Pediatric-onset inflammatory brain diseases are a group of potentially life-threatening central nervous system disorders. Overall, pediatric-onset inflammatory brain diseases are rare and therefore ...difficult to study. Patient registries are well suited to study the natural history of (rare) diseases and have markedly advanced the knowledge on pediatric-onset inflammatory brain diseases in other countries. Following their example, we established a national pediatric-onset inflammatory brain disease registry in Switzerland (Swiss-Ped-IBrainD).
The Registry aims to describe epidemiology, demographics, diagnostics, management, and treatment, since these areas remain understudied in Switzerland. Additionally, we want to promote research by fostering the knowledge exchange between study centers and setting up studies such as national quality of life surveys. We further aim to facilitate the access to national and international studies for patients with a pediatric-onset inflammatory brain disease living and/or treated in Switzerland.
The Swiss-Ped-IBrainD is a multicentric, population-based, observational cohort study (IRB number: 2019-00377) collaborating with 11 neuropediatric centers in Switzerland. Patient screening, information and recruitment is mainly conducted by the local principal investigators. The data collection is organized centrally by the Executive Office of the registry. The collected data is purely observational. Medical records are the primary data source. All patients who have been diagnosed with a pediatric-onset inflammatory brain disease since 2005 are eligible. We aim to include all pediatric-onset inflammatory brain disease patients living and/or treated in Switzerland who meet the inclusion criteria. Considering existing literature and our single-center experience we anticipate 300-400 eligible patients.
Currently, all 11 neuropediatric centers have been initiated and are recruiting. As of the first of May 2023, we have identified 275 eligible participants and obtained informed consent from 101 patients and/or families. None of the informed patients and/or families have refused participation.
Completeness is important in cancer registration. Identifying areas to improve registry procedures might help to maximise completeness. We examined characteristics of childhood cancer cases that were ...registered via death certificate notification (DCN) rather than during life, and estimated completeness of the Swiss Childhood Cancer Registry (SCCR).
We analysed data from all children who died from cancer in Switzerland between 1985-2009 at age <16 years (n = 978), and checked whether they had been registered in the SCCR. We used multivariable logistic regression to compare characteristics of DCN cases with deceased SCCR cases, and the DCN-to-incidence and mortality-to-incidence ratio method to estimate completeness for different diagnostic periods.
Among 978 deceased children with cancer, 126 (12.9%) were registered via DCN. Those with tumours of digestive organs (odds ratio OR 5.1; 95% confidence interval CI 1.9-13.7), tumours of endocrine glands (OR 4.5; 95% CI 1.6-12.3), and brain tumours (OR 3.1; 95% CI 1.7-5.5) were more likely to be DCN cases than those with leukaemia. Neonates (OR 14.1, 95% CI 5.3-37.3), infants (OR 7.5; 95% CI 3.1-18.0) and 14-15 year olds (OR 2.4; 95% CI 1.2-4.9) were more likely to be DCN cases than 1-4 year olds. The DCN proportion was particularly high in infants who lived in rural regions. Estimated completeness of the SCCR increased from 85% for 1985-89 to ≥ 95% for 1995-2009.
Childhood cancer registration in Switzerland was quite complete, but registration must improve for infants, particularly neonates, and children diagnosed with hepatic, endocrine and brain tumours.
Sinusoidal obstruction syndrome (SOS) is a potentially life-threatening complication after hematopoietic stem cell transplantation (HSCT) or antineoplastic treatment without HSCT. Genetic variants ...were investigated for their association with SOS, but the evidence is inconclusive. We performed a systematic literature review to identify genes, gene variants, and methods of association analyses of genetic markers with SOS. We identified 23 studies after HSCT and 4 studies after antineoplastic treatment without HSCT. One study (4%) performed whole-exome sequencing (WES) and replicated the analysis in an independent cohort, 26 used a candidate-gene approach. Three studies included >200 participants (11%), and six were of high quality (22%). Variants in 34 genes were tested in candidate gene studies after HSCT. Variants in
were associated with SOS in three studies,
in two, and
,
,
,
,
,
, and
in one study each.
and
variants were identified in a WES analysis. After exposure to antineoplastic agents without HSCT, variants in six genes were tested and only
was associated with SOS. There was a substantial heterogeneity of populations within and between studies. Future research should be based on sufficiently large homogenous samples, adjust for covariates, and replicate findings in independent cohorts.
