Vplyv chorioamnionitídy na morbiditu predčasne narodených novorodencov a možné terapeutické intervencie

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Autoři: L. Dočekalová ¹; J. Kopincová ²; M. Kolomazník ³; L. Časnocha-Lúčanová ¹; K. Maťašová ¹
Působiště autorů: Department of Neonatology, University Hospital Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic ¹; Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic ²; Biomedical Center Martin and Department of Physiology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Slovak Republic ³
Vyšlo v časopise: Čes-slov Pediat 2020; 75 (7): 436-442.
Kategorie: Přehledový článek

Souhrn

Incidencia predčasných pôrodov neustále narastá, pričom stále vyšší počet novorodencov sa zachraňuje v čoraz nižších gestačných týždňoch. Aj napriek výrazným pokrokom v starostlivosti o predčasne narodeného novorodenca, prematurita aj naďalej predstavuje limitujúci faktor pre ďalší vývoj týchto detí, keďže sa spája s veľkou mierou morbidity aj mortality.

Medzi najčastejšie príčiny spôsobujúce predčasný pôrod patrí chorioamnionitída. Jej problém nespočíva len v procesoch, ktoré vedú k predčasnému pôrodu, ale aj v samotnom zápale, ktorý môže spôsobiť výrazné komplikácie a signifikantne zhoršiť prognózu prematúrneho novorodenca. Negatívne účinky pritom nie sú pripísané len samotnému mikroorganizmu, ale hlavne prooxidačným a prozápalovým procesom, ktoré tieto patogény navodzujú. Keďže antibiotická liečba je zameraná len na ich usmrtenie alebo inhibíciu ďalšieho rastu a množenia, cieľom viacerých výskumov je nájsť takú terapeutickú intervenciu, ktorá by potlačila produkciu cytokínov a voľných radikálov. Najviac nádejnými sa zdajú byť melatonín, pentoxyfylín, erytropoetín a N-acetylcysteín. Tieto liečivá môžu zmierniť ničivé účinky oxidačného stresu a zápalu na rôzne orgánové systémy u novorodenca a tak znížiť komplikácie súvisiace s predčasným pôrodom vyvolaným chorioamnionitídou.

Klíčová slova:

chorioamnionitída – predčasne narodený novorodenec – oxidačný stres – zápal – neuroprotekcia

Zdroje

1. Boyle AK, Rinaldi SF, Norman JE, et al. Preterm birth: Inflammation, fetal injury and treatment strategies. J Reprod Immunol 2017; 119: 62–66.

2. Stojanovska V, Miller SL, Hooper SB, et al. The Consequences of Preterm Birth and Chorioamnionitis on Brainstem Respiratory Centers: Implications for neurochemical development and altered functions by inflammation and prostaglandins. Front Cell Neurosci 2018; 12: 26.

3. Zoban P. Nedonošený novorozenec. Čes-slov Pediat 2012; 67 (3): 203–208.

4. Marková D, Weberová-Chvílová M, Raušová P, et al. The care of prematurely born child: when to begin and end? Čes-slov Pediat 2014; 69 (1): 53–62.

5. Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG 2006; 113 (3): 17–42.

6. Strunk T, Inder T, Wang X, et al. Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis 2014; 14 (8): 751–762.

7. Pugni L, Pietrasanta C, Acaia B, et al. Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview. J Matern Fetal Neonatal Med 2016; 29 (9): 1525–1529.

8. Ericson JE, Laughon MM. Chorioamnionitis: implications for the neonate Jessica. Clin Perinatol 2014; 42 (1): 155–165.

9. Jin C, Londono I, Mallard C, et al. New means to assess neonatal inflammatory brain injury. J Neuroinflammation 2015; 12: 180.

10. Perez M., Robbins ME, Revhaug C, et al. Oxygen radical disease in the newborn, revisited: Oxidative stress and disease in the newborn period. Free Radic Biol Med 2019; 142: 61–72.

11. Lu L, Claud EC. Intrauterinne inflammation, epigenetics, and microbiome influences on preterm infant health. Curr Pathobiol Rep 2018; 6: 15.

12. DeLuca D, Van Kaam AH, Tingay DG, et al. The Montreux definition of neonatal ARDS: biological and clinical background behind th description of a new entity. Lancet Respir Med 2017; 5: 657–666.

13. Patra A, Huang H, Bauer JA, et al. Neurological consequences of systemic inflammation in the premature neonate. Neural Regen Res 2017; 12 (6): 890–896.

14. Kramer BW, Kallapur S, Newnham J, et al. Prenatal inflammation and lung development. Semin Fetal Neonatal Med 2009; 14: 2–7.

