Unexplained Infant Death Research Articles

Forensic Pathology and Epidemiology, Public Health and Population-Based Research

Forensic pathology can play a pivotal role in safeguarding public health. While medicolegal death investigation focuses on certifying cause and manner of individual deaths, taken in aggregate this information provides a powerful tool for epidemiologic research. The published literature provides numerous examples of the utility of forensic pathology in public health research, from describing trends in substance abuse deaths to reducing occupational fatalities and identifying unusual infectious disease deaths. Medical examiner and coroner (ME/C) offices contribute to public health research by participating in surveillance systems, including those for sudden unexplained infant deaths and violent deaths, and by alerting public health agencies to emerging threats. Accessing and utilizing ME/C data for epidemiologic research can be challenging, given the wide variation in types of jurisdictions and the availability of electronic data, but the rewards for researchers justify the endeavor. Mutually beneficial relationships can develop between epidemiologists and ME/Cs, improving both public health and medicolegal death investigation.

Neuropathology of the area postrema in sudden intrauterine and infant death syndromes related to tobacco smoke exposure

The area postrema is a densely vascularized small protuberance at the inferoposterior limit of the fourth ventricle, outside of the blood–brain barrier. This structure, besides to induce emetic reflex in the presence of noxious chemical stimulation, has a multifunctional integrative capacity to send major and minor efferents to a variety of brain centers particularly involved in autonomic control of the cardiovascular and respiratory activities.In this study we aimed to focus on the area postrema, which is so far little studied in humans, in a large sample of subjects aged from 25 gestational weeks to 10 postnatal months, who died of unknown (sudden unexplained perinatal and infant deaths) and known causes (controls). Besides we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant deaths and maternal smoking.By the application of morphological and immunohistochemical methods, we observed a significantly high incidence of alterations of the area postrema in fetal and infant victims of sudden death as compared with age-matched controls. These pathological findings, including hypoplasia, lack of vascularization, cystic formations and reactive gliosis, were related to maternal smoking. We hypothesize that components from maternal cigarette smoke, particularly in pregnancy, could affect neurons of the area postrema connected with specific nervous centers involved in the control of vital functions.In conclusion, we suggest that the area postrema should be in depth examined particularly in victims of sudden fetal or infant death with smoker mothers.

Challenges of genetic testing in adolescents with cardiac arrhythmia syndromes

The ability to sequence individual genomes is leading to the identification of an increasing number of genetic risk factors for serious diseases. Knowledge of these risk factors can often provide...

Masquerade of a Silent Killer

Masquerade of a Silent Killer

Brain iron accumulation in unexplained fetal and infant death victims with smoker mothers--the possible involvement of maternal methemoglobinemia.

BackgroundIron is involved in important vital functions as an essential component of the oxygen-transporting heme mechanism. In this study we aimed to evaluate whether oxidative metabolites from maternal cigarette smoke could affect iron homeostasis in the brain of victims of sudden unexplained fetal and infant death, maybe through the induction of maternal hemoglobin damage, such as in case of methemoglobinemia.MethodsHistochemical investigations by Prussian blue reaction were made on brain nonheme ferric iron deposits, gaining detailed data on their localization in the brainstem and cerebellum of victims of sudden death and controls. The Gless and Marsland's modification of Bielschowsky's was used to identify neuronal cell bodies and neurofilaments.ResultsOur approach highlighted accumulations of blue granulations, indicative of iron positive reactions, in the brainstem and cerebellum of 33% of victims of sudden death and in none of the control group. The modified Bielschowsky's method confirmed that the cells with iron accumulations were neuronal cells.ConclusionsWe propose that the free iron deposition in the brain of sudden fetal and infant death victims could be a catabolic product of maternal methemoglobinemia, a biomarker of oxidative stress likely due to nicotine absorption.

The Death of SIDS

Sudden Infant Death Syndrome (SIDS) is an overly broad classification bin for sudden unexplained infant deaths. SIDS has become a “diagnostic” phrase that encompasses unidentified, disease-related causes of death, deaths likely due to accidental asphyxia, and possibly unrecognized homicides. There is a prevailing false concept that SIDS is a “real” and discrete diagnostic entity rather than a phrase that signifies an inability to state why an infant has died. This has been perpetuated by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), which recognizes SIDS as a “cause” of death. We propose simplified, unambiguous language for the death certificate in cases of sudden unexplained infant death. We propose changes to ICD-10 nomenclature and vital statistics tabulation practices of the National Center for Health Statistics (a division of the Centers for Disease Control and Prevention) to end the use of SIDS as a diagnosis.

