Perinatal asphyxia of full-term newborns: from pathophysiology to long-term outcomes
https://doi.org/10.46563/2686-8997-2023-4-2-88-96
EDN: dxflzb
Abstract
The fetal environment and circulatory patterns are very different from that of extrauterine life. The fetus evolved to thrive and grow in a relative hypoxemic environment adapted several mechanisms in response to changes in oxygen concentration in the blood to ensure optimal oxygen delivery to the brain and heart. However according to estimates of the World Health Organization in the world from 4 to 9 million newborns are born annually in a state of perinatal asphyxia. In economically underdeveloped countries, this indicator is higher than in developed countries, but in general, the frequency of perinatal asphyxia remains at a rather high level in the modern world. Perinatal asphyxia or hypoxic-ischemic encephalopathy, in newborns can cause multiple organ dysfunction in the neonatal period, severe diseases in the future, lead to disability and infant mortality. Perinatal asphyxia is characterized by a violation of gas exchange, which can lead to varying degrees of hypoxia, hypercapnia and acidosis, depending on the duration and degree of interruption of air flow, however, obstructed perinatal gas exchange does not have precise biochemical criteria. In addition, the exact mechanisms of pathophysiology of perinatal asphyxia have not been fully studied, as a result of which the “gold standard” of treatment remains an active area of research. The publication reflects modern views on the main stages of the pathogenesis of perinatal asphyxia, shows changes in blood circulation during delivery and the neonatal period, presents current data on emerging disorders in the newborn’s body against the background of hypoxic ischemic encephalopathy.
Contribution:
Petrova A.S. — concept, writing text;
Zubkov V.V. — concept;
Zakharova N.I. — editing;
Lavrent’ev S.N. — writing text;
Kondrat’ev M.V. — writing text;
Gry‘zunova A.S. — writing text;
Serova O.F. — editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.
Acknowledgements. The study had no sponsorship.
Conflict of interest. The authors declare no conflict of interest.
Received: May 4, 2023
Accepted: May 26, 2023
Published: June 30, 2023
About the Authors
Anastasiya S. PetrovaRussian Federation
MD, PhD, DSci., leading researcher of the Moscow Regional Perinatal Center, Moscow, 115093, Russian Federation; deputy chief physician of Moscow Regional Perinatal Center, Balashikha, 143900, Russian Federation.
e-mail: as.petrova@icloud.com
Viktor V. Zubkov
Russian Federation
Nina I. Zakharova
Russian Federation
Semen N. Lavrent’Ev
Russian Federation
Maksim V. Kondrat’Ev
Russian Federation
Anastasiya S. Gry’Zunova
Russian Federation
Olga F. Serova
Russian Federation
References
1. Hug L., You D., Blencowe H., Mishra A., Wang Z., Fix M.J., et al. Global, regional, and national estimates and trends in stillbirths from 2000 to 2019: a systematic assessment. Lancet. 2021; 398(10302): 772–85. https://doi.org/10.1016/S0140-6736(21)01112-0
2. Shilova N.A., Kharlamova N.V., Andreev A.V., Mezhinskiy S.S., Panova I.A., Dudov P.R. Frequency of perinatal asphyxia and volume of provision of care to newborns in the delivery room. Neonatologiya: Novosti, Mneniya, Obuchenie. 2020; 8(2): 47–53. https://doi.org/10.33029/2308-2402-2020-8-2-47-53 https://elibrary.ru/itwwwr (in Russian)
