Abstract
In the last decade, knowledge regarding the neurodevelopment and functional aspects of the respiratory centers during postnatal maturation has increased substantially. However, an increase in such knowledge has not provided a basis for change in practice. The diagnosis of apnea of prematurity (AOP) is one of exclusion. All causes of secondary apnea must be ruled out before initiating treatment for AOP. Treatment will depend on the etiology as well as effectiveness and tolerability of the treatment by the patient. The primary goal of any treatment of AOP is to prevent the frequency of apnea lasting > 20 seconds, and/or those that are shorter, but associated with cyanosis and bradycardia.
The clinical management of AOP is not much different today than it was two decades ago, with pharmacologic and nonpharmacologic treatment options remaining the mainstay of therapy. Methylxanthines are still the most widely used pharmacologic agents. Due to the wider therapeutic index of caffeine and ease of once daily administration, it should be the preferred agent. Doxapram, or nonpharmacologic treatment measures such as nasal continuous positive airway pressure, may be considered in infants who are unresponsive to methylxanthine treatment alone. Treatment should be continued until there is complete resolution of apnea, and for some time thereafter. The choice of method for weaning treatment remains one of individual physician preference. Discharge from hospital after apnea requires close monitoring and some infants will require home apnea monitors. The decision to provide a home apnea monitor should be individualized for each patient, depending on the effectiveness of treatment and clinical response.
Similar content being viewed by others
References
Cheung PY, Barrington KJ, Finer NN, et al. Early childhood neurodevelopment in very low birth weight infants with predischarge apnea. Pediatr Pulmonol 1999; 27: 14–20
Marchal F, Bairam A, Vert P. Neonatal apnea and apneic syndromes. Clin Perinatol 1987; 14: 509–29
Adams JA, Zabaleta IA, Sackner MA. Hypoxic events in spontaneously breathing premature infants: etiologic basis. Pediatr Res 1997; 42: 463–71
Task Force on Prolonged Infantile Apnea, American Academy of Pediatrics. Prolonged infantile apnea: 1985. Pediatrics 1985; 76: 129–31
Jenni OG, Wolf M, Hengartner M, et al. Impact of central, obstructive and mixed apneas on cerebral hemodynamics in preterm infants. Biol Neonate 1996; 70: 91–100
Perlman J, Volpe J. Episodes of apneoa and bradycardia in the preterm newborn: impact on cerebral circulation. Pediatrics 1985; 76: 333–8
Poets CF, Samuels MP, Southhall DP. Epidemiology and pathophysiology of apnoea of prematurity. Biol Neonate 1994; 65: 211–9
Idiong N, Lemke RP, Lin YJ, et al. Airway closure during mixed apneas in preterm infants: is effort necessary. J Pediatr 1998; 133: 509–12
Henderson-Smart DJ, Pettigrew AG, Campbell DJ. Clinical apnoea and brainstem neural function in preterm infants. N Engl J Med 1983; 308: 353–7
Martin RJ, Miller MJ, Waldemar A, et al. Pathogenesis of apnea in preterm infants. J Pediatr 1986; 109: 733–41
Bolivar JM, Gerhardt T, Gonzalez A, et al. Mechanisms for episodes of hypoxemia in preterm infants undergoing mechanical ventilation. J Pediatr 1995; 127: 767–73
Poets C, Valerie A, Stebbens MP, et al. The relationship between bradycardia, apnea and hypoxemia in preterm infants. Pediatr Res 1993; 34: 144–7
Martin RJ, DiFiore JM, Jana L, et al. Persistence of the biphasic ventilatory response to hypoxia in preterm infants. J Pediatr 1998; 132: 960–4
Alden ER, Mandelkorn R, Woodrum DE, et al. Morbidity and mortality of infants weighing less than 1000 grams in an intensive care nursery. Pediatrics 1972; 50: 40–9
