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Objectives: To describe sudden unexpected infant deaths (SUIDs) occurring in safe sleep environments and explore differences in selected characteristics., Methods: We examined SUID from 22 jurisdictions from 2011 to 2020 and classified them as unexplained, no unsafe sleep factors (U-NUSF). Data were derived from the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry, a population-based Centers for Disease Control and Prevention surveillance system built on the National Center for Fatality Review and Prevention's child death review program. SUID classified as U-NUSF included infants who were (1) awake, under supervision, and witnessed to become unresponsive or (2) found unresponsive in a safe sleep environment after sleep (unwitnessed). We calculated frequencies and percentages for demographics, birth and environmental characteristics, medical history, and death investigation findings., Results: Most of the 117 U-NUSF SUID occurred before 4 months of age. Witnessed deaths most commonly occurred at <1 month of age (28%), whereas unwitnessed deaths most commonly occurred at ages 2 to 3 months (44%) Among all U-NUSF, 69% occurred in the infant's home (62% witnessed, 77% unwitnessed). All unwitnessed deaths occurred in a crib; most witnessed deaths occurred while being held (54%) or in a car seat traveling (18%). Most infants (84%) had no history of abuse or neglect. Abnormal autopsy findings were reported in 46% of deaths (49% witnessed, 42% unwitnessed)., Conclusions: Characterizing these deaths is key to advancing our knowledge of SUID etiology. Our study revealed a heterogeneous group of infants, suggesting physiologic, genetic, or environmental etiologies., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: Develop guidelines for child death review teams that will improve the consistency in classifying child maltreatment (CM) and distinguish between classification of exposure to hazards and neglect for sleep-related sudden unexpected infant deaths (SUID)., Methods: Sleep-related SUID (n = 25 797) were identified from the National Fatality Review-Case Reporting System between 2004 and 2018. Key variables considered when classifying CM among sleep-related SUID were identified. Logistic regression was used to assess the strength of associations and identify factors that distinguished between exposure to hazards and neglect. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Guidelines were developed based on these findings., Results: Among the 13 034 sleep-related SUID with CM identified, hazards in the infant sleep environment were strongly associated with classification of both exposure to hazards and neglect, as were supervisor impairment and child welfare substantiation of the death. Comparing neglect to exposure to hazards, there was no association with sleep environment hazards with ORs ranging from 0.8 to 1.3 (95% CI 0.4-3.0), but sleep-related SUID were approximately twice as likely to be classified as neglect when the supervisor was impaired (OR 2.3, 95% CI 2.0-2.7) or child welfare action was taken (OR 1.8, 95% CI 1.5-2.0). The guidelines recommend classification of exposure to hazards for sleep environment hazards with elevation to neglect if the supervisor was impaired or child welfare substantiated the death., Conclusions: Among sleep-related SUID, classification of exposure to hazards is based on presence of sleep environment hazards, whereas neglect is based on supervisor impairment and child welfare action., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Importance: Sudden infant death syndrome (SIDS) is a major cause of infant death in the US. Previous research suggests that inborn errors of metabolism may contribute to SIDS, yet the relationship between SIDS and biomarkers of metabolism remains unclear., Objective: To evaluate and model the association between routinely measured newborn metabolic markers and SIDS in combination with established risk factors for SIDS., Design, Setting, and Participants: This was a case-control study nested within a retrospective cohort using data from the California Office of Statewide Health Planning and Development and the California Department of Public Health. The study population included infants born in California between 2005 and 2011 with full metabolic data collected as part of routine newborn screening (NBS). SIDS cases were matched to controls at a ratio of 1:4 by gestational age and birth weight z score. Matched data were split into training (2/3) and testing (1/3) subsets. Data were analyzed from January 2005 to December 2011., Exposures: Metabolites measured by NBS and established risk factors for SIDS., Main Outcomes and Measures: The primary outcome was SIDS. Logistic regression was used to evaluate the association between metabolic markers combined with known risk factors and SIDS., Results: Of 2 276 578 eligible infants, 354 SIDS (0.016%) cases (mean [SD] gestational age, 38.3 [2.3] weeks; 220 male [62.1%]) and 1416 controls (mean [SD] gestational age, 38.3 [2.3] weeks; 723 male [51.1%]) were identified. In multivariable analysis, 14 NBS metabolites were significantly associated with SIDS in a univariate analysis: 17-hydroxyprogesterone, alanine, methionine, proline, tyrosine, valine, free carnitine, acetyl-L-carnitine, malonyl carnitine, glutarylcarnitine, lauroyl-L-carnitine, dodecenoylcarnitine, 3-hydroxytetradecanoylcarnitine, and linoleoylcarnitine. The area under the receiver operating characteristic curve for a 14-marker SIDS model, which included 8 metabolites, was 0.75 (95% CI, 0.72-0.79) in the training set and was 0.70 (95% CI, 0.65-0.76) in the test set. Of 32 infants in the test set with model-predicted probability greater than 0.5, a total of 20 (62.5%) had SIDS. These infants had 14.4 times the odds (95% CI, 6.0-34.5) of having SIDS compared with those with a model-predicted probability less than 0.1., Conclusions and Relevance: Results from this case-control study showed an association between aberrant metabolic analytes at birth and SIDS. These findings suggest that we may be able to identify infants at increased risk for SIDS soon after birth, which could inform further mechanistic research and clinical efforts focused on monitoring and prevention.

