What is it about?
The study is about the analysis of serotonin receptor-related pathology in the brainstem of infants dying of the Sudden Infant Death Syndrome (SIDS) in high risk, impoverished populations in the Cape Coloured in South Africa and the American Indians in the Northern Plains, US. SIDS is defined as the sudden and unexpected death of an apparently healthy infant in the first postnatal year, which remains unexplained after a complete autopsy and forensic investigation. Although SIDS is a leading cause of postneonatal infant death worldwide, the disorder is disproportionately represented in socioeconomically disadvantaged populations. Risk factors for SIDS include maternal drinking and smoking during pregnancy, prematurity, and low socioeconomic variables. Emerging autopsy data in SIDS compared to controls provide tissue-based evidence that a major subset of SIDS is due to a defect in the brainstem serotonin system mediating cardiorespiratory integration and arousal during sleep. Serotonin is a major neurotransmitter that plays an essential role in brainstem-mediated protective responses to life-threatening challenges, e.g., decreased oxygen (hypoxia), in compromised sleep, such as the prone sleep position. The newly released PLOS One paper represents the prospective multidisciplinary and international study, called the Safe Passage Study (SPS), of serotonergic receptor binding in the brainstem of SIDS infants. In the SPS, approximately 12,000 fetus-infant dyads were prospectively followed from socioeconomically improvised populations at especially high risk for SIDS with adverse maternal, infant, and environmental risk factors, including maternal drinking and smoking. We report that serotonin receptor pathology is present in the brainstem in the SIDS infants that closely reproduces similar findings in US cohorts. In the SPS, SIDS was significantly associated with indices of stress and low socio-economic status (SES) compared to non-SIDS controls, e.g., overcrowding, poor housing, and no phone (proxy for poverty), especially in SIDS infants born prematurely.
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Why is it important?
These new findings reinforce the concept that SIDS is a manifestation of one or more disorders of serotonin, i.e., serotonopathies, irrespective of the specific population in which it occurs. Nevertheless, individual features of the serotonopathy were different between the SPS and US cohorts, perhaps because the incidence of prematurity was higher in the SPS in South Africa. While unexpected, these differences may provide important clues regarding the role of serotonergic defects and a deflection in its developmental trajectory in the pathogenesis of SIDS. This study suggests that the serotonergic defect in SIDS infants impinges on brainstem homeostasis during a critical developmental period in infancy, including in populations experiencing high maternal and infantile stress, contributing to sleep-related sudden death.
Perspectives
The ubiquity of social stressors and poverty in the SPS mandates a rethinking of our models of the pathogenesis of SIDS. Stress is universal and exists in various forms, extending from the Cape Coloured, low-income populations in South Africa to low- and middle-income communities in the United States. Yet, social deprivation more often leads to additive, prolonged, and/or severe stress. The cumulative effects of harmful social risk factors potentially account for the increase in SIDS in socioeconomically disadvantaged populations. The multidisciplinary findings of the SPS suggest several broad areas for ongoing and future research in SIDS. Of paramount importance is the generation of new knowledge regarding the effects of maternal stress across multiple income brackets, on infant health and the risk for SIDS. We need clarification on how stress impacts the development and fetal programming of the medullary serotonergic system, focusing on all income brackets. We were honored to have participated with the Cape Coloured and American Indian communities in this significant and novel study in SIDS. The courage and humanism of the communities participating in this autopsy study of infants toward scientific advancement were profound and warrant the never-ending appreciation of SIDS communities everywhere.
Robin Haynes
Boston Children's Hospital
Read the Original
This page is a summary of: Serotonergic receptor binding in the brainstem in the Sudden Infant Death Syndrome in a high-risk population, PLOS One, September 2025, PLOS,
DOI: 10.1371/journal.pone.0330940.
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