Sudden Infant Death Research Articles

Diagnosing milk aspiration as a cause of death in sudden unexpected infant death: forensic insights from post-mortem analysis impacting criminal investigations.

Sudden unexpected infant death (SUID) encompasses both explained and unexplained infant fatalities. When a comprehensive investigation yields inconclusive results, the case is classified as sudden infant death syndrome (SIDS). On the other hand, the most frequent non-SIDS diagnoses may be attributed to specific causes of death including a heterogeneous spectrum of conditions and disorders (e.g., trauma, asphyxia, suffocation, infection and metabolic diseases). Although rare, milk aspiration is a recognized cause of SUID that can lead to acute respiratory failure. This case report describes the death of a three-month-old infant found unresponsive in a traditional African baby carrier. Gross examination revealed no significant anomalies other than increased lung weight and the presence of milk-like material in the airways, alveoli, and stomach. Histological and ultrastructural analyses identified granular brownish material with birefringent globules in the lungs, consistent with aspirated milk. Immunohistochemical staining was positive for beta-lactoglobulin, confirming formula milk aspiration. This evidence was crucial in excluding maternal negligence as a cause of death, instead supporting an ante-mortem aspiration event resulting from regurgitation. This case highlights the diagnostic challenges associated with fatal milk aspiration and emphasizes the critical importance of a multidisciplinary approach. The integration of clinical history, autopsy findings, and advanced histopathological techniques is essential for accurately determining the cause of death and ensuring a sound legal assessment within the Courtroom setting.

The association of public health interventions regarding both infant sleep position and pertussis immunization with sudden infant death syndrome rates: an ecological study.

Infections may play a role in the etiology of sudden infant death syndrome (SIDS), with Bordetella pertussis being a potential agent. The objective was to analyze the association of SIDS and infant pertussis hospitalization rates over time, comparing a previously unvaccinated population (West Germany) versus a predominantly vaccinated population (East Germany). We calculated SIDS rates per 1000 live births per state. Live births and SIDS were available from 1980 onwards for the West German states and from 1991 onwards for the East German states. We applied interrupted time series (ITS) analyses to investigate the role of two public health interventions in 1991 (West Germany) and in 2000 (West and East Germany), respectively. Infant pertussis hospitalizations were available for five West German and three East German states between 1994 and 2019. We used multilayer and multivariate correlation analyses to determine the correlation between SIDS and pertussis hospitalization rates, including Pearson correlation test and vector autoregressive (VAR) analysis. In West Germany, the average annual SIDS rate (per 1000 live births) increased from 1.08 in 1980 to 1.68 in 1991, before declining to 1.18 in 1992 and subsequently to 0.10 in 2020. In East Germany, the average annual SIDS rate (per 1000 live births) decreased from 0.79 in 1991 to 0.12 in 2020. The results of the ITS model indicated a significant change in both level and slope at the 1991 interventions (West Germany) and in slope at the 2000 interventions (West and East Germany). The correlation coefficients between SIDS and infant pertussis hospitalization rates were 0.69 (95% CI [confidence interval]0.41, 0.85; p < 0.001) in West Germany, and 0.41 (95% CI 0.03, 0.69; p = 0.037) in East Germany. The correlation decreased during later periods (2000-2019, 2010-2019), particularly in East Germany. The results of the VAR analysis corroborated the findings of the main analyses. SIDS and infant pertussis hospitalization rates were correlated in both West and East Germany. Further studies - including improved diagnostic assessment of pertussis - seem warranted. Not applicable.

Prevalence of sudden unexpected death of infants and its subcategories in low- or middle-income countries: a systematic review protocol.