Single coronary artery (SCA) is a rare malformation, particularly in isolation without other congenital heart defects. Here, we describe a case of sudden infantile death due to myocardial ischemia associated with undiagnosed SCA. A 1-year-and-7-month-old female infant died suddenly after vomiting at home. A medicolegal autopsy revealed that the orifice of the right coronary artery (RCA) was absent. As expected, the left coronary artery was detached from the left coronary sinus; however, the ostium was covered with a flap-like fibrous ridge. The thin RCA originated from the left main trunk (LMT) and passed between the aorta and pulmonary artery trunk. The left circumflex artery branched from the LMT at a right angle. Judging from the origin and course of the anomalous RCA, the deceased was diagnosed with SCA of Lipton's type LII-B. Microscopic examination revealed ischemic changes around the endocardium of the lateral wall of the left ventricle (LV) rather than on the side of the abnormal RCA. This evoked attention, as there appeared to be some discrepancy. To the best of our knowledge, this is the first case report describing sudden infantile death related to LV myocardial ischemia associated with undiagnosed SCA of Lipton's type LⅡ-B., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Organ weights are a possible diagnostic or pathophysiological clue to distinguishing sudden infant death syndrome (SIDS) cases from other infant deaths but suffer from major confounding. Using autopsy data from the Chicago Infant Mortality Study, a majority African-American case-control study of deceased infants under 1 year conducted 1993-96, we assessed differences in the weights of brain, thymus, kidneys, lungs, liver, spleen, total body, and four length anthropometry measures in SIDS-diagnosed infants compared to controls. Using exact and coarsened matching, we ran Bayesian linear models with these anthropometry outcomes and repeated the analyses substituting the corresponding fitted allometrically-scaled organ weight indices to account for body size. After detailed analysis and adjustment for potential confounders, we found that matched SIDS infants were generally bigger than controls, with higher mean brain, liver, spleen, thymus, lung, and total body weights, and higher mean head and chest circumference, crown-heel, crown-rump lengths. SIDS infants also had higher mean thymus, liver, spleen, lung and total body weight indices. The association with thymus weight was proportionately greater in magnitude than any other outcome measure and independent of body size. The results of these more detailed analyses are consistent with recent findings from other studies with differing racial compositions, and substantially confirm the primary organ sites for more detailed mechanistic research into the biological dysregulation contributing to underlying pathophysiology of SIDS., (© 2024 The Author(s). American Journal of Human Biology published by Wiley Periodicals LLC.)

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.

Sudden death in infants remains a common and poorly understood cause of childhood mortality in the USA. Pediatric cardiac tumors, although rare, may underlie some cases of unexplained sudden infant death. Autopsy is a crucial diagnostic step in these cases, as both gross and microscopic examination of the heart may uncover occult cardiac tumors. Rhabdomyomas are the most common cardiac tumors in childhood and may result in arrythmia and sudden death. We present a case of sudden death in a healthy 5-month-old infant which initially appeared "SIDS-like" until thorough histological analysis revealed an underlying cardiac rhabdomyoma. The case is of particular importance in that the gross examination of the heart was considered completely normal, and the tumor only involved certain portions of the heart microscopically. Had a single random section of myocardium been the only heart section examined microscopically, the diagnosis might have been missed. This case emphasizes the importance of thorough microscopic examination in infant cases, especially in cases where the heart appears grossly normal., (© 2024. The Author(s).)

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.

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.

We conducted an autopsy on a 3-month-old boy in whom Kawasaki disease (KD) was strongly suspected based on the autopsy findings. The infant had a fever and was brought to a nearby clinic, where he was prescribed antipyretics and kept under observation. However, 15 days after onset of the fever, he suddenly died in bed. He exhibited no obvious redness of the lips, tongue, or conjunctiva. Membranous desquamation was present on his distal fingers. Vasculitis was observed in the coronary arteries, renal artery, splenic artery, and pulmonary vein. In addition, coronary artery aneurysms were present in the right coronary artery and left anterior descending artery. Thrombotic occlusion was observed in one aneurysm in the right coronary artery, resulting in acute myocardial infarction. The coronary artery wall showed infiltration of numerous macrophages and neutrophils. This case was classified as incomplete KD because the coronary artery aneurysm could not be demonstrated before death and was only recognized at autopsy. Pathologists and forensic scientists need to be aware that there are cases in which KD goes undiagnosed and untreated, leading to coronary artery aneurysm formation and sudden death., (© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Aim: The supine sleeping position in the prevention of sudden infant death syndrome in preterm infants is poorly understood. We aimed to investigate the effect of sleep posture on cardiorespiratory parameters and movement patterns in preterm infants close to discharge., Methods: This observational study included neonates born in 2022 at the University Hospital Schleswig-Holstein, Lübeck, Germany. Motion sensor data, heart rate, respiratory rate and oxygen saturation were recorded for infants with postconceptional age 35-37 weeks during sleep in the prone and supine positions., Results: We recorded data from 50 infants, born at 31 (24-35) weeks of gestation (mean(range)), aged 5.2 ± 3.7 weeks (mean ± SD), of whom 48% were female. Five typical movement patterns were identified. In the prone position, the percentage of calm, regular breathing was higher and active movement was less frequent when compared to the supine position. The percentage of calm irregular breathing, number of apnoeas, bradycardias, desaturations and vital sign changes were not influenced by position., Conclusion: The prone position seems to be associated with a higher arousal threshold. The supine position appears advantageous for escape from life-threatening situations such as sudden infant death syndrome., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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.

