Sudden Unexpected Postnatal Collapse: Review and Management.

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.

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

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

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

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

Identifying infants at risk of sudden unexpected death with an automated predictive risk model.

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.

Risk factors for unexpected infant death among very premature infants in France.

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.

Infant death from accidental suffocation and strangulation in bed in England and Wales: rare or unrecognised events?

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.

Understanding the immune profile of sudden infant death syndrome - proteomic perspectives.

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.

A Systematic Approach to Evaluate Sudden Unexplained Death in Children.

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

Actualización de las recomendaciones sobre sueño seguro / Update on safe sleep recommendatios

La muerte súbita de un lactante puede ser de causa explicada, indeterminada ­si no se investigó en forma suficiente­ o inexplicada ­cuando una investigación completa no permite determinar su causa­. La muerte súbita inexplicada, o síndrome de muerte súbita infantil, afecta en particular a las poblaciones más vulnerables. La muerte de estos niños que nacen con alteraciones del neurodesarrollo es la parte visible de una problemática que se origina en el embarazo. Disminuir la cantidad de niños vulnerables depende de políticas de salud y, sobre todo, de lograr mejorar las condiciones de vida de la población. Son acciones a largo plazo. Conocer a fondo los factores de riesgo que pueden desencadenar la muerte inesperada es lo que se puede hacer ya. La actualización de las recomendaciones sobre sueño seguro refleja nuevos conocimientos basados en la evidencia científica y un enfoque integral de los aspectos socioculturales relacionados con esta problemática.

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.

[Update on safe sleep recommendatios]. / Actualización de las recomendaciones sobre sueño seguro.

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.

La muerte súbita de un lactante puede ser de causa explicada, indeterminada ­si no se investigó en forma suficiente­ o inexplicada ­cuando una investigación completa no permite determinar su causa­. La muerte súbita inexplicada, o síndrome de muerte súbita infantil, afecta en particular a las poblaciones más vulnerables. La muerte de estos niños que nacen con alteraciones del neurodesarrollo es la parte visible de una problemática que se origina en el embarazo. Disminuir la cantidad de niños vulnerables depende de políticas de salud y, sobre todo, de lograr mejorar las condiciones de vida de la población. Son acciones a largo plazo. Conocer a fondo los factores de riesgo que pueden desencadenar la muerte inesperada es lo que se puede hacer ya. La actualización de las recomendaciones sobre sueño seguro refleja nuevos conocimientos basados en la evidencia científica y un enfoque integral de los aspectos socioculturales relacionados con esta problemática.

Changes in background characteristics and risk factors among SIDS infants in England: cohort comparisons from 1993 to 2020.

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.

Impact of Prenatal Nicotine Exposure on Placental Function and Respiratory Neural Network Development.

Smoking during pregnancy is associated with multiple undesirable outcomes in infants, such as low birth weight, increased neonatal morbidity and mortality, and catastrophic conditions like sudden infant death syndrome (SIDS). Nicotine, the most addictive and teratogenic substance in tobacco smoke, reaches and crosses the placenta and can be accumulated in the amniotic fluid and distributed by fetal circulation, altering the cholinergic transmission by acting on the nicotinic acetylcholine receptors (nAChRs) expressed from very early gestational stages in the placenta and fetal tissue. Because nAChRs influence the establishment of feto-maternal circulation and the emergence of neuronal networks, prenatal nicotine exposure can lead to multiple alterations in newborns. In this mini-review, we discuss the undeniable effects of nicotine in the placenta and the respiratory neural network as examples of how prenatal nicotine and smoking exposition can affect brain development because dysfunction in this network is involved in SIDS etiology.

Procalcitonin is associated with sudden unexpected death in infancy due to infection.

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.

Current SIDS research: time to resolve conflicting research hypotheses and collaborate.

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.

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

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

Peripheral neuroplasticity of respiratory chemoreflexes, induced by prenatal nicotinic exposure: Implication for SIDS.

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-1ß and serotonin (5-hydroxytryptamine, 5-HT) release, along with the enhanced expression of TRPV1, NK1R, IL1RI and 5-HT3R 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.