SIDS-CDF hypothesis revisited: explaining hypoxia in SIDS

Dear Editor, The sudden infant death syndrome (SIDS)–critical diaphragm failure (CDF) hypothesis (1,2) continues to attract attention 5 years after the publication of the original article in this journal, and several colleagues have contributed perspectives and insights to the hypothesis (3–6). The basic premise of the SIDS-CDF hypothesis is that the diaphragm is a vital organ that must continuously generate adequate force to maintain ventilation and that critical diaphragm failure is a terminal event and the cause of death in SIDS. Respiratory failure is a common cause of death of adults with compromised diaphragm function, and key SIDS factors have been shown either to reduce the diaphragm force-generating capacity or to increase the respiratory workload of the diaphragm. Both can cause hypoxia that can in turn further compromise diaphragm function and initiate a self-reinforcing feedback loop characterized by: weakened diaphragm – hypoxia – weakened diaphragm (Figure 1). Various types of non-lethal infections are commonly observed in SIDS victims, and a large body of research shows that diverse infections can cause a rapid and significant reduction in the force-generating capacity of the diaphragm. The prone sleeping position is another well-known risk factor for SIDS and one that has been especially difficult to explain in the context of SIDS etiology. However, clinical studies in infants show that in prone position the respiratory workload of the diaphragm is significantly increased. SIDS typically occurs during deep sleep when the supportive respiratory muscles are partially or totally inactivated, there-with increasing the respiratory load on the diaphragm. Gestational prematurity and low birth weight are risk factors for SIDS, and both affect the developmental and structural maturity and the force-generating capacity of the diaphragm , which achieves structural maturity after 6 months. The non-monotonic death rate in SIDS-CDF has been another enigmatic characteristic of the syndrome. The SIDS-CDF hypothesis posits that this is due to the passive immune protection provided by maternal antibodies during the first month of life when the respiratory muscles are most vulnerable. However, the passive immune protection quickly wanes 1 month post partum, especially in the absence of breast-feeding. A considerable amount of research has been conducted on disturbances in the seroto-nergic system of SIDS victims, and earlier we discussed how the SIDS-CDF hypothesis would explain the role of the tryp-tophan–serotonin–melatonin pathway in the etiology of SIDS (1). Altitude has also been shown to be an independent risk factor for SIDS (7) and …