Sudden Infant Death Research Articles

Vosoritide therapy in children with achondroplasia aged 3−59 months: a multinational, randomised, double-blind, placebo-controlled, phase 2 trial

Vosoritide is a recombinant C-type natriuretic peptide analogue that increases annualised growth velocity in children with achondroplasia aged 5-18 years. We aimed to assess the safety and efficacy of vosoritide in infants and children younger than 5 years. This double-blind, randomised, placebo-controlled, phase 2 trial was done in 16 hospitals across Australia, Japan, the UK, and the USA. Children younger than 60 months with a clinical diagnosis of achondroplasia confirmed by genetic testing and who had completed a baseline growth study or observation period were enrolled into one of three sequential cohorts based on age at screening: 24-59 months (cohort 1); 6-23 months (cohort 2); and 0-5 months (cohort 3). Each cohort included sentinels who received vosoritide to determine appropriate daily drug dose, with the remainder randomly assigned (1:1) within each age stratum (except in Japan, where participants were randomly assigned within each cohort) to receive daily subcutaneous injections of vosoritide (30·0 μg/kg for infants aged 0-23 months; 15·0 μg/kg for children aged 24-59 months) or placebo for 52 weeks. Participants, caregivers, investigators, and the sponsor were masked to treatment assignment. The first primary outcome was safety and tolerability, assessed in all participants who received at least one study dose. The second primary outcome was change in height Z score at 52 weeks from baseline, analysed in all randomly assigned participants. This trial is registered with EudraCT, 2016-003826-18, and ClinicalTrials.gov, NCT03583697. Between May 13, 2018, and March 1, 2021, 75 participants were recruited (37 [49%] females). 11 were assigned as sentinels, whereas 32 were randomly assigned to receive vosoritide and 32 placebo. Two participants discontinued treatment and the study: one in the vosoritide group (death) and one in the placebo group (withdrawal). Adverse events occurred in all 75 (100%) participants (annual rate 204·5 adverse events per patient in the vosoritide group and 73·6 per patient in the placebo group), most of which were transient injection-site reactions and injection-site erythema. Serious adverse events occurred in three (7%) participants in the vosoritide group (decreased oxygen saturation, respiratory syncytial virus bronchiolitis and sudden infant death syndrome, and pneumonia) and six (19%) participants in the placebo group (petit mal epilepsy, autism, gastroenteritis, vomiting and parainfluenza virus infection, respiratory distress, and skull fracture and otitis media). The least-squares mean difference for change from baseline in height Z score between the vosoritide and placebo groups was 0·25 (95% CI -0·02 to 0·53). Children with achondroplasia aged 3-59 months receiving vosoritide for 52 weeks had a mild adverse event profile and gain in the change in height Z score from baseline. BioMarin Pharmaceutical.

Retraction: Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets.

Retraction: Sudden infant death syndrome: Melatonin, serotonin, and CD34 factor as possible diagnostic markers and prophylactic targets.

Characteristics Associated with Sudden Unexpected Infant Death in a Rural Hispanic Population: A Case-Control Study.

Sudden unexpected infant death (SUID) is the leading cause of death among U.S. infants aged 28 days to 1 year. In Kansas, Hispanic infant mortality is nearly 50% higher than non-Hispanic White. Further, the SUID rate did not change between 2005-2018, while rates for non-Hispanic Black and White infants decreased significantly. This study sought to identify characteristics and behaviors of Hispanic birthing persons related to SUID. Linked Kansas birth/death vital statistics data (2005-2018) identified Hispanic birthing persons with a singleton birth who experienced SUID. To reduce confounding effects, greedy nearest neighbor matching paired each SUID case sequentially with the four nearest controls based on age, race, payor source and parity. Matching procedures, likelihood-ratio χ2, Fisher exact test and multiple logistic regression model with Firth's penalized maximum likelihood estimation were computed. Of 86,052 Hispanic singleton births, 66 involved SUID and were matched with 264 controls. No differences were related to marital status, population density of residence, education level, language spoken, prenatal BMI, weight gained during pregnancy, adequacy of prenatal care, enrollment in WIC, or state immunization registry participation (all p>0.05). However, tobacco use during pregnancy contributed to a three times greater risk of SUID (OR=3.208; 95% CI=1.438 to 7.154). Multivariable models for behavioral variables revealed low predictive accuracy with area under the ROC curve=0.6303. This study suggests SUID deaths to rural Hispanic families are likely multifaceted. Study results inform educational programs on the importance of addressing tobacco cessation in SUID risk reduction interventions for Hispanic families.

