Potential asphyxia and brainstem abnormalities in sudden and unexpected death in infants

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, γ-aminobutyric acid-ergic, or 14-3-3 transduction proteins succumb even without asphyxial triggers (e.g., 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.

Keywords: 14-3-3 proteins; GABA receptors; bed-sharing; prone sleep; serotonin; sudden infant death syndrome.

FIGURE 1

Diagram of the potential interrelationships of sudden infant death, brainstem pathology, and asphyxia. Vulnerable infants with a severe underlying brainstem deficiency succumb even without asphyxia (Group A), whereas infants with intermediate deficiencies require asphyxial stressors to precipitate death (Group B). All infants die when the asphyxia is severe.

FIGURE 2

A, Serotonin_1A binding (fmol/mg) in NTS is different between Groups A and B (n = 14, n = 34) and Group F (n = 7) (P < .001) but not between Groups A and B. B, 14-3-3γ level (percentage standard) in GC is different between Groups A and B (n = 10, n = 19) and Group F (n = 7) (P = .001) but not between Groups A and B.

FIGURE 3

There is a positive association (P = .004) between serotonin_1A binding (in fmol/mg tissue) and the number of extrinsic risk factors in the dorsal accessory nucleus (component of olivary complex involved in motor control) in cases with sudden, unexpected, and unexplained death (Groups A and Group B combined [n = 19]). These data suggest that the higher the serotonin_1A binding, the less compromised the brainstem homeostatic system is, and the more exogenous triggers are needed to precipitate death.