Sudden Infant Death Syndrome Research Research Articles

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

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

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

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

The San Diego SIDS Definition - 20 Years On.

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

Is academic rigor in Sudden Infant Death Syndrome (SIDS) research in decline?

To determine how well definitions of SIDS in the literature are being cited and referenced. The "PubMed" database was searched for "sudden infant death syndrome" from 2020 to 2021. Of 421 original papers, 50 were randomly selected and checked to determine whether one of the three internationally accepted definitions of SIDS: Seattle, NICHD and San Diego definitions had been cited/quoted in the text and correctly referenced. Papers that incorrectly cited or did not cite one standard definitions were assigned into: (i) those that used mis-cited, idiosyncratic or other (alternative, non-standard) definitions and, (ii) those where there was no definition. Fifty-six per cent of papers correctly cited standard definitions, a 12% decrease from the 68% in a similar study in 2012. Of those only 22% both correctly cited/referenced one of the standard definitions. Major issues in 78% of papers involved citing one and referencing another standard definition (N=7, 14%), citing or referencing alternative, non-standard definitions (N=8, 16%) or not citing or referencing any definition (N=24, 48%). There is an increasing trend to not follow standard definitions of SIDS. This may hinder data interpretation where cases have not been appropriately defined and negatively impact upon the validity of SIDS research.

Sudden Infant Death Syndrome: Beyond Risk Factors

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”. A significant decrease of SIDS deaths occurred in the last decades in most countries after the beginning of national campaigns, mainly as a consequence of the implementation of risk reduction action mostly concentrating on the improvement of sleep conditions. Nevertheless, infant mortality from SIDS still remains unacceptably high. There is an urgent need to get insight into previously unexplored aspects of the brain system with a special focus on high-risk groups. SIDS pathogenesis is associated with a multifactorial condition that comprehends genetic, environmental and sociocultural factors. Effective prevention of SIDS requires multiple interventions from different fields. Developing brain susceptibility, intrinsic vulnerability and early identification of infants with high risk of SIDS represents a challenge. Progress in SIDS research appears to be fundamental to the ultimate aim of eradicating SIDS deaths. A complex model that combines different risk factor data from biomarkers and omic analysis may represent a tool to identify a SIDS risk profile in newborn settings. If high risk is detected, the infant may be referred for further investigations and follow ups. This review aims to illustrate the most recent discoveries from different fields, analyzing the neuroanatomical, genetic, metabolic, proteomic, environmental and sociocultural aspects related to SIDS.

An Integrated Analysis of Maternal-Infant Sleep, Breastfeeding, and Sudden Infant Death Syndrome Research Supporting a Balanced Discourse.

Breastfeeding and the place of sleep for the mother and the infant have been controversial internationally due to reported concerns regarding infant deaths despite the known benefits of exclusive and prolonged breastfeeding, which are increased by breastfeeding at night. The aims of this integrated analysis were to (a) review breastfeeding and maternal and infant sleep research literature via historical, epidemiological, anthropological, and methodological lenses; (b) use this information to determine where we are currently in safeguarding both infant lives and breastfeeding; and (c) postulate the direction that research might take from this point forward to improve our knowledge and inform our policy and practice. Despite well-meaning but unsuccessful campaigns in some countries to dissuade parents from sleeping with their babies, many breastfeeding mothers and caregivers do sleep with their infants whether intentionally or unintentionally. Taking cultural contexts and socio-ecological circumstances into consideration, data supports policies to counsel parents and caregivers on safe sleep practices, including bed-sharing in non-hazardous circumstances, particularly in the absence of parental smoking, recent parental alcohol consumption, or sleeping next to an adult on a sofa. Further research with appropriate methodology is needed to drill down on actual rates of infant deaths, paying close attention to the definitions of deaths, the circumstances of the deaths, and confounding factors, in order to ensure we have the best information with which to derive public health policy. Introduction and use of the concept of "breastsleeping" is a plausible way to remove the negative connotations of "co-sleeping" and redirect ongoing data-driven discussions and education of best practices of breastfeeding and sleep.

