Objectives
To investigate the contribution of whole-body post-mortem computed tomography (PMCT) in sudden unexpected death in infants and children.
Methods
Forty-seven cases of sudden unexpected ...death in children investigated with radiographic skeletal survey, whole-body PMCT and autopsy were enrolled. For imaging interpretation, non-specific post-mortem modifications and abnormal findings related to the presumed cause of death were considered separately. All findings were correlated with autopsy findings.
Results
There were 31 boys and 16 girls. Of these, 44 children (93.6 %) were younger than 2 years. The cause of death was found at autopsy in 18 cases (38.3 %), with 4 confirmed as child abuse, 12 as infectious diseases, 1 as metabolic disease and 1 as bowel volvulus. PMCT results were in accordance with autopsy in all but three of these 18 cases. Death remains unexplained in 29 cases (61.7 %) and was correlated with no abnormal findings on PMCT in 27 cases. Major discrepancies between PMCT and autopsy findings concerned pulmonary analysis.
Conclusions
Whole-body PMCT may detect relevant findings that can help to explain sudden unexpected death and is essential for detecting non-accidental injuries. We found broad concordance between autopsy and PMCT, except in a few cases of pneumonia. It is a non-invasive technique acceptable to relatives.
Key Points
• Whole-body post-mortem computed tomography (PMCT) is an effective non-invasive method.
• Whole-body PMCT is essential for detecting child abuse in unexpected death.
• There is concordance on cause of death between PMCT and autopsy.
• Whole-body PMCT could improve autopsy through dissection and sampling guidance.
• PMCT shows findings that may be relevant when parents reject autopsy.
Abstract Background French health authorities promoted a study on 553,167 newborns comparing the performances of IRT/DNA and IRT/PAP for CF newborn screening. Methods In parallel to IRT/DNA, PAP was ...assayed in newborns with IRT > 50 μg/L. Provisional PAP cutoffs at 3.0 μg/L when 50 < IRT < 100 μg/L and 1.7 μg/L when IRT > 100 were used. Positive newborns were subjected to sweat test. Optimal cutoffs were established by a non-inferiority method. Results 95 CF newborns were identified (83 classical forms (ClF), including 9 meconium ileus (MI), and 12 atypical (mild) forms (AF) Of them, IRT/DNA identified 85 (73 ClF including 5 MI and 12 AF). PAP cutoffs at 1.8 μg/L when 50< IRT<100 μg/L and 0.6 μg/L when IRT>100 μg/L would identify 82 CF: 77 ClF, including 8 MI, and 5 AF. The number of sweat tests was 314 and 1039 in the IRT/DNA and IRT/PAP strategies, respectively. Conclusions Using the optimal cutoffs, the sensitivity of the IRT/PAP strategy would not be inferior to that of IRT/DNA if identification of MF is not required.
Subtle disadvantages in patients with congenital hypothyroidism are related to disease severity and treatment adequacy and, to a greater extent than previously recognized, to the presence of ...associated chronic comorbidities.
Context:
Screening programs resulting in the early treatment of patients with congenital hypothyroidism (CH) have successfully improved neurodevelopmental outcome, but little is known about long-term health.
Objectives:
The aim of the study was to assess health status, and socioeconomic attainment, for a population-based registry of young adult patients.
Design, Setting, and Participants:
All 1748 eligible patients diagnosed during the first decade after the introduction of neonatal screening in France were invited to participate in this study at a median age of 23.4 yr. Completed questionnaires were obtained from 1202 of the selected patients. The comparison group included 5817 subjects from the last French Decennial Health Survey.
Main Outcome Measures:
Health indicators including medical conditions, hearing and visual status, sociodemographic characteristics, and quality of life were measured.