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., (© 2024. The Author(s).)

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests and have obtained consent from the family to publish this report. This case report was conducted with full transparency and adherence to ethical standards. There are no financial or personal relationships that could influence the work presented in this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome (SIDS) effects is lacking. We investigated the risk and protective factors related to SIDS., Methods: We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors. PubMed/MEDLINE, Embase, EBSCO, and Google Scholar were searched from inception until January 18, 2023. Data extraction, quality assessment, and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines. According to observational evidence, credibility was graded and classified by class and quality of evidence (CE; convincing, highly suggestive, suggestive, weak, or not significant). Our study protocol was registered with PROSPERO (CRD42023458696). The risk and protective factors related to SIDS are presented as equivalent odds ratios (eORs)., Results: We identified eight original meta-analyses, including 152 original articles, covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents. Several risk factors, including prenatal drug exposure [eOR = 7.84 (95% CI = 4.81-12.79), CE = highly suggestive], prenatal opioid exposure [9.55 (95% CI = 4.87-18.72), CE = suggestive], prenatal methadone exposure [9.52 (95% CI = 3.34-27.10), CE = weak], prenatal cocaine exposure [4.38 (95% CI = 1.95-9.86), CE = weak], prenatal maternal smoking [2.25 (95% CI = 1.95-2.60), CE = highly suggestive], postnatal maternal smoking [1.97 (95% CI = 1.75-2.22), CE = weak], bed sharing [2.89 (95% CI = 1.81-4.60), CE = weak], and infants found with heads covered by bedclothes after last sleep [11.01 (95% CI = 5.40-22.45), CE = suggestive], were identified. On the other hand, three protective factors, namely, breastfeeding [0.57 (95% CI = 0.39-0.83), CE = non-significant], supine sleeping position [0.48 (95% CI = 0.37-0.63), CE = suggestive], and pacifier use [0.44 (95% CI = 0.30-0.65), CE = weak], were also identified., Conclusions: Based on the evidence, we propose several risk and protective factors for SIDS. This study suggests the need for further studies on SIDS-related factors supported by weak credibility, no association, or a lack of adequate research., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

Background/objective: Sudden unexpected infant death (SUID) is a common cause of infant death. We evaluated whether a predictive risk model (PRM) - Hello Baby - which was developed to stratify children by risk of entry into foster care could also identify infants at highest risk of SUID and non-fatal unsafe sleep events., Participants and Setting: Cases: Infants with SUID or an unsafe sleep event over 5½ years in a single county., Controls: All births in the same county., Methods: Retrospective case-control study. Demographic and clinical data were collected and a Hello Baby PRM score was assigned. Descriptive statistics and the predictive value of a PRM score of 20 were calculated., Results: Infants with SUID (n = 62) or an unsafe sleep event (n = 37) (cases) were compared with 23,366 births (controls). Cases and controls were similar for all demographic and clinical data except that infants with unsafe sleep events were older. Median PRM score for cases was higher than controls (17.5 vs. 10, p < 0.001); 50 % of cases had a PRM score 17-20 vs. 16 % of controls (p < 0.001)., Conclusions: The Hello Baby PRM can identify newborns at high risk of SUID and non-fatal unsafe sleep events. The ability to identify high-risk newborns prior to a negative outcome allows for individualized evaluation of high-risk families for modifiable risk factors which are potentially amenable to intervention. This approach is limited by the fact that not all counties can calculate a PRM or similar score automatically., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., (© 2024. The Author(s).)

Sudden unexpected postnatal collapse (SUPC) of healthy newborns is a catastrophic event caused by cardiorespiratory collapse in a healthy newborn. The most common cause of SUPC is poor positioning of the newborn during skin-to-skin contact or breastfeeding when the newborn is not being observed by a health professional, attentive parent, or caretaker. Maternal/newborn health care professionals need to know about the essential information, definitions, incidence, risk factors, clinical presentation, outcomes, and prevention and management strategies to minimize the occurrence and impact of SUPC. A sample SUPC hospital policy is included in the manuscript., (© Copyright 2024 Springer Publishing Company, LLC.)

