Apnoea of prematurity: causes, treatment, prevention, consequences and genetic basis
DOI:
https://doi.org/10.6016/ZdravVestn.2919Keywords:
premature, respiration disorders, continuous positive airway pressure, caffeine, genetic predispositionAbstract
Apnoea (or apnoeic attacks, pauses) of prematurity is one of the most common diagnoses in neonatal intensive care units. Apnoeic attacks are transient in nature and are caused by a disruption in the adaptation of the respiratory centre and respiratory system to extrauterine life and immaturity of the receptors that detect partial oxygen and carbon dioxide pressure. They significantly prolong the duration of hospitalisation and have potentially adverse long-term consequences.
In our review article we provide a definition of apnoeic attacks of prematurity. We present the classification, epidemiology, pathophysiological background and cardiorespiratory monitoring of premature infants. We describe how to diagnose apnoea of prematurity, secondary causes of apnoea, and differential diagnostic options, as well as some conditions that are associated with apnoea of prematurity. A large part of the article is dedicated to presenting possible therapeutic interventions, including those that have not yet been implemented in general clinical practice as further research is needed to confirm their efficacy. The final part of the article provides an overview of the research on the genetic basis of apnoea of prematurity, and the presentation of their results.
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References
1. Zhao J, Gonzalez F, Mu D. Apnea of prematurity: from cause to treatment. Eur J Pediatr. 2011;170(9):1097-105.
DOI: 10.1007/s00431-011-1409-6
PMID: 21301866
2. Eichenwald EC; Committee on Fetus and Newborn, American Academy of Pediatrics. Apnea of Prematurity. Pediatrics. 2016;137(1):e20153757.
DOI: 10.1542/peds.2015-3757
PMID: 26628729
3. Picone F, Aufieri R, Paolillo P. Apnea of prematurity: challenges and solutions. Res Rep Neonatol. 2014;4:101-9.
DOI: 10.2147/RRN.S44810
4. Mathew OP. Apnea of prematurity: pathogenesis and management strategies. J Perinatol. 2011;31(5):302-10.
DOI: 10.1038/jp.2010.126
PMID: 21127467
5. Mishra S, Agarwal R, Jeevasankar M, Aggarwal R, Deorari AK, Vinod KP. Apnea in the Newborn. AIIMS NICU protocols updated 2007. New Delhi: All India Institute of Medical Sciences; 2007 [cited 2018 May 25]. Available from: http://www.newbornwhocc.org/>http://www.newbornwhocc.org/.
6. Martin RJ, Wilson CG. Apnea of prematurity. Compr Physiol. 2012;2(4):2923-31.
DOI: 10.1002/cphy.c100021
PMID: 23720269
7. Peček J, Fister P. Srčno-dihalni vzorci novorojenčkov. Med Razgl. 2018;57(3):325-43.
8. Sarnat HB, Flores-Sarnat L. Synaptogenesis and myelination in the nucleus/tractus solitarius: potential role in apnea of prematurity, congenital central hypoventilation, and sudden infant death syndrome. J Child Neurol. 2016;31(6):722-32.
DOI: 10.1177/0883073815615227
PMID: 26661483
9. Martin RJ, Di Fiore JM, Walsh MC. Hypoxic episodes in bronchopulmonary dysplasia. Clin Perinatol. 2015;42(4):825-38.
DOI: 10.1016/j.clp.2015.08.009
PMID: 26593081
10. Martin RJ, Di Fiore JM, Macfarlane PM, Wilson CG. Physiologic basis for intermittent hypoxic episodes in preterm infants. Adv Exp Med Biol. 2012;758:351-8.
DOI: 10.1007/978-94-007-4584-1_47
PMID: 23080182
11. Heman-Ackah YD, Pernell KJ, Goding GS. The laryngeal chemoreflex: an evaluation of the normoxic response. Laryngoscope. 2009;119(2):370-9.
DOI: 10.1002/lary.20007
PMID: 19172628
12. Thach BT. Reflux associated apnea in infants: evidence for a laryngeal chemoreflex. Am J Med. 1997;103(5):120S-4S.
DOI: 10.1016/S0002-9343(97)00336-7
PMID: 9422636
13. Xia L, Leiter JC, Bartlett D. Laryngeal reflex apnea in neonates: effects of CO2 and the complex influence of hypoxia. Respir Physiol Neurobiol. 2013;186(1):109-13.
DOI: 10.1016/j.resp.2013.01.004
PMID: 23348024
14. Schelegle ES. Functional morphology and physiology of slowly adapting pulmonary stretch receptors. Anat Rec A Discov Mol Cell Evol Biol. 2003;270(1):11-6.
DOI: 10.1002/ar.a.10004
PMID: 12494485
15. Alvarado RE. Control of breathing and apnea of prematurity. Neoreviews. 2018;19(4):e224-34.
DOI: 10.1542/neo.19-4-e224
16. Bratanič B, Paro Panjan D. Apnoične atake. In: Kržišnik C, Anderluh M, Arnež M. Pediatrija. Ljubljana: DZS; 2014. pp. 223-4.
17. Martin RJ, Wilson CG. What to do about apnea of prematurity? J Appl Physiol (1985). 2009;107(4):1015-6.
DOI: 10.1152/japplphysiol.00940.2009
PMID: 19696360
18. Robek D, Soltirovska Šalamon A. Neonatalne konvulzije. Slov Pediatr. 2018;25:148-56.
19. Westkamp E, Soditt V, Adrian S, Bohnhorst B, Groneck P, Poets CF. Blood transfusion in anemic infants with apnea of prematurity. Biol Neonate. 2002;82(4):228-32.