Pharmacogenetic Modulation of the Noradrenergic System Reveals Protective and Vulnerable Roles in the Neonate Autoresuscitation Reflex

A key feature of neonatal respiration is the autoresuscitation reflex, which restarts breathing and cardiac function after an infant has fallen into respiratory arrest and bradycardia due to extreme hypoxic conditions. Abnormalities in this reflex have been hypothesized to play a role in life threatening pathologies such as Sudden Infant Death Syndrome (SIDS), where infants are often found face down, resulting in asphyxiation and death. Disruptions to the development and maturation of the brainstem autonomic neural circuitry, including the noradrenergic (NA) system, are thought to be an underlying factor in SIDS. Despite the number of studies implicating the NA system in cardiorespiratory control and in SIDS pathology, the role of the NA system in the autoresuscitation reflex remains poorly understood. We hypothesize that the NA system plays a critical role in modulating the neonatal autoresuscitation reflex and that increased NA tone may offer a protective effect.To test this hypothesis, we pharmacogenetically excited and inhibited the whole NA system in P7‐P8 mice by expressing neuro‐excitatory (hM3D) and inhibitory (hM4D) clozapine‐N‐oxide (CNO) activated DREADD receptors throughout all NA producing cells utilizing conditional DREADD and DBH_FlpO mouse lines developed in the Ray lab. Respiratory parameters were measured using a modified facemask pneumotachograph while recording heart rate (HR) through an electrocardiogram (ECG). To induce the autoresuscitation reflex, pups were given a brief exposure to mild hypercapnic anoxia (3%CO2, 97%N2) to induce respiratory arrest and bradycardia. Upon apnea, anoxia was reversed by flushing the pneumotachograph with room air to facilitate the autoresuscitation reflex and recovery. Pups were exposed to repeated bouts of hypercapnic anoxia, followed by recovery periods, until succumbing. We recorded HR and respiratory waveforms continuously throughout the assay. We obtained the number of episodes before death, exposure time, time until first gasping (gasp latency), and frequency of gasping (Gasp ƒB). HR and eupnea recovery were also analyzed. Differences between experimental mice and littermate controls were assessed by a repeated measurement two‐way ANOVA. A p‐value< 0.05 was considered statistically significant. Bonferroni correction was used where multiple comparisons were necessary.Contrary to our hypothesis, preliminary data suggests that acute excitation of the NA system during the anoxic challenge results in a decreased number of successful autoresuscitation events, a higher gasp latency and frequency, and longer delay time to recovery heart rate and eupnea during the last episode. Conversely, when the NA system was inhibited, pups showed a tendency to survive more episodes than controls with a longer exposure time before they succumbed. These results suggest that the NA system might act as an acute modulator of the autoresuscitation reflex, an important neonatal reflex implicated in SIDS pathology.Support or Funding InformationMcNair Medical Institute, March of Dimes Award #1‐FY18‐403, Basil O'Connor Starter Scholar Research Award, R01HL130249, CJ Foundation for SIDS Research AwardThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Exome-Wide Rare Variant Analyses in Sudden Infant Death Syndrome

To determine whether a monogenic basis explains sudden infant death syndrome (SIDS) using an exome-wide focus. A cohort of 427 unrelated cases of SIDS (257 male; average age = 2.7 ± 1.9 months) underwent whole-exome sequencing. Exome-wide rare variant analyses were carried out with 278 SIDS cases of European ancestry (173 male; average age = 2.7 ± 1.98 months) and 973 ethnic-matched controls based on 6 genetic models. Ingenuity Pathway Analysis also was performed. The cohort was collected in collaboration with coroners, medical examiners, and pathologists by St George's University of London, United Kingdom, and Mayo Clinic, Rochester, Minnesota. Whole-exome sequencing was performed at the Genomic Laboratory, Kings College London, United Kingdom, or Mayo Clinic's Medical Genome Facility, Rochester, Minnesota. Although no exome-wide significant (P < 2.5 × 10-6) difference in burden of ultra-rare variants was detected for any gene, 405 genes had a greater prevalence (P < .05) of ultra-rare nonsynonymous variants among cases with 17 genes at P < .005. Some of these potentially overrepresented genes may represent biologically plausible novel candidate genes for a monogenic basis for a portion of patients with SIDS. The top canonical pathway identified was glucocorticoid biosynthesis (P = .01). The lack of exome-wide significant genetic associations indicates an extreme heterogeneity of etiologies underlying SIDS. Our approach to understanding the genetic mechanisms of SIDS has far reaching implications for the SIDS research community as a whole and may catalyze new evidence-based SIDS research across multiple disciplines. Perturbations in glucocorticoid biosynthesis may represent a novel SIDS-associated biological pathway for future SIDS investigative research.