Henderson-Smart DJ. The effects of gestational age on the incidence and duration of recurrent apnea in newborn babies. Aust Paediatr J 1981; 17: 273–6
Lindgren C, Grogaard J. Reflex apnea response and inflammatory mediators in infants with respiratory tract infection. Acta Paediatr 1996; 85: 798–803
Saxena A, Sharma M, Kothari SS, et al. Prostaglandin E1 in infants with congenital heart disease: the Indian experience. Indian Pediatr 1998; 35: 1063–9
Sheikh S, Stephen TC, Sisson B. Prevalance of gastroesophageal reflux in infants with recurrent brief apneic episodes. Can Respir J 1999; 6: 401–4
Sasidharan P, Heimler R. Transfusion-induced changes in the breathing pattern of healthy preterm anemic infants. Pediatr Pulmonol 1992; 12(3): 170–3
Peter CS, Sprodowski N, Bohnhorst B, et al. Gastroesophageal reflux and apnea of prematurity: no temporal relationship. Pediatrics 2002; 109: 8–11
Lagercrantz H. What does the preterm infant breath for: controversies on apnea of prematurity. Acta Paediatr 1992; 81: 733–6
Church MK, Featherstone RL, Cushley MJ, et al. Relationships between adenosine, cyclic nucleotides, and xanthines in asthma. J Allergy Clin Immunol 1986; 78: 670–5
Poison JB, Krzanowski JJ, Goldman AL, et al. Inhibition of human pulmonary phosphodiesterase activity by therapeutic levels of theophylline. Clin Exp Pharmacol Physiol 1978; 5: 535–9
Torphy TJ, Undem BJ. Phosphodiesterase inhibitors: new opportunities for the treatment of asthma. Thorax 1991; 46: 512–23
Barnes PJ, Pauwels RA. Theophylline in the management of asthma: time for reappraisal. Eur Respir J 1994; 7: 579–91
Gayan-Ramirez G, Janssens S, Himpens B, et al. Mechanism of theophylline-induced inotropic effects on foreshortened canine diaphragm. Eur Respir J 1995; 8: 1915–21
Kolbeck RC, Speir WA. Diltiazem, verapamil and nifedipine inhibit theophylline-enhanced diaphragmatic contractility. Am Rev Respir Dis 1989; 139: 130–45
Gliech GJ. The eosinophil and bronchial asthma: current understanding. J Allergy Clin Immunol 1990; 85: 422–36
Ohta K, Sawamoto S, Nakajima M, et al. The prolonged survival of human eosinophils with interlukine-5 and its inhibition by theophylline via apoptosis. Clin Exp Allergy 1996; 26Suppl. 2: 10–5
Torphy TJ, Livi GP. Phosphodiesterase isoenzymes in airways. Lung Biol Health Dis 1993; 67: 177–222
Banner KH, Page CP. Anti-inflammatory effects of theophylline and selective phosphodiesterase inhibitors. Clin Exp Allergy 1996; 26Suppl. 2: 2–9
Davi MJ, Koravangattu S, Simons KJ, et al. Physiologic changes induced by theophylline in the treatment of apnea in preterm infants. J Pediatr 1978; 92: 91–5
Giacoia G, Jusko WJ, Menke J, et al. Theophylline pharmacokinetics in premature infants with apnea. J Pediatr 1976; 89: 829–32
Hilligoss DM, Jusko WJ, Koup JR, et al. Factors affecting theophylline pharmacokinetics in premature infants with apnea. Dev Pharmacol Ther 1980; 1: 6–15
Latini R, Assael BM, Bonati M, et al. Kinetics and efficacy of theophylline in the treatment of apnea in premature infants. Clin Pharmacol Ther 1978; 13: 203–7
Neese AL, Soyka LF. Development of a radioimmunoassay for theophylline: application to studies in premature infants. Clin Pharmacol Ther 1977; 21: 633–41
Aranda JV, Sitar DS, Parsons WD, et al. Pharmacokinetic aspects of theophylline in premature newborns. N Engl J Med 1976; 295: 413–6
Boutroy MJ, Vert P, Royer RJ, et al. Caffeine, a metabolite of theophylline during the treatment of apnea in the premature infant. J Pediatr 1979; 94: 996–8
du Preeze MJ, Botha JH, McFadyen ML, et al. The pharmacokinetics of theophylline in premature neonates during the first few days after birth. Ther Drug Monit 1999; 21: 598–603
