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.

Rates of Sudden Unexpected Infant Death Before and During the COVID-19 Pandemic.

Importance: Infection has been postulated as a driver in the sudden infant death syndrome (SIDS) cascade. Epidemiologic patterns of infection, including respiratory syncytial virus and influenza, were altered during the COVID-19 pandemic. Comparing month-to-month variation in both sudden unexpected infant death (SUID) and SIDS rates before and during the pandemic offers an opportunity to generate and expand existing hypotheses regarding seasonal infections and SUID and SIDS. Objective: To compare prepandemic and intrapandemic rates of SUID and SIDS, assessing for monthly variation. Design, Setting, and Participants: This cross-sectional study assessed US mortality data provided by the Centers for Disease Control and Prevention for January 1, 2018, through December 31, 2021. Events with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for SIDS (R95), unknown (R99), and accidental suffocation and strangulation in bed (W75) causes of death were examined. The data analysis was performed between November 2, 2023, and June 2, 2024. Exposure: COVID-19 pandemic. Main Outcomes and Measures: The primary and secondary outcomes were the monthly rates of SUID and SIDS during the COVID-19 pandemic (March 1, 2020, to December 31, 2021) compared with the prepandemic period (March 1, 2018, to December 31, 2019) as measured using generalized linear mixed-effects models. Seasonal trends in RSV and influenza rates were also examined. Results: There were 14 308 SUID cases from January 1, 2018, to December 31, 2021 (42% female infants). Compared with the prepandemic period, the risk of SUID increased during the intrapandemic period (intensity ratio [IR], 1.06; 95% CI, 1.05-1.07). Monthly assessments revealed an increased risk of SUID beyond the prepandemic baseline starting in July 2020, with a pronounced epidemiologic shift from June to December 2021 (ranging from 10% to 14%). Rates of SIDS were elevated throughout the intrapandemic period compared with the prepandemic baseline, with the greatest increase in July 2021 (IR, 1.18; 95% CI, 1.13-1.22) and August 2021 (IR, 1.17; 95% CI, 1.13-1.22). Seasonal shifts in RSV hospitalizations correlated with monthly changes in SUID observed during 2021. Conclusions and Relevance: This cross-sectional study found increased rates of both SUID and SIDS during the COVID-19 pandemic, with a significant shift in epidemiology from the prepandemic period noted in June to December 2021. These findings support the hypothesis that off-season resurgences in endemic infectious pathogens may be associated with SUID rates, with RSV rates in the US closely approximating this shift. Further investigation into the role of infection in SUID and SIDS is needed.

The risk of sleep-related death in an inclined sleep environment.

BACKGROUND: Unsafe sleep environments are the primary modifiable risk factor for sudden unexpected infant death (SUID). Despite this knowledge, products that deviate from the American Academy of Pediatrics (AAP) safe sleep recommendations continue to be commonplace, such as inclined sleepers. Analyses to estimate risk among these products are lacking, perpetuating their presence in the marketplace. We present a method of comparing risk of SUID in an inclined sleeper to an AAP-recommended sleep environment. METHODS: A case-control analysis using publicly available and previously published survey data was conducted for SUID events occurring between January 1, 2018 and April 12, 2019 (the date of the first inclined sleeper recall). SUID deaths were categorized as occurring in an AAP-recommended sleep environments or in an inclined sleeper. Exposure Odds Ratios (OR) are reported as the risk of SUID among infants using inclined sleepers relative to an AAP-recommended sleep environment. RESULTS: During the study period, 4,900,573 births and 4,363 SUID deaths occurred in the US. Control characteristics were similar between previous night users of an AAP-recommended sleep environment (24%) and inclined sleepers (3.8%). Inclined sleepers were associated with a 5-fold (OR: 5.1; 95% CI: 3.2, 7.9) increased risk of SUID among infants < 12 months compared to infants in an AAP-recommended sleep environment. This risk was greatest among infants ≥ 4 months (RR: 10.4; 95% CI: 5.1, 21.5). CONCLUSIONS: This novel analysis fills a longstanding gap in risk assessments of inclined infant sleep products. More timely risk analyses may improve the safety of the marketplace.

Causes of sudden unexpected death in infants with and without pre-existing conditions: a retrospective autopsy study.