3. Gorbachev V.I., Anur’ev A.M. Hypoxic-ischemic brain damage in premature newborns. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019; 119(8): 63–9. https://doi.org/10.17116/jnevro201911908263 (in Russian)
4. Pluta R., Furmaga-Jabłońska W., Januszewski S., Tarkowska A. Melatonin: a potential candidate for the treatment of experimental and clinical perinatal asphyxia. Molecules. 2023; 28(3): 1105. https://doi.org/10.3390/molecules28031105
5. Thornton K.M., Dai H., Septer S., Petrikin J.E. Effects of whole body therapeutic hypothermia on gastrointestinal morbidity and feeding tolerance in infants with hypoxic ischemic encephalopathy. Int. J. Pediatr. 2014; 2014: 643689. https://doi.org/10.1155/2014/643689
6. Aslam H.M., Saleem S., Afzal R., Iqbal U., Saleem S.M., Shaikh M.W., et al. Risk factors of birth asphyxia. Ital. J. Pediatr. 2014; 40: 94. https://doi.org/10.1186/s13052-014-0094-2
7. Polglase G.R., Ong T., Hillman N.H. Cardiovascular alterations and multiorgan dysfunction after birth asphyxia. Clin. Perinatol. 2016; 43(3): 469–83. https://doi.org/10.1016/j.clp.2016.04.006
8. Shakir W., Rehman A., Arshad M.S., Fatima N. Burden of cardiovascular dysfunction and outcome among term newborns having birth asphyxia. Pakistan J. Med. Sci. 2022; 38(4 Part-II): 883–7. https://doi.org/10.12669/pjms.38.4.5160
9. Balashova E.N. Emergency Conditions in Newborn Children [Neotlozhnye sostoyaniya u novorozhdennykh detey]. Moscow: GEOTAR- Media; 2020. (in Russian)
10. Armstrong K., Franklin O., Sweetman D., Molloy E.J. Cardiovascular dysfunction in infants with neonatal encephalopathy. Arch. Dis. Child. 2012; 97(4): 372–5. https://doi.org/10.1136/adc.2011.214205
11. WHO. Lincetto O. Birth asphyxia summary of the previous meeting and protocol overview. Gevena; 2007.
12. Kamath-Rayne B.D., Hobe A. Birth Asphyxia. Clinics in Perinatology. Philadelphia: Elsevier; 2016.
13. Committee on Fetus and Newborn; American College of Obstetricians and Gynecologists; Committee on Obstetric Practice. The Apgar score. Adv. Neonatal Care. 2006; 6(4): 220–3. https://doi.org/10.1016/j.adnc.2006.04.008
14. Rainaldi M.A., Perlman J.M. Pathophysiology of Birth Asphyxia. Clin. Perinatol. 2016; 43(3): 409–22. https://doi.org/10.1016/j.clp.2016.04.002
15. Pacora P., Romero R., Jaiman S., Erez O., Bhatti G., Panaitescu B., et al. Mechanisms of death in structurally normal stillbirths. J. Perinat. Med. 2019; 47(2): 222–40. https://doi.org/10.1515/jpm-2018-0216
16. Makarovskaya E.A., Baranov A.N., Istomina N.G., Revako P.P. Fetal hypoxia as a cause of unfavorable pregnancy outcomes: a systematic review of assessment methods. Ekologiya cheloveka. 2021; (7): 4–11. https://doi.org/10.33396/1728-0869-2021-7-4-11 https://elibrary.ru/gyhrfm (in Russian)
17. Yli B.M., Kjellmer I. Pathophysiology of foetal oxygenation and cell damage during labour. Best Pract. Res. Clin. Obstet. Gynaecol. 2016; 30: 9–21. https://doi.org/10.1016/j.bpobgyn.2015.05.004
18. Babiyants A.Ya., Afonin A.A. Morphological and functional features respiratory-hemodynamic relationship in the antenatal period of development. Zhurnal fundamental’noy meditsiny i biologii. 2018; (1): 37–47. https://elibrary.ru/yabkdj (in Russian)
