A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

Several theories of the underlying mechanisms of Sudden Infant Death Syndrome (SIDS) have been proposed. These theories have born relatively narrow beach-head research programs attracting generous research funding sustained for many years at expense to the public purse. This perspective endeavors to critically examine the evidence and bases of these theories and determine their plausibility; and questions whether or not a safe and reasoned hypothesis lies at their foundation. The Opinion sets specific criteria by asking the following questions: 1. Does the hypothesis take into account the key pathological findings in SIDS? 2. Is the hypothesis congruent with the key epidemiological risk factors? 3. Does it link 1 and 2? Falling short of any one of these answers, by inference, would imply insufficient grounds for a sustainable hypothesis. Some of the hypotheses overlap, for instance, notional respiratory failure may encompass apnea, prone sleep position, and asphyxia which may be seen to be linked to co-sleeping. For the purposes of this paper, each element will be assessed on the above criteria

Pulmonary arterial medial smooth muscle thickness in sudden infant death syndrome: an analysis of subsets of 73 cases

Previous studies addressing pulmonary artery morphology have compared cases of sudden infant death syndrome (SIDS) to controls but none have compared demographic profiles, exposure to potentially hypoxic risk factors and other pathologic variables in SIDS cases grouped according to pulmonary artery medial smooth muscle thickness. Aims: To compare the relative medial thickness (RMT) in alveolar wall arteries (AW) in SIDS cases with that in age-matched controls and 2. Compare demographic, clinical, and pathologic characteristics among three subsets of SIDS cases based upon alveolar wall (AW) RMT. Retrospective morphometric planimetry of all muscularized arteries in standardized right apical lung sections in 73 SIDS cases divided into three groups based on increasing AW RMT as well as 19 controls age-matched to 19 of the SIDS cases. SIDS and age-matched control cases did not differ with respect to AW RMT or other demographic variables. The SIDS group with the thickest AW RMT had significantly more males and premature birth than the other groups, but the groups did not differ for known clinical risk factors that would potentially expose them to hypoxia. Pathologic variables, including pulmonary inflammation, gastric aspiration, intra-alveolar siderophages, cardiac valve circumferences, and heart and liver weights, were not different between groups. Age was not significantly correlated with RMT of alveolar wall and pre-acinar arteries but was significant at p = .018 for small intra-acinar arteries. The groups were different for RMT of small pre-acinar and intra-acinar arteries, which increased with increasing AW RMT. Statistical differences should not necessarily be equated with clinical importance, however future research incorporating more quantified historical data is recommended

Genes Expressed in Specific Areas of the Human Fetal Cerebral Cortex Display Distinct Patterns of Evolution

The developmental mechanisms through which the cerebral cortex increased in size and complexity during primate evolution are essentially unknown. To uncover genetic networks active in the developing cerebral cortex, we combined three-dimensional reconstruction of human fetal brains at midgestation and whole genome expression profiling. This novel approach enabled transcriptional characterization of neurons from accurately defined cortical regions containing presumptive Broca and Wernicke language areas, as well as surrounding associative areas. We identified hundreds of genes displaying differential expression between the two regions, but no significant difference in gene expression between left and right hemispheres. Validation by qRTPCR and in situ hybridization confirmed the robustness of our approach and revealed novel patterns of area- and layer-specific expression throughout the developing cortex. Genes differentially expressed between cortical areas were significantly associated with fast-evolving non-coding sequences harboring human-specific substitutions that could lead to divergence in their repertoires of transcription factor binding sites. Strikingly, while some of these sequences were accelerated in the human lineage only, many others were accelerated in chimpanzee and/or mouse lineages, indicating that genes important for cortical development may be particularly prone to changes in transcriptional regulation across mammals. Genes differentially expressed between cortical regions were also enriched for transcriptional targets of FoxP2, a key gene for the acquisition of language abilities in humans. Our findings point to a subset of genes with a unique combination of cortical areal expression and evolutionary patterns, suggesting that they play important roles in the transcriptional network underlying human-specific neural traits

SIDS: more facts and controversies

A more robust theory of the causation of sudden infant death syndrome (SIDS) is needed. The asphyxial theory of SIDS, which encompasses the prone sleeping position, relies on contradictory pathological evidence and fails to explain infants with SIDS who are found in the supine or lateral position. Many of the risk factors for SIDS point to an infective cause. The relative risks of these infection-related factors differ from study to study, as does the relative risk of prone sleeping position. I present the case for an infection model for SIDS causation, which has largely been neglected by mainstream SIDS researchers