Clinically relevant mouse models of severe spinal muscular atrophy with respiratory distress type 1.

Spinal Muscular Atrophy with Respiratory Distress (SMARD1) is a lethal infantile disease, characterized by the loss of motor neurons leading to muscular atrophy, diaphragmatic paralysis, and weakness in the trunk and limbs. Mutations in IGHMBP2, a ubiquitously expressed DNA/RNA helicase, have been shown to cause a wide spectrum of motor neuron disease. Though mutations in IGHMBP2 are mostly associated with SMARD1, milder alleles cause the axonal neuropathy, Charcot-Marie-Tooth disease type 2S (CMT2S), and some null alleles are potentially a risk factor for sudden infant death syndrome (SIDS). Variant heterogeneity studied using an allelic series can be informative in order to create a broad spectrum of models that better exhibit the human variation. We previously identified the nmd2J mouse model of SMARD1, as well as two milder CMT2S mouse models. Here, we used CRISPR-Cas9 genome editing to create three new, more severe Ighmbp2 mouse models of SMARD1, including a null allele, a deletion of C495 (C495del) and a deletion of L362 (L362del). Phenotypic characterization of the IGHMBP2L362del homozygous mutants and IGHMBP2C495del homozygous mutants respectively show a more severe disease presentation than the previous nmd2J model. The IGHMBP2L362del mutants lack a clear denervation in the diaphragm while the IGHMBP2C495del mutants display a neurogenic diaphragmatic phenotype as observed in SMARD1 patients. Characterization of the Ighmbp2-null model indicated neo-natal lethality (median lifespan = 0.5 days). These novel strains expand the spectrum of SMARD1 models to better reflect the clinical continuum observed in the human patients with various IGHMBP2 recessive mutations.

The Influence of Neurotrophins on the Brain-Lung Axis: Conception, Pregnancy, and Neonatal Period.

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD).

A Systematic Approach to Evaluate Sudden Unexplained Death in Children.

OBJECTIVE: To evaluate in the Netherlands the national outcomes in providing cause of and insights into sudden and unexplained child deaths among children via the Postmortem Evaluation of Sudden Unexplained Death in Youth (PESUDY) procedure. STUDY DESIGN: Children aged 0-18 years in the Netherlands who died suddenly were included in the PESUDY procedure if their death was unexplained and their parents gave consent. The PESUDY procedure consists of pediatric and forensic examination, biochemical, and microbiological tests; radiologic imaging; autopsy; and multidisciplinary discussion. Data on history, modifiable factors, previous symptoms, performed diagnostics, and cause of death were collected between October 2016 and December 2021. RESULTS: In total, 212 cases (median age 11 months, 56% boys, 33% comorbidity) were included. Microbiological, toxicological, and metabolic testing was performed in 93%, 34%, and 32% of cases. In 95% a computed tomography scan or magnetic resonance imaging was done and in 62% an autopsy was performed. The cause of death was explained in 58% of cases and a plausible cause was identified in an additional 13%. Most children died from infectious diseases. Noninfectious cardiac causes were the second leading cause of death found. Modifiable factors were identified in 24% of non-sudden infant death syndrome/unclassified sudden infant death cases and mostly involved overlooked alarming symptoms. CONCLUSIONS: The PESUDY procedure is valuable and effective for determining the cause of death in children with sudden unexplained deaths and for providing answers to grieving parents and involved health care professionals.

GFAP expression in the BRAIN during human postnatal development.

Glial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP-positive cells (density, GFAP+/mm2), and a reactivity score (R-score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed-sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with >60% of infants having an R-Score >120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region-dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.

The purpose of this study is to gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Whole Genome Sequencing (WGS) was performed on 144 infants that succumbed to SUID, and 573 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Variants of interest were identified in 88 genes, in 64.6% of our cohort. Seventy-three of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders and in two genes associated with immunological function. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria. Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.

Revisiting the association of sudden infant death syndrome (SIDS) with polymorphisms of NHE3 and IL13.