Central and peripheral chemoreceptors in sudden infant death syndrome.

The pathogenesis of sudden infant death syndrome (SIDS) has been ascribed to an underlying biological vulnerability to stressors during a critical period of development. This paper reviews the main data in the literature supporting the role of central (e.g. retrotrapezoid nucleus, serotoninergic raphe nuclei, locus coeruleus, orexinergic neurons, ventral medullary surface, solitary tract nucleus) and peripheral (e.g. carotid body) chemoreceptors in the pathogenesis of SIDS. Clinical and experimental studies indicate that central and peripheral chemoreceptors undergo critical development during the initial postnatal period, consistent with the age range of SIDS (<1year). Most of the risk factors for SIDS (gender, genetic factors, prematurity, hypoxic/hyperoxic stimuli, inflammation, perinatal exposure to cigarette smoke and/or substance abuse) may structurally and functionally affect the developmental plasticity of central and peripheral chemoreceptors, strongly suggesting the involvement of these structures in the pathogenesis of SIDS. Morphometric and neurochemical changes have been found in the carotid body and brainstem respiratory chemoreceptors of SIDS victims, together with functional signs of chemoreception impairment in some clinical studies. However, the methodological problems of SIDS research will have to be addressed in the future, requiring large and highly standardized case series. Up-to-date autopsy protocols should be produced, involving substantial, and exhaustive sampling of all potentially involved structures (including peripheral arterial chemoreceptors). Morphometric approaches should include unbiased stereological methods with three-dimensional probes. Prospective clinical studies addressing functional tests and risk factors (including genetic traits) would probably be the gold standard, allowing markers of intrinsic or acquired vulnerability to be properly identified.

Sudden infant death syndrome and the genetics of inflammation.

Several studies report signs of slight infection prior to death in cases of sudden infant death syndrome (SIDS). Based on this, a hypothesis of an altered immunological homeostasis has been postulated. The cytokines are important cellular mediators that are crucial for infant health by regulating cell activity during the inflammatory process. The pro-inflammatory cytokines favor inflammation; the most important of these are IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-18, TNF-α, and IFN-γ. These cytokines are controlled by the anti-inflammatory cytokines. This is accomplished by reducing the pro-inflammatory cytokine production, and thus counteracts their biological effect. The major anti-inflammatory cytokines are interleukin-1 receptor antagonist (IL-1ra), IL-4, IL-10, IL-11, and IL-13. The last decade there has been focused on genetic studies within genes that are important for the immune system, for SIDS with a special interest of the genes encoding the cytokines. This is because the cytokine genes are considered to be the genes most likely to explain the vulnerability to infection, and several studies have investigated these genes in an attempt to uncover associations between SIDS and different genetic variants. So far, the genes encoding IL-1, IL-6, IL-10, and TNF-α are the most investigated within SIDS research, and several studies indicate associations between specific variants of these genes and SIDS. Taken together, this may indicate that in at least a subset of SIDS predisposing genetic variants of the immune genes are involved. However, the immune system and the cytokine network are complex, and more studies are needed in order to better understand the interplay between different genetic variations and how this may contribute to an unfavorable immunological response.

Dummy (pacifier) use and sudden infant death syndrome: Potential advantages and disadvantages

The large decline in deaths due to the sudden infant death syndrome (SIDS) in the last 20 years in many countries is largely due to risk-reduction advice resulting from observational studies that examined the relationship between infant care practices and SIDS. Most of this advice remains largely uncontroversial and educators and researchers in this field are in agreement as to the specific recommendations that should be given to parents and health professionals. However, advice surrounding the apparent protective effect of dummies (also known as pacifiers) has been controversial. Several systematic reviews have demonstrated a strong association between the lack of a pacifier being used by the infant for the final sleep and SIDS, but it is not clear how pacifiers confer protection or if this is a marker for something as yet unmeasured. The Epidemiology and Physiology Working Groups of the International Society for the Study and Prevention of Perinatal and Infant Death (ISPID) are comprised of leading SIDS researchers with an objective to provide evidence-based position statements surrounding the factors associated with SIDS (http://www.ispid.org/) and risk-reduction strategies. The evidence, discussion and conclusions from these working groups regarding dummies (pacifiers) are described below to help inform this debate and describe the future evidence required so that we might find a common recommendation about dummies (pacifiers) and SIDS.