Kraus DM, Fischer JH, Reitz SJ, et al. Alterations in theophylline metabolism during the first year of life. Clin Pharmacol Ther 1993; 54: 351–9
Tateishi T, Asoh M, Yamaguchi A, et al. Developmental changes in urinary elimination of theophylline and its metabolites in pediatric patients. Pediatr Res 1999; 45: 66–70
Houge S, Phelps SJ. Evaluation of three dosing equations for use in infants up to one year of age. J Pediatr 1993; 123: 651–6
Bhatt Mehta V, Donn SM, Schork MA, et al. Prospective evaluation of two dosing equations for theophylline in premature infants. Pharmacotherapy 1996; 16: 769–76
Gorodischer R, Karplus M. Pharmacokinetic aspects of caffeine in premature infants with apnoea. Eur J Clin Pharmacol 1982; 22: 47–52
Pearlman SA, Duran CS, Wood MA, et al. Caffeine pharmacokinetics in preterm infants older than 2 weeks. Dev Pharmacol Ther 1989; 12: 65–9
Aranda JV, Cook CE, Gorman W, et al. Pharmacokinetic profile of caffeine in the premature newborn infant with apnea. J Pediatr 1979; 94: 663–8
Aldridge A, Aranda JV, Neims AH. Caffeine metabolism in the newborn. Clin Pharmacol Ther 1979; 25: 447–53
de Carolis MPD, Romagnoli C, Muzii U, et al. Pharmacokinetic aspects of caffeine in premature infants. Dev Pharmacol Ther 1991; 16: 117–22
Falcao AC, Gatta MF, Delgado MF, et al. Population pharmacokinetics of caffeine in premature neonates. Eur J Clin Pharmacol 1997; 52: 211–7
Aranda JV, Collinge JM, Zinman R, et al. Maturation of caffeine elimination in infancy. Arch Dis Child 1979; 54: 946–9
Carrier O, Pons G, Rey E, et al. Maturation of caffeine metabolic pathways in infancy. Clin Pharmacol Ther 1988; 44: 145–51
Pons G, Carrier O, Richard M, et al. Developmental changes of caffeine elimination in infancy. Dev Pharmacol Ther 1988; 11: 258–64
Giacoia GP, Jungbluth GL, Jusko WJ. Effect of feeding on oral absorption of caffeine in premature infants. Dev Pharmacol Ther 1989; 12: 205–10
Jamali F, Coutts RT, Malek F, et al. Lack of pharmacokinetic interaction between doxapram and theophylline in apnea of prematurity. Dev Pharmacol Ther 1991; 16: 78–82
Yazdani M, Kissling GE, Tran TH, et al. Phenobarbital increases the theophylline requirement of premature infants being treated for apnea. Am J Dis Child 1987; 141: 97–9
Somani SM, Khanna NN, Bada HS. Caffeine and theophylline: serum/CSF correlation in premature infants. J Pediatr 1980; 96: 1091–3
Turmen T, Davis J, Aranda JV. Relationship of dose and plasma concentrations of caffeine and ventilation in neonatal apnea. Semin Perinatol 1981; 5: 326–31
Aranda JV, Scalias E, Papageorgiou A, et al. Ontogeny of human caffeine and theophylline metabolism. Dev Pharmacol Ther 1984; 7: 18–25
Brazier JL, Sale B, Ribon B, et al. In vivo N7 methylation of theophylline to caffeine in premature infants. Dev Pharmacol Ther 1981; 2: 137–44
Bory C, Baltassat P, Porthault M, et al. Metabolism of theophylline to caffeine in premature newborn infants. J Pediatr 1979; 94: 988–93
Bada H, Khanna NN, Somani SM, et al. Interconversion of theophylline and caffeine in newborn infants. J Pediatr 1979; 94: 993–5
Lin JC, Strauss RG, Kulhavy JC, et al. Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics 2000; 106: El9
Blanchette VS, Zipursky A. Assessment of anemia in newborn infants. Clin Perinatol 1995; 22: 657–69
Ramasethu J, Luban NLC. Red blood cell transfusions in the newborn. Semin Neonatol 1999; 4: 5–16
Gorodischer R, Burtin P, Hwang P, et al. Saliva versus blood sampling for therapeutic drug monitoring in children: patient and parental preferences and an economic analysis. Ther Drug Monit 1994; 16: 437–43
Lee TC, Charles BG, Steer PA, et al. Saliva as a valid alternative to serum in monitoring intravenous caffeine treatment for apnea of prematurity. Ther Drug Monit 1996; 18: 288–93