OBJECTIVES: Disturbances of the central nervous system and immune system are thought to play a role in sudden infant death syndrome (SIDS). Dysregulated expression of sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) in the brainstem and of interleukin 13 (IL13) in the lungs has been observed in SIDS. An association of single-nucleotide polymorphisms (SNPs) in NHE3 and IL13 with SIDS has been proposed, but controversial results were reported. Therefore, there is a need to revisit the association of SNPs in NHE3 and IL13 with SIDS. METHODS: Genotyping of rs71597645 (G1131A) and rs2247114 (C2405T) in NHE3 and rs20541 (+ 4464A/G) in IL13 was performed in 201 SIDS cases and 338 controls. A meta-analysis was performed after merging our data with previously published data (all from European populations). RESULTS: Polymorphisms rs2247114 (NHE3) and rs20541 (IL13) were significantly associated with SIDS overall and in multiple subgroups, but no association was found for rs71597645 (NHE3). After combining our data with previously published data, a fixed-effect meta-analysis showed that rs2247114 in NHE3 retained a significant association with SIDS under a recessive model (OR 2.78, 95%CI 1.53 to 5.06; p = 0.0008). CONCLUSION: Our findings suggest an association of NHE3 variant rs2247114 (C2405T), though not rs71597645 (NHE3), with SIDS. A potential role of rs20541 (IL13) still has to be elucidated. Especially NHE3 seems to be an interesting topic for future SIDS research.

The French registry of sudden unexpected death in infancy (SUDI): a 7-year review of available data.

The French "OMIN registry" was established in 2015 to collect nationwide standardised data concerning biological, clinical, environmental and social characteristics of sudden unexpected death in infancy (SUDI) and unexpected death in children aged 1-2 years. A biobank has existed since July 2020 to store biological samples for each case. This article aimed to detail (1) a brief history and the objectives of the registry; (2) a description of the methodology used; (3) the first results of the registry, i.e. the main characteristics of the cases included so far; (4) the process for accessing the data for research projects; and (5) issues regarding weakness and improvement and perspectives offered by the registry. On 31 May 2024, 1975 cases were included in the OMIN registry; on 31 December 2022, 4606 biological samples from 176 cases were collected. For each deceased child, different types of data are registered on an electronic case report form: socio-demographic data, personal and familial medical background, environment and feeding data, clinical data, and biological and imaging results. A strict and continuous quality control process is used to ensure the reliability of the data, in parallel with specific actions to improve the exhaustiveness of the registry. The OMIN registry database is one of the largest and the most complete databases on SUDI, especially in Europe, and the first in the world to associate a standardised biological sample collection with it. Perspectives of research provided by our registry are numerous and could be supported by national and international scientific collaborations. CONCLUSION:  This article details the objectives and methods of the French registry of SUDI. It provides initial results relating to the population included in the register and the procedure for accessing the data. WHAT IS KNOWN: • In Western Europe, France is one of the countries with the highest SUDI rate, making it the first cause of death of infants between 28 and 364 days. • The development of epidemiological tools on a national and international scale is essential to advance research into the determinants and risk factors of unexpected death in children under 2 years of age. WHAT IS NEW: • The OMIN registry was created in France in 2015 to collect nationwide standardised social, environmental, clinical, and paraclinical data for cases of unexpected death in children aged 0 to 2 years. • To date, the OMIN registry has included 680 data from almost 2000 children unexpectedly deceased, completed by a biocollection since 2020. • Data from the OMIN registry, unique in its field, are freely available for scientific research teams, after acceptation by the scientific committee of the registry.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?

BACKGROUND: Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. METHODS: We did a detailed analysis of CDC data spanning over two decades (1983-2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. RESULTS: The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. CONCLUSIONS: We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control.

Promoting Safe Sleep: The Role of Doulas in Black Communities.

BACKGROUND: Accidental suffocation and strangulation in bed continues to be a critical issue in Black communities, despite the widespread initiatives to promote safe sleep. Doulas are in an ideal position to promote safe sleep, particularly in hard-to-reach communities that are more distrusting of conventional medical providers. Little is known about their practices and perspectives for putting infants down to rest. This study informs this gap in the literature. PURPOSE: The purpose of this study was to explore doulas' perspectives and practices in the field of putting infants down to sleep. The researchers aimed to determine whether Black caregivers that work with doulas are likely to encounter safe sleep education. METHODS: The researchers used a descriptive approach to inquiry. They conducted three focus groups with a total of 17 Black doulas. The researchers independently and critically reviewed the transcriptions and observation notes from each group to identify codes. They then triangulated the results using Artificial Intelligence-driven tools. FINDINGS: The study found four themes: (1) Individualized Services, (2) Cultural Sensitivity, (3) Negotiating Safety, and (4) Safe Sleep Education. CONCLUSIONS: The study concluded doulas have a commitment to promoting safe sleep. The researchers found that doulas engage in practices that help caregivers to integrate safe sleep practices into their lifestyle and to adapt them to meet their needs. The researchers also documented a desire for more information and instruction on safe sleep among practicing doulas.