Infant mortality in low or middle-income countries (LoMICs) is still triple that of high-income countries (HICs), and the high mortality burden regions are also weighed down by a triple or quadruple burden of disease such as HIV and tuberculosis; chronic illness; mental health; injury and violence; and maternal, neonatal and child mortality. Emerging data suggest that the sudden unexpected death in infancy (SUDI) burden in LoMICs is at least 10-fold that in HICs. While ending preventable deaths in the neonatal period has received some global attention, the postnatal period where SUDIs occur is a poorly understood and data-poor area in LoMICs. We propose conducting a systematic review to evaluate the burden and trends of SUDIs in LoMICs since 2004. We will systematically search PubMed, Web of Science, Scopus, African Index Medicus, EBSCOHost, Google Scholar, WHOIS and WHO database to identify studies published from July 2004 until October 2024. Two reviewers will screen titles and abstracts and select full-text articles independently for review. We will use the tool developed by the South African Medical Research Council-Burden of Disease Review Manager (BODRevMan)-to assess the risk of bias for each included study. Risk of bias will be assessed for each included study. Information on the prevalence and/or incidence of SUDI and its subcategories and case definitions will be extracted from each article. Where possible, data on prevalence, incidence and subcategories will be pooled using a random effects meta-analysis to account for variability between estimates. The I2 statistic will establish the level of heterogeneity due to variation in estimates rather than chance. Results will be presented in tables and graphs. The systematic review will be reported according to the PRISMA 2020 checklist. Ethical approval is not required as this is a protocol for a systematic review. Findings will be disseminated through peer-reviewed publications and conference presentations. CRD42023466162.

PPA2-associated cardiac arrest survivor.

Biallelic pathogenic variants in the inorganic pyrophosphatase 2 (PPA2) gene are a rare but established cause of sudden infant death, which may be precipitated by a pyrexial or viral illness. It has also been associated with sudden death secondary to alcohol ingestion in young adults. We describe the case of a thirteen-month-old female who presented following out-of- hospital cardiac arrest and was subsequently diagnosed with compound, heterozygous pathogenic variants of PPA2. She survived this episode and made excellent neurological recovery despite her prolonged out-of-hospital resuscitation. This case describes her initial presentation, consideration of PPA2-related cardiac arrest in the differential diagnosis, and the subsequent secondary preventative strategies. These included insertion of an implantable cardiac defibrillator, avoidance of alcohol in her medication preparations and administration of childhood vaccinations in a hospital environment due to risk of pyrexia-induced arrhythmias.

Sudden Unexpected Infant Death and Disparities in Infant Mortality in the US, 1999-2022

This cross-sectional study examines temporal trends and disparities in specific causes of infant death in the US from 1999 to 2022.

Sudden Death of a Four-Day-Old Newborn Due to Mitochondrial Trifunctional Protein/Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiencies and a Systematic Literature Review of Early Deaths of Neonates with Fatty Acid Oxidation Disorders

Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD.

Evolution of sleep disordered breathing in infants with achondroplasia.

Children with achondroplasia (ACH) are at risk for sudden death in infancy due to sleep disordered breathing (SDB) and foramen magnum stenosis (FMS). Sleep studies and neuroimaging are performed in infants with ACH, but interpretation of infant studies is challenging. We sought to describe baseline data on polysomnography (PSG) indices in infants with achondroplasia as well as effects of age and surgery on these parameters. Retrospective data were abstracted from the multisite CLARITY ACH database from years 2008-2017. Both obstructive apnea hypopnea index (OAHI) and central apnea index (CAI) were extracted, and effects of age and surgical intervention (adenoidectomy [AD] or cervicomedullary decompression [CMD]) were analyzed. 172 PSGs from 86 infants were analyzed. In surgically naive children, OAHI decreased over the first year but then increased in the second year, while CAI was mostly stagnant over the first two years. There were no significant differences between age at first PSG or PSG indices for surgically naive infants versus those who underwent AD or CMD. OAHI decreased after AD and CAI decreased after CMD. Similar to average stature infants, our results demonstrate the need to interpret sleep study findings of children with ACH in the context of age, particularly for obstructive indices. Neither OAHI nor CAI differentiated those infants who subsequently underwent surgery, suggesting that there were other important clinical factors in the surgical decision-making process. Independent of age, AD resulted in improvement in OSA and CMD with improvement in central sleep apnea.