15. Kemp MW, Kannan PS, Saito M, et al. Selective exposure of the fetal lung and skin/amnion (but not gastro-intestinal tract) to LPS elicits acute systemic inflammation in fetal sheep. PLoS One 2013; 8 (5): 1–9.

16. Wolfs TGAM, Kramer BW, Thuijls G, et al. Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation. Am J Physiol Gastrointest Liver Physiol 2014; 306 (5): G382–G393.

17. Elovitz MA, Brown AG, Breen K, et al. Intrauterinne inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci 2011; 29: 663–671.

18. Shatrov JG, Birch SC, Lam LT, et al. Chorioamnionitis and cerebral palsy. Obstet Gynecol 2010; 116: 387–392.

19. Chao MW, Chen CP, Yang YH, et al. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1– –expressing cortical neurons in the developing rat fetal brain. Sci Rep 2016; 6: 32373.

20. Ginsberg Y, Khatib N, Weiner Z, et al. Maternal inflammation, fetal brain implications and suggested neuroprotection: A summary of 10 years of research in animal models. Rambam Maimonides Med J 2017; 8 (2): e0028.

21. Barton SK, Tolcos M, Miller SL, et al. Ventilation-induced brain injury in preterm neonates: A review of potential therapies. Neonatology 2016; 110: 155–162.

22. Barrington KJ. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatr 2001; 1: 1.

23. Halliday HL. Update on postnatal steroids. Neonatology 2017; 111: 415–422.

24. Tataranno ML, Perrone S, Longini M, et al. New antioxidant drugs for neonatal brain injury. Oxid Med Cell Longev 2015; 2015: 108251.

25. Frargy ME, El-Sharkawy HM, Attia GF. Use of melatonin as an adjuvant therapy in neonatal sepsis. J Neonatal Perinatal Med 2015; 8 (3): 227–232.

26. Ofek-Shlomai N, Berger I. Inflammatory injury to the neonatal brain – what can we do?. Front Pediatr 2014; 2: 30.

27. Gitto E, Reiter RJ, Amodio A, et al. Early indicators of chronic lung disease in preterm infants with respiratory distress syndrome and their inhibition by melatonin. J Pineal Res 2004; 36 (4): 250–255.

28. Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: The need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014; 141 (2): 150–159.

29. Khatib N, Weiner Z, Ginsberg Y, et al. Protective effect of N-acetyl--cysteine (NAC) in lipopolysaccharide (LPS)-associated inflammatory response in rat neonates. Rambam Maimonides Med J 2017; 8 (2): e0026.

30. Samuni Y, Goldstein S, Dean OM, et al. The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 2013; 1830 (8): 4117–4129.

31. Kopincova J, Kolomaznik M, Mikolka P, et al. Recombinant human superoxide dismutase and N-acetylcysteine addition to exogenous surfactant in the treatment of meconium aspiration syndrome. Molecules 2019; 24 (5): E905.

32. Mikolka P, Kopincova J, Tomcikova-Mikusiakova L, et al. Antiinflammatory effect of N-acetylcysteine combined with exogenous surfactant in meconium-induced lung injury. Advs Epx Med Biol 2016; 934: 63–75.

33. Kopincova J, Mokra D, Mikolka P, et al. N-acetylcysteine advancement of surfactant therapy in experimental meconium aspiration syndrome: possible mechanisms. Physiol Res 2014; 63 (4): S629–S642.

34. Jenkins DD, Wiest DB, Mulvihill DM, et al. Fetal and neonatal effects of N-acetylcysteine when used for neuroprotection in maternal chorioamnionitis. J Pediatr 2016; 168: 67–76.

35. Kiuru A, Ahola T, Klenberg, L, et al. Postnatal N-acetylcysteine does not provide neuroprotection in extremely low birth weight infants: A follow-up of a randomized controlled trial. Early Hum Dev 2019; 132: 13–17.

36. Moazzen H, Lu X, Ma NL, et al. N-Acetylcysteine prevents congenital heart defects induced by pregestational diabetes. Cardiovasc Diabetol 2014; 13: 46.

37. Plotnikov EY, Pavlenko TA, Pevzner IB, et al. The role of oxidative stress in acute renal injury of newborn rats exposed to hypoxia and endotoxin. FEBS J 2017; 284: 3069–3078.

38. Hou Y, Wang L, Zhang L, et al. Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 2012; 43: 1233.

39. Koivusalo A, Kauppinen A, Anttila H, et al. Intraluminal casein model of necrotizing enterocolitis for assessment of mucosal destruction, bacterial translocation, and the effects of allopurinol and N-acetylcysteine. Pediatr Surg Int 2002; 18 (8): 712–717.