Khanna NN, Bada HS, Somani SM. Use of salivary concentrations in the prediction of serum caffeine and theophylline concentrations in premature infants. J Pediatr 1980; 96: 494–9
Walther FJ, Erickson R, Sims ME. Cardiovascular effects of caffeine therapy in preterm infants. Am J Dis Child 1990; 144: 1164–6
Dani C, Bertini G, Reali MF, et al. Brain hemodynamic changes in preterm infants after maintenance dose caffeine and aminophylline treatment. Biol Neonate 2000; 78: 27–32
Lundstrom KE, Larsen PB, Brendstrup L, et al. Cerebral blood flow and left ventricular output in spontaneously breathing newborn preterm infants treated with caffeine or theophylline. Acta Paediatr 1995; 84: 6–9
Saliba E, Autret E, Gold F, et al. Effect of caffeine on cerebral blood flow velocity in preterm infants. Biol Neonate 1989; 56: 198–203
McDonnell M, Ives NK, Hope PL. Intravenous aminophylline and cerebral blood flow in preterm infants. Arch Dis Child 1992; 67: 416–8
Robinson MJ, Clayden GS, Smith MF. Xanthines and necrotizing enterocolitis. Arch Dis Child 1980; 55: 494–5
Davis JM, Abbasi S, Spitzer AR, et al. Role of theophylline in pathogenesis of necrotizing enterocolitis. J Pediatr 1986; 109: 344–6
Lane AJP, Coombs RC, Evans DH, et al. Effect of caffeine on splanchnic blood flow. Arch Dis Child Fetal Neonatal Ed 1999; 80: 128–29F
Grosfeld JL, Dalsing MC, Hull M, et al. Neonatal apnea, xanthines, and necrotizing enterocolitis. J Pediatr Surg 1983; 18: 80–84
Kosloske A. Pathogenesis and prevention of necrotizing enterocolitis: ahypothesis based on personal observation and a review of the literature. Pediatrics 1984; 74: 1086–92
Gillot I, Gouyon JB, Guignard JP. Renal effects of caffeine in preterm infants. Biol Neonate 1990; 58: 133–6
Zanardo V, Dani C, Trevisanuto D, et al. Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 1995; 68: 169–74
Mazkereth R, Laufer J, Jordan S, et al. Effects of theophylline on renal function in premature infants. Am J Perinatol 1997; 14: 45–9
Wardrop CAJ, Holland BM, Veale KEA, et al. Non-physiologic anemia of prematurity. Arch Dis Child 1978; 53: 855–60
Bakris G, Sauter ER, Hussey JL, et al. Effects of theophylline on erythropoietin production in normal subjects and in patients with erythrocytosis after renal transplant. N Engl J Med 1990; 323: 86–90
Fang S, Sherwood RA, Gamsu HR, et al. Comparison of the effects of theophylline and caffeine on serum erythropoetin concentration in premature infants. Eur J Paediatr 1998; 157: 406–9
Carnielli VP, Verlato G, Benini F, et al. Metabolic and respiratory effects of theophylline in the preterm infant. Arch Dis Child Fetal Neonatal Ed 2000; 83: F39–43
Bauer J, Maier K, Linderkamp O, et al. Effect of caffeine on oxygen consumption and metabolic rate in very low birth weight infants with idiopathic apnea. Pediatrics 2001; 107: 660–3
Diderholm B, Ewald U, Gustafsson J. Effect of theophylline on glucose production and lipolysis in pretrm infants (≤32 weeks). Pediatr Res 1999; 45: 674–9
Vandenplas Y, De Wolf D, Sacre L. Influence of xanthines on gastroesophageal reflux in infants at risk of sudden infant death syndrome. Pediatrics 1986; 77: 807–10
American Academy of Pediatrics policy statement. Precautions concerning the use of theophylline. Pediatrics 1992; 89: 781–3
Banner W, Czajka PA. Acute caffeine overdose in the neonate. Am J Dis Child 1980; 134: 495–8
Kulkarni PB, Dorand RD. Caffeine toxicity in a neonate. Pediatrics 1979; 64: 254–5
van den Anker JN, Jongejan HT, Sauer PJ. Severe caffeine intoxication in a preterm neonate. Eur J Paediatr 1992; 151: 466–7
Davis PG, Doyle LW, Rickards AL, et al. Methylxanthines and sensorineural outcome at 14 years in children <1501g birthweight. J Paediatr Child Health 2000; 36: 47–50