OBJECTIVE: We investigated sudden unexpected death in infancy (SUDI) autopsy data from 1996 to 2015 inclusive, comparing findings from infants with and without pre-existing medical conditions. DESIGN: Large, retrospective single-centre autopsy series. SETTING: Tertiary paediatric hospital, London, UK. METHODS: Non-identifiable autopsy findings were extracted from an existing research database for infants older than 7 days up to and including 365 days old who died suddenly and unexpectedly (SUDI; n=1739). Cases were classified into SUDI with pre-existing condition (SUDI-PEC) (n=233) versus SUDI without PEC (SUDI non-PEC) (n=929), where PEC indicates a potentially life-limiting pre-existing medical condition. Findings were compared between groups including evaluation of type of PEC and whether the deaths were medically explained (infectious or non-infectious) or apparently unexplained. RESULTS: Median age of death was greater in SUDI-PEC compared with SUDI non-PEC (129 days vs 67 days) with similar male to female ratio (1.4:1). A greater proportion of deaths were classified as medically explained in SUDI-PEC versus SUDI non-PEC (73% vs 30%). Of the explained SUDI, a greater proportion of deaths were non-infectious for SUDI-PEC than SUDI non-PEC (66% vs 32%). SUDI-PEC (infectious) infants were most likely to have respiratory infection (64%), with susceptible PEC, including neurological, prematurity with a PEC, and syndromes or other anomalies. CONCLUSION: SUDI-PEC deaths occur later in infancy and are likely to have their death attributed to their PEC, even in the absence of specific positive autopsy findings. Future research should aim to further define this cohort to help inform SUDI postmortem guidelines, paediatric clinical practice to reduce infant death, and to reduce the risk of overattribution of deaths in the context of a PEC.

Using Social Vulnerability Indices to Predict Priority Areas for Prevention of Sudden Unexpected Infant Death in Cook County, IL: Cross-Sectional Study.

Background: The incidence of sudden unexpected infant death (SUID) in the United States has persisted at roughly the same level since the mid-2000s, despite intensive prevention efforts around safe sleep. Disparities in outcomes across racial and socioeconomic lines also persist. These disparities are reflected in the spatial distribution of cases across neighborhoods. Strategies for prevention should be targeted precisely in space and time to further reduce SUID and correct disparities. Objective: We sought to aid neighborhood-level prevention efforts by characterizing communities where SUID occurred in Cook County, IL, from 2015 to 2019 and predicting where it would occur in 2021-2025 using a semiautomated, reproducible workflow based on open-source software and data. Methods: This cross-sectional retrospective study queried geocoded medical examiner data from 2015-2019 to identify SUID cases in Cook County, IL, and aggregated them to "communities" as the unit of analysis. We compared demographic factors in communities affected by SUID versus those unaffected using Wilcoxon rank sum statistical testing. We used social vulnerability indicators from 2014 to train a negative binomial prediction model for SUID case counts in each given community for 2015-2019. We applied indicators from 2020 to the trained model to make predictions for 2021-2025. Results: Validation of our query of medical examiner data produced 325 finalized cases with a sensitivity of 95% (95% CI 93%-97%) and a specificity of 98% (95% CI 94%-100%). Case counts at the community level ranged from a minimum of 0 to a maximum of 17. A map of SUID case counts showed clusters of communities in the south and west regions of the county. All communities with the highest case counts were located within Chicago city limits. Communities affected by SUID exhibited lower median proportions of non-Hispanic White residents at 17% versus 60% (P<.001) and higher median proportions of non-Hispanic Black residents at 32% versus 3% (P<.001). Our predictive model showed moderate accuracy when assessed on the training data (Nagelkerke R2=70.2% and RMSE=17.49). It predicted Austin (17 cases), Englewood (14 cases), Auburn Gresham (12 cases), Chicago Lawn (12 cases), and South Shore (11 cases) would have the largest case counts between 2021 and 2025. Conclusions: Sharp racial and socioeconomic disparities in SUID incidence persisted within Cook County from 2015 to 2019. Our predictive model and maps identify precise regions within the county for local health departments to target for intervention. Other jurisdictions can adapt our coding workflows and data sources to predict which of their own communities will be most affected by SUID.

Imaging of sudden unexpected death in infancy: a comprehensive nationwide French survey.

