Abstract
Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are commonly underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia [IH] progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks six to eight. Over this period of unstable respiratory control, increased oxygen-sensitive peripheral chemoreceptor activity has been associated with a higher incidence of apnea of prematurity. In contrast, infants with bronchopulmonary dysplasia [chronic neonatal lung disease] exhibit decreased peripheral chemosensitivity, although the effect on respiratory stability in this population is unclear. Such episodic hypoxia/reoxygenation in early life has the potential to sustain a proinflammatory cascade with resultant multisystem, including respiratory, morbidity. Therapeutic approaches for intermittent hypoxic episodes comprise careful titration of baseline or supplemental inspired oxygen as well as xanthine therapy to prevent apnea of prematurity. Characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.
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References
Abu-Shaweesh JM, Martin RJ (2008) Neonatal apnea: what’s new? Pediatr Pulmonol 43:937–944
Adle-Biassette HBM, Matrot B, Favrais G, Gallego J, Gressens P (2011) Moderate intermittent hypoxia protects neurodevelopment in newborn mice. E-PAS 4534–4510
Al-Matary A, Kutbi I, Qurashi M, Khalil M, Alvaro R, Kwiatkowski K, Cates D, Rigatto H (2004) Increased peripheral chemoreceptor activity may be critical in destabilizing breathing in neonates. Semin Perinatol 28:264–272
Bucher HU, Duc G (1988) Does caffeine prevent hypoxaemic episodes in premature infants? a randomized controlled trial. Eur J Pediatr 147:288–291
Calder NA, Williams BA, Smyth J, Boon AW, Kumar P, Hanson MA (1994) Absence of ventilatory responses to alternating breaths of mild hypoxia and air in infants who have had bronchopulmonary dysplasia: implications for the risk of sudden infant death. Pediatr Res 35:677–681
Cardot V, Chardon K, Tourneux P, Micallef S, Stephan E, Leke A, Bach V, Libert JP, Telliez F (2007) Ventilatory response to a hyperoxic test is related to the frequency of short apneic episodes in late preterm neonates. Pediatr Res 62:591–596
Cattarossi L, Haxhiu-Poskurica B, Haxhiu MA, Litmanovitz I, Martin RJ, Carlo WA (1995) Carotid bodies and ventilatory response to hypoxia in aminophylline-treated piglets. Pediatr Pulmonol 20:94–100
Chavez-Valdez R, Wills-Karp M, Ahlawat R, Cristofalo EA, Nathan A, Gauda EB (2009) Caffeine modulates TNF-alpha production by cord blood monocytes: the role of adenosine receptors. Pediatr Res 65:203–208
Claure N, Bancalari E, D’Ugard C, Nelin L, Stein M, Ramanathan R, Hernandez R, Donn SM, Becker M, Bachman T (2011) Multicenter crossover study of automated control of inspired oxygen in ventilated preterm infants. Pediatrics 127:e76–e83
Darnall RA (2010) The role of CO(2) and central chemoreception in the control of breathing in the fetus and the neonate. Respir Physiol Neurobiol 173:201–212
Davis PG, Schmidt B, Roberts RS, Doyle LW, Asztalos E, Haslam R, Sinha S, Tin W (2010) Caffeine for apnea of prematurity trial: benefits may vary in subgroups. J Pediatr 156:382–387
Di Fiore JM, Bloom J, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ (2010) A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr 157:69–73
Di Fiore J, Walsh M, Finer N, Carlo W, Martin RJ, SUPPORT Study Group of the NICHD Neonatal Network (2011) Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. J Pediatr 2012 in press
Dimaguila MA, Di Fiore JM, Martin RJ, Miller MJ (1997) Characteristics of hypoxemic episodes in very low birth weight infants on ventilatory support. J Pediatr 130:577–583
Esquer C, Claure N, D’Ugard C, Wada Y, Bancalari E (2007) Role of abdominal muscles activity on duration and severity of hypoxemia episodes in mechanically ventilated preterm infants. Neonatology 92:182–186