Le Guennec JC, Sitruk F, Breault C, et al. Somatic growth in infants receiving prolonged caffeine therapy. Acta Paediatr Scand 1990; 79: 52–6
Perrin C, Debruyne D, Lacotte J, et al. Treatment of caffeine intoxication by exchange transfusion in the newborn. Acta Paediatr Scand 1987; 76: 679–81
Ernberg A, Leff RD, Haack DG, et al. Caffeine citrate for the treatment of apnea of prematurity: a double-blind, placebo-controlled study. Pharmacotherapy 2000; 20: 644–52
Romangoli C, De Carolis MP, Muzzi U, et al. Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants. Ther Drug Monit 1992; 14: 14–9
Anwar M, Mondestin H, Mojica N, et al. Effect of caffeine on pneumogram and apnoea of infancy. Arch Dis Child 1986; 61: 891–5
Murat I, Moriette G, Blin MC, et al. The efficacy of caffeine in the treatment of recurrent idiopathic apnea in premature infants. J Pediatr 1981; 99: 984–9
Aranda JV, Gorman W, Bergsteinsson H, et al. Efficacy of caffeine in the treatment of apnea in the low-birth-weight infant. J Pediatr 1977; 90: 467–72
Amato M, Isenschmid M, Huppi P. Percutaneous caffeine application in the treatment of neonatal apnoea. Eur J Paediatr 1991; 150: 592–4
Gupta JM, Mercer HO, Koo WWK. Theophylline in treatment of apnea of prematurity. Aust Paediatr J 1981; 17: 290–1
Sims ME, Yau G, Ranbhatla S, et al. Limitations of theophylline in the apnea of prematurity. Am J Dis Child 1985; 139: 567–70
Uauy R, Shapiro DL, Smith B, et al. Treatment of severe apnea in prematures with orally administered theophylline. Pediatrics 1975; 55: 595–8
Shannon DC, Gotay F, Stein IM, et al. Prevention of apnea and bradycardia in low-birthweight infants. Pediatrics 1975; 55: 589–94
Brouard C, Moriette D, Murat I, et al. Comparative efficacy of theophylline and caffeine in the treatment of idiopathic apnea in premature infants. Am J Dis Child 1985; 139: 698–700
Bairam A, Boutroy MJ, Badonnel Y, et al. Theophylline vs caffeine: comparative effects in the treatment of idiopathic apnea in the preterm infant. J Pediatr 1987; 110: 636–8
Scanlon JEM, Chin KC, Morgan MEI, et al. Caffeine or theophylline for neonatal apnoea. Arch J Dis Child 1992; 67: 425–8
Larsen PB, Brendstrup L, Skov L, et al. Aminophylline vs caffeine citrate for apnea and bradycardia prophylaxis in premature neonates. Acta Paediatr 1995; 84: 360–4
Peliowski A, Finer NN. Blinded, randomized, placebo-controlled, trial to compare theophylline and doxapram for the treatment of apnea of prematurity. J Pediatr 1990; 116: 648–53
Eyal F, Alpan G, Sagi E, et al. Aminophylline vs doxapram in idiopathic apnea of prematurity. Pediatrics 1985; 75: 709–13
Bopp P, Drummond G, Fisher J, et al. Effect of doxapram on control of breathing in cats. Can Anaesth Soc J 1979; 26: 191–5
Mitchell RA, Herbert DA. Potencies of doxapram and hypoxia in stimulating carotid-body chemoreceptors and ventilation in anesthetized cats. Anesthesiology 1975; 42: 559–66
Edwards G, Leszczynski SO. A double blind trial of five respiratory stimulants in patients with acute ventilatory failure. Lancet 1967; II: 226–9
Calverley PMA, Robson RH, Wraith PK, et al. The ventilatory effects of doxapram in normal man. Clin Sci (Lond) 1983; 65: 65–9
Scott RM, Whitwam JG, Chakrabarti MK. Evidence of a role for chemoreceptors in the ventilatory response to doxapram in man. Br J Anaesth 1977; 49: 227–31
Barrington KJ, Finer NN, Peters KL, et al. Physiologic effects of doxapram in idiopathic apnea of prematurity. J Pediatr 1986; 108: 125–9
Jamali F, Barrington KJ, Finer NN, et al. Doxapram dosage regimen in apnea of prematurity based on pharmacokinetic data. Dev Pharmacol Ther 1988; 11: 253–7
Hayakawa F, Hakamada S, Kuno K, et al. Doxapram in the treatment of idiopathic apnea of prematurity: desirable dosage and serum concentrations. J Pediatr 1986; 109: 138–40
