Cohort-based association study of germline genetic variants with acute and chronic health complications of childhood cancer and its treatment: Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study protocol.

INTRODUCTION: Childhood cancer and its treatment may lead to various health complications. Related impairment in quality of life, excess in deaths and accumulated healthcare costs are relevant. Genetic variations are suggested to contribute to the wide inter-individual variability of complications but have been used only rarely to risk-stratify treatment and follow-up care. This study aims to identify germline genetic variants associated with acute and late complications of childhood cancer. METHODS AND ANALYSIS: The Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. Eligible are patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Paediatric Biobank for Research in Haematology and Oncology, Geneva, host of the national Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS).GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study. Clinical outcome data consists of organ function testing, health conditions diagnosed by physicians, second primary neoplasms and self-reported information from participants. Germline genetic samples and sequencing data are collected in BISKIDS. We will perform association analyses using primarily whole-exome or whole-genome sequencing to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models. DISCUSSION: GECCOS will improve knowledge of germline genetic variants associated with childhood cancer-associated health conditions and help to further individualise cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects. ETHICS AND DISSEMINATION: The Geneva Cantonal Commission for Research Ethics has approved the GECCOS study.Research findings will be disseminated through national and international conferences, publications in peer-reviewed journals and in lay language online. TRIAL REGISTRATION NUMBER: NCT04702321.

Predictors for participation in DNA self-sampling of childhood cancer survivors in Switzerland.

BACKGROUND: Research on germline genetic variants relies on enough eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits, participants can contribute genetic samples conveniently from their home. Demographic and clinical factors were identified previously that influenced participation in mailed self-collection. People with pre-existing heritable diagnoses might participate differently in germline DNA collection which might render sampling biased in this group. In this nationwide cross-sectional study, we analysed predictive factors of participation in DNA self-collection including heritable diagnoses. METHODS: We identified childhood cancer survivors from the Swiss Childhood Cancer Registry for invitation to germline DNA self-sampling in September 2019. Participants received saliva sampling kits by postal mail at their home, were asked to fill them, sign an informed consent, and send them back by mail. Two reminders were sent to non-participants by mail. We compared demographic, clinical, and treatment information of participants with non-participants using univariable and multivariable logistic regression models. RESULTS: We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 19-37), of which 463 (50%) participated. After the initial send out of the sampling kit, 291 (63%) had participated, while reminder letters led to 172 additional participants (37%). Foreign nationality (odds ratio [OR] 0.5; 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5; CI 0.4-0.8), and survivors with a known cancer predisposition syndrome (OR 0.5; CI 0.3-1.0) were less likely to participate in germline DNA collection. Survivors with a second primary neoplasm (OR 1.9; CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3; CI 1.0-1.8) tended to participate more. CONCLUSIONS: We showed that half of childhood cancer survivors participated in germline DNA self-sampling relying completely on mailing of sample kits. Written reminders increased the response by about one third. More targeted recruitment strategies may be advocated for people of foreign nationality, aged 30-39 years, and those with cancer predisposition syndromes. Perceptions of genetic research and potential barriers to participation of survivors need to be better understood. TRIAL REGISTRATION: Biobank: https://directory.bbmri-eric.eu/#/collection/bbmri-eric:ID:CH_HopitauxUniversitairesGeneve:collection:CH_BaHOP Research project : Clinicaltrials.gov: NCT04702321 .

Diagnosis and management of iron deficiency in children with or without anemia: consensus recommendations of the SPOG Pediatric Hematology Working Group.

Iron deficiency is the most prevalent nutritional deficiency affecting children and adolescents worldwide. A consistent body of epidemiological data demonstrates an increased incidence of iron deficiency at three timepoints: in the neonatal period, in preschool children, and in adolescents, where it particularly affects females.Conclusion: This narrative review focuses on the most suggestive symptoms of iron deficiency in childhood, describes the diagnostic procedures in situations with or without anemia, and provides Swiss expert-based management recommendations for the pediatric context.What is Known:• Iron deficiency (ID) is one of the most common challenges faced by pediatricians.• Significant progress in the diagnosis and therapy of ID has been made over the last decade.What is New:• Our expert panel provides ID management recommendations based on the best available evidence.• They include strategies for ID diagnosis and therapy, both oral and intravenous.

[Iron deficiency with and without anemia in children: a brief update for caregivers]. / Carence en fer avec et sans anémie chez l'enfant : brève mise à jourpour le praticien.

Non anemic iron deficiency (NAID) is the most common nutritional deficiency. Symptoms more frequently observed in children and adolescents include fatigue, delayed psychomotor development as well as decreased school and athletic performances. Iron treatment is effective in improving symptoms in older children and adolescents. In children under 2 years of age, there is currently no evidence of the efficacy of substitution therapy on development. Preemptive treatment is not justified considering the available evidence beyond premature or small newborns for gestational age and should only be initiated if a diagnosis of iron deficiency is confirmed. Oral iron supplementation is the first-line treatment of NAID.

La carence en fer sans anémie (CF-sA) est le déficit nutritionnel le plus répandu. Les symptômes plus fréquemment observés chez l'enfant et l'adolescent sont une fatigue, un retard de développement psychomoteur et une diminution des performances scolaires et sportives. Une substitution martiale s'avère efficace dans l'amélioration de ces symptômes chez le grand enfant et l'adolescent. Chez l'enfant d'âge inférieur à deux ans, il n'existe actuellement pas d'évidence de l'efficacité d'un traitement substitutif sur le plan du développement. Un traitement préemptif, en dehors de la prématurité ou d'un retard de croissance intra-utérin, n'est à l'heure actuelle pas justifié en considérant l'évidence disponible, et devrait être débuté uniquement suite à un diagnostic formel de carence martiale. Le traitement de première intention de la CF-sA, en l'absence de contre-indications, est le traitement oral.