Integrating Infant Safe Sleep and Breastfeeding Education Into an App in a Novel Approach to Reaching High-Risk Populations: Prospective Observational Study.

Sudden unexpected infant death (SUID) is a leading cause of death for US infants, and nonrecommended sleep practices are reported in most of these deaths. SUID rates have not declined over the past 20 years despite significant educational efforts. Integration of prenatal safe sleep and breastfeeding education into a pregnancy app may be one approach to engaging pregnant individuals in education about infant care practices prior to childbirth. This study aims to assess whether pregnant individuals would engage with prenatal safe sleep and breastfeeding education provided within a pre-existing pregnancy app. Secondary objectives were to compare engagement among those at high and low risk of losing an infant to SUID and to assess the importance of end user push notifications for engagement. This prospective observational study was conducted from September 23, 2019 to March, 22 2022; push notifications were removed on October 26, 2021. TodaysBaby (University of Virginia, Boston University, and Washington University), a mobile health program in which safe sleep and breastfeeding video education was originally provided via texts, was embedded into the MyHealthyPregnancy app (Naima Health LLC). Pregnant mothers who received prenatal care within the University of Pittsburgh Medical Center hospital system were randomized to receive either safe sleep or breastfeeding education beginning at the start of the third trimester of pregnancy and ending 6 weeks post partum. Pregnant persons were designated as high risk if they lived in the 5% of zip codes in Allegheny County, Pennsylvania with the highest rates of SUID in the county. The primary outcome was engagement, defined as watching at least 1 video either in response to a push notification or directly from the app's learning center. A total of 7572 pregnant persons were enrolled in the TodaysBaby Program-3308 with push notifications and 4264 without. The TodaysBaby engagement rate was 18.8% with push notifications and 3.0% without. Engagement was highest in the initial weeks after enrollment, with a steady decline through pregnancy and very little postpartum engagement. There was no difference in engagement between pregnant persons who were low and high risk. The most viewed videos were ones addressing the use of pacifiers, concerns about infant choking, and the response of the body to the start of breastfeeding. Integrating safe sleep and breastfeeding education within a pregnancy app may allow for rapid dissemination of infant care information to pregnant individuals. Birthing parents at high risk of losing an infant to SUID-a leading cause of infant death after 1 month of age-appear to engage with the app at the same rates as birth parents who are at low risk. Our data demonstrate that push notifications increase engagement, overall and for those in high-risk zip codes where the SUID education is likely to have the most impact.

Identification of Mutations of the RYR2 in Sudden Infant Death Syndrome

Identification of Mutations of the <i>RYR2</i> in Sudden Infant Death Syndrome

Neurodevelopmental and Neuropsychiatric Perspectives on Respiratory Control: Understanding Congenital and Developmental Disorders

: Breathing is an automatic process generated by the central nervous system, crucial for the homeostasis of several body processes. This vital process is underpinned by an intricate network in which distinct functional and anatomical factors and structures play a role. Transcription factors (i.e., PHOX2B and Pbx proteins), as well as neuromodulators (i.e., serotonin, noradrenaline, GABA, and glycine), have been demonstrated as implicated in the regulation of breathing. Besides, the several intertwined excitatory and inhibitory brainstem neural circuits comprising the so-called central pattern generator (CPG) have recently demonstrated a potential role of cerebellar structures and circuits in coordinating the complex and coordinated respiratory act in eupnea. A disruption affecting one of these components, which may also occur on a genetic basis, may indeed result in complex and heterogeneous disorders, including neurodevelopmental ones (such as Rett and Prader-Willi syndrome), which may also present with neuropsychiatric and breathing manifestations and potentially lead to sudden infant death syndrome (SIDS). Herein, we discuss the main factors and systems involved in respiratory control and modulation, outlining some of the associated neurodevelopmental disorders (NDDs) deriving from an impairment in their expression/ function. Further studies are needed to deepen our knowledge of the complexity underpinning “breathing” and the relation between respiratory implications and congenital and developmental disorders.