RATIONALE AND OBJECTIVES: Introduction of post-mortem imaging has helped improve sudden unexpected death in infancy (SUDI) management in Europe. French guidelines were issued in 2007 to homogenise SUDI investigations including imaging. The aim of this study was to evaluate current imaging management of SUDI in France. MATERIAL AND METHODS: Between January 2022 and July 2022, all 35 SUDI French referral centres were invited to answer an e-mailed online survey including 29 questions divided into four different sections covering imaging practices for SUDI including radiology department organisation, imaging modalities performed, methods of reading, and current training resources. Partial responses were secondarily completed by a personal call to the SUDI imaging consultant. The current implementation of the 2007 recommendations was compared with a previous evaluation from 2015 and with current North American practices. RESULTS: The participation rate of centres performing SUDI imaging was 100% (35/35). Imaging was systematically performed in 94.3% (33/35) of the centres: 74.3% (26/35) using radiography; 5.7% (2/35) using ultrasound; 94.3% (33/35) using computed tomography (CT), including 89% (31/35) whole-body CT and 5.7% (2/35) brain CT; and 20% (7/35) using magnetic resonance imaging (MRI). Two centres (5.7%, 2/35) did not systematically perform brain imaging. One (2.9%, 1/35) used ultrasound-guided biopsy. In comparison with 2015, rates of brain imaging increased by 25.4% (P=0.008). There was no significant difference in the number of forensic MRIs performed between France and North America (P=0.663). CONCLUSION: Despite improvements since 2015, full compliance with French guidelines for SUDI investigations remains incomplete. The use of imaging, particularly CT and brain imaging, has increased. Further efforts are needed to standardise imaging practices for optimal SUDI investigations.

The study of the microbiome in forensic investigations on pediatric deaths.

Background: Sudden infant death syndrome (SIDS) is a tragic and devastating condition whose causes remain largely unknown. Recent studies have shown that the composition of a child's gut flora can play a significant role in the development of SIDS. Methods: This work aims to research those factors that influence the composition of the intestinal flora, the role they have in the development of SIDS and the new strategies for preventing SIDS showing a new interpretation through a detailed review of the literature. The gut in physiological conditions is mainly composed of Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria, but when there is the presence of dysbiotic or different microbial communities, the onset of the disease is more likely as an altered microbial community can lead to an interruption of the gut-brain axis and an increased risk of SIDS. Conclusions: All this implies that the composition of the microbiome can be modified to reduce the risk of sudden death in newborns. The results of the literature provide valuable information on the potential role of the intestinal microbiome in SIDS even if not all mechanisms are yet clear, especially in the mechanisms of death. Therefore, it is necessary in cases of SIDS when carrying out an autopsy to also investigate this area; to this end, we suggest a questionnaire to be administered to family members to understand the eating habits of the newborn and the family and integrate with microbiological investigations to explore every possible hypothesis.

Death from Failed Protection? An Evolutionary-Developmental Theory of Sudden Infant Death Syndrome.

Sudden infant death syndrome (SIDS) has been mainly described from a risk perspective, with a focus on endogenous, exogenous, and temporal risk factors that can interact to facilitate lethal outcomes. Here we discuss the limitations that this risk-based paradigm may have, using two of the major risk factors for SIDS, prone sleep position and bed-sharing, as examples. Based on a multipronged theoretical model encompassing evolutionary theory, developmental biology, and cultural mismatch theory, we conceptualize the vulnerability to SIDS as an imbalance between current physiologic-regulatory demands and current protective abilities on the part of the infant. From this understanding, SIDS appears as a developmental condition in which competencies relevant to self-protection fail to develop appropriately in the future victims. Since all of the protective resources in question are bound to emerge during normal infant development, we contend that SIDS may reflect an evolutionary mismatch situation-a constellation in which certain modern developmental influences may overextend the child's adaptive (evolutionary) repertoire. We thus argue that SIDS may be better understood if the focus on risk factors is complemented by a deeper appreciation of the protective resources that human infants acquire during their normal development. We extensively analyze this evolutionary-developmental theory against the body of epidemiological and experimental evidence in SIDS research and thereby also address the as-of-yet unresolved question of why breastfeeding may be protective against SIDS.

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.

Maternal Obesity and Risk of Sudden Unexpected Infant Death.