The paper by Luijk et al. 1 in this issue of the European Respiratory Journal is a highlight for two reasons: it is the first to investigate parent-child bed-sharing practices and risk of childhood ...asthma; and it uses novel statistical approaches to explore causal relationships.
Previous studies on occupational exposures in parents and cancer risks in their children support a link between solvents and paints with childhood leukaemia. Few studies have focused specifically on ...benzene.
To examine whether parental occupational exposure to benzene is associated with an increased cancer risk in a census-based cohort of children.
From a census-based cohort study in Switzerland, we included children aged <16years at national censuses (1990, 2000). We retrieved parental occupations reported at census and assessed exposure to benzene using a job exposure matrix. We identified incident cancer cases through record linkage with the Swiss Childhood Cancer Registry. We fitted Cox proportional-hazards models to assess associations between exposures and the following outcomes: any cancer, leukaemia, acute lymphoid leukaemia (ALL), acute myeloid leukaemia (AML), lymphoma, non-Hodgkin lymphoma, central nervous system (CNS) tumours, and glioma. We adjusted models for a range of socio-economic, perinatal and environmental factors.
Analyses of maternal (paternal) exposure were based on 9.0 (13.2)millionperson years at risk and included 1004 (1520) cases of cancer, of which 285 (438) had leukaemia, 186 (281) lymphoma, 227 (339) a CNS tumour. Maternal exposure was associated with an increased risk of childhood leukaemia (hazard ratio 1.73, 95% CI 1.12–2.67) and ALL (1.88, 1.16–3.04). We found little evidence of an association for other outcomes or for paternal exposure. Adjusting for potential confounders did not materially affect the results.
This nationwide cohort study suggests an increased risk of leukaemia among children whose mothers were exposed to benzene at work.
•Children of mothers occupationally exposed to benzene had a higher leukaemia risk.•The association was not explained by differences in socio-economic status.•The association was strongest in children aged <5years at exposure assessment.•We found no evidence of an association for other cancer types.•We found no evidence of an association for paternal exposure.
Newborn screening (NBS) for cystic fibrosis (CF) was introduced in Switzerland in 2011 based on an immunoreactive trypsinogen (IRT)-DNA-IRT protocol. CF diagnosis was confirmed by sweat test and/or ...genetics but remained inconclusive for some newborns (cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS)/CF screen positive, inconclusive diagnosis (CFSPID)). We aimed to (1) Describe IRT levels in healthy newborns in the first year of life and by gestational age (GA), and (2) Compare IRT at two time points between healthy newborns and newborns with CF and CRMS/CFSPID.
Retrospective study.
National NBS database.
All children with an IRT measurement by heel prick test from 2011 to 2019.
None.
IRT values were extracted from the National NBS Laboratory, and clinical characteristics of positively screened children from the CF-NBS database. Second IRT assessment in positively screened children was usually performed after 18-24 days. We calculated internal IRT Z-Scores and multiples of the median to compare our results across different laboratory tools.
Among 815 899 children; 232 were diagnosed with CF, of whom 36 had meconium ileus (MI); 27 had CRMS/CFSPID. Among all samples analysed, mean IRT Z-Scores were higher for newborns with GA <33 weeks and ≥43 weeks (all Z-Scores >0.11) compared with term babies (all Z-Scores ≤0.06). Repeated IRT Z-Scores after a median (IQR) of 19 (17-22) days remained high for infants with CF with or without MI but decreased for infants with CRMS/CFSPID.
Measurement of a second IRT value can help distinguish between children with CRMS/CFSPID and CF, early in life.
Background
Taking care of children diagnosed with cancer affects parents’ professional life and may place the family at risk‐of‐poverty. We aimed to (i) compare the household income and ...risk‐of‐poverty of parents of childhood cancer survivors (CCS) to parents of the general population, and (ii) identify sociodemographic and cancer‐related factors associated with risk‐of‐poverty.
Methods
As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to parents of CCS aged 5–15 years, who survived ≥5 years after diagnosis. Information on parents of the general population came from the Swiss Household Panel (parents with ≥1 child aged 5–15 years). Risk‐of‐poverty was defined as having a monthly household income of <4,500 Swiss Francs (CHF) for single parents and <6,000 CHF for parent‐couples. We used logistic regression to identify factors associated with risk‐of‐poverty.