Postmortem gastric perforation (gastromalacia) mimicking abusive injury in sudden unexplained infant death

Gastromalacia is a postmortem autolysis of gastric tissue that can culminate in gastric perforation. This entity is well-recognized by pathologists but is rarely encountered by diagnostic radiologists. We are reporting a case of sudden unexplained infant death (SUID) in which a boy was found to have pneumoperitoneum on postmortem radiographs, subsequently proved by autopsy to be caused by postmortem gastric perforation resulting from gastromalacia. It is important for radiologists to recognize this entity so as not to mistake it for bowel perforation caused by antemortem pathology, including inflicted trauma.

Axonal Injury in Young Pediatric Head Trauma: A Comparison Study of β-amyloid Precursor Protein (β-APP) Immunohistochemical Staining in Traumatic and Nontraumatic Deaths*

We tested the independent utility of β-amyloid precursor protein (β-APP) immunohistochemical staining as evidence of brain trauma in the deaths of young children. Blinded reviewers retrospectively reviewed immunostained brain tissues from homicidal deaths, age-matched control cases without evidence of trauma, as well as cases of sudden infant death syndrome (SIDS). The reviewers correctly identified five of the seven cases with documented inflicted head trauma. However, one of seven age-matched control cases and one of 10 SIDS/sudden unexplained death in infancy (SUDI) cases demonstrated staining patterns similar to those seen in cases of inflicted trauma. We discuss these cases and the circumstances surrounding them with the intent to explain the difficulties associated with immunohistological interpretation of axonal injury. Although the utility of β-APP is quite powerful if not confounded by global hypoxic-ischemic injury, ultimately, β-APP studies should be only one piece of information in the determination of cause and manner of death.

Use of child death review to inform sudden unexplained infant deaths occurring in a large urban setting

ObjectiveTo illustrate the benefits and utility of the child death review (CDR) reporting system when examining risk factors associated with infant death occurring within two subgroups of sudden unexpected infant...

Variation and uncertainties in the classification of sudden unexpected infant deaths among paediatric pathologists in the UK: findings of a National Delphi Study

AimsPresently, pathologists in the UK use diverse terminologies for the classification of sudden unexpected infant deaths, including ‘unascertained,’ ‘sudden unexpected death in infancy’ (SUDI) and ‘sudden infant death syndrome’ (SIDS)....

The medico-legal investigation of sudden, unexpected and/or unexplained infant deaths in South Africa: where are we—and where are we going?

Sudden Infant Death Syndrome (SIDS) has been reported to be the leading cause of death in infants under 1 year of age in many countries. Unfortunately, a paucity of published research data exists in South Africa, with regard to the incidence of and investigation into the circumstances surrounding Sudden Unexplained Deaths in Infants (SUDI) and/or SIDS. Currently, even though most academic centers conform to a protocol consistent with internationally accepted standards, there exists no nationally accepted infant death investigation protocol in South Africa. It is the aim of this study to review the current practice of infant death investigation in two representative but geographically and demographically distinct centers. Retrospective case audit over a five-year period (2000-2004) was conducted at two large medico-legal mortuaries in Pretoria (Gauteng) and Tygerberg (Cape Town). Case files on all infants younger than 1 year of age were reviewed. The outcome measures included number of deaths, demographic details and the nature and final outcome of the post mortem examinations. A total of 512 cases were identified as possible SIDS cases and of these, 171 was classified as SIDS. The study showed marked inter-case and inter-divisional variation in terms of the investigation of infant deaths at the two institutions. It is envisaged that this study will focus attention on the current lack of usable data regarding sudden/unexplained/unexpected infant deaths in South Africa, and aid in the formulation and implementation of a practical (yet internationally accountable) infant death investigation protocol, which could facilitate comparisons with other countries and initiate further structured research in this field.

Propionic acidemia mimicking diabetic ketoacidosis

Propionic acidemia manifesting with hyperglycemia is rare. Few cases have been reported mainly of the neonatal-onset form associated with high mortality. We report a 9-month-old Palestinian boy who manifested with coma, severe hyperglycemia and ketoacidosis mimicking diabetic ketoacidosis. Family history of unexplained infant deaths was helpful in reaching the correct diagnosis. In response to therapy, the patient regained consciousness without neurologic deficits and had normal examination. This is, to our knowledge, the first case report of late-onset propionic acidemia that had this presentation and survived.

Sudden unexpected deaths in infancy part I: The phenomena of sudden and unexplained infant Death

The phenomena of sudden and unexpected infant deaths has been extensively studied and is informed by an increasingly large literature base. This article has reviewed and summarized some of the more credible areas of study and seeks to make the evidence more accessible to influence practices within the nursing domain.

Is Automated Auditory Brainstem Response Hearing Screening Predictive of Sudden Infant Death Syndrome?

