Control of ventilation in subsequent siblings of victims of sudden infant death syndrome

doi:10.1016/S0022-3476(85)80289-4

The Journal of Pediatrics

Volume 106, Issue 2, February 1985, Pages 212-217

https://doi.org/10.1016/S0022-3476(85)80289-4 Get rights and content

To learn whether the ventilatory responses to hypoxia (17% O₂) and hypercapnea (4% CO₂) differ in the subsequent siblings of sudden infant death victims (SIDS), we studied seven normal control infants, nine infants who had had a prolonged apneic spell (apneic infants), and 10 subsequent siblings of SIDS (mean ages 10.4 weeks, 15 weeks, and 10 weeks, respectively). With inhalation of 17% O₂, one of seven controls, two of nine apneic infants, and seven of 10 siblings of SIDS breathed periodically (controls vs siblings, p<0.04). Heart rate and end-tidal Pco₂ did not change, but respiratory rate decreased in the siblings (45 to 31 breaths per minute, P<0.001). Arousal occurred during 25% of the hypoxic challenges in the controls and apneic infants but was not seen in the siblings of SIDS (control vs sibling P<0.08, apneic vs siblings P<0.05). With inhalation of 4% CO₂ there was a similar increase in estimated ventilation among the three groups. Arousal occurred 33% of the time in all three groups. Our findings show that, after 5 weeks of age, siblings of SIDS have a normal response to hypercapnea but respond to mild hypoxia with periodic breathing.

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Cited by (42)