Measuring Work of Breathing in an Infant Model: Comparison of Static and Dynamic Test Methods

Abstract When an infant’s face becomes engaged with soft bedding materials, a suffocation hazard may be present that is associated with increased work of breathing (WOB). When resistive materials impede airflow, an infant must work harder to breathe and maintain homeostasis. Airway stressors within the infant sleep environment are felt to be risk factors for sudden unexpected infant death (SUID). To quantify the WOB, experiments were performed using a mechanical breathing model for dynamic measurements and compared with a static test method. The model was configured to measure the dynamic pressure and volume of the lungs as they changed during the breathing cycle. Pressure and volume data were used to calculate the WOB per cycle for a range of 12 restrictive bedding materials and 3 types of foam. In addition, static airflow resistance measurements were made using the same materials. It was found that there is a useful correlation between static airflow measurements and dynamic measurements of WOB. The measurement methods and apparatus are described herein.

Metabolomics Biomarkers in Prediction of Sudden Infant Death Syndrome: The Role of Short Chain Fatty Acids

Metabolomics Biomarkers in Prediction of Sudden Infant Death Syndrome: The Role of Short Chain Fatty Acids

The development of sudden infant death syndrome awareness scale-mother form and examination of its psychometric properties

PurposeThis study aimed to develop the “Sudden Infant Death Syndrome Awareness Scale-Mother Form” (SIDSAS-MF) and assess its psychometric properties. Design and methodsThe methodological study involved mothers (n = 450) with infants aged 0–12 months. Data were collected using a socio-demographic information form and the draft of the SIDSAS-MF. Factor analysis and reliability analyses were conducted to assess the data. ResultsExploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of the scale revealed a structure consisting of six items and two sub-dimensions. The factor loadings of the scale were found to be above 0.30. Fit indices following CFA were achieved at excellent levels. Both McDonald's omega and Cronbach's alpha values for each sub-dimension of the scale exceeded 0.6. Furthermore, the correlation values of the items with the total factor score ranged from 0.661 to 0.839. ConclusionsThe study concluded that the six-item form of the SIDSAS-MF is a valid and reliable measurement tool for mothers with infants aged 0–12 months in the Turkish population. Practical implicationsMidwives and nurses can use this scale in their clinical training to determine the level of awareness mothers have towards SIDS. It is also recommended that the developed scale should be adapted to different cultures.

Design of Sleep Apnea Monitoring and Postural Intervention System Based on Snoring Recognition

Design of Sleep Apnea Monitoring and Postural Intervention System Based on Snoring Recognition

Use of Practices to Reduce of Sudden Unexpected Infant Death among Caregivers of Opioid Exposed Newborns.

Sudden unexpected infant death (SUID) occurs disproportionately among opioid exposed newborns (OENs) compared to those unexposed. The extent that primary caregivers of OENs adhere to SUID-reducing infant care practices is unknown. We examined rates of SUID-reducing practices (smoking cessation, breastfeeding, and safe sleep [supine sleep, room-sharing not bed-sharing, nonuse of soft bedding or objects]) in a pilot sample of caregivers of OENs. We surveyed 50 English-speaking mothers and other primary caregivers of OENs 1-6 months old between 02/2022 and 10/2023. We examined prenatal and postnatal cigarette smoking exposure, breastfeeding initiation and duration, and sleep position (side, back, or stomach), sleep location (bed-sharing, room-sharing not bed-sharing, or separate room), and soft bedding or objects in the infant sleep space. Thirty-six (72%) of 50 respondents were birth mothers and 14/50 (28%) were other caregivers. Sixty-one percent of infants were exposed to cigarette smoking prenatally (mothers only) and 34% postnatally (41% mothers vs 14% other caregivers). Sixty percent of infants received breast milk ≤4 weeks. Among respondents, 32% placed infants in nonsupine sleep position (36% mothers vs 21% other caregivers), 38% shared a bed with their infant for sleep (47% mothers vs 14% other caregivers), and 30% used soft bedding in the infant sleep space (33% among mothers vs 21% among other caregivers). Infant care practices associated with SUID were highly prevalent in our pilot sample of OENs and differed among mothers versus other caregivers. Further investigation and tailored approaches to this population are needed.

AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.

Ventilatory drive is modulated by a variety of neurochemical inputs that converge on spatially oriented clusters of cells within the brainstem. This regulation is required to maintain energy homeostasis and is essential to sustain life across all mammalian organisms. Therefore, the anatomical orientation of these cellular clusters during development must have a defined mechanistic basis with redundant genomic variants. Failure to completely develop these features causes several conditions including apnea of prematurity (AOP) and sudden infant death syndrome (SIDS). AOP is associated with many adverse outcomes including increased risk of interventricular hemorrhage. However, there are no pharmacological interventions that reduce SIDS and AOP prevalence by promoting brainstem development. AMP-activated protein kinase (AMPK) is a kinase that regulates ventilatory control to maintain homeostasis. This study identifies a signaling axis in which the pharmacological activation of AMPK in vivo via metformin in brainstem ventilatory control centers results in the phosphorylation of LIM homeobox transcription factor 1-beta (Lmx1b), a key player in dorsal-ventral patterning during fetal development. The phosphorylation of Lmx1b transactivates a neurogenic interactome important for the development and regulation of ventilatory control centers. These findings highlight the potential for metformin in the treatment and prevention of AOP.

Bereaved Parents' Perceptions of the Doll Reenactment After Sudden Unexpected Infant Deaths.

A death scene investigation is required to determine sudden infant death syndrome, and a doll reenactment optimizes the information obtained. The aim of this study was to explore how acutely bereaved parents experience doll reenactments that are conducted after the sudden and unexpected deaths of their infants. A mixed-methods design, including surveys and semi-structured interviews, was used in a cross-sectional, national study to explore the experiences of doll reenactment among 45 bereaved parents. Forty-four percent of parents reported moderate to high distress during the doll reenactment, with significantly heightened distress in those who discovered their child lifeless and who later reported posttraumatic intrusions. An analysis of parents' narratives showed that the doll reenactment was challenging, particularly because of the doll's appearance and the activation of intrusive images in those who found their child lifeless. Parents overall experienced less distress than anticipated during the reenactment, and no lasting difficulties were reported. Some parents identified benefits from the reenactment, such as sharing a coherent narrative of the death. The parents' reactions to the doll reenactment were multifaceted and complex. These findings illuminate the emotional challenges parents face during a doll reenactment and emphasize the delicate balance between obtaining crucial information and avoiding additional trauma in the aftermath of infant deaths. Because the doll reenactment's diagnostic utility or benefits to post-loss coping are uncertain, anticipatory guidance about its psychological dimensions may mitigate distress, and incorporating a gateway for professional support may further align it with the needs of acutely bereaved parents.

Features of Prenatal Ultrasound Diagnosis of Fetal Tachyarrhythmias (literature review)