Background: Prematurity is one of the risk factors for sudden unexpected infant death (SUID), a phenomenon that remains poorly explained., Materials and Methods: The analysis of specific factors associated with SUID among very premature infants (VPI) was performed through a retrospective review of data collected in the French SUID registry from May 2015 to December 2018. The factors associated with SUID among VPI were compared with those observed among full-term infants (FTI). Results are expressed as means (standard deviation [SD]) or medians (interquartile range [IQR)]., Results: During the study period, 719 cases of SUID were included in the registry, 36 (incidence: 0.60 ‰) of which involved VPI (gestational age: 29.2 [2] weeks, 1157 [364]) g] and 313 (0.18 ‰) involved FTI (gestational age: 40 [0.8] weeks, 3298 [452] g). The infants' postnatal age at the time of death was similar in the two groups: 15.5 (12.2-21.8) vs. 14.5 (7.1-23.4) weeks. We observed low breastfeeding rates and a high proportion of fathers with no occupation or unemployment status among the VPI compared to the FTI group (31% vs. 55 %, p = 0.01 and 32% vs. 13 %, p = 0.05, respectively). Among the VPI, only 52 % were in supine position, and 29 % were lying prone at the time of the SUID (compared to 63 % and 17 %, respectively, in the FTI group)., Conclusion: This study confirms prematurity as a risk factor for SUID with no difference in the SUID-specific risk factors studied except for breastfeeding and socioeconomic status of the fathers. VPI and FTI died at similar chronological ages with a high proportion of infants dying in prone position. These results argue for reinforcement of prevention strategies in cases of prematurity., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Masson SAS.)

A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We present the case of a 23-month-old child who died less than 24 h after the onset of cardiac symptoms, despite being admitted to the hospital 72 h earlier. Autopsy revealed no significant macroscopic changes, and histologic examination revealed focal lymphocytic myocarditis with myocyte disruption, diffuse alveolar damage in the exudative phase, and generalized lymphocytic immune activation in other organs. Ante-mortem and post-mortem microbiological exams did not clearly prove a causative role of infectious agents. The peculiarity of this case was characterized by the contrast between the severe clinical features and the mild cardiac histological findings. This discrepancy, coupled with the suspicion of a viral causative role based on both ante-mortem and post-mortem microbiological examinations, presented significant challenges in reaching an etiological diagnosis. This case also confirms that the diagnosis of myocarditis in children cannot be made solely on the basis of histological cut-offs or microbiological results. Using abductive reasoning, various diagnostic hypotheses were formulated and evaluated to arrive at the final diagnosis of fatal myocarditis of viral or post-viral origin. Data from post-mortem examination are often the only source of information that is available to the experts, especially in cases of sudden infant death syndrome. In such cases, the forensic pathologists should accurately evaluate findings that may appear to indicate a different etiology, and, in the absence of clinical or radiological data, interpret post-mortem data in a logically correct manner. The autopsy is the first essential step to evaluate the cause of death and must be integrated with the results of ante- and post-mortem diagnostic tests in a holistic approach, which is crucial to allow forensic pathologists to provide an appropriate and relevant opinion., (© 2023. The Author(s).)

Background: Mandatory joint police and healthcare investigations of sudden unexpected death in infancy (SUDI) have been in place since 2008 in England. These include death scene examination with cause of death determined at multiprofessional case conference. Detailed evidence on sleep arrangements is available for most cases potentially leading to more being identified as due to accidental suffocation. SUDI remaining unexplained following investigation are classified as SIDS (sudden infant death syndrome) or unspecified deaths.Our objective was to determine whether detailed SUDI investigation has led to an increase in deaths classified as accidental suffocation or strangulation in bed (ASSB)?, Methods: We obtained official mortality data for England and Wales for infants dying aged 0-364 days for International Statistical Classification of Diseases and Related Health Problems, 10th revision codes R95 (SIDS), R96, R98, R99 (unspecified causes of mortality) and W75 (ASSB) for the years 2000-2019.We calculated the mortality rate for ASSB, SIDS and unspecified causes based on total live births each year., Results: Unexplained SUDI decreased from 353 in 2000 to 175 in 2019, with the mortality rate falling from 0.58 to 0.29 per 1000 live births. The total postneonatal mortality rate fell during this time from 1.9 to 0.9 per 1000 live births suggesting this is a genuine fall. SIDS accounted for 70% of unexplained SUDI in 2000 falling to 49% in 2020 with a corresponding increase in R99 unspecified deaths.Few deaths were recorded as ASSB (W75), ranging between 4 in 2010 and 24 in 2001. The rate for ASSB ranged from 0.6 to 4.0 per 100000 live births., Conclusions: There is a shift away from SIDS (R95) towards unspecified causes of death (R96, R98, R99). Improved investigation of deaths has not led to increased numbers of death identified as due to ASSB. There needs to be clear guidelines on accurate classification of deaths from ASSB to facilitate learning from deaths and inform prevention efforts., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; JGG has received research grants from NIHR for research into improving parental involvement in child death review (NIHR 203045), she is paid by the National Child Mortality Database as a specialist clinical advisor. JGG has been paid for developing and delivering educational presentations relating to Child Death for the Primary Care Conference, Stirling Events. JGG acts as expert witness for legal cases related to sudden child death, JGG has received funding from the Lullaby Trust to attend scientific meetings overseas; JGG is Chair of the Association of Child Death Review Professionals (UK), medical advisor to SUDC-UK (Sudden Unexplained Death in Childhood) and a member of the Lullaby Trust scientific committee no other relationships or activities that could appear to have influenced the submitted work. MM has no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The aim of this study was to investigate a panel of immune proteins in cases of sudden infant death syndrome (SIDS). It was hypothesised that, in at least a subset of SIDS, a dysregulated immune response may be a contributing factor leading to death., Methods: The subjects included 46 SIDS cases and 41 controls autopsied at the Department of Forensic Sciences, Norway. The causes of death in the controls were accidents/trauma. Samples of cerebrospinal fluid (CSF) were analysed quantitatively by Proximity Extension Assay (PEA)., Results: Initial results revealed that normalised protein expression differed in 35 proteins. For the purposes of this report five proteins that are involved in immune system were selected for analysis: IFNLR1 (p = 0.003), IL10 (p = 0.007), IRAK4 (p < 0.001) and IL6 (p = 0.035); all had lower protein concentrations in SIDS cases compared to controls except for CD28 (p = 0.024) which had higher protein concentrations in SIDS cases., Conclusion: The results confirm previous studies indicating that a dysregulation of the immune system may be a predisposing factor for SIDS. The results may indicate that these aberrant protein concentrations could lead to an inadequate response to immune triggers and uncontrolled defence mechanisms towards the common cold or other non-fatal infections., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

