A Systematic Approach to Evaluate Sudden Unexplained Death in Children

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

The Achilles heel of decision making system in termites

Mitochondrial beta-oxidation of long-chain fatty acids requires the concerted action of three tightly integrated membrane-bound enzymes (carnitine palmitoyltransferase I and II and carnitine/acylcarnitine translocase) that transport them into mitochondria. Neonatal onset of carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive, often lethal disorder of this transport. We describe a novel splice-site mutation in the CPT II gene, found in a Moroccan family, of which four out of five children have died from the neonatal form of CPT II deficiency. Mutation detection studies at the mRNA level in the CPT II gene implied that the affected children were homozygous for the previously reported 534T insertion followed by a 25-bp deletion (encompassing bases 534-558). Studies of genomic DNA, however, revealed all patients to be compound heterozygous for this 534T ins/del 25 mutation, and for a new g-->a splice-site mutation in the splice-acceptor site of intron 2. Because of these findings, prenatal diagnosis was performed in chorionic villi of three new pregnancies. This did not reveal new compound heterozygous genotypes, and, after uneventful pregnancies, all children appeared to be healthy. The new mutation is the first splice-site mutation ever identified in CPT II deficiency. The fact that it was not discovered in the patient's cDNA makes this study another example of the incompleteness of mutation detection at the mRNA level in cases where a mutation leads to aberrant splicing or nonsense-mediated messenger deca

A Systematic Approach to Evaluate Sudden Unexplained Death in Children

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

Surveillance study of apparent life-threatening events (ALTE) in the Netherlands

SIDS and ALTE are different entities that somehow show some similarities. Both constitute heterogeneous conditions. The Netherlands is a low-incidence country for SIDS. To study whether the same would hold for ALTE, we studied the incidence, etiology, and current treatment of ALTE in The Netherlands. Using the Dutch Pediatric Surveillance Unit, pediatricians working in second- and third-level hospitals in the Netherlands were asked to report any case of ALTE presented in their hospital from January 2002 to January 2003. A questionnaire was subsequently sent to collect personal data, data on pregnancy and birth, condition preceding the incident, the incident itself, condition after the incident, investigations performed, monitoring or treatment initiated during admission, any diagnosis made at discharge, and treatment or parental support offered after discharge. A total of 115 cases of ALTE were reported, of which 110 questionnaires were filled in and returned (response rate 97%). Based on the national birth rate of 200,000, the incidence of ALTE amounted 0.58/1,000 live born infants. No deaths occurred. Clinical diagnoses could be assessed in 58.2%. Most frequent diagnoses were (percentages of the total of 110 cases) gastro-esophageal reflux and respiratory tract infection (37.3% and 8.2%, respectively); main symptoms were change of color and muscle tone, choking, and gagging. The differences in diagnoses are heterogeneous. In 34%, parents shook their infants, which is alarmingly high. Pre- and postmature infants were overrepresented in this survey (29.5% and 8.2%, respectively). Ten percent had recurrent ALTE. In total, 15.5% of the infants were discharged with a home monitor. In conclusion, ALTE has a low incidence in second- and third-level hospitals in the Netherlands. Parents should be systematically informed about the possible devastating effects of shaking an infant. Careful history taking and targeted additional investigations are of utmost importance

Congenital cytomegalovirus infection: review of the epidemiology and outcome

Cytomegalovirus (CMV) is one of the most common viral causes of congenital infection. A future decision to lower its incidence by vaccination will depend on epidemiological conditions within a country and on the safety of the vaccine to be used, because a life vaccine may cause latency and subsequent reactivation that still may harm the fetus. The aim was to review the epidemiological studies published so far, with respect to factors that affect the incidence of congenital CMV infection, and factors that may influence its outcome, such as preexisting maternal immunity. The study included the data of 19 studies that were retrieved from a MEDLINE search during the period 1977 to 1997. The incidence of congenital CMV infection varied between 0.15% and 2.0% and seemed to correlate with the level of preexisting immunity in the population. Although preexisting maternal immunity was reported to strongly reduce transmission, the severity of congenital CMV infection (symptoms at birth and or sequelae later in life) was not significantly greater after virus transmission due to a primary infection of the mother as compared with recurrence or reinfection. The data indicate that preexisting immunity of the mother does not significantly mitigate the outcome of congenital infection. Moreover, life vaccines may bear a serious risk when transmittable to the fetus. Target Audience: Obstetricians and Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe the natural course of a CMV infection, to list the potential sequelae of a congenital CMV infection, to outline potential strategies to prevent transmission of CMV, and to summarize the diagnostic work up of a patient with a potential CMV infection