Objective. To determine the incidence of unilateral deficits on newborn hearing screening in babieswho have died of SIDS.Methods. Records of universal newborn hearing screening outcomes for the state of Queensland,from October 1, 2004 to December 31, 2006, were accessed. A list of all sudden, unexplained infantdeaths in the period January 1, 2005 to December 31, 2006 was acquired from the Queensland StateCoroner. For each child whose death was attributed to SIDS, individual hearing screening results werereviewed. The screening process in Queensland utilises Automated Auditory Brainstem Response(AABR) equipment.Results. Between January 1, 2005 and December 31, 2006, 44 deaths in Queensland were attributedto SIDS. Only 18 of the 44 babies who died with SIDS had had their hearing screened. All 18 passedthe hearing screen. Of the remaining 26 babies who died with SIDS who did not have their hearingscreened: 25 were born in places that did not practice routine screening at the time of their births; oneinfant of the list from the coroner could not be located on the lists of births.Conclusion. In Queensland there is no association with failing a hearing screening test and dyingwith SIDS.

Sudden Unexplained Death in Infancy and Long QT Syndrome

After more than 30 years of research into the hypothesis that long QT syndrome (LQTS) might be a cause of arrhythmic sudden infant death, we are now at the point where we can state with certainty that some sudden unexplained deaths in infancy, about 10%, are indeed due to long QT syndrome. The evidence for this lies in large population ECG screening programmes, post-mortem molecular genetic testing of sudden infant death victims, and some informative case reports. The cardiac sodium channel gene SCN5A (LQTS type 3) is the most common culprit, but LQTS types 1,2, 6, 9 and 12 have also been found. There is also new evidence that other arrhythmic syndromes sometimes cause SUDI, in particular short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). These conditions are also due to disordered cardiac ion channel function like LQTS, and are usually inherited in an autosomal dominant fashion. There remain, however, many unanswered questions, most particularly whether all populations are affected equally, and what should clinicians do with this knowledge? Should newborn ECG screening become mandatory? How should we best investigate SUDI at post mortem in order to diagnose LQTS? This review summarises the evidence to date and addresses these questions.

Neuropathology of the intermediolateral nucleus of the spinal cord in sudden unexplained perinatal and infant death

Experimental studies have demonstrated that breathing activity in rats is generated early in embryonic stages in rostral spinal cord, precisely in the intermediolateral nucleus, then establishing a spinal cord–brainstem network.In this study we aimed to individuate and to define the developmental steps of the intermediolateral nucleus, still inadequately known in humans, in the thoracic spinal cord of a large series of perinatal and infant death victims, aged from 17 gestational weeks to 10 months of life. Besides we investigated a possible link between alterations of this nucleus and sudden unexplained perinatal and infant death.The normal developmental pattern of the human intermediolateral nucleus consists of a progressive maturation of its neurons, that change from a round to a polygonal shape with long axons and significantly decrease in number.Various degrees of intermediolateral nucleus hypodevelopment (neuronal immaturity in a normal structure/hypoplasia/agenesis) were found almost exclusively in unexplained fetal and infant death victims. Besides, a significant correlation was found between maternal smoking in pregnancy and the neuropathological results.In conclusion this work underlines the negative effects of prenatal nicotine exposure on the development of autonomic nervous centers checking the vital functions, already in early gestational stages, when the integrity of the intermediolateral nucleus is indispensable for the first breathing bursts.

Ependymal alterations in sudden intrauterine unexplained death and sudden infant death syndrome: possible primary consequence of prenatal exposure to cigarette smoking

BackgroundThe ependyma, the lining providing a protective barrier and filtration system separating brain parenchyma from cerebrospinal fluid, is still inadequately understood in humans. In this study we aimed to define, by morphological and immunohistochemical methods, the sequence of developmental steps of the human ependyma in the brainstem (ventricular ependyma) and thoracic spinal cord (central canal ependyma) of a large sample of fetal and infant death victims, aged from 17 gestational weeks to 8 postnatal months. Additionally, we investigated a possible link between alterations of this structure, sudden unexplained fetal and infant death and maternal smoking.ResultsOur results demonstrate that in early fetal life the human ependyma shows a pseudostratified cytoarchitecture including many tanycytes and ciliated cells together with numerous apoptotic and reactive astrocytes in the subependymal layer. The ependyma is fully differentiated, with a monolayer of uniform cells, after 32 to 34 gestational weeks. We observed a wide spectrum of ependymal pathological changes in sudden death victims, such as desquamation, clusters of ependymal cells in the subventricular zone, radial glial cells, and the unusual presence of neurons within and over the ependymal lining. These alterations were significantly related to maternal smoking in pregnancy.ConclusionsWe conclude that in smoking mothers, nicotine and its derivatives easily reach the cerebrospinal fluid in the fetus, immediately causing ependymal damage. Consequently, we suggest that the ependyma should be examined in-depth first in victims of sudden fetal or infant death with mothers who smoke.