Herlenius E, Aden U, Tang LQ, Lagercrantz H (2002) Perinatal respiratory control and its modulation by adenosine and caffeine in the rat. Pediatr Res 51:4–12
Hibbs AM, Johnson NL, Rosen CL, Kirchner HL, Martin R, Storfer-Isser A, Redline S (2008) Prenatal and neonatal risk factors for sleep disordered breathing in school-aged children born preterm. J Pediatr 153:176–182
Julien CA, Joseph V, Bairam A (2010) Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia. Pediatr Res 68:105–111
Katz-Salamon M, Jonsson B, Lagercrantz H (1995) Blunted peripheral chemoreceptor response to hyperoxia in a group of infants with bronchopulmonary dysplasia. Pediatr Pulmonol 20:101–106
Martin RJ, Di Fiore JM, Jana L, Davis RL, Miller MJ, Coles SK, Dick TE (1998) Persistence of the biphasic ventilatory response to hypoxia in preterm infants. J Pediatr 132:960–964
Martin RJ, Wang K, Köroglu Ö, Di Fiore J, Prabha KC (2011) Intermittent hypoxic episodes in preterm infants: Do they matter? review. Neonatology 100:303–310
Mayer CA, Haxhiu MA, Martin RJ, Wilson CG (2006) Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats. J Appl Physiol 100:91–97
Nock ML, Di Fiore JM, Arko MK, Martin RJ (2004) Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants. J Pediatr 144:291–295
Paavonen EJ, Strang-Karlsson S, Raikkonen K, Heinonen K, Pesonen AK, Hovi P, Andersson S, Jarvenpaa AL, Eriksson JG, Kajantie E (2007) Very low birth weight increases risk for sleep-disordered breathing in young adulthood: the Helsinki study of very Low birth weight adults. Pediatrics 120:778–784
Pawar A, Peng YJ, Jacono FJ, Prabhakar NR (2008) Comparative analysis of neonatal and adult rat carotid body responses to chronic intermittent hypoxia. J Appl Physiol 104:1287–1294
Rigatto H, Brady JP (1972) Periodic breathing and apnea in preterm infants I. Evidence for hypoventilation possibly due to central respiratory depression. Pediatrics 50:202–218
Rosen CL, Larkin EK, Kirchner HL, Emancipator JL, Bivins SF, Surovec SA, Martin RJ, Redline S (2003) Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity. J Pediatr 142:383–389
Sands SA, Edwards BA, Kelly VJ, Skuza EM, Davidson MR, Wilkinson MH, Berger PJ (2009) A model analysis of arterial oxygen desaturation during apnea in preterm infants. PLoS Comp Biol 5:1–14
Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W (2007) Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 357:1893–1902
Smith CA, Forster HV, Blain GM, Dempsey JA (2010) An interdependent model of central/peripheral chemoreception: evidence and implications for ventilatory control. Respir Physiol Neurobiol 173:288–297
Stenson B, Brocklehurst P, Tarnow-Mordi W (2011) Increased 36-week survival with high oxygen saturation target in extremely preterm infants. N Engl J Med 364:1680–1682
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network, Carlo WA, Finer NN, Walsh MC, Rich W, Gantz MG, Laptook AR, Yoder BA, Faix RG, Das A, Poole WK, Schibler K, Newman NS, Ambalavanan N, Frantz ID, Piazza AJ, Sánchez PJ, Morris BH, Laroia N, Phelps DL, Poindexter BB, Cotten CM, Van Meurs KP, Duara S, Narendran V, Sood BG, O’Shea TM, Bell EF, Ehrenkranz RA, Watterberg KL, Higgins RD (2010) Target ranges of oxygen saturation in extremely preterm infants. N Engl J Med 362:1959–1969
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Supported by: NIH Grants R21 HL098628 [RJM] and RO3 HD064830 [CGW] grant
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Martin, R.J., Di Fiore, J.M., MacFarlane, P.M., Wilson, C.G. (2012). Physiologic Basis for Intermittent Hypoxic Episodes in Preterm Infants. In: Nurse, C., Gonzalez, C., Peers, C., Prabhakar, N. (eds) Arterial Chemoreception. Advances in Experimental Medicine and Biology, vol 758. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4584-1_47
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