Arousal and ventilatory responses to mild hypoxia in sleeping preterm infants

A failure to adequately respond to hypoxia has been implicated in the Sudden Infant Death Syndrome (SIDS). Preterm infants are at increased risk for SIDS, thus we compared ventilatory and arousal responses to mild hypoxia [15% oxygen (O2)] in preterm and term infants. Eight preterm and 15 term infants were serially studied with daytime polysomnography during which nasal airflow was monitored by pneumotachograph at 2–5 weeks, 2–3 and 5–6 months. At each age, in both groups, hypoxia induced a significant decrease in oxygen saturation (SpO2) during both active sleep (AS) and quiet sleep (QS). Infants invariably aroused in AS; and in QS either aroused or failed to arouse. In preterm infants arousal latency in AS was longer than in term infants (P < 0.05) at 2–5 weeks. Compared with term infants, preterm infants reached significantly lower SpO2 levels at 2–5 weeks in both AS and QS non‐arousing tests and at 2–3 months in QS. A biphasic hypoxic ventilatory response was observed in QS non‐arousing tests in both groups of infants at all three ages. We conclude that the greater desaturation during a hypoxic challenge combined with the longer arousal latency in preterm infants could contribute to greater risk for SIDS.

[1]  A. Walker,et al.  Maturation of the initial ventilatory response to hypoxia in sleeping infants , 2007, Journal of sleep research.

[2]  R. Harding,et al.  Postnatal development of ventilatory and arousal responses to hypoxia in human infants , 2005, Respiratory Physiology & Neurobiology.

[3]  The scoring of arousals in healthy term infants (between the ages of 1 and 6 months) , 2005, Journal of sleep research.

[4]  R. Harding,et al.  Arousal and ventilatory responses to hypoxia in sleeping infants: effects of maternal smoking , 2004, Respiratory Physiology & Neurobiology.

[5]  Richard J Martin,et al.  Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants. , 2004, The Journal of pediatrics.

[6]  H. Lagercrantz,et al.  Respiratory and arousal responses to hypoxia in apnoeic infants reinvestigated , 1989, European Journal of Pediatrics.

[7]  G. Ottaviani,et al.  Identification of neurons responding to hypoxia in sudden infant death syndrome , 2003, Pathology international.

[8]  R. Harding,et al.  Ventilatory responses preceding hypoxia-induced arousal in infants: effects of sleep-state , 2003, Respiratory Physiology & Neurobiology.

[9]  D. Gozal,et al.  Vascular endothelial growth factor in the cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia. , 2003, Pediatrics.

[10]  R. Horne,et al.  The prone sleeping position impairs arousability in term infants. , 2001, The Journal of pediatrics.

[11]  R. Horne The prone sleeping position impairs arousability in healthy term infants , 2001 .

[12]  R. Horne,et al.  Effects of Prematurity on Arousal from Sleep in the Newborn Infant , 2000, Pediatric Research.

[13]  T. Rognum,et al.  Hypoxanthine Levels in Vitreous Humor: A Study of Influencing Factors in Sudden Infant Death Syndrome , 1998, Pediatric Research.

[14]  R. Davis,et al.  Persistence of the biphasic ventilatory response to hypoxia in preterm infants. , 1998, The Journal of pediatrics.

[15]  R. Bandler,et al.  Finding the failure mechanism in Sudden Infant Death Syndrome , 1998, Nature Medicine.

[16]  D. Henderson-smart,et al.  Ventilatory response of the newborn infant to mild hypoxia , 1997, Pediatric pulmonology.

[17]  H. Rigatto,et al.  The biphasic ventilatory response to hypoxia in preterm infants is not due to a decrease in metabolism , 1996, Pediatric pulmonology.

[18]  K. Lewis,et al.  Deficient hypoxia awakening response in infants of smoking mothers: possible relationship to sudden infant death syndrome. , 1995, The Journal of pediatrics.

[19]  H. Kinney,et al.  Decreased muscarinic receptor binding in the arcuate nucleus in sudden infant death syndrome , 1995, Science.

[20]  H. Gautier,et al.  Ventilatory strategy in hypoxic or hypercapnic newborns. , 1994, Biology of the Neonate.

[21]  H. Hoffman,et al.  Epidemiology of the sudden infant death syndrome: maternal, neonatal, and postneonatal risk factors. , 1992, Clinics in perinatology.

[22]  T. Keens,et al.  Hypoxic arousal responses in normal infants. , 1992, Pediatrics.

[23]  G. Fox,et al.  Arousal responses in babies at risk of sudden infant death syndrome at different postnatal ages. , 1992, Irish medical journal.

[24]  K. Barrington,et al.  Periodic Breathing and Apnea in Preterm Infants , 1990, Pediatric Research.

[25]  B. Olaisen,et al.  Elevated levels of hypoxanthine in vitreous humor indicate prolonged cerebral hypoxia in victims of sudden infant death syndrome. , 1988, Pediatrics.

[26]  A. Côté,et al.  Exponential and diphasic ventilatory response to hypoxia in conscious lambs. , 1986, Journal of applied physiology.

[27]  C. W. Sargent,et al.  Hypoxic and hypercapneic arousal responses and prediction of subsequent apnea in apnea of infancy. , 1985, Pediatrics.

[28]  J. Brady,et al.  Control of ventilation in subsequent siblings of victims of sudden infant death syndrome. , 1985, The Journal of pediatrics.

[29]  D. Hudgel,et al.  Hypoxic ventilatory response decreases during sleep in normal men. , 2015, The American review of respiratory disease.

[30]  K. Mcculloch,et al.  Arousal responses in near-miss sudden infant death syndrome and in normal infants. , 1982, The Journal of pediatrics.

[31]  M. Durand,et al.  Ventilatory response to 100% and 15% O2 during wakefulness and sleep in preterm infants. , 1982, Early human development.

[32]  C. Hunt ABNORMAL HYPERCARBIC AND HYPOXIC SLEEP AROUSAL RESPONSES IN NEAR-MISS SIDS INFANTS , 1981, Pediatric Research.

[33]  C. Sullivan,et al.  Arousal: the forgotten response to respiratory stimuli. , 1978, The American review of respiratory disease.

[34]  H. Rigatto,et al.  Chemoreceptor reflexes in preterm infants: I. The effect of gestational and postnatal age on the ventilatory response to inhalation of 100% and 15% oxygen. , 1975, Pediatrics.

[35]  J. Allan Hobson,et al.  A manual of standardized terminology, techniques and criteria for scoring of states of sleep and wakefulness in newborn infants , 1972 .

[36]  H. Rigatto,et al.  Periodic breathing and apnea in preterm infants. II. Hypoxia as a primary event. , 1972, Pediatrics.

[37]  J. Brady,et al.  Chemoreceptor reflexes in the new‐born infant: effects of varying degrees of hypoxia on heart rate and ventilation in a warm environment * , 1966, The Journal of physiology.

[38]  H. C. Miller,et al.  The effects of hypoxia on the respiration of newborn infants. , 1954, Pediatrics.

[39]  K. W. Cross,et al.  The effect of inhalation of high and low concentrations of oxygen on the respiration of the premature infant , 1952, The Journal of physiology.

[40]  K. W. Cross,et al.  The effect of inhalation of high and low oxygen concentrations on the respiration of the newborn infant , 1951, The Journal of physiology.