GFAP expression in the BRAIN during human postnatal development.

Glial fibrillary acidic protein (GFAP) immunohistochemistry was investigated in the developing human brain using two measures; the number of GFAP-positive cells (density, GFAP+/mm2), and a reactivity score (R-score), which we recently introduced to indicate astrogliosis, with scores ≥120 indicative of pathological processes. The primary aim was to report on GFAP expression and cell soma size in 26 microscopically defined regions of the amygdala, basal ganglia, cerebellum, hippocampus and medulla, and to determine whether they are affected by postconceptional age (PCA) from 40 to 83 weeks. The secondary aim was to determine if GFAP expression differs according to the classification of sudden infant death syndrome (SIDS) as opposed to infant deaths of known causes, or for the presence of major SIDS risk factors of male sex, cigarette smoke exposure, upper respiratory tract infection (URTI), bed-sharing and prone sleeping. The cerebellar molecular layer was void of GFAP+ cells, while the internal granular layer (IGL) had the highest density, with >60% of infants having an R-Score >120. GFAP expression decreased with increasing PCA in the entorhinal and temporal cortex, subiculum and regions of the cerebellum and medulla. GFAP cell soma size corresponded with astrogliosis score and no effect of PCA was evident. Various region-dependent GFAP expressional differences were seen according to SIDS classification and the risk factors studied. The findings indicate that the density of GFAP decreases in specific regions of the brain within the first year of postnatal development, and that reactive astrocytes are common, particularly within the early postnatal months.

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

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

New Step in Understanding the Pathogenetic Mechanism of Sudden Infant Death Syndrome: Involvement of the Pontine Reticular Gigantocellular Nucleus.

This study aimed to investigate, for the first time, the potential role of the gigantocellular nucleus, a component of the reticular formation, in the pathogenetic mechanism of Sudden Infant Death Syndrome (SIDS), an event frequently ascribed to failure to arouse from sleep. This research was motivated by previous experimental studies demonstrating the gigantocellular nucleus involvement in regulating the sleep-wake cycle. We analyzed the brains of 48 infants who died suddenly within the first 7 months of life, including 28 SIDS cases and 20 controls. All brains underwent a thorough histological and immunohistochemical examination, focusing specifically on the gigantocellular nucleus. This examination aimed to characterize its developmental cytoarchitecture and tyrosine hydroxylase expression, with particular attention to potential associations with SIDS risk factors. In 68% of SIDS cases, but never in controls, we observed hypoplasia of the pontine portion of the gigantocellular nucleus. Alterations in the catecholaminergic system were present in 61% of SIDS cases but only in 10% of controls. A strong correlation was observed between these findings and maternal smoking in SIDS cases when compared with controls. In conclusion we believe that this study sheds new light on the pathogenetic processes underlying SIDS, particularly in cases associated with maternal smoking during pregnancy.

Cardiac rhabdomyoma: an uncommon culprit in sudden infant death.

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

Organ weights and length anthropometry measures at autopsy for sudden infant death syndrome cases and other infant deaths in the Chicago infant mortality study.

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

Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing.

The purpose of this study is to gain insights into potential genetic factors contributing to the infant's vulnerability to Sudden Unexpected Infant Death (SUID). Whole Genome Sequencing (WGS) was performed on 144 infants that succumbed to SUID, and 573 healthy adults. Variants were filtered by gnomAD allele frequencies and predictions of functional consequences. Variants of interest were identified in 88 genes, in 64.6% of our cohort. Seventy-three of these have been previously associated with SIDS/SUID/SUDP. Forty-three can be characterized as cardiac genes and are related to cardiomyopathies, arrhythmias, and other conditions. Variants in 22 genes were associated with neurologic functions. Variants were also found in 13 genes reported to be pathogenic for various systemic disorders and in two genes associated with immunological function. Variants in eight genes are implicated in the response to hypoxia and the regulation of reactive oxygen species (ROS) and have not been previously described in SIDS/SUID/SUDP. Seventy-two infants met the triple risk hypothesis criteria. Our study confirms and further expands the list of genetic variants associated with SUID. The abundance of genes associated with heart disease and the discovery of variants associated with the redox metabolism have important mechanistic implications for the pathophysiology of SUID.

Autopsy report of a sudden infant death that was strongly suspicious of Kawasaki disease.

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

Sudden death with cardiac involvement in a neonate with carnitine-acylcarnitine translocase deficiency.

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases.

Multiomic Analysis of Neuroinflammation and Occult Infection in Sudden Infant Death Syndrome.