Peripheral neuroplasticity of respiratory chemoreflexes, induced by prenatal nicotinic exposure: Implication for SIDS
2023, Respiratory Physiology and Neurobiology
Sudden Infant Death Syndrome (SIDS) occurs during sleep in seemingly healthy infants. Maternal cigarette smoking and hypoxemia during sleep are assumed to be the major causal factors. Depressed hypoxic ventilatory response (dHVR) is observed in infants with high risk of SIDS, and apneas (lethal ventilatory arrest) appear during the fatal episode of SIDS. Disturbance of the respiratory center has been proposed to be involved, but the pathogenesis of SIDS is still not fully understood. Peripherally, the carotid body is critical to generate HVR, and bronchopulmonary and superior laryngeal C-fibers (PCFs and SLCFs) are important for triggering central apneas; however, their roles in the pathogenesis of SIDS have not been explored until recently. There are three lines of recently accumulated evidence to show the disorders of peripheral sensory afferent-mediated respiratory chemoreflexes in rat pups with prenatal nicotinic exposure (a SIDS model) in which acute severe hypoxia leads to dHVR followed by lethal apneas. (1) The carotid body-mediated HVR is suppressed with a reduction of the number and sensitivity of glomus cells. (2) PCF-mediated apneic response is largely prolonged via increased PCF density, pulmonary IL-1β and serotonin (5-hydroxytryptamine, 5-HT) release, along with the enhanced expression of TRPV1, NK₁R, IL1RI and 5-HT₃R in pulmonary C-neurons to strengthen these neural responses to capsaicin, a selective stimulant to C-fibers. (3) SLCF-mediated apnea and capsaicin-induced currents in superior laryngeal C-neurons are augmented by upregulation of TRPV1 expression in these neurons. These results, along with hypoxic sensitization/stimulation of PCFs, gain insight into the mechanisms of prenatal nicotinic exposure-induced peripheral neuroplasticity responsible for dHVR and long-lasting apnea during hypoxia in rat pups. Therefore, in addition to the disturbance in the respiratory center, the disorders of peripheral sensory afferent-mediated chemoreflexes may also be involved in respiratory failure and death denoted in SIDS victims.
The carotid body and arousal in the fetus and neonate
2013, Respiratory Physiology and Neurobiology
Citation Excerpt :
When the arousal failure rate is examined, it is also clear that the level of hypoxia is also important. In one study, all infants failed to arouse when exposed to an FiO2 of 0.17 for 10 min (Brady and McCann, 1985) whereas in another all infants aroused when exposed to an FiO2 of 0.11 (van der Hal et al., 1985). Less is known about arousal to hypoxia during prematurity.
Arousal from sleep is a major defense mechanism in infants against hypoxia and/or hypercapnia. Arousal failure may be an important contributor to SIDS. Areas of the brainstem that have been found to be abnormal in a majority of SIDS infants are involved in the arousal process. Arousal is sleep state dependent, being depressed during AS in most mammals, but depressed during QS in human infants. Repeated exposure to hypoxia causes a progressive blunting of arousal that may involve medullary raphe GABAergic mechanisms. Whereas CB chemoreceptors contribute heavily to arousal in response to hypoxia, serotonergic central chemoreceptors have been implicated in the arousal response to CO₂. Pulmonary or chest wall mechanoreceptors also contribute to arousal in proportion to the ventilatory response and decreases in their input may contribute to depressed arousal during AS. Little is known about specific arousal pathways beyond the NTS. Whether CB chemoreceptor stimulation directly stimulates arousal centers or whether this is done indirectly through respiratory networks remains unknown. This review will focus on arousal in response to hypoxia and CO₂ in the fetus and newborn and will outline what we know (and do not know) about the involvement of the carotid body in this process.
Postnatal development of ventilatory and arousal responses to hypoxia in human infants
2005, Respiratory Physiology and Neurobiology
During the first year of life there is significant maturation of the hypoxic ventilatory response (HVR) in human infants. Compared with adults, healthy term infants have an immature HVR until at least 6 months of age. There are few studies in infants on the effects of sleep state on the HVR but these suggest that at early postnatal ages there is initially no sleep-state related difference; this is followed by a developmental trend towards the adult situation in which the response is depressed in REM sleep compared with NREM. Maternal cigarette smoking is a major risk factor for SIDS and the mechanism for this may involve a depressed HVR in the exposed infant; however studies are limited and the wide variation in cigarette consumption makes interpretation of results difficult. Arousal responses to hypoxia are of vital importance and a failure to arouse has been implicated in SIDS. Sleeping infants frequently fail to arouse in response to hypoxia in QS, whereas in AS they invariably arouse; furthermore arousal latency is longer in QS compared with AS. The oxygen saturation at which infants arouse is not different between sleep states, suggesting that desaturation is more rapid in AS. In QS younger infants arouse more readily than at older ages and arousal is depressed by maternal smoking. These findings suggest that depression of the arousal response to hypoxia in AS may have life-threatening consequences. Infants at increased risk for SIDS have been shown to have both depressed ventilatory and arousal responses to hypoxia, thus they may be at even greater risk.
Ventilatory responses preceding hypoxia-induced arousal in infants: Effects of sleep-state
2003, Respiratory Physiology and Neurobiology