Abstract 339: Causes and Initial Cardiac Arrest Rhythms in a National Paediatric Cohort From Norway

Background: Mortality following paediatric out-of-hospital cardiac arrest (POHCA) is high. Registration of any resuscitation attempt is mandated by law in the Norwegian Cardiac Arrest Registry (NorCAR), providing an opportunity to study precipitating causes from a nationwide population perspective. Research questions and aims The study set out to investigate the precipitating causes and the presenting rhythms of OHCA in children; enabling a focused approach to prevention and treatment of cardiac arrest in children. Methods: NorCAR data for children aged 0-17 years was extracted for 2016-21. Cases of perinatal resuscitation and children not receiving ongoing cardiopulmonary resuscitation by ambulance personnel were excluded. Descriptive statistics were used to create age-stratified summaries for presumed causes of POCHA and presenting rhythms. Results: In total, 308 children were included. Presumed causes of cardiac arrest included choking (n=67), cardiac aetiology (n=55), respiratory failure (n=51), sudden infant death syndrome (n=51), and drowning (n=37). The presumed causes differed substantially according to age (Figure). Non-shockable rhythms dominated (87%, 250 of 287 with available rhythm data). The proportion of shockable rhythms increased with age to 15 % (19 of 127) in the 13-17 year age group. Conclusion: The causes of POHCA were diverse and highly age dependent. This knowledge may inform both parents and caretakers, health professionals, and the whole community with respect to effective prevention, proper first aid, and focused emergency medical treatment.

Abstract 17335: Novel Functional Genomic Studies in Scn1bb Variant Associated With Brugada Syndrome and the Ameliorative Effect of Acacetin

Background: Brugada syndrome (BrS) is a channelopathy associated with the development of life-threatening ventricular tachycardia and fibrillation (VT/VF). At present, pharmacological approaches to therapy are very limited. Objective: To evaluate the effect of an SCN1Bb variant and the effects of acacetin in experimental models of BrS. Methods: We evaluated the effect of acacetin in: 1) HEK293 cells expressing Kv4.3+ KChIP2 and Nav1.5+ SCN1B using patch clamp techniques (22 O C), 2) canine ventricular epicardial myocytes 3) coronary-perfused canine right (RV) preparations and 4) Langendorff-perfused canine whole-heart models of BrS in which the sodium channel blocker ajmaline or the calcium channel blocker verapamil, together with the transient outward current agonist NS5806 were used to provoke the arrhythmic phenotype. Results: Co-expression of SCN5A -WT+ KCND3-WT with KChIP2 + SCN1Bb -R214Q (variant associated with 3 cases of BrS and 1 case of sudden infant death (SIDS)), resulted in a 210% increase in total charge of the transient outward potassium current (I to ) as well as a 56.5% reduction in sodium channel current (I Na ) when compared to SCN1Bb-WT . In the absence of the mutation, acacetin inhibited I to with an IC 50 of 7.2±1.0 μM (n=3) in HEK cells, similar to the value obtained in native epicardial myocytes (6 μM). In the presence of the SCB1Bb mutant, IC 50 was dramatically reduced to 2.6±1 μM (n=5, p<0.05) Mean ±SEM. In the wedge and whole-heart models of BrS, acacetin dose-dependently reduced the epicardial action potential notch recorded from the RV or RVOT. Acacetin (5-10 μM) totally suppressed the electrocardiographic and arrhythmic manifestation of BrS, regardless of the pharmacologic model used to induce the arrhythmic phenotype. All repolarization defects were reversed, resulting in marked diminution of J waves leading to total suppression of VT/VF. Conclusions: Our findings demonstrate the ability of an SCN1Bb variant to dramatically shift the balance of current in the early phases of the RV epicardial action potential by reducing I Na as well as augmenting I to , thus predisposing to the development of the BrS phenotype. Our observations also hold promise for acacetin as a safe and effective pharmacologic treatment for BrS and some cases of SIDS.