Importance: Rates of maternal obesity are increasing in the US. Although obesity is a well-documented risk factor for numerous poor pregnancy outcomes, it is not currently a recognized risk factor for sudden unexpected infant death (SUID). Objective: To determine whether maternal obesity is a risk factor for SUID and the proportion of SUID cases attributable to maternal obesity. Design, Setting, and Participants: This was a US nationwide cohort study using Centers for Disease Control and Prevention National Center for Health Statistics linked birth-infant death records for birth cohorts in 2015 through 2019. All US live births for the study years occurring at 28 weeks' gestation or later from complete reporting areas were eligible; SUID cases were deaths occurring at 7 to 364 days after birth with International Statistical Classification of Diseases, Tenth Revision cause of death code R95 (sudden infant death syndrome), R99 (ill-defined and unknown causes), or W75 (accidental suffocation and strangulation in bed). Data were analyzed from October 1 through November 15, 2023. Exposure: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Main Outcome and Measure: SUID. Results: Of 18 857 694 live births eligible for analysis (median [IQR] age: maternal, 29 [9] years; paternal, 31 [9] years; gestational, 39 [2] weeks), 16 545 died of SUID (SUID rate, 0.88/1000 live births). After confounder adjustment, compared with mothers with normal BMI (BMI 18.5-24.9), infants born to mothers with obesity had a higher SUID risk that increased with increasing obesity severity. Infants of mothers with class I obesity (BMI 30.0-34.9) were at increased SUID risk (adjusted odds ratio [aOR], 1.10; 95% CI, 1.05-1.16); with class II obesity (BMI 35.0-39.9), a higher risk (aOR, 1.20; 95% CI, 1.13-1.27); and class III obesity (BMI ≥40.0), an even higher risk (aOR, 1.39; 95% CI, 1.31-1.47). A generalized additive model showed that increased BMI was monotonically associated with increased SUID risk, with an acceleration of risk for BMIs greater than approximately 25 to 30. Approximately 5.4% of SUID cases were attributable to maternal obesity. Conclusions and Relevance: The findings suggest that infants born to mothers with obesity are at increased risk of SUID, with a dose-dependent association between increasing maternal BMI and SUID risk. Maternal obesity should be added to the list of known risk factors for SUID. With maternal obesity rates increasing, research should identify potential causal mechanisms for this association.

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.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.

The use of in-hospital guidelines for prevention of sudden unexpected postnatal collapse: A national survey.

AIM: Sudden unexpected postnatal collapse is a life-threatening event and may occur in any newborn infant. Safe skin-to-skin contact, and awareness of sudden unexpected postnatal collapse are key to its prevention. The aim of this study was to survey the presence of skin-to-skin contact and/or sudden unexpected postnatal collapse protocols in the 70 perinatal centres in the Netherlands. METHODS: We performed a survey among Dutch paediatricians to examine the safe skin-to-skin contact and sudden unexpected postnatal collapse protocols. RESULTS: We received data from 59/70 (85%) perinatal centres. At least one case of sudden unexpected postnatal collapse was reported in 35/59 (59%) of these centres. Nearly half the centres had safe skin-to-skin contact and/or sudden unexpected postnatal collapse protocols. Ultimately, 16 protocols were available for analysis. They showed considerable differences in the type of perinatal care provided. Most protocols lacked recently published insights on safe skin-to-skin contact. Besides, protocols failed to incorporate awareness of and knowledge on how to prevent sudden unexpected postnatal collapse. CONCLUSION: This study underlines the importance of drawing up uniform, multidisciplinary guidelines containing recommendations for the prevention of sudden unexpected postnatal collapse in the Netherlands.

Dysregulation of platelet serotonin, 14-3-3, and GPIX in sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14-3-3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14-3-3 signaling pathways similar to brain neurons, are abnormal in SIDS. We also studied platelet surface glycoprotein IX (GPIX), a cell adhesion receptor which is physically linked to 14-3-3. In infants dying of SIDS compared to infants dying of known causes, we found significantly higher intra-platelet 5-HT and 14-3-3 and lower platelet surface GPIX. Serum and plasma 5-HT were also elevated in SIDS compared to controls. The presence in SIDS of both platelet and brainstem 5-HT and 14-3-3 abnormalities suggests a global dysregulation of these pathways and the potential for platelets to be used as a model system to study 5-HT and 14-3-3 interactions in SIDS. Platelet and serum biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of SIDS risk in living infants.