Importance: Antemortem infection is a risk factor for sudden infant death syndrome (SIDS)-the leading postneonatal cause of infant mortality in the developed world. Manifestations of infection and inflammation are not always apparent in clinical settings or by standard autopsy; thus, enhanced resolution approaches are needed. Objective: To ascertain whether a subset of SIDS cases is associated with neuroinflammation and occult infection. Design, Setting, and Participants: In this case-control study, postmortem fluids from SIDS cases and controls collected between July 2011 and November 2018 were screened for elevated inflammatory markers, specifically cerebrospinal fluid (CSF) neopterin and CSF and serum cytokines. CSF, liver, and brain tissue from SIDS cases with elevated CSF neopterin were subjected to metagenomic next-generation sequencing (mNGS) to probe for infectious pathogens. Brainstem tissue from a subset of these cases was analyzed by single-nucleus RNA sequencing (snRNAseq) to measure cell type-specific gene expression associated with neuroinflammation and infection. All tissue and fluid analyses were performed from April 2019 to January 2023 in a pathology research laboratory. Included was autopsy material from infants dying of SIDS and age-matched controls dying of known causes. Exposures: There were no interventions or exposures. Main Outcomes and Measures: CSF neopterin levels were measured by high-performance liquid chromatography. Cytokines were measured by multiplex fluorometric assay. mNGS was performed on liver, CSF, brain, and brainstem tissue. snRNAseq was performed on brainstem tissue. Results: A cohort of 71 SIDS cases (mean [SD] age, 55.2 [11.4] postconceptional weeks; 42 male [59.2%]) and 20 controls (mean [SD] age, 63.2 [16.9] postconceptional weeks; 11 male [55.0%]) had CSF and/or serum available. CSF neopterin was screened in 64 SIDS cases and 15 controls, with no exclusions. Tissues from 6 SIDS cases were further analyzed. For CSF neopterin measures, SIDS samples were from infants with mean (SD) age of 54.5 (11.3) postconceptional weeks (38 male [59.4%]) and control samples were from infants with mean (SD) age of 61.5 (17.4) postconceptional weeks (7 male [46.7%]). A total of 6 SIDS cases (9.3%) with high CSF neopterin were identified, suggestive of neuroinflammation. mNGS detected human parechovirus 3 (HPeV3) in tissue and CSF from 1 of these 6 cases. snRNAseq of HPeV3-positive brainstem tissue (medulla) revealed dramatic enrichment of transcripts for genes with predominately inflammatory functions compared with 3 age-matched SIDS cases with normal CSF neopterin levels. Conclusions and Relevance: Next-generation molecular tools in autopsy tissue provide novel insight into pathogens that go unrecognized by normal autopsy methodology, including in infants dying suddenly and unexpectedly.

Assessing retinal hemorrhages with non-invasive post-mortem fundus photographs in sudden unexpected death in infancy.

INTRODUCTION: In the case of sudden unexpected death in infancy (SUDI), eye examination is systematic to detect retinal hemorrhages (RH) that are a crucial hallmark for abusive head trauma (AHT). The aim of this study is to assess the ability of non-invasive post-mortem fundus photographs (PMFP) to detect RH in case of SUDI. METHODS: Bicentric retrospective analysis of consecutive cases of SUDI under 2 years of age were managed by two French SUDI referral centers with PMFP by RetCam (Clarity Medical Systems USA). PMFP were reviewed randomly, twice, by three independent ophthalmologists blinded for clinical data. RESULTS: Thirty cases (60 eyes) were included. Median age was 3.5 months (interquartile [1.6; 6.0]). No child died of AHT. Image quality was sufficient to assert presence or absence of RH in 50 eyes (83%). Sufficient quality rate was significantly higher when the post-mortem interval was inferior to 18 h (91%, 42/46) as opposed to over 18 h (57%, 8/14, p=0.0096). RH were found in six eyes (10%), four children (13%), with excellent inter and intra-raters' concordance (Cohen's Kappa from 0.81 [0.56-1.00] to 1.00 [1.00-1.00]). CONCLUSION: PMFP can detect RH in case of SUDI and is a relevant systematic screening test to be carried out as soon as the deceased child arrives in the hospital. It can decrease the need of eye removal for pathological examination, but further studies are needed to define the best decision algorithm.

Gastric aspiration in sudden unexpected infant death of Prader-Willi syndrome: immunohistochemical detection of feeding components.

Prader-Willi syndrome (PWS) in infants is characterized by hypotonia and poor sucking with feeding difficulties. Two autopsy cases of sudden unexpected death during sleep after tube feeding are described herein. For one, gastric aspiration caused by the possible milk regurgitation was suspected. Immunohistochemical examination of lung sections was performed using three antibodies to human α-lactalbumin, human gross cystic disease fluid protein 15, and cow whey ß-lactoglobulin. Five cases of sudden unexpected infant death occurring earlier than at 6 months old were selected as controls. Marked immune-staining for infant formula in one PWS subject was evident within terminal bronchioles and alveoli with granular and amorphous features. However, no positive staining was apparent in the other subject, who exhibited contrasting features in milk distribution. Among control cases, one showed mild staining in the bronchiole, but the others did not. The antibody to ß-lactoglobulin reacted specifically with formula, with no nonspecific background. Gastric contents in the airway can be a difficult issue because of the consequent terminal gasping. However, because of an episode of antemortem symptoms of potential regurgitation, and from findings at autopsy such as petechiae, we inferred that fatal regurgitation occurred in this PWS infant after tube feeding. Several clinical reports have described milk aspiration, but this pathological report is the first related to aspiration in PWS during tube feeding.