Guarding All Infants in Sleep

The loss of a baby is an extremely traumatic event and has enduring effects that ripple out from parents to their extended families, friends, and co-workers. Educating parents and other infant caregivers about making infants’ sleep settings safer can help prevent these tragedies and the considerable resulting emotional despair and productivity loss. A sizable racial disparity in rates of Sudden Infant Death Syndrome (SIDS) also troubles many people from a social justice perspective, spurring interest in understanding why the gap persists and how to reduce it. Although death rates from SIDS for both non-Hispanic white and non-Hispanic black babies fell during the back-to-sleep campaigns of the early 1990s, the gap between the two groups remains large. This is true in Illinois as well as the nation. Understanding of SIDS has changed markedly from the times of heightened concern during the 1980s and early 1990s, when healthy babies mysteriously died in their cribs. Putting babies on their backs to sleep was a tangible protective factor with a clear and easy-to-implement behavioral change. Positioning offered a simple target for reducing SIDS risk; and, in its initial recommendation of 1992, the American Academy of Pediatrics (AAP) Task Force focused principally on this issue of positioning. Sleep positioning campaigns that followed in the United States and around the world were widely seen as producing sizable declines in SIDS deaths. Strategies to further reduce SIDS are less clear-cut and more controversial. The latest AAP policy statement makes 18 recommendations, each with several subparts. One of the most controversial is AAP’s recommendation that adults not sleep in the same bed with an infant. Other stakeholders perceive these recommendations as inhibiting breastfeeding, which they view as easiest when mothers spend the entire night on the same sleep surface as the infant. Some controversy also stems from subcultures that value and practice bed sharing, sometimes with very low SIDS rates. Yet other controversy stems from different reading of the evidence cited by the AAP, which some interpret as indicating that bed sharing should be recommended against only when other risks are present (e.g., soft bedding, maternal smoking, parental inebriation or exhaustion). What next steps can help resolve the debate and advance evidence for policymaking? A collaboration between medical doctors, epidemiologists, anthropologists, and other SIDS researchers – including those prominent on both sides of this issue – would likely move more quickly toward resolving disagreements than would more research done independently by each side.

SIDS Risk Factors: Time for New Interpretations. The Role of Bacteria

The aim of this paper is to help draw attention to perceived ideas regarding the risk factors and the implied pathogenesis of Sudden Infant Death Syndrome (SIDS), and SIDS research in general. Our paper shows there is little if any evidence to support the broadly held notion of an association between respiratory function and sudden infant death syndrome. Researchers who hold to this approach to explain the risk factors of bed-sharing and prone sleep position, etc. have failed to meet the standards of scientific endeavour that we would expect of good research. To counter this imbalance we have proposed an evidence-based explanation for SIDS risk factors showing that microbiological studies of SIDS corroborate epidemiologic and pathological data in establishing a plausible pathogenetic mechanism. We reviewed recent publications on current research and the epidemiology of SIDS and publications on the microbiology of SIDS. Conclusion: Comparison of the data presented, suggest that the risk factors of bed-sharing, and smoke exposure, prone sleep position and alcohol can be explained by the theories of a microbiological infection model of SIDS pathogenesis.

Sudden and unexpected death in early life: proceedings of a symposium in honor of Dr. Henry F. Krous

Reported here are the proceedings of a symposium given in honor of Dr. Henry F. Krous upon his retirement as Clinical Professor of Pathology and Pediatrics at the University of California Schools of Medicine, and as Director of the San Diego SIDS/SUDC Research Project. Dr. Krous' distinguished 37-year-career was dedicated to research into sudden unexpected death in infancy and childhood, notably the sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC). The presentations were given at the International Conference on Stillbirth, SIDS, and infant survival on October 5, 2012, in Baltimore, MD, USA. Eight colleagues of Dr. Krous whose own professional careers were touched by his efforts discussed forensic issues related to SIDS, tissue banking, animal models in SIDS, brainstem studies in SIDS, genetic studies in SIDS, establishment of a SUDC registry, neuropathologic research in SUDC, and potential shared mechanisms underlying sudden and unexpected death in early life. The wide scope of the presentations crossed the disciplines of forensic pathology, pediatric pathology, neuropathology, neuroscience, physiology, genetics, and bereavement, and attest to Dr. Krous' far-reaching influence upon SIDS and SUDC research.