Exome analysis focusing on epilepsy-related genes in children and adults with sudden unexplained death

PurposeGenetic studies in sudden infant death syndrome (SIDS) and sudden unexplained death (SUD) cohorts have indicated that cardiovascular diseases might have contributed to sudden unexpected death in 20–35 % of autopsy-negative cases. Sudden unexpected death can also occur in people with epilepsy, termed as sudden unexpected death in epilepsy (SUDEP). The pathophysiological mechanisms of SUDEP are not well understood, but are likely multifactorial, including seizure-induced hypoventilation and arrhythmias as well as genetic risk factors. The sudden death of some of the SIDS/SUD victims might also be explained by genetic epilepsy, therefore this study aimed to expand the post-mortem genetic analysis of SIDS/SUD cases to epilepsy-related genes. MethodsExisting whole-exome sequencing data from our 155 SIDS and 45 SUD cases were analyzed, with a focus on 365 epilepsy-related genes. Nine of the SUD victims had a known medical history of epilepsy, seizures or other underlying neurological conditions and were therefore classified as SUDEP cases. ResultsIn our SIDS and SUD cohorts, we found epilepsy-related pathogenic/likely pathogenic variants in the genes OPA1, RAI1, SCN3A, SCN5A and TSC2. ConclusionPost-mortem analysis of epilepsy-related genes identified potentially disease-causing variants that might have contributed to the sudden death events in our SIDS/SUD cases. However, the interpretation of identified variants remains challenging and often changes over time as more data is gathered. Overall, this study contributes insight in potentially pathophysiological epilepsy-related mechanisms in SIDS, SUD and SUDEP victims and underlines the importance of sensible counselling on the risk and preventive measures in genetic epilepsy.

Newborn Screening with (C16 + C18:1)/C2 and C14/C3 for Carnitine Palmitoyltransferase II Deficiency throughout Japan Has Revealed C12/C0 as an Index of Higher Sensitivity and Specificity.

Carnitine palmitoyltransferase (CPT) II deficiency is a long-chain fatty acid oxidation disorder. It manifests as (1) a lethal neonatal form, (2) a hypoglycemic form, or (3) a myopathic form. The second form can cause sudden infant death and is more common among Japanese people than in other ethnic groups. Our study group had earlier used (C16 + C18:1)/C2 to conduct a pilot newborn screening (NBS) study, and found that the use of C14/C3 for screening yielded lower rates of false positivity; in 2018, as a result, nationwide NBS for CPT II deficiency started. In this study, we evaluated the utility of these ratios in 71 NBS-positive infants and found that the levels of both C14/C3 and (C16 + C18:1)/C2 in patients overlapped greatly with those of infants without the disease. Among the levels of acylcarnitines with various chain lengths (C18 to C2) and levels of free carnitine (C0) as well as their ratios of various patterns, C12/C0 appeared to be a promising index that could reduce false-positive results without missing true-positive cases detected by current indices. Although some cases of the myopathic form may go undetected even with C12/C0, its use will help prevent life-threatening onset of the hypoglycemic form of CPT II deficiency.