40. Sandberg K, Fellman V, Stigson L, et al. N-Acetylcysteine administration during the first week of life does not improve lung function in extremely low birth weight infants. Biol Neonate 2004; 86: 275–279.

41. Wiest DB, Chanbe E, Fanning D, et al. Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection. J Pediatr 2014; 165 (4): 672–677.

42. Szakmany T, Hauser B, Radermacher P. N-acetylcysteine for sepsis and systemic inflammatory response in adults. Cochrane Database Syst Rev 2012; 9: CD006616.

43. Pammi M, Haque KN. Pentoxifylline for treatment of sepsis and nercotising enterocolitis in neonates. Cochrane Database Syst Rev 2015; 3: CD004205.

44. Peng P, Xia Y. Influency of pentoxifylline treatment for neonatal sepsis: A meta-analysis of randomized controlled studies. Hong Kong J Emerg Med 2019: 1–8.

45. Schulzke SM, Deshmukh M, Nathan EA, et al. Nebulized pentoxifylline for reducing the duration of oxygen supplementation in extremely preterm neonates. J Pediatr 2015; 166 (5): 1158–1162.

46. Hamilçıkan Ş, Can E, Büke Ö, et al. Pentoxifylline treatment of very low birth weight neonates with nosocomial sepsis. Amer J Perinatol 2017; 34 (8): 795–800.

47. Speer EM, Dowling DJ, Ozog LS, et al. Pentoxifylline inhibits TLR-and inflammasome -mediated in vitro inflammatory cytokine production in human blood with greater efficacy and potency in newborns. Pediatr Res 2017; 81 (5): 806–816.

48. Wu YW, Bauer LA, Ballard RA, et al. Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics. Pediatrics 2012; 130 (4): 683–691.

49. Tolsma KW, Allred EN, Chen ML, et al. Neonatal bacteremia and retinopathy of prematurity: the ELGAN study. Arch Ophthalmol 2011; 129 (12): 1555–1563.

50. Ehrenreich H, Weissenborn K, Prange H, et al. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 2009; 40 (12): e647–56.

51. Fauchère JC, Koller BM, Tschopp A, et al. Safety of early high-dose recombinant Erythropoietin for neuroprotection in very preterm infants. J Pediatr 2015; 167 (1): 52–57.

52. Fischer HS, Reibel NJ, Bührer CH, et al. Prophylactic early erythropoietine for neuroprotection in preterm infants: A meta-analysis. Pediatrics 2017; 139 (5): e20164317.

53. Abdel-Hady H, Nasef N, Shabaan AE, et al. Caffeine therapy in preterm infants. World J Clin Pediatr 2015; 4 (4): 81–93.

54. Crowther CA, Brown J, McKinlay CJ, et al. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2014; 8: CD001060.

55. Usman S, Foo L, Tay J, et al. Use of magnesium sulfate in preterm deliveries for neuroprotection of the neonate. Obstetrician & Gynaecologist 2017; 19: 21–28.

56. Zeng X, Xue Y, Tian Q, et al. Effects and safety of magnesium sulphate on neuroprotection: A meta-analysis Based on PRISMA Guidelines. Medicine (Baltimore) 2016; 95 (1): e2451.

57. Morag I, Yakubovich D, Stern O, et al. Short–term morbidities and neurodevelopmental outcomes in preterm infants exposed to magnesium sulphate treatment. J Paediatr Child Health 2016; 52 (4): 397–401.

58. Poggi C, Dani C. Antioxidant strategies and respiratory disease of the preterm newborn: an update. Oxid Med Cell Longev 2014; 2014: 721043.

59. Bouhafs RK, Jarstrand C. Effects of antioxidants on surfactant peroxidation by stimulated human polymorhponuclear leukocytes. Free Radic Res 2002; 36 (7): 727–734.

60. Kopincova J, Mikolka P, Kolomaznik M, et al. Modified porcine surfactant enriched by recombinant human superoxide dismutase for experimental meconium aspiration syndrome. Life Sci 2018; 203: 121–128.

61. Davis JM, Parad RB, Michele T, et al. Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics 2003; 111 (3): 469–476.

62. Benterud T, Ystgaard MB, Manueldas S, et al. N-Acetylcysteine amide exerts possible neuroprotective effects in newborn pigs after perinatal asphyxia. Neonatology 2017; 111: 12–21.

63. Fink NH, Collins CT, Gibson RA, et al. Targeting inflammation in the preterm infant: The role of the omega-3 fatty acid docosahexaenoic acid. J Nutr Intermed Metab 2016; 5: 55–60.

64. Lai MC, Yang SN. Perinatal hypoxic-ischemic encephalopathy. J Biomed Biotechnol 2011; 2011: 609813.