DOI: 10.1159/000065891
PMID: 12381929
20. Slocum C, Hibbs AM, Martin RJ, Orenstein SR. Infant apnea and gastroesophageal reflux: a critical review and framework for further investigation. Curr Gastroenterol Rep. 2007;9(3):219-24.
DOI: 10.1007/s11894-007-0022-3
PMID: 17511920
21. Arad-Cohen N, Cohen A, Tirosh E. The relationship between gastroesophageal reflux and apnea in infants. J Pediatr. 2000;137(3):321-6.
DOI: 10.1067/mpd.2000.107847
PMID: 10969254
22. Amin RS. Gastroesophageal reflux and infant apnea. J Pediatr. 2000;137(3):298-300.
DOI: 10.1067/mpd.2000.109737
PMID: 10969250
23. Rambaud C, Guilleminault C. “Back to sleep” and unexplained death in infants. Sleep. 2004;27(7):1359-66.
DOI: 10.1093/sleep/27.7.1359
PMID: 15586789
24. Lemyre B, Davis PG, De Paoli AG. Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Cochrane Database Syst Rev. 2000(3):CD002272.
PMID: 10908544
25. Kubicka ZJ, Limauro J, Darnall RA. Heated, humidified high-flow nasal cannula therapy: yet another way to deliver continuous positive airway pressure? Pediatrics. 2008;121(1):82-8.
DOI: 10.1542/peds.2007-0957
PMID: 18166560
26. Henderson-Smart DJ, De Paoli AG. Prophylactic methylxanthine for prevention of apnoea in preterm infants. Cochrane Database Syst Rev. 2010;12(12):CD000432.
DOI: 10.1002/14651858.CD000432.pub2
PMID: 21154344
27. Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, et al.; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006;354(20):2112-21.
DOI: 10.1056/NEJMoa054065
PMID: 16707748
28. Shrestha B, Jawa G. Caffeine citrate - Is it a silver bullet in neonatology? Pediatr Neonatol. 2017;58(5):391-7.
DOI: 10.1016/j.pedneo.2016.10.003
PMID: 28446386
29. Neubauer D, Erjavec M. Uporaba kardiorespirografije v neonatologiji. Zdravstveno varstvo v perinatalni dobi. 1983;1983:65-7.
30. Doyle J, Davidson D, Katz S, Varela M, Demeglio D, DeCristofaro J. Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge. J Perinatol. 2016;36(2):141-4.
DOI: 10.1038/jp.2015.167
PMID: 26562367
31. Aranda JV, Collinge JM, Zinman R, Watters G. Maturation of caffeine elimination in infancy. Arch Dis Child. 1979;54(12):946-9.
DOI: 10.1136/adc.54.12.946
PMID: 533298
32. Aranda JV, Turmen T, Davis J, Trippenbach T, Grondin D, Zinman R, et al. Effect of caffeine on control of breathing in infantile apnea. J Pediatr. 1983;103(6):975-8.
DOI: 10.1016/S0022-3476(83)80735-5
PMID: 6644439
33. Henderson-Smart D, Steer P. Doxapram treatment for apnea in preterm infants. Cochrane Database Syst Rev. 2004(4):CD000074.
DOI: 10.1002/14651858.CD000074.pub2
PMID: 15494987
34. Al-Saif S, Alvaro R, Manfreda J, Kwiatkowski K, Cates D, Qurashi M, et al. A randomized controlled trial of theophylline versus CO2 inhalation for treating apnea of prematurity. J Pediatr. 2008;153(4):513-8.
DOI: 10.1016/j.jpeds.2008.04.025
PMID: 18534618
35. Edraki M, Pourpulad H, Kargar M, Pishva N, Zare N, Montaseri H. Olfactory stimulation by vanillin prevents apnea in premature newborn infants. Iran J Pediatr. 2013;23(3):261-8.
PMID: 23795247
36. Eichenwald EC, Aina A, Stark AR. Apnea frequently persists beyond term gestation in infants delivered at 24 to 28 weeks. Pediatrics. 1997;100(3 Pt 1):354-9.
DOI: 10.1542/peds.100.3.354
PMID: 9282705
37. Tamim H, Khogali M, Beydoun H, Melki I, Yunis K; National Collaborative Perinatal Neonatal Network. Consanguinity and apnea of prematurity. Am J Epidemiol. 2003;158(10):942-6.
DOI: 10.1093/aje/kwg226
PMID: 14607801
38. Bloch-Salisbury E, Hall MH, Sharma P, Boyd T, Bednarek F, Paydarfar D. Heritability of apnea of prematurity: a retrospective twin study. Pediatrics. 2010;126(4):e779-87.
DOI: 10.1542/peds.2010-0084
PMID: 20837586
39. Kumral A, Tuzun F, Yesilirmak DC, Duman N, Ozkan H. Genetic basis of apnoea of prematurity and caffeine treatment response: role of adenosine receptor polymorphisms: genetic basis of apnoea of prematurity. Acta Paediatr. 2012;101(7):e299-303.
DOI: 10.1111/j.1651-2227.2012.02664.x
PMID: 22462821
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