BREAST MILK BANKS – THE WAY TO GLOBAL BREASTFEEDING SUPPORT IN UKRAINE AND THE WORLD

Breast milk is the standard of infant nutrition, recognized worldwide as the optimal fi rst source of food, and breastfeedingis the ideal way to feed children, meeting all their needs. Breast milk is especially valuable for premature infants, who require specialized medical care from the fi rst seconds of life and for a long time, and for sick newborns born at term. Preterm or sick preterm infants are most vulnerable to perinatal illness, have a high probability of dying and, most importantly, are at the greatest risk of not receiving the life-saving benefi ts of breast milk. In today’s world, the World Health Organization and the American Academy of Pediatrics recommend the use of donor human milk as the fi rst alternative for feeding preterm infants of any gestational age, including very preterm infants (<32 weeks gestation) or very low birth weight infants (<1500 g), when human milk is not available. Studies have shown that breastfeeding, even partial breastfeeding, reduces the risk of necrotizing enterocolitis and late neonatal sepsis, retinopathy of prematurity, and sudden infant death, improves cognitive outcomes in preterm infants, and helps establish optimal functioning of the digestive system and enteric digestive processes. In many countries around the world, targeted support for breastfeeding in neonatal intensive care units, including enteral feeding of sick and premature infants, is provided by donor human breast milk that is concentrated and stored in an established and functioning network of breast milk banks.A breast milk bank is an institution whose purpose is to collect breast milk from mothers who produce more than theirinfants need, and to process and store breast milk for the feeding of infants who, for medical or other reasons, cannot receive it temporarily or for a long period. International associations of breast milk banks have been established throughout the world to promote the activities of banks and to establish international cooperation among breast milk banks.The European Milk Banks Association (EMBA) was offi cially launched on October 15, 2010. There are currently 282 activebanks in 31 European countries and 18 banks in the process of becoming active. The Southern African Milk Banks Association (HMBASA) was established in 2009. HMBASA coordinates the activities of the network of milk banks throughout the country. The North American Milk Banks Association (HMBANA) was founded in 1985 and brings together 30 non-profi t breast milk banks in the United States and Canada. There is a positive trend in the establishment of new breast milk banks in all countries of the world. There are currently about 500 in 37 countries. Brazil is the world leader in breast milk banks, with 222 breast milk banks and 217 milk collection centers. The first donor breast milk bank in Ukraine was established in 2019 in Kyiv at the Perinatal Center, where about 80 % of all premature babies in the city are born. In December 2022, when the country was at war, a high-tech breast milk bank was opened at the Lviv Regional Clinical Perinatal Center. This is the second bank of donated breast milk successfully operating in Ukraine on the basis of perinatal centers.The operation of the breast milk bank at the Lviv Oblast Clinical Perinatal Center is one of the many modern high-tech areasof the healthcare facility. The breast milk bank is equipped with all the necessary equipment, which meets the highest modern world standards. Active daily teamwork of obstetricians, neonatologists, lactation consultants and mothers has allowed the bank to attract 32 donors of breast milk and collect more than 380 liters of donor milk since its opening. The fi rst batch of donor milk was received on January 12, 2023.Promoting the creation of a network of mother’s milk banks in Ukraine at the state level will help to make a signifi cantcontribution to the preservation of the full healthy development of newborns and infants in our country, which has becomeespecially important in the current military situation in Ukraine.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks.

The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Health impact assessment of the chemical exposome in European children

