Risk of childhood neoplasms related to neonatal phototherapy- a systematic review and meta-analysis.

CONTEXT: Observational studies have shown conflicting results as to whether exposure to neonatal phototherapy is associated with increased rates of childhood cancer. OBJECTIVE: To describe the rates of childhood neoplasms and cancer after neonatal phototherapy. DATA SOURCES: The CENTRAL, PubMed, Scopus, and Web of Science databases. STUDY SELECTION: Observational studies regardless of design were included. DATA EXTRACTION: The data were extracted by one author and validated by another. The risk-of-bias assessment was performed using the ROBINS-E and Joanna Briggs Institute critical appraisal tools. RESULTS: Six cohort and 10 case-control studies were included. The overall risk of bias was high in seven and low in nine studies. In cohort studies, the odds ratio (OR) was increased for hematopoietic cancer (1.44; confidence interval [CI]: 1.16-1.80) and solid tumors (OR: 1.18; CI: 1.00-1.40). In case-control studies, the OR was 1.63 (CI: 0.99-2.67) for hematopoietic cancers and 1.18 (CI: 1.04-1.34) for solid tumors. CONCLUSIONS: Children with a history of neonatal phototherapy had increased risk of hematopoietic cancer and solid tumors. The evidence quality was limited due to the high risk of bias and potential residual confounding. IMPACT STATEMENT: Exposure to neonatal phototherapy increased later risk of hematopoietic cancer and solid tumors. This is the most comprehensive study on the association between phototherapy and cancer, but the evidence quality was limited due risk of bias and residual confounding. Future large scale well conducted studies are still needed to better estimate the association and.

Dual direction associations between common autoimmune diseases and leukemia among children and young adults: A systematic review.

BACKGROUND: Childhood leukemia and many autoimmune (AI) diseases are severe pediatric conditions with lifelong consequences. AI diseases form a heterogeneous disease group affecting about 5 % of children worldwide, while leukemia is the most common malignancy among children aged 0-14 years. The timing and similarities in suggested inflammatory and infectious triggers of AI disease and leukemia have raised a question whether the diseases share common etiological origins. We conducted a systematic review to evaluate the evidence linking childhood leukemia and AI diseases. DATA SOURCES: In the systematic literature search CINAHL (from 1970), Cochrane Library (form 1981), PubMed (from 1926) and Scopus (from 1948) were queried in June 2023. REVIEW METHODS: We included studies covering the association between any AI disease and acute leukemia, limiting it to children and adolescents under 25 years old. The studies were reviewed independently by two researchers and the risk of bias was assessed. RESULTS: A total of 2119 articles were screened and 253 studies were selected for detailed evaluation. Nine studies met the inclusion criteria, of which eight were cohort studies and one was a systematic review. The diseases covered were type 1 diabetes mellitus, inflammatory bowel diseases and juvenile arthritis alongside acute leukemia. Five cohort studies were suitable for more detailed analysis: a rate ratio for leukemia diagnosis after any AI disease was 2.46 (95 % CI 1.17-5.18; heterogeneity I2 15 %) with a random-effects model. CONCLUSIONS: The results of this systematic review indicate that AI diseases in childhood are associated with a moderately increased risk of leukemia. The association for individual AI diseases needs further investigation.

Residential mobility and childhood inflammatory bowel disease: a nationwide case-control study.

PURPOSE: To examine the association of residential mobility, as a proxy for environmental influences, with childhood inflammatory bowel disease (IBD) risk. METHODS: Using nationwide register-based dataset, all 2038 IBD cases in Finland diagnosed at ages less than 15 years in 1992-2016 were individually matched by sex and age with five controls employing risk set sampling. Complete residential histories of the subjects were constructed from birth until the index date (diagnosis date of the case). Movement patterns were assessed by age, distance, and demographics of the departure and destination municipalities. Conditional logistic regression was employed to estimate the association between movements and IBD risk. RESULTS: Overall, residential movement was associated with a slightly decreased odds ratio (OR) for childhood IBD (OR 0.97, 95% confidence interval (CI) 0.95-1.00 for each movement). Further examination showed reduced ORs for moving to rural municipalities (OR 0.94, 95% CI 0.90-0.98) and to distances less than 50 km (OR 0.96, 95% CI 0.93-0.99). In disease subtype analyses, the effect mainly persisted in ulcerative colitis. CONCLUSIONS: Our findings suggest lower childhood IBD risk associated with residential mobility. The effect was found in ulcerative colitis, but not in Crohn's disease. Movements to nearby and rural areas may reduce IBD risk, though this requires further investigation.

Long-term mortality in pediatric solid organ recipients-A nationwide study.

BACKGROUND: The present study aimed at investigating long-term mortality of patients who underwent solid organ transplantation during childhood and at identifying their causes of death. METHODS: A cohort of 233 pediatric solid organ transplant recipients who had a kidney, liver, or heart transplantation between 1982 and 2015 in Finland were studied. Year of birth-, sex-, and hometown-matched controls (n = 1157) were identified using the Population Register Center registry. The Causes of Death Registry was utilized to identify the causes of death. RESULTS: Among the transplant recipients, there were 60 (25.8%) deaths (median follow-up 18.0 years, interquartile range of 11.0-23.0 years). Transplant recipients' risk of death was nearly 130-fold higher than that of the controls (95% CI 51.9-1784.6). The 20-year survival rates for kidney, liver, and heart recipients were 86.1% (95% CI 79.9%-92.3%), 58.5% (95% CI 46.2%-74.1%), and 61.4% (95% CI 48.1%-78.4%), respectively. The most common causes of death were cardiovascular diseases (23%), infections (22%), and malignancies (17%). There were no significant differences in survival based on sex or transplantation era. CONCLUSION: The late mortality is still significantly higher among pediatric solid organ recipients in comparison with controls. Cardiovascular complications, infections, and cancers are the main causes of late mortality for all studied transplant groups. These findings emphasize the cruciality of careful monitoring of pediatric transplant recipients in order to reduce long-term mortality.