Augmented ventilation and/or arousal in response to hypoxia are important protective mechanisms during sleep. We aimed to quantify ventilatory responses preceding hypoxia-induced arousal in infants and determine the effects of sleep-state. Fifteen term infants were studied at 2–4 weeks, 2–3 and 5–6 months of age. Ventilatory responses to 15% oxygen inhalation were expressed as breath-by-breath changes from normoxic levels and averaged over 5, 10 and 15 breaths preceding arousal. Minute ventilation preceding arousal significantly increased above normoxic levels only in AS at 5–6 months. There were no sleep-state related differences in minute ventilation, oxygen saturation or carbon dioxide levels (expressed as changes from normoxic values) at 5, 10 or 15 breaths preceding arousal. However, the rate of oxygen desaturation during hypoxia in AS was two to four times faster than in QS at each age. We conclude that the ventilatory responses preceding hypoxia-induced arousal do not differ between sleep-states and that arousal occurs at similar levels of desaturation in both states.
Modeling instability in the control system for human respiration: Applications to infant non-REM sleep
2000, Applied Mathematics and Computation
Mathematical models of the human respiratory control system have been developed since 1940 to study a wide range of features of this complex system. The phenomena collectively referred to as periodic breathing (including Cheyne–Stokes respiration and apneustic breathing) have important medical implications. The hypothesis that periodic breathing is the result of delay in the feedback signals to the respiratory control system has been studied since the work of F.S. Grodins, J. Gray, A.I. Norins, R.W. Jones [J. Appl. Physiol. 1 (1954) 283–308] in the early 1950s. The purpose of this paper is to extend the model presented by M.C.K. Khoo, R.E. Kronauer, K.P. Strohl, A.S. Slutsky [J. Appl. Physiol. 53 (3) (1982) 644–659] in 1991 to include variable delay in the feedback control loop and to study the phenomena of periodic breathing and apnea as they occur during quiet sleep in infant sleep respiration at around 4 months of age. The nonlinear mathematical model consists of a feedback control system of five delay differential equations. Numerical simulations are performed to study instabilities in the control system and the occurrence of periodic breathing and apnea in the above case which is a time frame of high incidence of sudden infant death syndrome (SIDS).
Obstructive sleep apnea in infants: Relation to family history of sudden infant death syndrome, apparent life-treatening events, and obstructive sleep apnea
2000, Journal of Pediatrics
Citation Excerpt :
It was speculated that the SIDS case may have been related to the OSA within the family. The potential link among SIDS, ALTE, and OSA in infants is unclear; however, an increased incidence of OSA in subsequent siblings of SIDS and infants with ALTE has been described previously.10,19 In addition, several studies have documented obstructive events during sleep in infants who subsequently became victims of SIDS.11-13
Objectives: Familial aggregation of obstructive sleep apnea (OSA) has been shown to be associated with sudden infant death syndrome (SIDS) and apparent life-threatening events (ALTE) in infants. We wanted to determine the incidence of OSA in infants with siblings with ALTE and SIDS referred to our sleep clinic and to ascertain whether OSA was more common in infants who have family histories of SIDS, ALTE, and OSA. Study design: We studied 125 infants (mean age, 11.5 ± 0.6 weeks) who were separated into 2 groups on the basis of their family history; polysomnographic studies were performed on each infant. Results: Twenty infants had a multiple family history of SIDS, ALTE, or OSA (group 1), whereas the other 105 infants (group 2) had only one case of SIDS or ALTE within the family and no known history of OSA. We found that 19 of 20 infants in group 1 had OSA, whereas only 31 of 105 infants in group 2 had OSA (chi-squared analysis, P <.05). The OSA recorded was more frequent in infants of group 1 than in those of group 2. Follow-up studies in some infants with OSA demonstrated a progressive decrease in OSA, which resolved between 6 and 12 months of age. Conclusion: We conclude that infants of families with multiple histories of SIDS, ALTE, and OSA are more likely to have OSA than infants of families with only one case of SIDS or ALTE. (J Pediatr 2000;136:318-23)

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^*

Supported by the Northern California Chapter of the National SIDS Foundation, the Strobel Medical Research Fund of the American Lung Association of San Francisco, and Grant HL24075 from the National Heart, Lung, and Blood Institute.

Presented in part at the Society for Pediatric Research, San Francisco, April 1981.

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Original articleControl of ventilation in subsequent siblings of victims of sudden infant death syndrome*

J Pediatr

J Pediatr

J Pediatr

Adv Pediatr

Epidemiology of sudden unexpected death in infants (“cot death”) in Northern Ireland

Br J Prev Soc Med

Periodic breathing in siblings of sudden infant death syndrome victims

Pediatrics

Sudden infant death syndrome: Sleep apnea and respiration in subsequent siblings

Pediatrics

Apnea, hypoxemia, and aborted sudden infant death syndrome

Pediatrics

The “structure” of alveolar Pco2 and Po2 during periodic breathing in preterm infants

Pediatr Res

A simple method for estimating the ventilatory response to CO2 in infants

Am Rev Respir dis

Original article
Control of ventilation in subsequent siblings of victims of sudden infant death syndrome*

The “structure” of alveolar Pco₂ and Po₂ during periodic breathing in preterm infants

A simple method for estimating the ventilatory response to CO₂ in infants