Abstract Background We aimed to assess the impact of the chemical exposome on the health of European children since previous health impact assessments (HIA) were limited to a few chemicals. Methods 74 out of 484 substance-outcome associations had an overall level of evidence at least likely and were therefore considered for HIA. For 51 of the 74 associations, dose-response relationships were identified from systematically searched meta-analyses or epidemiological studies. For 41 of these, exposure levels were compatible for HIA. Exposure levels were based on biomarker concentrations assessed in 1301 pregnant women and children of the HELIX cohorts in 6 European countries. The baseline burden of disease were from national estimates of the World Health Organisation for 8 outcomes. The attributable burden of disease was estimated by combining exposures and dose-response relationships and expressed in terms of population attributable fraction, disability-adjusted life years (DALYs) or variations in mean level for quantitative health outcomes. Associated uncertainty was taken into account using Monte-Carlo simulations. Results Each substance harmful for cognition or birth weight entailed an average estimated decrease in Intellectual Quotient by 1.7 points (95% confidence interval (CI) 0, 4.3) and in birth weight by 57 g (95%CI 0, 138). The chemical exposome entailed 1.65 (95%CI 0.63; 2.90) DALYs for 1,000 children per year. The main contributors to the impact were perfluoroalkyl substances, other persistent organic pollutants and tobacco. The impact was mainly due to neurodevelopment (0.4 DALY), congenital heart defects (0.6 DALY), respiratory health (0.4 DALY) and sudden infant death syndrome (0.3 DALY). Conclusions Our study is one of the largest HIA in terms of number of chemicals considered. The results exclude urban exposures such as air pollution and are probably largely underestimated because of a lack of data on dose-response relationships and baseline burden of disease. Key messages • Chemical exposures (mainly perfluoroalkyl substances, persistent organic pollutants, metals and tobacco) contribute to the burden of disease in European children. • Chemical exposures have an impact on fetal and infant death, neurodevelopment, cardiometabolism, respiratory and reproductive health of children.

Aberrant colon metabolome and the sudden infant death syndrome.

The Sudden Infant Death Syndrome (SIDS) has been associated with increased peripheral serotonin and an abnormal colonic microbiome, suggesting the colonic metabolome may also be abnormal. This study addresses this potential correlation by comparing colonic autopsy tissue from SIDS to age-matched non-SIDS controls. Untargeted metabolomic analysis by mass spectrometry is used to assess human colonic metabolomic differences including serotonin. Expression of genes associated with colonic serotonin synthesis and transport (TPH1, TPH2, DDC, SCL6A4) is measured by qRT-PCR. Microbiome analysis is performed to compare the SIDS and non-SIDS colonic microbiome. Unsupervised hierarchical cluster and principal component analyses of metabolomic data shows increased variability in the SIDS cohort and separation of SIDS cases from the non-SIDS controls. There is a trend toward increased serotonin in the SIDS cohort but there is no significant difference in expression of the serotonin synthesis and transport genes between SIDS and non-SIDS control cohorts. Microbiome analysis shows no significant difference between the SIDS and non-SIDS control cohorts. This study demonstrates increased variability in the colonic metabolome and a trend towards increased colonic serotonin in SIDS. The underlying cause of colon metabolomic variability, and its potential role in SIDS pathogenesis, warrants further investigation. The key message of this article is that SIDS is associated with an aberrant colonic metabolome. This is a novel observation suggesting another component in the pathophysiology underlying SIDS. Investigation of why the colonic metabolome is aberrant may offer new insights to SIDS pathogenesis and new strategies to reduce risk.

Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and Sudden Infant Death Syndrome: A Potential Model for Investigation.

Sudden infant death syndrome (SIDS) represents a significant cause of post-neonatal mortality, yet its underlying mechanisms remain unclear. The triple-risk model of SIDS proposes that intrinsic vulnerability, exogenous triggers, and a critical developmental period are required for SIDS to occur. Although case-control studies have identified potential risk factors, no in vivo model fully reflects the complexities observed in human studies. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide with diverse physiological functions, including metabolic and thermal regulation, cardiovascular adaptation, breathing control, stress responses, sleep-wake regulation and immunohomeostasis, has been subject to early animal studies, which revealed that the absence of PACAP or its specific receptor (PAC1 receptor: PAC1R) correlates with increased neonatal mortality similar to the susceptible period for SIDS in humans. Recent human investigations have further implicated PACAP and PAC1R genes as plausible contributors to the pathomechanism of SIDS. This mini-review comprehensively synthesizes all PACAP-related research from the perspective of SIDS and proposes that PACAP deficiency might offer a promising avenue for studying SIDS.

Sudden infant death syndrome: revealing this mystery is possible

Dear Editor, The sudden and unexpected loss of an infant in the first months of life is a heartbreaking and devastating experience for any parent. Understandably, it can be an extremely distressing time for the mother, who may often find herself unfairly burdened with guilt. When this tragic event occurs, a thorough investigation becomes necessary to determine the cause of death and also absolve the mother of any responsibility. [...]