Barrington KJ, Finer NN, Torok-Both G, et al. Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity. Pediatrics 1987; 80: 22–7
Beaudry MA, Bradley JM, Gramlich LM, et al. Pharmacokinetics of doxapram in idiopathic apnea of pematurity. Dev Pharmacol Ther 1988; 11: 65–72
Bairam A, Blanchard PW, Mullahoo K, et al. Pharmacodynamic effects and pharmacokinetic profiles of keto-doxapram and doxapram in newborn lambs. Pediatr Res 1990; 28: 142–6
Bairam A, Branchaud C, Beharry K, et al. Doxapram metabolism in human fetal hepatic organ culture. Clin Pharmacol Ther 1991; 50: 32–8
Alpan G, Eyal F, Sagi E, et al. Doxapram in the treatment of idiopathic apnea of prematurity unresponsive to aminophylline. J Pediatr 1984; 104: 634–7
Sagi E, Eyal F, Alpan G, et al. Idiopathic apnoea of prematurity treated with doxapram and aminophylline. Arch Dis Child 1984; 59: 281–3
Yamazaki T, Kajiwara M, Itahashi K, et al. Low-dose doxapram therapy for idiopathic apnea of prematurity. Pediatr Int 2001; 43: 124–7
Barrington KJ, Muttitt SC. Randomized, controlled, blinded trial of doxapram for extubation of the very low birthweight infant. Acta Paediatr 1998; 87: 191–4
Bairam A, Faulon M, Monin P, et al. Doxapram for the initial treatment of apnea of prematurity. Biol Neonate 1992; 61: 209–13
Tay-Uyboco J, Kwiatkowski K, Cates DB, et al. Clinical and physiological responses to prolonged nasogastric administration of doxapram for apnea of prematurity. Biol Neonate 1991; 59: 190–200
Poets C, Darraj S, Bohnhorst B. Effects of doxapram on episodes of apnoea, bradycardia and hypoxaemia in preterm infants. Biol Neonate 1990; 76: 207–13
Huon C, Rey E, Mussat P, et al. Low-dose doxapram for treatment of apnoea following early weaning in very low birthweight infants: a randomized, double-blind study. Acta Paediatr 1998; 87: 1180–4
Fancourt GJ, Aston RJ, Talbot IC, et al. Hepatic necrosis with doxapram hydrochloride. Postgrad Med J 1985; 61: 833–5
De Villiers GS, Walele A, Van Der Marwe PL, et al. Second-degree atrioventricular heart block after doxapram administration. J Pediatr 1998; 133: 149–50
Hunt CE, Inwood RJ, Shannon DC, et al. Respiratory and nonrespiratory effects of doxapram in congenital central hypoventilation syndrome. Am Rev Resp Dis 1979; 119: 263–9
Barbe F, Hansen C, Badonnel Y, et al. Severe side effects and drug plasma concentrations in preterm infants treated with doxapram. Ther Drug Monit 1999; 21: 547–52
Sreenan C, Etches PC, Demianczuk N, et al. Isolated mental developmental delay in very low birth weight infants: association with prolonged doxapram therapy for apnea. J Pediatr 2001; 139: 832–7
Finer NN, Barrington KJ, Hayes BJ, et al. Obstructive, mixed, and central apnea in the neonate: physiologic correlates. J Pediatr 1992; 121(6): 943–50
Rigatto H, Brady JP. Periodic breathing and apnea in preterm infants (II): hypoxia as a primary event. Pediatrics 1972; 50(2): 219–28
Fenner A, Schalk U, Hoenicke H, et al. Periodic breathing in premature and neonatal babies: incidence, breathing pattern, respiratory gas tensions, response to changes in the composition of ambient air. Pediatr Res 1973; 7(4): 174–83
Weintraub Z, Alvaro R, Kwiatkowski K, et al. Effects of inhaled oxygen (up to 40%) on periodic breathing and apnea in preterm infants. J Appl Physiol 1992; 72(1): 116–20
Blank JP, Sheagren TG, Vajaria J, et al. The role of RBC transfusion in the premature infant. Am J Dis Child 1984; 138(9): 831–3
Joshi A, Gerhardt T, Shandloff P, et al. Blood transfusion effect on the respiratory pattern of preterm infants. Pediatrics 1987; 80(1): 79–84
DeMaio JG, Harris MC, Deuber C, et al. Effect of blood transfusion on apnea frequency in growing premature infants. J Pediatr 1989; 114(6): 1039–41