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., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sudden unexpected infant death may be explained, cause by an etiology, unexplained but insufficiently investigated, or unexplained when a full investigation fails to determine the cause. Unexplained sudden death in infancy or sudden infant death syndrome particularly affects the most vulnerable populations. The death of these children who are born with alterations in their neurodevelopment is the visible part of a problem that originates in pregnancy. Reducing the number of vulnerable children depends on health policies and, above all, on improving the living conditions of the population. These are long-term actions. Knowing in depth the risk factors that can trigger unexpected death is what can be done now. The update of the recommendations on safe sleep reflects new knowledge based on scientific evidence and a comprehensive approach to the sociocultural aspects related to this problem., (Sociedad Argentina de Pediatría.)

Objectives: Using the National Child Mortality Database, this work aims to investigate background characteristics and risk factors in the sleeping environment associated with sudden infant death syndrome (SIDS) and compare the prevalence with previous English SIDS case-control studies., Design: Cohort of SIDS in 2020 compared with a combined analysis of two case-control studies conducted in 1993-1996 and 2003-2006., Setting: England, UK PARTICIPANTS: 138 SIDS deaths in 2020 compared with 402 SIDS deaths and 1387 age-equivalent surviving controls, combined from previous studies., Results: The increased vulnerability of SIDS infants identified in previous studies has become more marked. The infants who died in 2020 were younger (median=66 days (IQR: 34-118) vs 86 days (IQR: 52-148), p=0.003) with an increased prevalence of low birth weight (30.5% vs 21.6%, p=0.04) and preterm births (29.6% vs 19.3%, p=0.012). The excess of socioeconomically deprived families, male infants and high levels of maternal smoking during pregnancy were still evident. Among recent deaths, fewer infants were put down or found on their side; however, there was no significant change in the proportion of infants who were put down (15.6% vs 14.6%, p=0.81) and found prone (40.4% vs 35.3%, p=0.37), despite population wide risk reduction advice over three decades. The proportional increase observed in 2003-2006 of half the deaths occurring while sleeping next to an adult was maintained in 2020, and for the vast majority (90%), this was in hazardous circumstances (adult had consumed alcohol, smoked, slept on a sofa, or the infant was premature or low birth weight and less than 3 months old). More deaths also occurred when there was a disruption in infant care routine compared with previous observations (52.6% vs 20.7%, p<0.001)., Conclusions: A more targeted approach is needed with vulnerable families emphasising the importance of sleeping infants on their back and proactive planning infant sleep when there are disruptions to the normal routine, in particular to avoid hazardous co-sleeping., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

From the earliest publications on cot death or sudden infant death syndrome (SIDS) through to this day, clinical pathology and epidemiology have strongly featured infection as a constant association. Despite mounting evidence of the role of viruses and common toxigenic bacteria in the pathogenesis of SIDS, a growing school of thought featuring a paradigm based on the triple risk hypothesis that encompasses vulnerability through deranged homoeostatic control of arousal and/or cardiorespiratory function has become the mainstream view and now dominates SIDS research. The mainstream hypothesis rarely acknowledges the role of infection despite its notional potential role as a cofactor in the triple hit idea. Decades of mainstream research that has focussed on central nervous system homoeostatic mechanisms of arousal, cardiorespiratory control and abnormal neurotransmission has not been able to provide consistent answers to the SIDS enigma. This paper examines the disparity between these two schools of thought and calls for a collaborative approach. IMPACT: The popular research hypothesis explaining sudden infant death syndrome features the triple risk hypothesis with central nervous system homoeostatic mechanisms controlling arousal and cardiorespiratory function. Intense investigation has not yielded convincing results. There is a necessity to consider other plausible hypotheses (e.g., common bacterial toxin hypothesis). The review scrutinises the triple risk hypothesis and CNS control of cardiorespiratory function and arousal and reveals its flaws. Infection-based hypotheses with their strong SIDS risk factor associations are reviewed in a new context., (© 2023. The Author(s).)