19. Britton J.R. The transition to extrauterine life and disorders of transition. Clin. Perinatol. 1998; 25(2): 271–94.
20. Morton S.U., Brodsky D. Fetal physiology and the transition to extrauterine life. Clin. Perinatol. 2016; 43(3): 395–407. https://doi.org/10.1016/j.clp.2016.04.001
21. Kaladze N.N., Rybalko O.N., Dosikova G.V., Semenchuk T.V., Karadon V.A. Structural and bioelectric characteristics of brain damage in full-term newborns who underwent perinatal asphyxia. Vestnik fizioterapii i kurortologii. 2018; 24(1): 114. https://elibrary.ru/xqwted (in Russian)
22. Wyss M.T., Jolivet R., Buck A., Magistretti P.J., Weber B. In vivo evidence for lactate as a neuronal energy source. J. Neurosci. 2011; 31(20): 7477–85. https://doi.org/10.1523/JNEUROSCI.0415-11.2011
23. Zheng Y., Wang X.M. Expression changes in lactate and glucose metabolism and associated transporters in basal ganglia following hypoxic-ischemic reperfusion injury in piglets. AJNR Am. J. Neuroradiol. 2018; 39(3): 569–76. https://doi.org/10.3174/ajnr.A5505
24. Chen Y., Engidawork E., Loidl F., Dell’Anna E., Goiny M., Lubec G., et al. Short- and long-term effects of perinatal asphyxia on monoamine, amino acid and glycolysis product levels measured in the basal ganglia of the rat. Brain Res. Dev. Brain Res. 1997; 104(1-2): 19–30. https://doi.org/10.1016/s0165-3806(97)00131-4
25. Herrera M.I., Otero-Losada M., Udovin L.D., Kusnier C., Kölliker-Frers R., de Souza W., et al. Could perinatal asphyxia induce a synaptopathy? New highlights from an experimental model. Neural. Plast. 2017; 2017: 3436943. https://doi.org/10.1155/2017/3436943
26. Summanen M., Bäck S., Voipio J., Kaila K. Surge of peripheral arginine vasopressin in a rat model of birth asphyxia. Front. Cell Neurosci. 2018; 12: 2. https://doi.org/10.3389/fncel.2018.00002
27. Evers K.S., Wellmann S. Arginine vasopressin and copeptin in perinatology. Front. Pediatr. 2016; 4: 75. https://doi.org/10.3389/fped.2016.00075
28. Baev O.R. Antenatal and intranatal risk factors associated with fetal hypoxia in childbirth. Akusherstvo i ginekologiya. 2022; (8): 47–53. https://doi.org/10.18565/aig.2022.8.47-53 https://elibrary.ru/gbslgu (in Russian)
29. Taranushenko T.E. Risk factors for asphyxia at birth. Meditsinskiy sovet. 2022; (19): 21–8. https://doi.org/10.21518/2079-701X-2022-16-19-21-28 https://elibrary.ru/jtezau (in Russian)
30. Klyuchnikova M.A. Causal Aspects of the birth of newborns in severe asphyxia. Byulleten’ Severnogo gosudarstvennogo meditsinskogo universiteta. 2022; (2): 98–100. https://elibrary.ru/bgagfq (in Russian)
31. Giussani D.A. The fetal brain sparing response to hypoxia: physiological mechanisms. J. Physiol. 2016; 594(5): 1215–30. https://doi.org/10.1113/JP271099
32. Prikhod’ko V.A., Selizarova N.O., Okovityy S.V. Molecular mechanisms for hypoxia development and adaptation to it. Part I. Arkhiv patologii. 2021; 83(3): 52–61. https://doi.org/10.17116/patol20218302152 https://elibrary.ru/rejnhm (in Russian)
33. Fattuoni C., Palmas F., Noto A., Fanos V., Barberini L. Perinatal asphyxia: a review from a metabolomics perspective. Molecules. 2015; 20(4): 7000–16. https://doi.org/10.3390/molecules20047000
34. Denihan N.M., Boylan G.B., Murray D.M. Metabolomic profiling in perinatal asphyxia: a promising new field. Biomed. Res. Int. 2015; 2015: 254076. https://doi.org/10.1155/2015/254076
35. LaRosa D.A., Ellery S.J., Walker D.W., Dickinson H. Understanding the full spectrum of organ injury following intrapartum asphyxia. Front. Pediatr. 2017; 5: 16. https://doi.org/10.3389/fped.2017.00016
36. Volodin N.N., Keshishyan E.S., Pankrat’eva L.L., Mostovoy A.V., Ovsyannikov D.Yu., Karpova A.L. Strategies of domestic neonatology: challenges of the present and look into the future. Pediatriya. Zhurnal im. G.N. Speranskogo. 2022; 101(1): 8–20. https://doi.org/10.24110/0031-403X-2022-101-1-8-20 https://elibrary.ru/bnnnyw
37. Bhatti A., Kumar P. Systemic effects of perinatal asphyxia. Indian. J. Pediatr. 2014; 81(3): 231–3. https://doi.org/10.1007/s12098-013-1328-9
38. Jensen A., Garnier Y., Berger R. Dynamics of fetal circulatory responses to hypoxia and asphyxia. Eur. J. Obstet. Gynecol. Reprod. Biol. 1999; 84(2): 155–72. https://doi.org/10.1016/s0301-2115(98)00325-x
39. Pertierra Cortada À. Asfixia perinatal: Relación entre afectación cardiovascular, neurológica y multisistémica. Acta Pediatr. Esp. 2008; 66(10): 494–501.