Results
We included parents of 383 CCS and 769 control parent households. Parent‐couples of CCS had a lower household income (Ptrend < 0.001) and were at higher risk‐of‐poverty (30.4% vs. 19.3%, P = 0.001) compared to control parent‐couples. Household income and risk‐of‐poverty of single parents of CCS was similar to control single parents. Parents of CCS were at higher risk‐of‐poverty if they had only standard education (ORmother = 3.77 where OR is odds ratio, confidence interval CI: 1.61–8.82; ORfather = 8.59, CI: 4.16–17.72) and were from the German language region (OR = 1.99, CI: 1.13–3.50). We found no cancer‐related risk factors.
Conclusion
Parents of long‐term CCS reported lower household income and higher risk‐of‐poverty than control parents. Support strategies may be developed to mitigate parents’ risk‐of‐poverty in the long term, particularly among parents with lower education.
It is unclear if predictors of asthma attacks are the same as those of asthma symptom control in children.
We evaluated predictors for these two outcomes in a clinical cohort study.
The Swiss ...Paediatric Airway Cohort (SPAC) is a multicentre prospective clinical cohort of children referred to paediatric pulmonologists. This analysis included 516 children (5-16 years old) diagnosed with asthma. At baseline, we collected sociodemographic information, symptoms, personal and family history and environmental exposures from a parental baseline questionnaire, and treatment and test results from hospital records. Outcomes were assessed 1 year later by parental questionnaire: asthma control in the last 4 weeks as defined by GINA guidelines, and asthma attacks defined as any unscheduled visit for asthma in the past year. We used logistic regression to identify and compare predictors for suboptimal asthma control and asthma attacks.
At follow-up, 114/516 children (22%), reported suboptimal asthma control, and 114 (22%) an incident asthma attack. Only 37 (7%) reported both. Suboptimal asthma control was associated with poor symptom control at baseline (e.g. ≥1 night wheeze/week OR: 3.2; 95% CI: 1.7-6), wheeze triggered by allergens (2.2; 1.4-3.3), colds (2.3; 1.4-3.6) and exercise (3.2; 2-5), a more intense treatment at baseline (2.4; 1.3-4.4 for Step 3 vs. 1), history of preschool (2.6; 1.5-4.4) and persistent wheeze (2; 1.4-3.2), and exposure to tobacco smoke (1.7; 1-2.6). Incident asthma attacks were associated with previous episodes of severe wheeze (2; 1.2-3.3) and asthma attacks (2.8; 1.6-5 for emergency care visits), younger age (0.8; 0.8-0.9 per 1 year) and non-Swiss origin (0.3; 0.2-0.5 for Swiss origin). Lung function, exhaled nitric oxide (FeNO) and allergic sensitization at baseline were not associated with control or attacks.
Children at risk of long-term suboptimal asthma control differ from those at risk of attacks. Prediction tools and preventive efforts should differentiate these two asthma outcomes.
Anthracycline-based chemotherapy is associated with increased subsequent breast cancer (SBC) risk in female childhood cancer survivors, but the current evidence is insufficient to support early ...breast cancer screening recommendations for survivors treated with anthracyclines. In this study, we pooled individual patient data of 17,903 survivors from six well-established studies, of whom 782 (4.4%) developed a SBC, and analyzed dose-dependent effects of individual anthracycline agents on developing SBC and interactions with chest radiotherapy. A dose-dependent increased SBC risk was seen for doxorubicin (hazard ratio (HR) per 100 mg m−2: 1.24, 95% confidence interval (CI): 1.18–1.31), with more than twofold increased risk for survivors treated with ≥200 mg m−2 cumulative doxorubicin dose versus no doxorubicin (HR: 2.50 for 200–299 mg m−2, HR: 2.33 for 300–399 mg m−2 and HR: 2.78 for ≥400 mg m−2). For daunorubicin, the associations were not statistically significant. Epirubicin was associated with increased SBC risk (yes/no, HR: 3.25, 95% CI: 1.59–6.63). For patients treated with or without chest irradiation, HRs per 100 mg m−2 of doxorubicin were 1.11 (95% CI: 1.02–1.21) and 1.26 (95% CI: 1.17–1.36), respectively. Our findings support that early initiation of SBC surveillance may be reasonable for survivors who received ≥200 mg m−2 cumulative doxorubicin dose and should be considered in SBC surveillance guidelines for survivors and future treatment protocols.
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