Sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death syndrome (SIUDS)

Sudden intrauterine unexpected fetal death syndrome (SIUDS) and sudden infant death syndrome (SIDS) represent facets of a multifactorial problem that has not yet found a univocal approach on the clinical plane. The fundamental component is pathological anatomy.

SIDS is defined as the sudden death of an infant under one year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and a review of the clinical history. The SIDS strikes one infant every 750-1,000 live births, being the most frequent cause of demise within the first year of life. As reported by WHO, in the Western Countries the SIUDS is about ten-fold more frequent than SIDS.

The inherent emotional consequences among families are devastating and the cost of adaptation therapies is particularly heavy, in addition to the damage due to the loss of many potentially productive individuals. The need to submit the young victims to necropsy procedures is unanimously recognized and the chance of preventing SIUDS and SIDS relies mainly on a better knowledge of the underlying alterations of the autonomic nervous system and etiopathogenetic mechanisms. Similarly, for diagnostic purposes, an accurate and careful examination of the circumstantial and environmental situation is extremely important.

Our studies have revealed frequent morphological alterations of the autonomic nervous system centers checking the vital functions and/or of the cardiac conduction system in victims of SIUDS and SIDS. These alterations are mainly of congenital nature and therefore represent a common morphological substrate in both fetal and infant sudden death.

Alterations of the autonomic nervous system

Brainstem and cerebellum developmental alterations are frequently observed in both SIUDS and SIDS. These defects are more widespread and more intensive as earlier is the death.

Frequent is the hypoplasia of the arcuate nucleus, a component of the ventral surface of the medulla oblongata which partecipates in chemoreception (1-4). This hypoplasia is associated in sudden intra-partum deaths to hypodevelopment of the Kölliker-Fuse nucleus, that has an important function during intrauterine life inhibiting the response of central and peripheral chemoreceptors, and therefore any respiratory reflex. After birth, the Kölliker-Fuse becomes active as a respiratory center (5,6). The agenesis/hypoplasia of the parafacial nucleus, a "pre-inspiratory" center, is frequently observed in unexpected fetal deaths, in association with the hypoplasia of the arcuate nucleus (7).

Delayed maturation of the cortex layers and of the deep nuclei of the cerbellum (8,9), and the immaturity with decreased number of pyramidal cells in the cerebral cortex (prevalently in the prefrontal area) are signigicant findings. (10).

Among the functional alterations, defective expression of neurotransmitters are frequently observed in the brainstem, particularly of catecholamines in the locus coeruleus (11), and of the somatostatin in the hypoglossus nucleus (12), besides altered apoptotic programs in the cerebellum (8,9).

Alterations of the cardiac conduction system

The finding of accessory AV communications, particularly nodo-fascicular ventricular bundles (Mahaim fibers) is frequent in perinatal unexplained loss and SIDS. Accessory AV communications of Kent and James type are uncommon (13,14). These lesions have been attributed to the variable outcome of a “resorptive degeneration” process that normally reshapes the functional pathways in fetal and early neonatal period. The accessory pathways represent the main cause of perinatal reentrant arrhythmias and also of the sudden death of the young, especially of the sportsman and of the athlete, often coincident with physical and/or psychic stress in competitive activities.

Risk factors

Among the causes which trigger unexplained death, exogenous risk factors that alter the intrauterine environment are relevant, such as tobacco smoking, drug abuse, maternal alcoholism and air pollution (15,16). Such toxic agents are responsible of deep changes in blood-brain barrier which enhance their penetration into the brain parenchyma (17,18). Besides they are able to alter the structure of genes involved in the development of the nervous system, causing mutations, or to affect their expression leading to morphological and functional alterations of the vital nervous centers (19).


The scientific-financial advantages deriving from a better understanding of SIDS and late unexpected fetal death are certainly significant. Indeed, the identification of the pathogenetic mechanisms of these deaths can be the premise for understanding many diseases of adulthood and even the elderly. Numerous postnatal disorders of fetal origin are already been identified, such as defective maturation of the lung (20), substratum of frequent inflammatory and allergic respiratory diseases in infants, and developmental abnormalities of the cerebral cortex, plausible pathogenesis of behavioral troubles, attention and memory disorders in infants. Intersting is the identification of the fetal origin of the atherosclerosis , frequently due to cigarette smoke absorption (21 -23).


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