Distribution of interleukin-1 receptor antagonist genotypes in Sudden Unexpected Death in Infancy (SUDI); unexplained SUDI have a higher frequency of allele 2

Aims. This investigation was designed to explore the role of IL-1RN genotype in unexplained infant deaths (including sudden infant death syndrome (SIDS)), non-infectious infant deaths, and infectious infant deaths, and to investigate whether IL-1RN genotype is related to the finding of organisms in normally sterile sites in infant deaths.Methods. IL-1RN 89bp variable number of tandem repeat polymorphism genotype was determined using polymerase chain reaction for 49 cases of unexplained sudden unexpected death in infancy (uSUDI), 13 cases of infectious sudden unexpected death in infancy, 10 cases of non-infectious sudden unexpected death in infancy, and 103 live control infants. IL-1RN genotype was then compared with the presence of bacteria in normally sterile sites in infant deaths.Results. An association was found between the homozygous A2 allele and uSUDI (P = 0.007; 95% confidence interval 1.41-17.67) where carriage of the 2/2 genotype was 4.85 times more likely to increase risk of uSUDI compared with the predominant 1/1 genotype.Conclusions. The role of infection in uSUDI and SIDS may be via an immune response pathway where IL-1RN A2 affects interleukin (IL)-1 regulation. These results are consistent with previous research where polymorphic genotypes conferring more severe proinflammatory responses are found more frequently in uSUDI/SIDS infants than in controls.

Child deaths: confidential enquiry into the role and quality of UK primary care

In 2006 the Confidential Enquiry into Maternal and Perinatal Deaths was extended to pilot a collection of child deaths. This helped optimise data collection for local safeguarding children's boards, which, since April 2008, have a statutory responsibility to review all child deaths. Reviewing primary care records may highlight areas in which systems, skills, and care could be improved. To review the role and quality of primary care in child deaths. Confidential enquiry into child deaths. Five regions of the UK: North-East, South-West and West Midlands, Wales, and Northern Ireland. The confidential enquiry collected core data for all child deaths (age range 28 days to 17 years) and an age-stratified sample was assessed by multidisciplinary panels for avoidable factors. An independent detailed review was conducted of the primary care records on all children in the North-East region and all children who were reviewed by panel in the other four regions. Primary care records were reviewed for 168 child deaths. There were 25 (15%) deaths from acute infection, 22 (13%) from cancer, and 11 (7%) from asthma or epilepsy. Fifty-nine (35%) deaths were sudden: sudden unexplained death in infancy, suicides, and assaults. Of 149 with immunisation records, only 88 (59%) had been fully vaccinated on time. One or more primary care professionals were involved in the management of 90 (54%) children. Avoidable primary care factors were identified in 18 (20%) of these deaths. Avoidable primary care factors included failure in the recognition and management of serious infection, failure to vaccinate, and inadequate management of asthma and epilepsy. Decisions made about diagnosis and management in primary care may affect the cause, time, and circumstances of a child's death. Maintaining skills in assessing the acutely ill child remains an essential part of good clinical practice.

Using Death Certificates to Characterize Sudden Infant Death Syndrome (SIDS): Opportunities and Limitations

To examine cause-of-death terminology written on death certificates for sudden infant death syndrome (SIDS) and to determine the adequacy of this text data in more fully describing circumstances potentially contributing to SIDS deaths. With 2003 and 2004 US mortality files, we analyzed all deaths that were assigned the underlying cause-of-death code for SIDS (R95). With the terminology written on the death certificates, we grouped cases into SIDS-related cause-of-death subcategories and then assessed the percentage of cases in each subcategory with contributory or possibly causal factors described on the certificate. Of the 4408 SIDS-coded deaths, we subcategorized 67.2% as "SIDS" and 11.0% as "sudden unexplained (or unexpected) infant death." The terms "probable SIDS" (2.8%) and "consistent with SIDS" (4.6%) were found less frequently. Of those death certificates that described additional factors, "bedsharing or unsafe sleep environment" was mentioned approximately 80% of the time. Most records (79.4%) did not mention any additional factors. Our death certificate analysis of the cause-of-death terminology provided a unique opportunity to more accurately characterize SIDS-coded deaths. However, the death certificate was still limited in its ability to more fully describe the circumstances leading to SIDS death, indicating the need for a more comprehensive source of SIDS data, such as a case registry.