New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus.

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

Opportunities and challenges for circular economy in the Maldives: A stakeholder analysis of informal E-waste management in the Greater Malé Region.

In the Maldives, the contribution of the informal sector to e-waste management is significant as a formal e-waste management system is not yet established. The opportunities for advancing the circular economy in the Maldives' e-waste sector rely on the possibility of its formalization. This study aimed to examine the current and anticipated situations of e-waste management in the Greater Malé Region of the Maldives, with a specific focus on formalizing the informal sector. Interviews and questionnaire-based surveys were conducted followed by statistical analysis of the data. The t-test performed for the consumer survey data (n = 202) suggests that formalization encourages consumers to engage with the informal sector, resulting in increased resource recovery. Thematic analysis of interviews conducted with both formal and informal sector stakeholders (n = 17) revealed that the informal sector plays a substantial role in managing e-waste. It also underscored the need for government assistance to enhance safety and productivity in this sector. Various opportunities and challenges for establishing a circular economy in the country were identified, such as the rise in e-waste generation, the presence of an active informal workforce, the lack of sufficient government support, and prevailing stereotypes among consumers regarding informal workers. These findings provide a fresh perspective on the solutions for waste management in the Maldives and open the door to further explore the significance of the informal sector and feasible formalization initiatives. This study could contribute to the literature on the role of the informal sector in waste management in the Maldives and other small island developing states.

Implementing a Safe Sleep Shelter and Baby Bundle Kit Distribution Program.

The Georgia Department of Public Health developed the Safe Sleep Shelter Program to expand Georgia Safe to Sleep campaign efforts. The program focused on engaging with housing support agencies, homeless shelters, and domestic violence shelters. The program offered a menu of resources that agencies could choose from, including portable cribs for agency use and distribution to families, safe sleep education for staff, assistance with creating/updating agency safe sleep policies, and Baby Bundle Safe Sleep kits with education and resources for families. The program showed promising results: 44 agencies across the state applied, serving an estimated 20,950 individuals annually. Agencies expressed strong interest in expanding safe sleep education and resources for the families they served. Most agencies reported that the program filled gaps in services, including having enough cribs to meet demand and limited safe sleep education and resources. Agencies reported that parents appreciated the cribs and Baby Bundle Safe Sleep kits as most did not have money to purchase an infant sleep surface. Agencies reported that the resources provided new information to infant parents, facilitated discussion, and reinforced safe sleep messaging. Evaluation challenges included difficulties collecting distribution data and a low response rate for parent surveys. Implications are discussed for others interested in implementing such a program, including to develop processes for communicating updated recommendations, leverage existing relationships to engage additional agencies, evaluate efforts to refine program components, and consider strategies to increase parent survey response rates.

The role of alcohol in infant cosleeping deaths.

The well-established epidemiological and neuropathological differences between infants who die alone compared to those in shared sleeping environments indicate that these cohorts have differences. Risk factors in both situations depend on both exogenous and endogenous factors. Although parental consumption of alcohol continues to be cited as a risk factor for sudden infant death syndrome (SIDS) it is difficult to understand how a substance which impairs parental consciousness rather than infant arousal could contribute to SIDS. Surely a more logical mechanism to explain these deaths would be suffocation by a sedated adult rather than evoking predisposing factors for SIDS.

Does citing early SIDS research skew contemporary conclusions?

