Potential Asphyxia and Brainstem Abnormalities in Sudden and Unexpected Death in Infants

Abstract

WHAT'S KNOWN ON THIS SUBJECT: Certain characteristics of the sleep environment increase the risk for sleep-related, sudden, and unexplained infant death. These characteristics have the potential to generate asphyxia. The relationship between the deaths occurring in these environments and neurochemical abnormalities in the brainstem that may impair protective responses to asphyxia is unknown. WHAT THIS STUDY ADDS:We report neurochemical brainstem abnormalities underlying cases of sudden infant death that are associated with and without potential asphyxial situations in the sleep environment at death. The means to detect and treat these abnormalities in infants at risk are needed. abstract OBJECTIVE: Sudden and unexplained death is a leading cause of infant mortality.Certain characteristics of the sleep environment increase the risk for sleep-related sudden and unexplained infant death. These characteristics have the potential to generate asphyxial conditions. We tested the hypothesis that infants may be exposed to differing degrees of asphyxia in sleep environments, such that vulnerable infants with a severe underlying brainstem deficiency in serotonergic, g-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (eg, supine), whereas infants with intermediate or borderline brainstem deficiencies require asphyxial stressors to precipitate death. METHODS:We classified cases of sudden infant death into categories relative to a "potential asphyxia" schema in a cohort autopsied at the San Diego County Medical Examiner' s Office. Controls were infants who died with known causes of death established at autopsy. Analysis of covariance tested for differences between groups. RESULTS:Medullary neurochemical abnormalities were present in both infants dying suddenly in circumstances consistent with asphyxia and infants dying suddenly without obvious asphyxia-generating circumstances. There were no differences in the mean neurochemical measures between these 2 groups, although mean measures were both significantly lower (P , .05) than those of controls dying of known causes. CONCLUSIONS:We found no direct relationship between the presence of potentially asphyxia conditions in the sleep environment and brainstem abnormalities in infants dying suddenly and unexpectedly. Brainstem abnormalities were associated with both asphyxia-generating and non-asphyxia generating conditions. Heeding safe sleep messages is essential for all infants, especially given our current inability to detect underlying vulnerabilities. Pediatrics 2013;132:e1616-e1625 AUTHORS:

Proposal for mechanisms of protection of supine sleep against sudden infant death syndrome: an integrated mechanism review

“…In 70% of SIDS cases, the abnormality or defect involves serotonin (5-HT) metabolism (5), ~10-20% have cardiac ion channelopathy defects (7), and other more rare defects have been found. No defects have been reported in control cases (5,6). Secondly, there is a "vulnerable period", reflecting the epidemiological peak of cases in the 2nd and 3rd month of life.…”

“…Kinney and Thach emphasize the importance of this in stating that according to the Triple Risk Model (5), SIDS occurs "only in infants with an underlying abnormality" (page 797). This applies regardless of safe or unsafe potentially asphyxiating sleeping environment (6). In 70% of SIDS cases, the abnormality or defect involves serotonin (5-HT) metabolism (5), ~10-20% have cardiac ion channelopathy defects (7), and other more rare defects have been found.…”

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

“…SIDS mostly occurs during sleep, leading to the proposal that SIDS infants have dysfunctional maturation of sleep-and respiratory-related control [97]. In support of this hypothesis, multiple neurochemical abnormalities have been found in SIDS victims, in areas associated with sleep regulation, arousal and physiological responses to hypoxic and/or hypercapnic stressors [17,27,54,65,81,82]. Hypoxia (and/or hypercapnia) has been shown to be associated with co-sleeping or a prone sleeping position; known risk factors for SIDS [43,48].…”

Classification System for the Sudden Unexpected Infant Death Case Registry and its Application

“…2 Differentiating between these causes, especially SIDS and infant suffocation, can be challenging, because SUID case investigations are not always conducted in a standard manner, and universally accepted definitions or biological markers to distinguish SIDS from suffocation do not exist. 3,4 To complicate matters, both SIDS and accidental sleep-related suffocations are frequently unwitnessed and occur in unsafe sleeping environments. SIDS is reserved for deaths that remain unexplained after a thorough case investigation.…”