Unexplained stillbirth versus SIDS: Common congenital diseases of the autonomic nervous system—pathology and nosology

https://doi.org/10.1016/j.earlhumdev.2010.12.009Get rights and content

Abstract

Objective

To contribute to a more balanced assessment of the morphological substrates underlying unexplained perinatal death and SIDS.

Methods

In-depth histological, immunohistochemical and genetic examinations were performed on the autonomic nervous and cardiac conduction systems in 95 unexpected perinatal deaths, 140 SIDS and 78 controls (44 infants and 34 perinatal death victims).

Results

The study revealed the localization and the nature of a variety of specific congenital abnormalities of the autonomic nervous system, central and peripheral, and of the cardiac conduction system that represent the morphological substrates of the pathophysiological mechanism of sudden fetal death and SIDS.

Conclusions

The observation of similar anomalies of the autonomic nervous and the cardiac conduction systems in both unexplained perinatal deaths and SIDS indicates their common congenital nature. Therefore, the definitions of these deaths, currently nosographically distinct, should be unified.

Introduction

Perinatal loss and the Sudden Infant Death Syndrome (SIDS) are still an unresolved, major social and health problem today [1].

This paper will tackle unexplained stillbirth and early neonatal deaths, as well as the SIDS, which are apparently accounted for by exclusively or preeminently neurovegetative abnormalities which were not suspected during prenatal clinical examinations. So far, only a few studies have made a close examination of the nervous system, although abnormalities of this system are obviously extremely relevant to any analysis aiming to gain a better understanding of unexplained death during gestation and in early infancy. Thus, today's basic information in this field is still inadequate [2], [3], [4], [5].

To contribute to a more balanced assessment of the morphological substrates underlying unexplained perinatal death and SIDS, the present article will focus upon the multifaceted involvement of the central and peripheral autonomic nervous system, as well as the cardiac conduction system, subject to autonomic nervous system control.

The results presented herein, obtained from in-depth histological examinations of the autonomic nervous and cardiac conduction systems in a very wide sample of unexpected perinatal deaths (65 stillbirths and 30 early neonatal deaths), SIDS (140 victims) and 78 controls (44 infants and 34 perinatal death victims), show similar alterations in unexplained death victims, indicating their common congenital nature and then that unexplained fetal and early neonatal death should not be regarded as distinct from the SIDS.

Section snippets

Study subjects

The study included 313 subjects. This was a selected set of cases, sent to our Research Center according to the application of the guidelines recognized by Italian law n.31 “Regulations for Diagnostic Post Mortem Investigation in Victims of SIDS and Unexpected Fetal Death” over a 9-year period (2000–2009). This law decrees that all infants suspected of SIDS who died suddenly in Italian regions within the first year of age, as well as all fresh fetuses who died after the 25th week of gestation

Results

We firstly analyzed the distribution of different information extracted from the data bank related to 129 perinatal deaths (65 sudden fetal deaths, 30 sudden early neonatal deaths and 34 control perinatal deaths) and 184 infant deaths (140 SIDS and 44 controls) to evaluate the potential risk factors. Table 1, Table 2 display the rates and percentage distributions of these variables related to perinatal and infant deaths, respectively. Significant correlations (p < 0.05) were observed between

Discussion

The problem of unexpected perinatal loss and the SIDS at post-mortem examination is a Gordian knot that needs to be untied, not cut. Pathologic data on the SIDS, beginning from the so-called thymus-death, a possible lethal thymus-lymphatic state marked by gland enlargement, occasionally related to stenotic respiratory diseases, has been accumulating since 1800. From the 1970s, inflammatory respiratory diseases, namely pneumonia, bronchiolitis, tracheo-bronchitis, from bacterial or viral causes,

Neuropathology of stillbirth versus SIDS

While the data reported in the literature in unexpected perinatal loss and SIDS refer to non-specific alterations of the autonomic nervous system, our investigations in this field have contributed to reveal the localization and the nature of a variety of specific neuronal congenital anomalies, particularly of the brainstem, spinal cord and cerebellum.

From the overall analysis of the neuropathologic results, the following prominent data emerged:

  • -

    in 92% of sudden perinatal and infant deaths one or

Cardiovascular pathology of stillbirth versus SIDS

Unexpected perinatal loss and the SIDS are also significantly associated with developmental disturbances of the cardiovascular system.

Sudden death can occur due to changes in the cardiac action, mostly manifesting with arrhythmias, that may be caused by microscopic malformations of the conduction system. The finding of accessory AV communications, particularly nodo-fascicular ventricular bundles (Mahaim fibers) is quite frequent in perinatal unexplained loss, as also in SIDS (but a

Exogenous-environmental risk factors

Among the causes which trigger and/or promote unexplained death, exogenous risk factors that alter the intrauterine environment are relevant,such as infections (pulmonary virosis with respiratory impairment), familial tobacco smoking, maternal drug abuse, maternal alcoholism and likely atmospheric pollution.

In particular, exposure to tobacco smoke in utero is the most important preventable risk factor. Smoking, by affecting fetal oxygenation, causes vasoconstriction and reduces the fetal blood

Nosology

The observation of similar anomalies of the autonomic nervous system and of the cardiac conduction system in both unexplained perinatal deaths and SIDS indicates their common congenital nature and supports the statement in the National Institute of Child Health and Development SIDS Strategic Plan 2000 that “SIDS is a developmental disorder. Its origins are during fetal development” [31]. These observations supported a new holistic approach to the SIDS, analogically linked with unexpected

Conflict of interest statement

All Authors declare that they have no conflicts of interest, financial or otherwise to declare.

Funding

No financial assistance was received to support the study.

Acknowledgments

The authors thank Dr. Graziella Alfonsi for her precious technical assistance and Dr. Mary Victoria Candace Pragnell, B.A. for English language assistance.

References (32)

  • L. Matturri et al.

    Guidelines for neuropathologic diagnostics of perinatal unexpected loss and sudden infant death sindrome (SIDS). A technical protocol

    Virchows Arch

    (2008)
  • D.E. Weese-Mayer et al.

    Association of the serotonin transporter gene with the Sudden Infant Death Syndrome: a haplotype analysis

    Am J Med Genet

    (2003)
  • L. Matturri et al.

    Italian National Data Bank of Stillbirth versus SIDS

    Public Health Rep

    (2010)
  • Matturri et al.

    Severe hypoplasia of medullary arcuate nucleus: quantitative analysis in sudden infant death syndrome

    Acta Neuropathol (Berl)

    (2000)
  • Matturri et al.

    Hypoplasia of medullary arcuate nucleus in unexpected late fetal death (stillborn infants): a pathologic study

    Pediatrics

    (2002)
  • A.M. Lavezzi et al.

    Functional neuroanatomy of the human pre-Bötzinger complex with particular reference to sudden unexplained perinatal and infant death

    Neuropathology

    (2008)
    • View full text
    Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.