Never again will there be in it an infant who lives but a few days, or an old man who does not live out his years; he who dies at a hundred will be thought a mere youth; he who fails to reach a hundred will be considered accursed. (Isaiah 65:20)
Crib death or SIDS is defined as the sudden death of an infant which is unexpected from the history and not explained by post-mortem examination or review of the death scene [280]. Despite a wide spectrum of proposed theories, its etiology re- mains uncertain.
SIUD (sudden intrauterine unexplained death) is late fetal death before the com- plete expulsion or removal of the fetus from the mother [115]. Advances in maternal and fetal care have produced a significant reduction in perinatal mortality, but have not significantly changed the prevalence of SIUD. SIUD represents about one-half of perinatal mortalities, with a prevalence of 5–12 per 1,000 births [1, 253].
Knowledge of the ante- and post-mortem aspects of SIDS and SIUD is of interna- tional public concern, since its prevention would save a great number of potentially productive citizens. However, the classification criteria for SIDS and late fetal unex- plained death, the criteria for study and the methods of post-mortem examination are still too multifaceted and controversial. Nevertheless, in recent years, further progress in the diagnostic and scientific–instrumental procedures in SIDS and still- birth (“the last diagnosis”) have opened to the anatomic and forensic pathologist important new avenues for research in this area.
In order to obtain a correct epicritic diagnosis, anatomic and forensic patholo- gists are required to analyze, in as complete a way as possible, all morphological aspects of each SIDS as well as SIUD case. It is necessary that the pathologist applies new tools and methodologies of investigation to each case and acquires a deepen- ing knowledge in order to be able to interpret those signs that may be considered significant.
The observation of frequent anomalies, mostly congenital, of the autonomic ner- vous system structures in both SIDS [133, 163, 174] and SIUD [167, 171, 174] in- dicates a continuity between these two pathologies. Our research upholds a new approach to SIDS which involves the recognition of its analogical link with SIUD.
Indeed, early SIDS may well depend upon postnatal block of respiratory reflexes for fetal survival, involving the Kölliker-Fuse nucleus, or upon impaired development of central circuitry for respiratory reflexogenesis [79]. The acronym SIUD-SIDS un- derlines a possible common morphological substrate.
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V Concluding Remarks 120
Despite the nonspecificity of most of the cardiac conduction findings in SIDS, it is believed that they, in association with altered neurovegetative stimuli [163, 254], could underlie potentially malignant arrhythmias, providing morphological support for the cardiac concept of crib death [210]. In fact, the coincidence of other events (such as fever, vomiting or diarrhea and electrolytic imbalance) and active cell death in the conduction system seems to be crucial in causing crib death, whereas cell death and otherwise innocuous events are harmless if they occur separately. It is therefore important that we recognize and act upon as many of these contributing causes, including sleeping position, as possible.
Respiratory derangements in infants appear to be predominantly neurogenic in nature since our observations indicate that such derangements can mainly be ascribed to prenatal and/or congenital developmental abnormalities compromis- ing the reflexogenic neuroreceptors, whether central or peripheral. Their anatomi- cal location and their particular functional effects are likely to interfere with the rhythmic and biochemical modulation of breathing and heartbeat. But what makes the problem more complicated is the very dichotomous difference in reflexogenic physiology. This dichotomy may even became life-threatening during the pre- and postpartum periods. This may account for the fact that the problem of SIDS is still a perplexing and incompletely understood dilemma, and this has motivated our anatomopathological team to pursue coordinated investigations into the crib death infant side by side with the unexpected stillborn fetus in late pregnancy, such deaths being intimately related to the pathological/anatomical/physiological problem of vital oxygen supply before and after birth [171]. As the exact mechanism of cardio- pulmonary failure in SIDS and SIUD is still unknown, all autonomic related central nervous system regions and neurotransmitters are open to further investigation.
It is not up to the pathologist to draw conclusions about the clinical diagnosis and prevention of SIDS. Even though the pathologist is always involved too late to avoid the tragedy, he/she yet can underline the need for a thorough post-mortem examination of every SIDS victim.
The search will be continued in the infant and fetal cardiac conduction and au- tonomic nervous systems. To supplement the clinicophysiological findings in in- fants and term fetuses dying suddenly and unexpectedly, a deeper insight is needed from microscopic research (histology, ultrastructure, immunohistochemistry), the extreme specialization of which requires centers with the necessary expertise [174, 210].
The necessary cardiac and neuropathological studies seeking to identify the mor- phological substrate in crib death requires the examination of a large number of cases using homogeneous and standardized criteria. A complete examination of the cardiac conduction and nervous systems in serial sections allows an objective dimen- sional and architectural evaluation of all the inherent pertinent anatomic areas [174, 210, 214]. This requires many sections and the systematic application of appropri- ate histological techniques (e.g. H&E, Klüver-Barrera, and trichromic Heidenhain stains), histochemical techniques (e.g. Glees-Marsland for neurons and neurofibrils, Bielschowsky for axons and dendrites, Mallory’s PTAH for glia), and immunohisto- chemical techniques (to study apoptosis, various neuroreceptor structures, the ex-
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pression of specific genes, etc.). Moreover, such complete examination of the cardiac conduction system requires the availability of properly trained histotechnicians. It should also be underlined that, due to the architectural variability of the conduction system and brainstem, wrong indications on the involved structures and extension can result from the examination of single and casually chosen sections [174, 210].
I am therefore convinced that the autopsy protocol for SIDS victims, as already in- ternationally approved [30, 125], should always include examination of the cardiac conduction and central, peripheral and autonomic nervous systems according to the guidelines described in this work and available on the web site of the Institute of Pathology, University of Milan (http://users.unimi.it/~pathol/pathol_e.html).