Results:
Patients with CH were significantly more likely than their peers to report associated chronic diseases (5.7 vs. 2.9%), hearing impairment (9.5 vs. 2.5%), visual problems (55.4 vs. 47.9%), and being overweight with a body mass index of at least 25 kg/m2 (22.8 vs. 15.7%) (P < 0.0001). Furthermore, fewer patients attained the highest socioeconomic category (14.6 vs. 23.1%) and were in full-time employment (39.9 vs. 44.8%) (P < 0.0001). They were more likely to still be living with their parents and had a lower health-related quality of life than their healthy peers, particularly for mental dimensions, with a mean difference for the mental summary component of 0.35 sd score (P < 0.0001). CH severity at diagnosis, treatment adequacy, and the presence of other chronic health conditions were the main determinants of educational achievement and health-related quality of life scores.
Conclusion:
These findings highlight the need for careful monitoring of neurosensory functioning, weight, and long-term treatment adequacy throughout childhood and adulthood.
The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with a sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification of two ...CF-causing mutations. A challenging problem is the significant number of children for whom no definitive diagnosis is possible because they present with symptoms suggestive of CF, a sweat chloride level in the intermediate range between 30 and 60 mmol/L, and only one or no identified CF-causing mutation.
To investigate the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in the airways of children with intermediate sweat tests and inconclusive genetic findings in correlation with clinical phenotype and genotype.
We developed a composite nasal potential difference (NPD) diagnostic score to discriminate patients with CF from non-CF patients. We tested NPD in 50 children (age, 6 mo to 18 yr) with equivocal diagnoses and correlated the NPD diagnostic score with clinical phenotypes and genotypes.
Fifteen of the 50 children had NPD scores in the CF range. Eight of the 15 carried two CFTR mutations compared with only 5 of the 35 children with normal NPD scores (P = 0.01). They were significantly younger at evaluation and had recurrent lower respiratory tract infections, chronic productive coughs, and chronic Staphylococcus aureus colonization significantly more often than the 35 children with normal NPD results.
Evaluation of CFTR function in the nasal epithelium of children with inconclusive CF diagnoses can be a useful diagnostic tool and help clinicians to individualize therapeutic strategy.
A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) with sweat chloride levels in the intermediate range and ...only one or no identified CF-causing mutations.
To investigate the diagnostic value for CF of assessing CF transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference in children with HIRT.
A specially designed protocol was used to assess nasal potential difference (NPD) in 23 young children with HIRT (3 months-4 years) with inconclusive neonatal screening. Results were analysed with a composite score including CFTR-dependent sodium and chloride secretion. Results were correlated with genotype after extensive genetic screening and with clinical phenotype at follow-up 3 years later.
NPD was interpretable for 21 children with HIRT: 13 had NPD composite scores in the CF range. All 13 were finally found to carry two CFTR mutations. At follow-up, nine had developed a chronic pulmonary disease consistent with a CF diagnosis. The sweat test could be repeated in nine children, and six had sweat chloride values >or=60 mmol/l. Of the eight children with normal NPD scores, only two had two CFTR mutations, both wide-spectrum mutations. None had developed a CF-like lung disease at follow-up. The sweat test could be reassessed in five of these eight children and all had sweat chloride values <60 mmol/l. CF diagnosis was ruled out in six of these eight children.
Evaluation of CFTR function in the nasal epithelium of young children with inconclusive results at CF newborn screening is a useful diagnostic tool for CF.
Aim: To evaluate formative evaluation, a pedagogic method that sensitizes mothers to sudden infant death syndrome (SIDS), as a new way to improve prevention of SIDS.
Methods: Prospective and ...randomized study. Mothers in a test group (n = 148) received an educative questionnaire about SIDS during maternity stay. Three months later, we evaluated, by a telephonic interview, their scores of knowledge and observance of the recommendations in comparison with a control group (n = 144).
