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Simple Summary:& nbsp;Maternal thyroid disease, especially hypothyroidism, is known to affect pregnancy and its outcome. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. In our study, maternal hypothyroidism was associated with an increased risk of lymphoma in the offspring. The association remained stable when possible familial cancers were excluded.Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00-2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29-10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers.

Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943–2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24, 95% confidence interval (CI) 1.76–2.85) than after osteosarcoma (RR 1.67, 95% CI 1.41–1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.

Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977-2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1-2.6) and a corresponding AER of 52 (95% CI 44-60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7-5.4), endocrine diseases (3.6 [3.1-4.2]), circulatory system diseases (3.1 [2.5-3.8]), and diseases of the nervous system (3.0 [2.6-3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared to background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics.

Because of the rarity of neuroblastoma and poor survival until the 1990s, information on late effects in neuroblastoma survivors is sparse. We comprehensively reviewed the long-term risk for somatic disease in neuroblastoma survivors. We identified 721 5-year survivors of neuroblastoma in Nordic population-based cancer registries and identified late effects in national hospital registries covering the period 1977-2012. Detailed treatment information was available for 46% of the survivors. The disease-specific rates of hospitalization of survivors and of 152,231 randomly selected population comparisons were used to calculate standardized hospitalization rate ratios (SHRRs) and absolute excess risks (AERs). During 5,500 person-years of follow-up, 501 5-year survivors had a first hospital contact yielding a SHRR of 2.3 (95% CI 2.1-2.6) and a corresponding AER of 52 (95% CI 44-60) per 1,000 person-years. The highest relative risks were for diseases of blood and blood-forming organs (SHRR 3.8; 95% CI 2.7-5.4), endocrine diseases (3.6 [3.1-4.2]), circulatory system diseases (3.1 [2.5-3.8]), and diseases of the nervous system (3.0 [2.6-3.3]). Approximately 60% of the excess new hospitalizations of survivors were for diseases of the nervous system, urinary system, endocrine system, and bone and soft tissue. The relative risks and AERs were highest for the survivors most intensively treated. Survivors of neuroblastoma have a highly increased long-term risk for somatic late effects in all the main disease groups as compared with background levels. Our results are useful for counseling survivors and should contribute to improving health care planning in post-therapy clinics. This article is protected by copyright. All rights reserved.

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all one-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR=6.9) and leukaemia (HR=1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR=3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications. This article is protected by copyright. All rights reserved.

Background: Childhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries. Methods: We identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference. Results: We observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4-2.7) and an AER of 229 (95% CI 210-248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs. Conclusion: Survivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours. (C) 2016 Elsevier Ltd. All rights reserved.

Introduction: The growing number of survivors of childhood cancer, with many years of life ahead, demonstrates the increasing clinical and public health relevance of investigating the risks of social and socioeconomic impairment after a childhood cancer diagnosis and the life-saving treatment. To enrich understanding of the mental, social and socioeconomic difficulties that childhood cancer survivors may face during their life-course, identify particularly vulnerable survivors and overcome the limitations of previous research, we initiated the Socioeconomic Consequences in Adult Life after Childhood Cancer in Scandinavia (SALiCCS) research programme. Methods: This Nordic cross-border research programme is a collaboration between the Danish Cancer Society, the Finnish Cancer Registry and Karolinska Institutet to investigate a broad range of mental, social and socioeconomic conditions in long-term childhood cancer survivors in Denmark, Finland and Sweden. SALiCCS is based on a registry-based matched cohort design, comprising five-year survivors of cancer diagnosed at ages 0���19 years (1971���2008 in Denmark, 1971���2009 in Finland, 1971���2011 in Sweden), age-, sex- and country-matched population comparisons and sibling comparisons who were followed over time. Outcomes of interest included mental disorders, educational achievements, employment and profession, family life and the need of social security benefits. Individual-level data linkage among various national registries provided the data for the research programme. Results: The SALiCCS core population comprises 21,292 five-year survivors, 103,303 population comparisons and 29,644 siblings as a second comparison group. The most common diagnoses in survivors were central nervous system tumours, leukaemias and lymphomas. Discussion: SALiCCS is the largest, most comprehensive population-based research initiative in this field, based on high-quality registry data with minimal risk of bias. The findings will be informative for evidence-based survivorship care targeting not only somatic late effects but also psychosocial impairments.