Causes of Sudden Unexpected Death in Childhood: Autopsy Findings from a Specialist Centre.

OBJECTIVES: To investigate the aetiologies of sudden unexpected death from natural causes in children aged 1-18 years by retrospective examination of autopsy records from a single centre. MATERIALS AND METHODS: The post-mortem findings from 548 children (1996-2015) were examined. Details were entered into an established research database and categorized according to >400 pre-defined criteria. RESULTS: There were 265 previously apparently healthy children and 283 with pre-existing, potentially life-limiting, conditions. There were more males than females (M:F 1.4:1), and deaths were more frequent in the winter. Infection was commonest accounting for 43% of all deaths. Non-infectious diseases were identified as cause of death in 28%, and 29% of all deaths were unexplained. There was no significant difference in the proportions of deaths in each category between the previously healthy children and those with pre-existing conditions. CONCLUSION: Sudden unexpected death is a rare presentation of death in childhood and those with pre-existing conditions may be more at risk. Standardisation of the post-mortem procedure in such cases may result in more ancillary investigations performed as routine and may reduce the number of cases that are 'unexplained'.

[Morphofunctional characteristics of the heart in sudden death of children under 1 year of age in the forensic medical aspect]. / Morfofunktsional'naya kharakteristika serdtsa pri vnezapnoi smerti detei do 1 goda v sudebno-meditsinskom aspekte.

The aim of this study is to describe the morphological and functional characteristics of the cardiac in sudden infants death syndrome (SIDS) in children under one year of age. Twenty eight cases of SIDS were studied histologically and immunohistochemically. Histological examination of the sectional material was carried out using standard and additional stains. The study of cardiac muscle tissue with routine staining with haematoxylin-eosin revealed interstitial oedema, uneven plethora of blood vessels: dystonia and weak plethora of part of the coronary arteries, excess of red blood cells in the veins as well as microcirculatory plethora with stasis of the erythrocytes. An immunohistochemical study revealed a mild over expression of p53 in cellular elements, small-focal expression of CD68 in cardiomyocytes apoptosis intramural areas, activation of mast cells (CD117), expression of ki-67 in macrophages, proliferation of fibroblasts. Additional forensic criteria for the diagnosis of SIDS were determined in the form of atrial endocardial fibrosis and interventricular septum; the expression of CD68, CD117 in fibroblasts, mast cells and lymphocytes; apoptosis of cardiomyocytes (expression of p53), proliferation of fibroblasts and remodeling of the heart (expression of ki-67).

Novel chemical-physical autopsy investigation in sudden infant death and sudden intrauterine unexplained death syndromes.

Aim: Verify the presence of inorganic nanoparticle entities in brain tissue samples from sudden infant death syndrome (SIDS)/sudden intrauterine unexplained death syndrome (SIUDS) cases. The presence of inorganic debris could be a cofactor that compromises proper brain tissue functionality. Materials & methods: A novel autopsy approach that consists of neuropathological analysis procedures combined with energy dispersive spectroscopy/field emission gun environmental scanning electron microscopy investigations was implemented on 10 SIDS/SIUDS cases, whereas control samples were obtained from 10 cases of fetal/infant death from known cause. Results: Developmental abnormalities of the brain were associated with the presence of foreign bodies. Although nanoparticles were present as well in control samples, they were not associated with histological brain anomalies, as was the case in SIDS/SIUDS. Conclusion: Inorganic particles present in brain tissues demonstrate their ability to cross the hemato-encephalic barrier and to interact with tissues and cells in an unknown yet pathological fashion. This gives a rationale to consider them as cofactors of lethality.

Pathologizing the Unknown: A Sociological Explanation for the (Mis-)Use of Sudden Infant Death Syndrome as a Diagnosis.

Sudden infant death syndrome (SIDS) is a diagnosis given to infants who die suddenly and unexpectedly before the age of one. After decades of research into SIDS, little has been conclusively determined regarding the etiology of this phenomenon. While SIDS deaths are in reality undetermined deaths, there is resistance to abandon SIDS and synonymous terminology. This paper identifies the social functions that a diagnosis of SIDS provides both to the families of the deceased, as well as the physicians who treat them. It is suggested that these social functions help to explain why, despite being inaccurate and misleading, SIDS is still widely used today. It is argued, however, that the forensic pathology and medical community as a whole should lead a systematic shift away from the use of SIDS as a diagnosis. Adopting more medically-appropriate terminology would better serve the goals of the medical profession and the families they serve.