Results: Mothers’ scores at the educative questionnaire was 5.12 (1.52) mean(standard deviation). The scores performed 3 months later were better in test group for knowledge 7.64 (1.56) vs. 7.16 (1.61), p < 0.01 and for observance 8.28 (1.51) vs. 7.62 (1.72), p < 0.001. Logistic regression analysis confirmed the benefits in test group regarding knowledge of SIDS risk factors ORa = 1.69 (1.02–2.77), p < 0.05, of the advice to avoid overheating infants ORa = 2.50 (1.43–4.38), p < 0.01 and of the risks of bed sharing ORa = 2.7 (1.6–4.5), p < 0.001. There was a significant association between non‐compliance with the sleeping position recommendation and unemployment (p < 0.01) and absence of postsecondary school education (p < 0.01).
Conclusion: Formative evaluation using an educative questionnaire could improve maternal awareness on SIDS risk factors and their compliance with recommendations about SIDS prevention.
Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)–10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was ...designed to investigate a possible association between alleles carried at position −1082 in the promoter region of the IL-10 gene and clinical data on 378 patients with CF. After adjustment for potential confounding variables, a significant relationship was found between the −1082GG genotype and both colonization with Aspergillus fumigatus and allergic bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were observed in patients colonized with A. fumigatus. These results suggest that polymorphisms in the promoter region of the IL-10 gene may influence the host response to A. fumigatus in the context of CF
The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in ...newborns screened for CF has created a dilemma.
Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.
97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation.
Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD.
Newborn screening for inherited disorders enables early identification of affected children and intervention to prevent or mitigate morbidity and mortality associated with these conditions. Since ...1962, most areas throughout the world have developed newborn screening (NBS) programmes including for more than 50 serious disorders. 1 2 While most diseases are screened by biochemical techniques only, the NBS programme for cystic fibrosis (CF), which is being implemented in an increasing number of countries (USA, UK, Spain, France, Italy, Australia, Czech Republic, Poland ...), 3 4 relies on determination of immunoreactive trypsinemia (IRT) and subsequent screening for 30 common mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene when IRT is above 65 μg/l.
Cystic fibrosis newborn screening is now implemented universally in France, as well as in many states in the United States and in various areas of Europe and Australia. Because the screening protocol ...usually includes the analysis of the most common CFTR mutations, it is of the utmost importance that only mutations that result in classical cystic fibrosis are included in this test. The panels of mutations used in most cystic fibrosis newborn screening programs enable the detection of a relatively frequent CFTR variant (R117H) whose implication in cystic fibrosis remains unclear. Physicians, therefore, have difficulty managing detected compound heterozygotes with this variant, which raises the issue of the appropriateness of extended testing in families and of the legitimate use of prenatal diagnosis.
The aim of this study was to describe the clinical outcome of the children found to be compound heterozygous for R117H by screening in Brittany (western France), where cystic fibrosis newborn screening was set up in 1989, and to assess whether this CFTR variant should be included in the newborn screening mutation panels.
Data on clinical status were obtained by the referring pediatricians.
Since our screening protocol has enabled detection of R117H (ie, in 1995), 360466 newborns have been screened for cystic fibrosis in Brittany, of whom 124 had elevated immunoreactive trypsin and 2 mutations in the CFTR gene. Nine of these children (7.3%) were compound heterozygous for R117H, which in all cases was linked to the 7T_11TG haplotype IVS8-nT variant/m(TG) repeat. Their genotypes were F508del/R117H (n = 7), I507del/R117H (n = 1), or G551D/R117H (n = 1). At the time of this writing, the mean age of these 9 children was 7.0 years (the oldest being >10 years of age), and none of them had yet developed any signs of cystic fibrosis; they have been pancreatic sufficient and have had good nutritional status and pulmonary function. Moreover, we observed that, in Brittany, all the patients carrying the R117H variant have been identified exclusively through cystic fibrosis newborn screening.
In view of the high frequency of R117H-7T identified by cystic fibrosis newborn screening, the uncertain outcome of the asymptomatic children, and physicians' difficulty in managing these situations, we propose the withdrawal of the R117H variant from the panels of CFTR mutations used in cystic fibrosis newborn screening, given the expanding implementation of cystic fibrosis newborn screening.
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