Neuropathology provides new insight in the pathogenesis of the sudden infant death syndrome

The sudden infant death syndrome (SIDS) is deWned as the sudden, sleep-related death of an infant less than 12 months of age that remains unexplained after a complete autopsy, death scene investigation, and review of the clinical history [35]. Typically, a seemingly healthy infant is unexpectedly found dead after a sleep period. Despite a dramatic reduction in the overall rate with national campaigns advocating the supine (back) sleep position [43], SIDS remains the leading cause of postneonatal infant mortality and the third leading cause of infant mortality in general in the United States today [43]. The brain has long been thought to play a critical role in the cause and pathogenesis of SIDS. The recent publication of three excellent articles on brain pathology in SIDS in Acta Neuropathologica indicates that brain research into this major pediatric disorder continues to be important in guiding all SIDS research. Basically, brain research in SIDS follows three directions: (1) analysis to determine a primary (neural) cause of death, (2) analysis to uncover secondary changes that points to the primary cause, either within the brain or in other organ systems, and (3) analysis to determine the age of onset of the chain of events—prenatally and/or postnatally—that results in sudden death in the vulnerable postnatal period. The search for a primary cause is driven by the hypothesis that SIDS is due to intrinsic abnormalities in brain regions critical for the control of arousal and/ or state-dependent respiratory and/or autonomic function that lead to sleep-related death which is precipitated by a homeostatic stressor within a susceptible age-range. Secondary changes in the brain are postulated to result mainly from hypoxia–ischemia complicating repetitive apnea and/or bradycardia prior to the lethal cardiorespiratory event, as well as during the lethal event itself. Finally, the brain disorder is postulated to be developmental in origin due to the parallel onset and occurrence of SIDS with the major critical period in human brain development, i.e., gestation through the Wrst year of life. Yet, despite the compelling rationale for a key role of the brain in SIDS, the brain looks normal under the light microscope, or at the very most, demonstrates seemingly trivial or nonspeciWc changes. Thus, the challenge for us as neuropathologists in the analysis of SIDS brains—as in the analysis of autistic and schizophrenic brains—is to uncover neurochemical, cellular, and/or molecular abnormalities with the right quantitative tools. The three recent SIDS studies in Acta Neuropathologica cover the spectrum of neuropathological directions in SIDS research with quantitative methodologies: (1) the search for the primary abnormality in the brainstem with the application of an antibody to the serotonin 1A (5-HT1A) receptor by Machaalani et al. [37], (2) the determination of secondary hypoxic–ischemic changes in the cerebral cortex and hippocampus with MAP2 immunostaining by Oehmichen et al. [49], and (3) the report of critical evidence for a developmental origin of brain pathology, i.e., increased leptomeningeal neurons in the brainstem by Rickert et al. [62]. In the following commentary, I highlight the new insights that these studies bring to our understanding of the brain’s role in SIDS in the context of previous neuropathologic and other SIDS studies. H. C. Kinney (&) Department of Pathology, Enders Building 1112, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA e-mail: Hannah.kinney@childrens.harvard.edu

Mechanisms of pathogenesis in the Sudden Infant Death Syndrome

The likely processes of the Sudden Infant Death Syndrome (SIDS) were identified many years ago (apnea, failed arousal, failed autoresuscitation, etc.). The neurophysiological basis of these processes and the neurophysiological reasons some infants die of SIDS and others do not are, however, only emerging now. We reviewed recent studies that have shed light on the way in which epidemiological risk factors, genetics, neurotransmitter receptor defects and neonatal cardiorespiratory reflex responses interact to lead to sudden death during sleep in a small number of normal appearing infants. As a result of this review and analysis, we hypothesize that the neurophysiological basis of SIDS resides in a persistence of fetal reflex responses into the neonatal period, amplification of inhibitory cardiorespiratory reflex responses and reduced excitatory cardiorespiratory reflex responses. The hypothesis we developed explores the ways in which multiple subtle abnormalities interact to lead to sudden death and emphasizes the difficulty of ante-mortem identification of infants at risk for SIDS, although identification of infants at risk remains an essential goal of SIDS research.