Stute H, Greiner B, Linderkamp O. Effect of blood transfusion on cardiorespiratory abnormalities in preterm infants. Arch Dis Child Fetal Neonatal Ed 1995; 72(3): F194–6
Poets CF, Pauls U, Bohnhorst B. Effect of blood transfusion on apnoea, bradycardia and hypoxaemia in preterm infants. Eur J Pediatr 1997; 156(4): 311–6
Heimler R, Langlois J, Hodel DJ, et al. Effect of positioning on the breathing pattern of preterm infants. Arch Dis Child 1992; 67(3): 312–4
Kurlak LO, Ruggins NR, Stephenson TJ. Effect of nursing position on incidence, type, and duration of clinically significant apnoea in preterm infants. Arch Dis Child Fetal Neonatal Ed 1994; 71(1): F16–9
Keene DJ, Wimmer Jr JE, Mathew OP. Does supine positioning increase apnea, bradycardia, and desaturation in preterm infants. J Perinatol 2000; 20(1): 17–20
Jenni OG, von Siebenthal K, Wolf M, et al. Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants. Pediatrics 1997; 100(4): 622–5
van Someren V, Linnett SJ, Stothers JK, et al. An investigation into the benefits of resiting nasoenteric feeding tubes. Pediatrics 1984; 74(3): 379–83
Henderson-Smart DJ, Osborn DA. Kinesthetic stimulation for preventing apnea in preterm infants. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002
Osborn DA, Henderson-Smart DJ. Kinesthetic stimulation for treating apnea in preterm infants (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002
Korner AF, Kraemer HC, Haffner ME, et al. Effects of waterbed flotation on premature infants: a pilot study. Pediatrics 1975; 56(3): 361–7
Tuck SJ, Monin P, Duvivier C, et al. Effect of a rocking bed on apnoea of prematurity. Arch Dis Child 1982; 57(6): 475–7
Jirapaet K. The effect of vertical pulsating stimulation on apnea of prematurity. J Med Assoc Thai 1993; 76(6): 319–26
Henderson-Smart DJ, Subramanian P, Davis PG. Continuous positive airway pressure versus theophylline for apnea in preterm infants (Cochrane Review). Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 2. Oxford: Update Software, 2000: CD001072
Speidel BD, Dunn PM. Use of nasal continuous positive airway pressure to treat severe recurrent apnoea in very preterm infants. Lancet 1976; II(7987): 658–60
Kattwinkel J, Nearman HS, Fanaroff AA, et al. Apnea of prematurity: comparative therapeutic effects of cutaneous stimulation and nasal continuous positive airway pressure. J Pediatr 1975; 86(4): 588–92
Miller MJ, Carlo WA, Martin RJ. Continuous positive airway pressure selectively reduces obstructive apnea in preterm infants. J Pediatr 1985; 106(1): 91–4
Sreenan C, Lemke RP, Hudson-Mason A, et al. High-flow nasal cannulae in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001; 107(5): 1081–3
Daily WJ, Klaus M, Meyer HB. Apnea in premature infants: monitoring, incidence, heart rate changes, and an effect of environmental temperature. Pediatrics 1969; 43(4): 510–8
Perlstein PH, Edwards NK, Sutherland JM. Apnea in premature infants and incubator-air-temperature changes. N Engl J Med 1970; 282(9): 461–6
Berterottiere D, D’Allest AM, Dehan M, et al. Effects of increase in body temperature on the breathing pattern in premature infants. J Dev Physiol 1990; 13(6): 303–8
Belgaumkar TK, Scott KE. Effects of low humidity on small premature infants in servo control incubators (II): increased severity of apnea. Biol Neonate 1975; 26(5–6): 348–52
Acknowledgements
No outside sources of funding were used in the preparation/development of this manuscript and the authors have no conflicts of interest.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bhatt-Mehta, V., Schumacher, R.E. Treatment of Apnea of Prematurity. Pediatr-Drugs 5, 195–210 (2003). https://doi.org/10.2165/00128072-200305030-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00128072-200305030-00006