Infection is an important cause of death during infancy worldwide and is a frequent etiology of sudden unexpected death in infancy (SUDI). Procalcitonin (PCT) is a useful marker to diagnose infection in patients, and several studies report the stability of PCT after death. The added value of a biological marker, such as the PCT level in the blood, remains controversial in investigating SUDI. The aim of this study was to determine if PCT can help clinicians determine whether infection caused SUDI. We conducted a retrospective, multicenter study with the French SUDI registry (Observatoire National des Morts Inattendues du Nourrisson; OMIN). We collected data from this registry on children who died between May 2015 and June 2021. The levels of PCT in the blood of 540 SUDI patients were measured. We compared PCT and other biological tests performed in terms of infection status, autopsy results, and cause of death using clinical and biological data compiled by pediatricians at the SUDI referral center. PCT levels were significantly higher in the children who died from infection than in those who did not (0.12 µg/L vs. 0.08 µg/L, p < 0.001). A PCT blood level exceeding 0.2 µg/L was more frequently observed when infection was present than in the absence of infection (44.3% vs. 15.4%, p < 0.001). The same data were obtained with a 0.5 µg/L cut-off (36.1% with infection vs. 9.2% without, p < 0.001).  Conclusions: PCT is a sensitive biomarker for detecting infections postmortem; thus, additional samples may be necessary during autopsy. What is known: • PCT is a stable marker postmortem and increases earlier than CRP, i.e., 2-4 h after the beginning of an infection vs. 6 h. • PCT can be measured up to 140 h after death. What is new: • PCT is a sensitive marker for detecting infection in SUDI patients postmortem. • This test can reveal an infection from non-standardized samples obtained during autopsy if such an infection was not determined before death., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim was to study whether non-combustible nicotine (Swedish snuff) use in pregnancy is associated with elevated risk of post neonatal mortality, Sudden Infant Death Syndrome (SIDS), and Sudden Unexpected Infant Death (SUID) and to study how cessation before the antenatal booking influenced these risks., Methods: This was a population-based register study of all infants with information on tobacco exposure in early pregnancy born in Sweden 1999-2019, n = 2,061,514. Self-reported tobacco use in early pregnancy was categorized as nonuse, snuff use, and moderate and heavy smoking. Multiple logistic regression models were used to estimate crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs)., Results: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. The risks of snuff use and moderate smoking were of similar magnitude. Heavy smoking was associated with the highest risks. Cessation of smoking and snuff use before the antenatal booking was associated with lower risks of SIDS and SUID compared to that of continuous usage., Conclusions: Maternal snuff use was associated with increased risks of post neonatal mortality, SIDS, and SUID. Nicotine is the common substance in cigarette smoke and snuff. These findings support the hypothesis that nicotine contributes to an elevated risk of SIDS., Impact: Maternal snuff use and smoking in early pregnancy were associated with increased risks of post neonatal mortality, SIDS, and SUID. Cessation of smoking and snuff use before the first antenatal visit was associated with reduced risks of SIDS and SUID. The common substance in cigarette smoke and snuff is nicotine. Our findings suggest that nicotine contributes to an elevated risk of SIDS and SUID. The implication of our findings is that all forms of nicotine should be avoided in pregnancy., (© 2023. The Author(s).)

Sudden Infant Death Syndrome (SIDS) occurs during sleep in seemingly healthy infants. Maternal cigarette smoking and hypoxemia during sleep are assumed to be the major causal factors. Depressed hypoxic ventilatory response (dHVR) is observed in infants with high risk of SIDS, and apneas (lethal ventilatory arrest) appear during the fatal episode of SIDS. Disturbance of the respiratory center has been proposed to be involved, but the pathogenesis of SIDS is still not fully understood. Peripherally, the carotid body is critical to generate HVR, and bronchopulmonary and superior laryngeal C-fibers (PCFs and SLCFs) are important for triggering central apneas; however, their roles in the pathogenesis of SIDS have not been explored until recently. There are three lines of recently accumulated evidence to show the disorders of peripheral sensory afferent-mediated respiratory chemoreflexes in rat pups with prenatal nicotinic exposure (a SIDS model) in which acute severe hypoxia leads to dHVR followed by lethal apneas. (1) The carotid body-mediated HVR is suppressed with a reduction of the number and sensitivity of glomus cells. (2) PCF-mediated apneic response is largely prolonged via increased PCF density, pulmonary IL-1β and serotonin (5-hydroxytryptamine, 5-HT) release, along with the enhanced expression of TRPV1, NK 1 R, IL1RI and 5-HT 3 R in pulmonary C-neurons to strengthen these neural responses to capsaicin, a selective stimulant to C-fibers. (3) SLCF-mediated apnea and capsaicin-induced currents in superior laryngeal C-neurons are augmented by upregulation of TRPV1 expression in these neurons. These results, along with hypoxic sensitization/stimulation of PCFs, gain insight into the mechanisms of prenatal nicotinic exposure-induced peripheral neuroplasticity responsible for dHVR and long-lasting apnea during hypoxia in rat pups. Therefore, in addition to the disturbance in the respiratory center, the disorders of peripheral sensory afferent-mediated chemoreflexes may also be involved in respiratory failure and death denoted in SIDS victims., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To describe pre-COVID-19 pandemic current practices in virological investigations, including type, frequency of samplings, and documented viruses, in sudden unexpected death in infancy (SUDI) and to compare results according to the cause of death., Study Design: Between May 2015 and December 2019, infants under 2 years of age included in the French SUDI registry were classified in one of 4 groups by causes of death according to the classification by Goldstein et al. : unexplained (SIDS), infectious, explained but noninfectious, and undetermined. Sampling sites and viruses detected were described, and then SIDS and explained deaths (control group) were compared., Results: Among 639 infants, 3.6% died of an established viral infection. From 23 sampling sites and 2238 samples, 19 virus species were detected. Overall, 43.3% of infants carried a virus, with no significant difference between SIDS infants and the control group (P = .06). We found wide variations in frequencies of samples by site (550 for nasopharynx to one for saliva). The highest positivity rate was from the nasopharynx (195/2238; 8.7%). Rhinovirus was the predominant virus detected (135/504; 26.8%), mostly in SIDS (83/254; 32.7%). We found no significant difference between positivity rates and distribution of viruses between the SIDS and control groups. At-autopsy virological analysis never contributed to determining the cause of death., Conclusion: Current practices in virological investigations in SUDI are heterogeneous, with wide variability despite published guidelines. Investigations should be limited to the most relevant sites, and systematic at-autopsy sampling should be reconsidered. We found no association between virus detection and SIDS., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