Choline-acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the human infant dorsal motor nucleus of the Vagus (DMNV), and alterations according to sudden infant death syndrome (SIDS) category

Amongst other molecules, the cholinergic system consists of choline-acetyltransferase (ChAT, − synthesis enzyme), acetylcholinesterase (AChE – primary hydrolysis enzyme), and butyrylcholinesterase (BuChE – secondary hydrolysis enzyme). In the brainstem, the Dorsal Motor Nucleus of The Vagus (DMNV) has high cholinergic expression and is a region of interest in the neuropathology of sudden infant death syndrome (SIDS). SIDS is the unexpected death of a seemingly healthy infant, but postmortem brainstem abnormalities suggesting altered cholinergic regulation have been found.This study aimed to determine the percentage of positive ChAT and AChE neurons within the infant DMNV through immunohistochemistry at the three levels of the brainstem medulla (caudal, intermediate, and rostral), to investigate whether the proportion of neurons positive for these enzymes differs amongst the diagnostic subgroups of SIDS compared to those with an explained cause of Sudden unexpected death in infancy (eSUDI), and whether there were any associations with SIDS risk factors (male gender, cigarette smoke exposure, co-sleeping/bed sharing, and prone sleeping). Results showed that ChAT-positive neurons were lower in the rostral DMNV in the SIDS II cohort, and within the caudal and intermediate DMNV of infants who were exposed to cigarette smoke. These findings suggest altered cholinergic regulation in the brainstem of SIDS infants, with potential contribution of cigarette smoke exposure, presumably via the nicotinic acetylcholinergic receptor system.

THU121 Dopamine Regulates Neuroendocrine Cell Expansion In The Developing Lung

Abstract Disclosure: T. Watanabe: None. M. Stupnikov: None. Y. Zhou: None. X. Ke: None. J. Qien: None. A. Ozawa: None. M. Horigome: None. M. Yamada: None. M. Mori: None. W.V. Cardoso: None. Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells in the lung that have function as neurosensory and endocrine cells. They arise from naive epithelial progenitor cells in mice on embryonic day (E) 12.5, migrate to branch point of proximal airway and rare found as solitary or in clusters of 5 to 20 cells termed neuroepithelial bodies (NEBs). PNECs can be aberrantly increased in a variety of human diseases, including asthma, neuroendocrine hyperplasia of infants (NEHI) and sudden infant death syndrome (SIDS). Ascl1, an Achaete-Scute family bHLH transcriptional factor is the earliest marker and master regulator of PNEC fate specification. No PNECs form in Ascl1 null mice. In an effort to identify Ascl1 downstream targets involved in PNEC specification and expansion, we performed transcriptional analysis of E14.5 lungs from Ascl1 null mouse. Gene Ontology analysis showed a number of genes associated with the catecholamine pathway downregulated in mutants, compared to WT. These included tyrosine hydroxylase (Th) dopa decarboxylase (Ddc), dopamine beta-hydroxylase (Dβh). To gain initial insights into how catecholamine signaling influence PNEC development, we cultured E12.5 lung explants with various inhibitors of the catecholamine biosynthesis pathway and examined the effects on cell differentiation and proliferation. Treatment with Metyrosine (Met) and Benserazide (Benz) which inhibits dopamine production, resulted in a striking increase in PNEC number in NEBs as seen by expansion in Ascl1+ cells, without affecting cell proliferation. By contrast, no effect was observed with Zamicastat (Zami) which inhibits norepinephrine production. To examine whether dopamine regulated PNEC differentiation, we used the D1-like receptor antagonist, SCH-23390 and the D2-like receptor antagonist, Haloperidol in lung explant cultures, as before. Only Haloperidol increased PNECs in cultured lungs. This effect was similarly observed by maternal administration of Haloperidol intraperitoneally from E9.5 to 13.5 and analysis of harvested embryos at E14.5 and 18.5. Current studies mapping expression of other components of the dopamine pathway in the developing airway epithelium suggests a complex interaction of PNECs with neighbor cells in the regulation of the proper number of NEBs and solitary NE cells. These observations may provide a link between catecholamine signaling and aberrant PNEC behavior in the pathogenesis of human conditions affecting these cells. Presentation: Thursday, June 15, 2023