40. Giussani D.A., Spencer J.A., Hanson M.A. Fetal cardiovascular reflex responses to hypoxaemia. Fetal. Matern. Med. Rev. 1994; 6(1): 17–37.
41. Cullen P., Salgado E. Conceptos básicos para el manejo de la asfixia perinatal y la encefalopatía hipóxico-isquémica en el neonate. Rev. Mex. Pediatr. 2009; 76(4): 174–80.
42. Basu R.K., Zappitelli M., Brunner L., Wang Y., Wong H.R., Chawla L.S., et al. Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int. 2014; 85(3): 659–67. https://doi.org/10.1038/ki.2013.349
43. Bhasin H., Kohli C. Myocardial dysfunction as a predictor of the severity and mortality of hypoxic ischaemic encephalopathy in severe perinatal asphyxia: a case-control study. Paediatr. Int. Child Health. 2019; 39(4): 259–64. https://doi.org/10.1080/20469047.2019.1581462
44. Sadoh W.E., Eregie C.O., Nwaneri D.U., Sadoh A.E. The diagnostic value of both troponin T and creatinine kinase isoenzyme (CK-MB) in detecting combined renal and myocardial injuries in asphyxiated infants. PLoS One. 2014; 9(3): e91338. https://doi.org/10.1371/journal.pone.0091338
45. Popescu M.R., Panaitescu A.M., Pavel B., Zagrean L., Peltecu G., Zagrean A.M. Getting an early start in understanding perinatal asphyxia impact on the cardiovascular system. Front. Pediatr. 2020; 8: 68. https://doi.org/10.3389/fped.2020.00068
46. Perlman J.M., Tack E.D., Martin T., Shackelford G., Amon E. Acute systemic organ injury in term infants after asphyxia. Am. J. Dis. Child. 1989; 143(5): 617–20. https://doi.org/10.1001/archpedi.1989.02150170119037
47. Gunn A.J., Bennet L. Fetal hypoxia insults and patterns of brain injury: insights from animal models. Clin. Perinatol. 2009; 36(3): 579–93. https://doi.org/10.1016/j.clp.2009.06.007
48. Aggarwal A., Kumar P., Chowdhary G., Majumdar S., Narang A. Evaluation of renal functions in asphyxiated newborns. J. Trop. Pediatr. 2005; 51(5): 295–9. https://doi.org/10.1093/tropej/fmi017
49. Sweetman D.U., Molloy E.J. Biomarkers of acute kidney injury in neonatal encephalopathy. Eur. J. Pediatr. 2013; 172(3): 305–16. https://doi.org/10.1007/s00431-012-1890-6
50. Xiong T., Dong W., Fu H., Li Q., Deng C., Lei X., et al. Involvement of the nuclear factor-κB pathway in the adhesion of neutrophils to renal tubular cells after injury induced by neonatal postasphyxial serum. Mol. Cell Biochem. 2014; 388(1-2): 85–94. https://doi.org/10.1007/s11010-013-1901-6
51. Keles E., Wintermark P., Groenendaal F., Borloo N., Smits A., Laenen A., et al. Serum creatinine patterns in neonates treated with therapeutic hypothermia for neonatal encephalopathy. Neonatology. 2022; 119(6): 686–94. https://doi.org/10.1159/000525574
52. Argyri I., Xanthos T., Varsami M., Aroni F., Papalois A., Dontas I., et al. The role of novel biomarkers in early diagnosis and prognosis of acute kidney injury in newborns. Am. J. Perinatol. 2013; 30(5): 347–52. https://doi.org/10.1055/s-0032-1326985