Research on infants who have allegedly succumbed to sudden infant death syndrome (SIDS) has been of variable quality over the years. Even now peer-reviewed papers are being published on cases termed 'SIDS' without autopsies having been performed, despite this being a requirement of the three major definitions for over five decades. Clearly cases used in earlier research studies could not have complied with the requirements of as-yet unpublished definitions/guidelines. For this reason care must be taken in citing initial papers as their results may have been skewed by the presence of non-SIDS cases. This may have particular relevance for meta analyses. Reviewing the literature on substance P and its relationship to SIDS provides an excellent example of how diametrically opposed conclusions were reached at different time points. Early studies on SIDS, and studies that use cases that were classified before the standard NICHD and San Diego definitions, should, therefore, be approached with a degree of scepticism and not cited in contemporary papers or at meetings as they have the potential to confuse rather than clarify.

Food insecurity, COVID-19 and diets in Fiji - a cross-sectional survey of over 500 adults.

INTRODUCTION: Food insecurity is associated with inadequate nutrition and increased rates of chronic disease. The primary aim of this study was to assess self-reported food insecurity and the perceived impact of COVID-19 on food security, in two regional districts of Central Fiji, as part of a broader program of work on strengthening and monitoring food policy interventions. The secondary aim was to explore the relationship between food insecurity and salt, sugar and fruit and vegetable intake. METHODS: Seven hundred adults were randomly sampled from the Deuba and Waidamudamu districts of Viti Levu, Fiji. Interview administered surveys were conducted by trained research assistants with data collected electronically. Information was collected on demographics and health status, food security, the perceived impact of COVID-19 on food security, and dietary intake. Food insecurity was assessed using nine questions adapted from Fiji's 2014/5 national nutrition survey, measuring markers of food insecurity over the last 12 months. Additional questions were added to assess the perceived effect of COVID-19 on responses. To address the secondary aim, interview administered 24-hour diet recalls were conducted using Intake24 (a computerised dietary recall system) allowing the calculation of salt, sugar and fruit and vegetable intakes for each person. Weighted linear regression models were used to determine the relationship between food insecurity and salt, sugar and fruit and vegetable intake. RESULTS: 534 people participated in the survey (response rate 76%, 50.4% female, mean age 42 years). 75% (75.3%, 95% CI, 71.4 to 78.8%) of people reported experiencing food insecurity in the 12 months prior to the survey. Around one fifth of people reported running out of foods (16.8%, 13.9 to 20.2%), having to skip meals (19.3%, 16.2 to 22.9%), limiting variety of foods (19.0%, 15.9 to 22.5%), or feeling stressed due to lack of ability to meet food needs (19.5%, 16.4 to 23.0%). 67% (66.9%, 62.9 to 70.7%) reported becoming more food insecure and changing what they ate due to COVID-19. However, people also reported positive changes such as making a home garden (67.8%, 63.7 to 71.6%), growing fruit and vegetables (59.5%, 55.6 to 63.8%), or trying to eat healthier (14.7%, 12.0 to 18.0%). There were no significant associations between food insecurity and intakes of salt, sugar or fruit and vegetables. CONCLUSION: Participants reported high levels of food insecurity, exceeding recommendations for salt and sugar intake and not meeting fruit and vegetable recommendations, and becoming more food insecure due to COVID-19. Most participants reported making home gardens and/or growing fruit and vegetables in response to the pandemic. There is an opportunity for these activities to be fostered in addressing food insecurity in Fiji, with likely relevance to the Pacific region and other Small Island Developing States who face similar food insecurity challenges.

Qualitative assessment of infant sleep practices and other risk factors of sudden infant death syndrome (SIDS) among mothers in Lusaka, Zambia.

BACKGROUND: There is very little information on the beliefs and perceptions of mothers about SIDS and its related risk factors in Africa. To better understand parental decisions about infant sleep practices and other risk factors for SIDS, we conducted focus group discussions (FGDs) with mothers of infants in Lusaka, Zambia. METHODS: FGDs involved 35 purposively sampled mothers aged 18-49 years. FGDs were conducted using a semi-structured interview guide in the local language, Nyanja. These were translated, transcribed verbatim into English, and then coded and analyzed using thematic analysis in NVivo 12. RESULTS: Six FGDs were conducted with 35 mothers in April-May 2021 across two study sites. FGD Participants were generally aware of sudden unexplained infant deaths, with several describing stories of apparent SIDS in the community. The side sleeping position was preferred and perceived to be safer for the infant with most believing the supine position posed an aspiration or choking risk to the infant. Bedsharing was also preferred and perceived to be convenient for breastfeeding and monitoring of the infant. Experienced family members such as grandmothers and mothers-in-law, and health care workers were frequently cited as sources of information on infant sleep position. A heightened awareness of the infant's sleeping environment was suggested as a mechanism to prevent SIDS and smothering. CONCLUSIONS: Decisions about bedsharing and infant sleep position were guided by maternal beliefs and perceptions about what is convenient for breastfeeding and safer for the infant. These concerns are vital to designing tailored interventions to address sleep-related sudden infant losses in Zambia. Public health campaigns with tailored messages that address these concerns are likely to be effective at ensuring optimal uptake of safe sleep recommendations.