Primary Carnitine Deficiency: Rare Cause of Paediatric Dilated Cardiomyopathy, Often Underdiagnosed

Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid beta-oxidation. Which results from a defect in the transport of carnitine and is one of the rare treatable etiologies of metabolic cardiomyopathies. Affected patients may present with acute metabolic decompensation in infancy or severe cardiomyopathy in childhood. There have also been reports of dramatic sudden infant death syndrome. Early disease detection and treatment with L-carnitine can be lifesaving. We present in this report, a severe case of decompensation of previously undiagnosed dilated cardiomyopathy in a 14-year-old boy, who presented to the pediatric emergency department with acute heart failure, initially suspected to be viral myocarditis. Chest x-ray showed cardiomegaly, echocardiographic findings included hypokinetic dilated cardiomyopathy with reduced ejection fraction at 22%, the respiratory multiplex PCR came back in favor of a SARS-CoV-2 infection, Laboratory test results showed hepatic failure and a low rate of free and total plasma carnitine. His clinical condition deteriorated rapidly, with the onset of cardiogenic shock leading up to his death in the intensive care unit before carnitine therapy was initiated. The aim of this case report is to highlight the importance of searching for a metabolic cause, particularly primary carnitine deficiency, for early treatment and improved prognosis of the disease.

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

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. 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). 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. 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.

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

ObjectivesUsing 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...

Hats Off for Full-Term Healthy Newborns: No Benefits for Thermoregulation.

Hyperthermia is a known risk for sudden unexpected infant death. The practice of hat placement at birth to prevent transient hypothermia may not be necessary and sets an early standard for clothing infants that may lead to hyperthermia postnatally. To examine the elimination of hats on thermoregulation (eg, hypothermia, <97.6°F) in full-term newborns with no abnormalities within 24 hours of birth. In 2018, an institution guideline discontinued the use of hats at birth. Subsequently, newborn body temperatures were respectively extracted from electronic health records and data were compared from 482 infants (>38 weeks' gestation and newborn birth weight >2500 g) prior to ( n = 257) and following ( n = 225) the practice change. Body temperatures prior to and after the practice change to eliminate hats use were compared. No statistically significant difference was observed: (1) in the proportion of infants experiencing hypothermia with or without hat use, respectively, 23.7% compared with 31.1% ( P = .09) and (2) in the odds of an infant experiencing hypothermia when adjusting for relevant covariates (odds ratio = 1.44; 95% confidence interval 0.89-2.32; P = .14). Our findings demonstrate that the use of hats on infants at birth had no measurable impact on newborn thermoregulation.

Factors in Infancy That May Predict Autism Spectrum Disorder.

The global increase in the prevalence of ASD (Autism Spectrum Disorder) is of great medical importance, but the reasons for this increase are still unknown. This study sought to identify possible early contributing factors in children who were later diagnosed with ASD. In this retrospective cohort study, postnatal records of 1105 children diagnosed with ASD were analyzed to determine if any signs of ASD could be found in a large database of births and well-baby care programs. We compared the recordings of typically developing children and analyzed the differences statistically. Rapid increases in weight, height, and head circumference during early infancy predict the development of ASD. In addition, low birth weight, older maternal age, and increased weight and height percentiles at six months of age together predict the development of ASD. At two years of age, these four parameters, in addition to impaired motor development, can also predict the development of ASD. These results suggest that the recent increase in ASD prevalence is associated with the "obesity epidemic" and with recommendations of supine sleeping to prevent Sudden Infant Death Syndrome, associated with atypical neural network development in the brain.