In addition to the well-established risk factors of hereditary predisposition syndromes and high doses of ionizing radiation, reports suggest that high birth weight, certain infectious agents and some environmental factors have an association with cancer. The impact of in utero exposures and perinatal factors on childhood cancer risk have been explored, but many studies have been based on self-reported data. Using Finnish national registries, we conducted a population-based, case-control study by identifying all the patients from the Finnish Cancer Registry who had their first cancer diagnosed before age 20 between 1996 and 2014 (n = 2,037). For each case, five population controls were identified from the Medical Birth Register (n = 10,185). Data on the mothers of both cases and controls were gathered from several registries and included maternal chronic diseases, maternal medication use one month prior to and during pregnancy and data on perinatal factors and the neonatal period until 7 days of age or until hospital discharge. Conditional logistic regression was used to analyze the risk of childhood cancer after exposure to maternal diabetes, inflammatory bowel disease, connective tissue disease, thyroid disease and/or medication for these conditions. Perinatal factors, such as gestational age and neonatal therapies and their association with childhood cancer risk, were studied. Maternal diabetes, especially gestational diabetes, was associated with an increased risk of childhood cancer in the offspring, in particular acute lymphoblastic leukemia. Interestingly, maternal diabetes medication seemed to have a possible risk-reducing impact on childhood cancer. Maternal hypothyroidism, based on the diagnosis and maternal thyroid hormone purchases, was associated with an increased childhood lymphoma risk. No association with other maternal diseases and childhood cancer and/or their medication was found. A weak signal of a time-dependent risk of maternal medication use in pregnancy was seen, with an increasing risk towards the end of the pregnancy. This warrants further confirmation. Preterm, especially early preterm, birth increased the childhood cancer risk in this study. The risk was increased for acute myeloid leukemia, germ-cell tumors and retinoblastoma. Peri- and neonatal therapies, such as resuscitation at birth, mechanical ventilation, antibiotics and antenatal steroid use, were also associated with an increased childhood cancer risk. Moreover, the risk was increased also for children born at term. This risk seems to be associated with hypoxia. Germ cell tumors were diagnosed earlier on preterm children compared to term. In utero exposure to maternal diabetes and hypothyroidism is associated with childhood cancer in the offspring. More information about the impact of maternal medication use on childhood cancer in the pregnancy timeframe is needed. Preterm birth per se and/or the neonatal therapies are associated with an increased childhood cancer risk. This association needs to be accounted for in the follow-up of these children. Lapsuusiän syövän taustatekijät tunnetaan huonosti. Perinnöllisten syöpäoireyhtymien lisäksi lapsuusiän syövän riskitekijöiksi aiemmissa tutkimuksissa on raportoitu mm. suuri ja pieni syntymäpaino, säteily, tulehdustaudit sekä erilaiset ympäristötekijät. Tunnistimme Syöpärekisteristä kaikki alle 20-vuotiaana ensimmäisen syöpädiagnoosinsa vuosina 1996–2014 saaneet henkilöt, joita oli 2037. Heille poimittiin Terveyden ja hyvinvoinnin laitoksen (THL) Syntymärekisteristä väestöverrokit, joita oli yhteensä 10 185. Tapausten ja verrokkien äitien tiedot koskien äitien kroonisia sairauksia, äitien lääkityksiä sekä tiedot raskauden ja synnytyksen sekä lapsivuodeajan tapahtumista, kerättiin useista suomalaisista THL: n ja Kelan rekistereistä THL: n Lääkehoito ja raskaus -tietokantaa apuna käyttäen. Analysoimme jälkeläisen syöpäriskiä äidin diabetekseen, sidekudostautiin, tulehdukselliseen suolistosairauteen tai kilpirauhassairauteen tai näiden lääkitykseen liittyen, verrattuna niihin jälkeläisiin, jotka eivät altistuneet näille sairauksille tai lääkityksille raskausaikana. Erityisesti äidin raskausdiabetes oli yhteydessä jälkeläisen kohonneeseen riskiin sairastua akuuttiin lymfaattiseen leukemiaan. Äidin diabeteslääkityksellä näyttää olevan mahdollisesti riskiä vähentävä vaikutus. Äidin kilpirauhasen vajaatoiminta oli myös yhteydessä jälkeläisen lisääntyneeseen riskiin sairastua lapsuus- ja nuoruusiän lymfoomaan. Muut äidin krooniset autoimmuunisairaudet tai näiden lääkitykset eivät näyttäisi olevan yhteydessä lisääntyneeseen syöpäriskiin. Keskosena, erityisesti pienenä keskosena syntyminen, oli yhteydessä kohonneeseen syöpäriskiin lapsuus- ja nuoruusiässä. Riski sairastua erityisesti akuuttiin myelooiseen leukemiaan, itusolukasvaimiin ja retinoblastoomaan oli kohonnut. Totesimme myös vastasyntyneisyyskauden hoitojen, kuten hengityskonehoidon, vastasyntyneen elvytyksen, antibioottihoitojen sekä antenataalisen kortikosteroidin olevan yhteydessä lisääntyneeseen syöpäriskiin. Tämä riski oli kohonnut myös näitä hoitoja saaneilla täysiaikaisilla lapsilla verrattuna niihin, jotka eivät hoitoja tarvinneet. Myös hypoksia eli hapenpuute raskauden tai synnytyksen aikana lisäsi lapsuusiän syöpäriskiä. Kohdunsisäiset altisteet ovat yhteydessä lapsuusiän syöpään. Äidin diabetes ja kilpirauhasen vajaatoiminta lisäävät jälkeläisen riskiä lapsuus- ja nuoruusiän syöpään. Nämä löydökset tulisi huomioida raskauksien seurannassa ja suunnittelussa. Äidin raskaudenaikaisten lääkitysten vaikutuksista jälkeläisen syöpäriskiin eri vaiheissa raskautta ja sitä ennen tarvitaan lisää tutkimustietoa. Ennenaikainen syntymä, hypoksia ja vastasyntyneisyyskauden tehohoito ovat yhteydessä lapsuusiän syöpään. Nämä löydökset tulisi puolestaan ottaa huomioon ennenaikaisena syntyneiden tai tehohoitoa saaneiden lasten jatkoseurannassa.