/10.1055/a-0855-4001; PMID: 30870873.

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Degtyarev Dmitriy Nikolaevich
Doctor of Medical Sciences, Professor, Deputy Director for Scientific Research of the V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Head of the Chair of Neonatology at the Clinical Institute of Children's Health named after N.F. Filatov, I.M. Sechenov First Moscow State Medical University, Chairman of the Ethics Committee of the Russian Society of Neonatologists, Moscow, Russian Federation

ORCID iD 0000-0001-8975-2425

Journals of «GEOTAR-Media»