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., (© 2023. The Author(s).)

Background: Infection is thought to play a part in some infant deaths. Maternal infection in pregnancy has focused on chlamydia with some reports suggesting an association with sudden unexpected infant death (SUID)., Objectives: We hypothesized that maternal infections in pregnancy are associated with subsequent SUID in their offspring., Setting: All births in the United States, 2011-2015., Data Source: Centers for Disease Control and Prevention (CDC) Birth Cohort Linked Birth-Infant Death Data Files., Study Design: Cohort study, although the data were analysed as a case control study. Cases were infants that died from SUID. Controls were randomly sampled infants that survived their first year of life; approximately 10 controls per SUID case., Exposures: Chlamydia, gonorrhea and hepatitis C., Results: There were 19,849,690 live births in the U.S. for the period 2011-2015. There were 37,143 infant deaths of which 17,398 were classified as SUID cases (a rate of 0.86/1000 live births). The proportion of the control mothers with chlamydia was 1.7%, gonorrhea 0.2% and hepatitis C was 0.3%. Chlamydia was present in 3.8% of mothers whose infants subsequently died of SUID compared with 1.7% of controls (unadjusted OR = 2.35, 95% CI = 2.15, 2.56; adjusted OR = 1.08, 95% CI = 0.98, 1.19). Gonorrhea was present in 0.7% of mothers of SUID cases compared with 0.2% of mothers of controls (OR = 3.09, (2.50, 3.79); aOR = 1.20(0.95, 1.49)) and hepatitis C was present in 1.3% of mothers of SUID cases compared with 0.3% of mothers of controls (OR = 4.69 (3.97, 5.52): aOR = 1.80 (1.50, 2.15))., Conclusions: The marked attenuation of SUID risk after adjustment for a wide variety of socioeconomic and demographic factors suggests the small increase in the risk of SUID of the offspring of mothers with infection with hepatitis C in pregnancy is due to residual confounding., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Weatherly et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: Although PJF was a member of the NICE guidance committee that reached the conclusions on the risks associated with bed-sharing in 2021, he was excluded by NICE from the discussion and decisions on this part of the guidance because of his personal contribution to so many of the papers being discussed. HLB is Chair of the Lullaby Trust Scientific Committee (which awards research funding when this is available) and serves on the Scientific Advisory Panel, as does AP.

Objective: Although the US infant mortality rate reached a record low in 2020, the sudden infant death syndrome (SIDS) rate increased from 2019. To understand if the increase was related to changing death certification practices or the coronavirus disease 2019 (COVID-19) pandemic, we examined sudden unexpected infant death (SUID) rates as a group, by cause, and by race and ethnicity., Methods: We estimated SUID rates during 2015 to 2020 using US period-linked birth and death data. SUID included SIDS, unknown cause, and accidental suffocation and strangulation in bed. We examined changes in rates from 2019 to 2020 and assessed linear trends during prepandemic (2015-2019) using weighted least squares regression. We also assessed race and ethnicity trends and quantified COVID-19-related SUID., Results: Although the SIDS rate increased significantly from 2019 to 2020 (P < .001), the overall SUID rate did not (P = .24). The increased SIDS rate followed a declining linear trend in SIDS during 2015 to 2019 (P < .001). Other SUID causes did not change significantly. Our race and ethnicity analysis showed SUID rates increased significantly for non-Hispanic Black infants from 2019 to 2020, widening the disparities between these two groups during 2017 to 2019. In 2020, <10 of the 3328 SUID had a COVID-19 code., Conclusions: Diagnositic shifting likely explained the increased SIDS rate in 2020. Why the SUID rate increased for non-Hispanic Black infants is unknown, but warrants continued monitoring. Interventions are needed to address persistent racial and ethnic disparities in SUID., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: For sudden infant death syndrome (SIDS), an impaired immunocompetence has been discussed for a long time. Cytokines and chemokines are soluble immune mediators (SIM) whose balance is essential for the immune status. We hypothesized that an imbalanced immune response might contribute to the etiology of SIDS., Methods: We investigated 27 cytokines, chemokines, and growth factors in protein lysates of lungs derived from 29 SIDS cases and 15 control children deceased for other reasons., Results: Except for the CCL5, no significant differences were detected in the lungs between SIDS cases with and without mild upper respiratory tract infections. In contrast, IL-1RA, IL-7, IL-13, and G-CSF were decreased in the merged SIDS cases compared to control cases without evidence of infection. Plotting SIM concentrations against infant age resulted in increasing concentrations in control but not in SIDS lungs, indicating a disturbed immune maturation. Moreover, an age-dependent shift towards a Th2-related pattern was observed in SIDS., Conclusions: Our findings suggest that an impaired maturation of the immune system, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in triggering SIDS. These findings might in part be explained by chronic stress., Impact: Maturation of the cytokine and chemokine network may be impaired in SIDS. An imbalance between Th1- and Th2-related cytokines, which may reflect a state of chronic stress causing a more Th2 shift. An impaired immune maturation, an insufficient response to respiratory pathogens, and an immune response modulated by Th1/Th2 imbalance might play a possible role in SIDS., (© 2022. The Author(s).)