An audit of the use of definitions of sudden infant death syndrome (SIDS)

Given that there are a number of contradictions in the SIDS literature and that the definition of SIDS that was relied upon to authenticate cases in reports is not always specified, an audit of publications was undertaken. Fifty papers dealing with SIDS that were published in 2005 were reviewed. The majority (58%) of reports had either not specified a definition of SIDS, or had used non-standard or idiosyncratic definitions. Of the papers that had documented a definition: 30% used the 1989 NICHD definition, 10% used the 2004 San Diego definition, and 2% used the 1969 Seattle definition. Failure to use standard published definitions of SIDS and/or to clearly specify the definition that has been followed may severely hamper the evaluation of SIDS research.

Putting sudden infant death syndrome research into practice: Paediatricians’ perspective

Putting sudden infant death syndrome research into practice: Paediatricians’ perspective

Association between pacifier use and breast-feeding, sudden infant death syndrome, infection and dental malocclusion

Objective To critically review all literature related to pacifier use for full-term healthy infants and young children. The specific review questions addressed are: What is the evidence of adverse and/or positive outcomes of pacifier use in infancy and childhood in relation to each of the following subtopics: • breast-feeding; • sudden infant death syndrome; • infection; • dental malocclusion. included in the review: (i) the types of participants; (ii) the types of research design; and (iii) the types of outcome measures. To be included a study has to meet all criteria. Types of participants The participants included in the review were healthy term infants and healthy children up to the age of 16 years. Studies that focused on preterm infants, and infants and young children with serious illness or congenital malformations were excluded. However, some total population studies did include these children. Types of research design It became evident early in the review process that very few randomised controlled trials had been conducted. A decision was made to include observational epidemiological designs, specifically prospective cohort studies and, in the case of sudden infant death syndrome research, case–control studies. Purely descriptive and cross-sectional studies were excluded, as were qualitative studies and all other forms of evidence. A number of criteria have been proposed to establish causation in the scientific and medical literature. These key criteria were applied in the review process and are described as follows: (i) consistency and unbiasedness of findings; (ii) strength of association; (iii) temporal sequence; (iv) dose–response relationship; (v) specificity; (vi) coherence with biological background and previous knowledge; (vii) biological plausibility; and (viii) experimental evidence. Studies that did not meet the requirement of appropriate temporal sequencing of events and studies that did not present an estimate of the strength of association were not included in the final review. Types of outcome measures Our specific interest was pacifier use related to: • breast-feeding; • sudden infant death syndrome; • infection; • dental malocclusion. Studies that examined pacifier use related to procedural pain relief were excluded. Studies that examined the relationship between pacifier use and gastro-oesophageal reflux were also excluded as this information has been recently presented as a systematic review. Search strategy The review comprised published and unpublished research literature. The search was restricted to reports published in English, Spanish and German. The time period covered research published from January 1960 to October 2003. A protocol developed by New Zealand Health Technology Assessment was used to guide the search process. The search comprised bibliographic databases, citation searching, other evidence-based and guidelines sites, government documents, books and reports, professional websites, national associations, hand search, contacting national/international experts and general internet searching. Assessment of quality All studies identified during the database search were assessed for relevance to the review based on the information provided in the title,abstract and descriptor/MeSH terms, and a full report was retrieved for all studies that met the inclusion criteria. Studies identified from TRUNCATED AT 600 WORDS

Current controversies in the pathophysiology and prevention of sudden infant death syndrome

To examine recent research relevant to sudden infant death syndrome (SIDS) to determine whether there is a place for home monitoring in the care of children believed to be at risk. Current SIDS research has focused on the genetics of SIDS, brainstem abnormalities and arousal failures, the effects of tobacco smoke and other environmental agents, the role of infectious diseases, and prenatal factors that may contribute to SIDS. Investigations have suggested that there are infants who appear to respond less effectively when challenged by certain environmental or infectious agents. These infants have blunted responses to stress and diminished arousal to hypoxemia, in part because of failures in genetically determined brainstem function. It is unclear at this time whether home monitoring would offer protection in all circumstances, but it may be helpful in certain patients. There appears to be progress in understanding the causes of SIDS. As additional studies emerge, the optimal approaches to care will become more apparent, with home monitoring one of the possible interventions.