Timely prenatal diagnosis of various pathological conditions of the fetal heart is a particularly important problem of obstetric practice. For this purpose, the most frequently used are innovative ultrasound diagnostic technologies that give the opportunity to timely detect various fetal arrhythmias. Clinically significant arrhythmias are established to develop in fetuses and newborns in 1 out of 4,000 live births and are one of the causes of morbidity and mortality. About 10% of fetal arrhythmias require intrauterine treatment or constant monitoring, and they may also indicate the presence of serious hereditary syndromes associated with cardiac rhythm disorders and the likelihood of sudden infant death. The purpose of the review is to study the material of literature sources devoted to the primary prenatal ultrasound diagnosis of clinically significant fetal arrhythmias and dynamic echographic control in the management of pregnant women with fetal tachyarrhythmia. During the research, available domestic and foreign sources were used, which presented the features of the course of fetal cardiac arrhythmias, their types, and the possibilities of prenatal ultrasound diagnosis of this pathology. The search for publications is performed in databases eLIBRARY.RU , RSCI, PubMed, Embase. Based on the results of the analysis and generalization of the studied publications, it was found that ultrasound examination of the fetal heart plays a key role in the diagnosis of arrhythmias, it helps to determine the main mechanism of rhythm disturbance, assess the effect of arrhythmia on the fetal heart's functioning, exclude possible structural changes in the fetal heart, as well as enables to monitor the fetal condition during antiarrhythmic therapy. If fetal arrhythmias are suspected, an urgent ultrasound examination with ultrasound Dopplerography is recommended with an extension of the standard protocol for examining the fetal heart with an assessment of the frequency of atrial and ventricular contractions.

Individual-, Hospital-, and Community-Level Factors Associated with Sudden Unexpected Infant Death Among Infants Born Preterm in 5 US States.

To investigate individual-, hospital-, and community-level factors associated with sudden unexpected infant death (SUID) among infants born preterm. The following linked dataset from 5 states (California, Michigan, Oregon, Pennsylvania, and South Carolina) from 2005 through 2020 was used: (1) infant birth and death certificates; (2) maternal and infant birth hospitalization discharge records; (3) birthing hospital data from the American Hospital Association; and (4) community-level data from the Social Vulnerability Index (SVI).) Multivariable models were used to assess the independent association between these multilevel factors and SUID, adjusting for several maternal and infant characteristics. Overall, we found that maternal demographic factors (race and ethnicity, education, insurance) and infant gestational age were significant predictors of SUID. There was no difference in SUID odds by state, urban influence code, and maternal complications of pregnancy. Compared with mothers who lived in areas with the lowest SVI, those who resided in the highest SVI were more likely to experience SUID. There was no difference in SUID odds between infants who did or did not experience one or more complications of prematurity. For hospital-level factors, there was no difference in SUID odds among infants cared for in teaching vs nonteaching hospitals or in low vs high volume preterm birth hospitals. Individual- and community-level factors were associated with SUID among infants born preterm. The neonatal intensive care unit hospitalization may provide a critical window of opportunity to engage families about SUID-risk reducing practices.

Genetic Association Study of Acetylcholinesterase (ACHE) and Butyrylcholinesterase (BCHE) Variants in Sudden Infant Death Syndrome (SIDS).

Sudden infant death syndrome (SIDS) is the leading cause of death among infants aged between one month and one year. Altered enzyme activities or expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been observed in SIDS patients that might lead to disturbed autonomic function and, together with other risk factors, might trigger SIDS. To explore the contribution of AChE and BChE from a genomic viewpoint, we sought to investigate the association between SIDS and selected single nucleotide polymorphisms (SNPs) in the ACHE and BCHE genes. In this case-control study, 13 potentially regulatory SNPs were selected from ACHE and BCHE and were genotyped in 201 SIDS cases and 338 controls. The association of SIDS with the 11 successfully genotyped candidate variants was examined using statistical analyses of overall or stratified cases and haplotype analyses. No significant overall associations were observed between SIDS and ACHE and BCHE variants in allele, genotype, and haplotype analyses. In subgroup analyses, eight variants were found to be nominally associated with SIDS, though these associations did not remain statistically significant after correction for multiple comparisons. One haplotype (T-C-G-C-C in rs3495-rs1803274-rs1355538-rs2048493-rs1126680) of BCHE was associated with the female SIDS subgroup (57.3% in controls vs. 46.3% in female SIDS cases, p = 0.010). The selected variants in ACHE and BCHE were not overall associated with SIDS in this study, and thus cannot generally explain the previously reported dysregulation of enzyme activities in SIDS. However, some evidence of association in subgroups and a possible contribution of variants other than those tested here would need to be explored in larger studies.