Background: Prenatal smoking increases the risk of Sudden Unexpected Infant Death (SUID). Whether exposure patterns and associations differ by race requires further study., Objectives: Determine if patterns of exposure and associations between SUID and maternal smoking before and during pregnancy differ by race., Methods: Using U.S. National Center for Health Statistics linked birth/infant death files 2012-2013, we documented SUID by smoking duration and race. Maternal smoking history: never, pre-pregnancy only, and pre-pregnancy plus first, first, second, or all trimesters., Results: Smoking was more common in non-Hispanic White (NHW) than non-Hispanic Black (NHB) mothers and more evident for both in SUID cases. The most common exposure duration is from before and throughout pregnancy (SUID: 78.3% NHW, 66.9% NHB; Survivors: 60.22% and 53.96%, respectively). NHB vs. NHW SUID rates per 1000 live births were 1.07 vs. 0.34 for non-smokers and 3.06 and 1.79 for smokers, ORs trended upward for both with increasing smoking duration., Conclusion: Fewer NHB mothers smoked, but both NHB and NHW groups exhibited a dose-response relationship between smoking duration and SUID. The most common duration was from before to the end of pregnancy, suggesting difficulty in quitting and a need for effective interventions., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Competing Interests: Competing interests: None declared.

Importance: Sudden infant death syndrome (SIDS) remains a leading cause of death during the first year of life. The etiology of SIDS is complex and remains largely unknown., Objective: To evaluate whether siblings of children who died of SIDS have a higher risk of SIDS compared with the general pediatric population., Design, Setting, and Participants: This register-based cohort study used Danish nationwide registers. Participants were all infants (<1 year) in Denmark between January 1, 1978, and December 31, 2016, including siblings of children who died of SIDS. Siblings were followed up from the index cases' date of SIDS, date of birth, or immigration, whichever came first, and until age 1 year, emigration, developing SIDS, death, or study end. The median (IQR) follow-up was 1 (1-1) year. Data analysis was conducted from January 2017 to October 2022., Main Outcomes and Measures: Standardized incidence ratios (SIRs) of SIDS were calculated with Poisson regression models relative to the general population., Results: In a population of 2 666 834 consecutive births (1 395 199 [52%] male), 1540 infants died of SIDS (median [IQR] age at SIDS, 3 [2-4] months) during a 39-year study period. A total of 2384 younger siblings (cases) to index cases (first sibling with SIDS) were identified. A higher rate of SIDS was observed among siblings compared with the general population, with SIRs of 4.27 (95% CI, 2.13-8.53) after adjustment for sex, age, and calendar year and of 3.50 (95% CI, 1.75-7.01) after further adjustment for mother's age (<29 years vs ≥29 years) and education (high school vs after high school)., Conclusions and Relevance: In this nationwide study, having a sibling who died of SIDS was associated with a 4-fold higher risk of SIDS compared with the general population. Shared genetic and/or environmental factors may contribute to the observed clustering of SIDS. The family history of SIDS should be considered when assessing SIDS risk in clinical settings. A multidisciplinary genetic evaluation of families with SIDS could provide additional evidence.

Background: Observational studies have improved our understanding of the risk factors for sudden infant death syndrome, but separate examination of risk for sleep-related suffocation and unexplained infant deaths has been limited. We examined the association between unsafe infant sleep practices and sudden infant deaths (sleep-related suffocation and unexplained causes including sudden infant death syndrome)., Methods: We conducted a population-based case-control study using 2016 to 2017 Centers for Disease Control and Prevention data. Controls were liveborn infants from the Pregnancy Risk Assessment Monitoring System; cases were from the Sudden Unexpected Infant Death Case Registry. We calculated risk factor prevalence among cases and controls and crude and adjusted odds ratios., Results: We included 112 sleep-related suffocation cases with 448 age-matched controls and 300 unexplained infant death cases with 1200 age-matched controls. Adjusted odds for sleep-related suffocation ranged from 18.7 (95% confidence interval [CI]: 6.8-51.3) among infants not sharing a room with their mother or caregiver to 1.9 (95% CI: 0.9-4.1) among infants with nonsupine sleep positioning. Adjusted odds for unexplained death ranged from 7.6 (95% CI: 4.7-12.2) among infants not sharing a room with their mother or caregiver to 1.6 (95% CI: 1.1-2.4) among nonsupine positioned infants., Coclusions: We confirmed previously identified risk factors for unexplained infant death and independently estimated risk factors for sleep-related suffocation. Significance of associations for suffocation followed similar patterns but was of larger magnitude. This information can be used to improve messaging about safe infant sleep., (Copyright © 2023 by the American Academy of Pediatrics.)