Brainstem mechanisms underlying the sudden infant death syndrome: evidence from human pathologic studies

Dev Psychobiol. 2009 Apr;51(3):223-33. doi: 10.1002/dev.20367.


The brainstem hypothesis is one of the leading hypotheses concerning the sudden infant death syndrome (SIDS). It states that SIDS, or an important subset of SIDS, is due to abnormal brainstem mechanisms in the control of respiration, chemosensitivity, autonomic regulation, and/or arousal which impairs the infant's response to life-threatening, but often occurring, stressors during sleep (e.g., hypoxia, hypercarbia, asphyxia, hyperthermia) and leads to sudden death in a vulnerable developmental period. In this review, we summarize neuropathologic evidence from SIDS cases that support this hypothesis, beginning with the seminal report of subtle brainstem gliosis three decades ago. We focus upon recent neurochemical studies in our laboratory concerning the neurotransmitter serotonin (5-HT) and its key role in mediating protective responses to homeostatic stressors via medullary circuits. The possible fetal origin of brainstem defects in SIDS is reviewed, including evidence for adverse effects of prenatal exposure to maternal cigarette smoking and alcohol upon the postnatal development of human brainstem 5-HT pathways.

Publication types

  • Review

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / pathology
  • Arcuate Nucleus of Hypothalamus / pathology
  • Arcuate Nucleus of Hypothalamus / physiopathology
  • Autonomic Nervous System / pathology
  • Autonomic Nervous System / physiopathology
  • Brain Stem / pathology*
  • Brain Stem / physiopathology
  • Female
  • Gliosis / pathology
  • Gliosis / physiopathology
  • Homeostasis / physiology
  • Humans
  • Infant
  • Infant, Newborn
  • Medulla Oblongata / pathology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology
  • Prenatal Exposure Delayed Effects / physiopathology
  • Prone Position / physiology
  • Raphe Nuclei / pathology
  • Raphe Nuclei / physiopathology
  • Receptors, Serotonin / physiology
  • Risk Factors
  • Serotonin / physiology
  • Sudden Infant Death / etiology
  • Sudden Infant Death / pathology*


  • Receptors, Serotonin
  • Serotonin