53. Zou Z., Chen B., Tang F., Li X., Xiao D. Predictive value of neutrophil gelatinase-associated lipocalin in children with acute kidney injury: A systematic review and meta-analysis. Front. Pediatr. 2023; 11: 1147033. https://doi.org/10.3389/fped.2023.1147033
54. Oncel M.Y., Canpolat F.E., Arayici S., Alyamac Dizdar E., Uras N., Oguz S.S. Urinary markers of acute kidney injury in newborns with perinatal asphyxia. Ren. Fail. 2016; 38(6): 882–8. https://doi.org/10.3109/0886022X.2016.1165070
55. Konoplev B.A., Alekseev A.V., Khashim R.A. Neutrophil gelatinase-associated lipocalin (NGAL) – a new marker of acute kidney injury and perinatal asphyxia. Meditsinskiy vestnik Bashkortostana. 2017; 12(1): 93–9. https://elibrary.ru/yfuhpn (in Russian)
56. Rumpel J., Spray B.J., Chock V.Y., Kirkley M.J., Slagle C.L., Frymoyer A., et al. Urine biomarkers for the assessment of acute kidney injury in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia. J. Pediatr. 2022; 241: 133–40.e3. https://doi.org/10.1016/j.jpeds.2021.08.090
57. Mota-Rojas D., Villanueva-García D., Solimano A., Muns R., Ibarra-Ríos D., Mota-Reyes A. Pathophysiology of perinatal asphyxia in humans and animal models. Biomedicines. 2022; 10(2): 347. https://doi.org/10.3390/biomedicines10020347
58. Zhang Y., Lei Y., Jiang H., Li X., Feng H. Analysis of the correlation between the severity of neonatal hypoxic ischemic encephalopathy and multiple organ dysfunction. Am. J. Transl. Res. 2022; 14(1): 311–9.
59. Hankins G.D., Koen S., Gei A.F., Lopez S.M., Van Hook J.W., Anderson G.D. Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstet. Gynecol. 2002; 99(5 Pt. 1): 688–91. https://doi.org/10.1016/s0029-7844(02)01959-2
60. 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; 9: 1–6. https://doi.org/10.4137/CMPed.S21426
61. Elsadek A.E. Hepatic injury in neonates with perinatal asphyxia. Glob. Pediatr. Health. 2021; 8: 2333794X20987781. https://doi.org/10.1177/2333794x20987781
62. Golub I.E., Zarubin A.A., Mikheeva N.I., Vanyarkina A.S., Ivanova O.G. The effect of severe birth asphyxia on the hemostasis system in newborns during the first hour of life. Obshchaya reanimatologiya. 2017; 13(1): 17–23. https://doi.org/10.15360/1813-9779-2017-1-17-23 https://elibrary.ru/xwvlrp (in Russian)
63. Kaplina A., Kononova S., Zaikova E., Pervunina T., Petrova N., Sitkin S. Necrotizing enterocolitis: the role of hypoxia, gut microbiome, and microbial metabolites. Int. J. Mol. Sci. 2023; 24(3): 2471. https://doi.org/10.3390/ijms24032471
Review
For citations:
Petrova A.S., Zubkov V.V., Zakharova N.I., Lavrent’Ev S.N., Kondrat’Ev M.V., Gry’Zunova A.S., Serova O.F. Perinatal asphyxia of full-term newborns: from pathophysiology to long-term outcomes. L.O. Badalyan Neurological Journal. 2023;4(2):88-96. (In Russ.) https://doi.org/10.46563/2686-8997-2023-4-2-88-96. EDN: dxflzb