Clustering of pediatric onset inflammatory bowel disease in Finland: a nationwide register-based study.

BACKGROUND: The incidence of pediatric inflammatory bowel disease (PIBD) has increased dramatically during the past decades. This implies involvement of environmental factors in etiology but lends no clues about specific agents. We evaluated clustering in time and place of residence at PIBD onset using a case-control setting with comprehensive nationwide register data. METHODS: We included all PIBD cases diagnosed at ages < 18 years during 1992-2017 (3748 cases; median age of 14.6; 2316 (58%) with ulcerative colitis (UC), 1432 with Crohn's, and 18,740 age- and sex-matched controls) and constructed complete residential histories (including coordinates) from the national database until the date of the diagnosis of the case assigned as index date for the controls. Using the coordinates of the addresses of the subjects and the diagnosis/index dates, we evaluated clustering in time and place using the Knox test. Four temporal (2, 4, 6, 12 months) and four distance (0.25, 0.5, 1, 5 km) thresholds were used, and results were calculated separately for Crohn´s disease and UC. Similar analyses were conducted using the addresses at birth and the addresses five years before the diagnosis or index date. Based on the threshold values displaying the most clustering in the Knox test, logistic regression models were built to identify whether sex, age at diagnosis or the year of diagnosis affected the probability of belonging to a cluster. To analyze clustering in time and place throughout the residential histories, we used Jacquez's Q with an open-access python program pyjacqQ. RESULTS: The mean number of residencies until the index date was 2.91 for cases and 3.05 for controls (p = 0.0003). Knox test indicated residential clustering for UC with thresholds of 500 m between locations and time-period of four months (p = 0.004). In the regression analysis, sex, age at diagnosis or year of UC diagnosis did not show differences between the clustered and other cases. Jacquez Q analyses showed higher than expected frequency of clustered cases throughout residential histories (p < 10- 8). CONCLUSION: Our findings suggest that the incidence of PIBD, especially of UC, exhibits clustering in locations of residencies over time. For the clustered cases, environmental triggers warrant future studies.

Incidence trends of childhood central nervous system tumors in Finland 1990-2017.

INTRODUCTION: Central nervous system (CNS) tumors are a leading cause of cancer-related morbidity and mortality in children. Our aim is to characterize incidence trends of pediatric CNS tumors in Finland over the last three decades. METHODS: Data on all benign and malignant incident CNS tumors diagnosed in children aged 0-14 years in 1990-2017 were extracted from the Finnish Cancer Registry and classified according to the 2016 WHO classification of CNS tumors. We analyzed age-standardized incidence rates (ASR) for pediatric CNS tumors overall and by sex, age, tumor histology, grade, and location using Poisson regression. We used joinpoint regression to evaluate changes in trends. RESULTS: Overall, 1117 pediatric CNS tumor cases were registered in Finland with a 1.2:1 male to female ratio. The average annual ASR was 4.3 per 100,000 person-years (95% CI 4.26, 4.34). The most common tumor type was pilocytic astrocytoma (30% of tumors), followed by medulloblastoma (10%) with incidence rates of 1.30 and 0.45 per 100,000 person-years, respectively. The overall incidence of pediatric CNS tumors increased by an annual percentage change (APC) of 0.8% (95% CI 0.2, 1.4). We observed no major changes in incidence trends of tumor histology groups or tumor location groups. The ASR of benign tumors increased by an APC of 1.0 (95% CI 0.1, 2.0). CONCLUSIONS: Utilizing the high-quality and completeness of data in the Finnish Cancer registry, we found that the incidence of pediatric CNS tumors in Finland has increased slightly from 1990 until 2017. Although variations in diagnostic and registration practices over time might have affected the rates, the trend may also reflect a true increase in incidence.

Trends in ferritin measurements in children and adolescents: A Finnish 9-year observational study.

AIM: A lack of stored iron, indicated by low serum ferritin, has been associated with various clinical symptoms. There are no longitudinal data on the frequency of ferritin measurements in children and adolescents. METHODS: A total of 2834 children aged <18 years with serum ferritin and other anaemia-related blood parameters taken during an outpatient visit between 2012 and 2019 were investigated. Patients with acute infections were excluded. Nationwide temporal and regional variations and correlations with public information searches through Google were analysed. RESULTS: A significant increase in the frequency of ferritin measurements was seen starting in 2018, with a 47-fold rise in 2019 compared to 2012. A simultaneous escalation in Google Search activity was seen. Deficiency of stored iron was relatively common: 21.6% of children with normal haemoglobin and 14.9% of non-anaemic children with normal red cell indices exhibited ferritin levels below 15 µg/L. CONCLUSION: Ferritin measurement has increased greatly among children and adolescents. Our results suggest that public interest and popular trends can significantly influence health care practices. This calls for further investigation into the causes and consequences of such a phenomenon. Prospective randomised intervention studies are needed to evaluate the utility of iron supplementation in patients with low iron storage levels.

Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.