Morphology of the Dentate Gyrus in a Large Cohort of Sudden Infant Deaths-Interrelation Between Features but Not Diagnosis.

Morphological differences in the dentate gyrus (DG) have been reported in sudden unexpected deaths in infancy (SUDI), with the feature of focal granule cell (GC) bilamination (FGCB) reported as increased in unexplained SUDI, including sudden infant death syndrome (SIDS), compared with explained SUDI (eSUDI). However, it remains to be determined how these morphologies relate to each other and their extent along the anteroposterior length. This retrospective study evaluated the prevalence of FGCB, single or clustered ectopic GCs, granule cell dispersion (GCD), heterotopia, hyperconvolution, gaps, thinning, blood vessel dissection (BVD), and cuffing (BV cuffing), in an Australian SUDI cohort, and compared the prevalence of these features in eSUDI and unexplained SUDI. We analyzed 850 formalin-fixed paraffin-embedded serial and subserial sections of the hippocampus at the level of the lateral geniculate nucleus from 90 infants, and identified GCD in 97% of infants, single ectopic cells, hyperconvolution, thinning, and BVD in 60%-80%, heterotopia in 36%, gaps, clusters of ectopic cells and BV cuffing in 9%-15%, and FGCB in 18%. These features are clustered within 3-5 serial sections. The presence of FGCB correlated with single ectopic GCs and hyperconvolution. There were no differences in the prevalence of these features between unexplained SUDI (n = 74) and eSUDI (n = 16). Our findings highlight that DG morphological features are highly localized, extending 14-35 µm at their focal location(s) along the anteroposterior length. Consequently, multiple sections along the longitudinal extent are required to identify them. No feature differentiated SUDI from eSUDI in our cohort, thus we cannot conclude that any of these features are abnormal and it remains to be determined their functional significance.

Local recommendations for death scene investigation of sudden unexpected death in infants (SUDI) based on prospective observations.

BACKGROUND: The analyses of death scenes of sudden unexpected death in infants (SUDI) form an integral part of postmortem investigations. However, previous research has suggested that death scene investigation in SUDI cases is inconsistent and limited in South Africa. OBJECTIVES: To suggest realistic and feasible improvements for SUDI scene investigation by means of prospective observation. METHODS: Ten SUDI cases were followed up from death scene until autopsy and detailed observations were made using a semi-structured checklist. Data were analysed in conjunction with published data from the same mortuary to suggest realistic improvements. RESULTS: In all observed cases, the infant was moved prior to the arrival of forensic pathology officers; yet, reconstruction of the events leading to death were never demonstrated with a doll. The use of photography varied, with a median of 15 (standard deviation 6.5) photographs taken at each scene. However, critical photographs, such as those of medication, were often omitted. Furthermore, medicine was not collected from any scene. The use of documentation was inconsistent, where the intended longitudinal use was achieved in only 2 of 10 cases. Forms were inadequately filled in, due to the sensitivity or lack of understanding of various questions, rendering the forms incomplete. CONCLUSIONS: Training of specialised staff should therefore focus on five areas: doll re-enactment, photography, handling of medicine, accurate use of relevant documentation and use of a glossary. The implementation of these recommendations is deemed to be feasible in a resource-scarce mortuary setting and could assist other mortuaries in the development of locally relevant strategies.

Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis.

In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death.

Aquaporin 4 expression in the hippocampus in sudden infant death syndrome and sudden unexplained death in childhood.

Aquaporin 4 (AQP4) is the main membrane water channel in the brain involved in regulating water homeostasis. The water distribution in neural tissue is often dysregulated after hypoxic neural injury. Previous research has indicated that victims of sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) have an underlying brain dysfunction that impairs their critical arousal response to hypoxic stress during sleep. The aim of this study was to determine the expression levels of AQP4 in the hippocampus in SIDS/SUDC cases and controls, and compare the findings with AQP4 genotypes that previously have been shown to be associated with SIDS. Immunochemical staining and morphometry were used to evaluate the density of AQP4-positive astrocytes in 30 SIDS/SUDC cases and 26 controls. AQP4-positive cells were counted in grids covering three layers in the hippocampus, which revealed that their count in any of the layers did not differ significantly between cases and controls. A decline in AQP4 expression was observed for infants older than 12 weeks. The AQP4 expression was lower in infants and children with the rs2075575 CT/TT genotype than in those with the CC genotype. This study indicates that AQP4 expression may be influenced by both age and genotype in infants. The role of AQP4 in the pathogenesis of SIDS remains to be elucidated.