Investigating genetic variants in microRNA regulators of Neurokinin-1 receptor in sudden infant death syndrome.

Sudden infant death syndrome (SIDS) occurs more often in male than in female infants, suggesting involvement of the X-chromosome. Histopathological studies have suggested that altered expression of the Neurokinin-1 receptor may also play a role in the pathogenesis of SIDS. It was hypothesised that genetic variants in three X-chromosome-encoded microRNA (miRNA/miR), known to down-regulate expression of the Neurokinin-1 receptor, may contribute to SIDS. AIM: To identify sequence variants in the miRNAs within a study cohort (27 cases of SIDS and 28 controls) and determine if there was a difference in the frequencies in male and female SIDS infants. METHODS: Genomic DNA prepared from stored blood spots was amplified and sequenced to identify genetic variants in miR500A, miR500B and miR320D2. RESULTS: No novel variants in the miRNAs were identified in our study cohort. We identified one known single-nucleotide polymorphism (SNP) in miR320D2: rs5907732 G/T, in both cases and controls. No significant difference in the SNP frequency was observed between male and female SIDS cases. CONCLUSION: This pilot study suggests that sequence variants in three miRNAs do not contribute to the reported higher prevalence of SIDS in male infants and do not contribute to the pathogenesis of SIDS in our cohort.

Changing diagnostic patterns in cases of sudden and unexpected natural death in infants and young children: 1994-2018.

AIM: To determine whether there has been a change in the incidence and type of conditions causing sudden and unexpected natural death in infants and young children in recent years. METHODS: A search was undertaken of pathology records at Forensic Science SA in Adelaide, Australia for all cases of sudden and unexpected natural death in children aged less than 10 years at the time of death over two time periods: 1994-1998 and 2014-2018. RESULTS: Overall, 136 cases were identified consisting of 81 boys and 55 girls (M:F = 16:11; age range 0-9 years). No difference was shown in the numbers of sudden unexplained deaths in infants and young children between the two time periods (80 vs. 56; p = 0.18). A trend was shown for a prominent decrease in SIDS cases (55 vs. 12) with an increase in undetermined cases, <1 year (5 vs. 18). However, when the two categories were combined there was no statistical difference between the two periods (60/80 vs. 30/56) (p = 0.26), although a decrease in numbers had occurred. CONCLUSION: Analysis of numbers of fatalities reported from medicolegal institutes should be undertaken with an awareness of the potential effect of diagnostic shift.

The San Diego SIDS definition-20 Years on.

AIM: As it is now 20 years since the San Diego definition of sudden infant death syndrome (SIDS) was proposed, it is timely to examine the impact of this consensus statement. RESULTS: Concerns at the time were expressed that 'death scene' had been replaced by circumstances of death and so it may have been more useful to have a more inclusive statement of 'death scene, including circumstances of death'. The category of unclassified sudden infant deaths (USID) that was proposed has not been widely adopted. More disturbing, however, is the increasing failure to use either the San Diego or earlier definitions in published research, with recent studies showing that almost two-thirds of peer-reviewed SIDS publications (2019-2021) did not quote or reference internationally accepted definitions. This is a decrease of 33% from the 68% of papers that correctly used SIDS definitions in 2011. The definition is therefore not being uniformly applied and in addition, diagnostic shift is occurring, with more pathologists favouring 'undetermined' over a designation of SIDS. CONCLUSIONS: Given these developments, how can we correctly interpret conclusions relating to SIDS research, and can we accurately monitor trends in SIDS mortality? The authors would suggest that unfortunately, at present we cannot with any precision.