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The dynamic growth of the skeleton during childhood and adolescence renders it vulnerable to adverse effects of cancer treatment. The lifetime risk and patterns of skeletal morbidity have not been described in a population‐based cohort of childhood cancer survivors. A cohort of 26 334 1‐year cancer survivors diagnosed before 20 years of age was identified from the national cancer registries of Denmark, Finland, Iceland and Sweden as well as a cohort of 127 531 age‐ and sex‐matched comparison subjects randomly selected from the national population registries in each country. The two cohorts were linked with data from the national hospital registries and the observed numbers of first‐time hospital admissions for adverse skeletal outcomes among childhood cancer survivors were compared to the expected numbers derived from the comparison cohort. In total, 1987 childhood cancer survivors had at least one hospital admission with a skeletal adverse event as discharge diagnosis, yielding a rate ratio (RR) of 1.35 (95% confidence interval, 1.29‐1.42). Among the survivors, we observed an increased risk for osteonecrosis with a RR of 25.9 (15.0‐44.5), osteoporosis, RR 4.53 (3.28‐6.27), fractures, RR 1.27 (1.20‐1.34), osteochondropathies, RR 1.57 (1.28‐1.92) and osteoarthrosis, RR 1.48 (1.28‐1.72). The hospitalization risk for any skeletal adverse event was higher among survivors up to the age of 60 years, but the lifetime pattern was different for each type of skeletal adverse event. Understanding the different lifetime patterns and identification of high‐risk groups is crucial for developing strategies to optimize skeletal health in childhood cancer survivors. What's new? The dynamic growth of the skeleton during childhood renders it vulnerable to adverse effects of cancer treatment. In this comprehensive, large‐scale population‐based retrospective cohort study, childhood cancer survivors were more likely to be hospitalised for skeletal adverse events than matched population comparison subjects. Although the risk of adverse events was highest in the period close to the cancer treatment, the excess risk continued for decades. Osteonecrosis, osteoporosis, fractures, osteochondropathies, and osteoarthrosis all showed different lifetime patterns. Understanding the lifetime patterns of skeletal adverse events and identifying high‐risk groups could help develop strategies to optimise skeletal health in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: A recent cohort study in women with multiple sclerosis (MS) reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon beta (IFNβ) before or during pregnancy. However, differing prevalence by maternal characteristics is unknown. Objectives: To describe the prevalence of serious adverse pregnancy outcomes (SAPOs) among pregnant women with MS exposed to only IFNβ and those unexposed to any MS disease-modifying drugs, with stratification by maternal characteristics. Methods: This cohort study extracted register data from Finland (1996-2014) and Sweden (2005-2014) on pregnant women with MS who were 1) dispensed only IFNβ within 6 months before the last menstrual period (LMP) or during pregnancy (IFNβ-exposed, n = 718 pregnancies) and 2) without dispensed MS disease-modifying drugs (unexposed, n = 1397 pregnancies). The prevalence (%) of SAPOs (consisting of elective terminations due to fetal anomaly, major congenital anomalies in live birth, and stillbirth) with 95% CIs was analyzed with stratification by maternal characteristics at LMP: time since MS diagnosis, duration of MS treatment, maternal age, and presence of chronic disease. Results: The prevalence of SAPOs appeared similar among the IFNβ-exposed and unexposed groups when MS was diagnosed ≤2 years (0.9% [95% CI 0.1%-3.2%] vs 3.0% [1.6%- 5.2%]) or 3-5 years (2.4% [0.9%-5.1%] vs 6.0% [4.0%-8.6%]) before LMP, and was comparable for >5 years (3.3% [1.4%-6.4%] vs 3.0% [1.7%-4.8%]). When stratified by duration of MS treatment, the prevalence among the IFNβ-exposed vs unexposed with ≤2-year treatment was 1.3% (0.4%-3.4%) vs 4.6% (2.9%-6.9%), 3- to 5-year treatment 1.7% (0.5%-4.4%) vs 4.9% (2.9%-7.7%), and >5-year treatment 4.3% (1.9%- 8.3%) vs 2.7% (1.2%-5.0%). The prevalence was similar among the IFNβ- exposed vs unexposed in strata by maternal age (≤20, 21-25, 26-30, 31-35, 36-40, >40 years) and presence of chronic diseases (yes/no). Conclusions: In this population-based observational study, the descriptive prevalence of SAPOs appeared similar with IFNβ exposure before or during pregnancy, when pregnant women with MS were stratified by maternal characteristics. [ABSTRACT FROM AUTHOR]

Background: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. Objectives: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. Methods: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005–2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. Results: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. Conclusions: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference. [ABSTRACT FROM AUTHOR]

Background: Previous studies reported no increase in the prevalence of adverse pregnancy outcomes after exposure to interferon-beta (IFN-beta). However, no study has investigated if the prevalence of these outcomes after IFN-beta exposure is modified by maternal and newborn characteristics. Our objective was to describe the stratified prevalence of adverse pregnancy outcomes among women with multiple sclerosis (MS) exposed only to IFN-beta or unexposed to any MS disease modifying drugs (MSDMDs)., Methods: This population-based cohort study using Finnish (1996-2014) and Swedish (2005-2014) register data included pregnancies of women with MS exposed only to IFN-beta 6 months before or during pregnancy (n=718) or unexposed to MSDMDs (n=1397). The outcome prevalences were described stratified by maternal and newborn characteristics, with 95% confidence intervals (CIs). Confounder-adjusted analyses were performed if the prevalence results indicated modified effect of IFN-beta in specific strata., Results: The stratified analysis indicated that the prevalence of serious (anomaly or stillbirth) and other adverse pregnancy outcomes was similar among the exposed and unexposed, with no statistically significant difference. Among women treated for MS >5 years, serious adverse pregnancy outcomes occurred in 4.3% (95%CI: 1.9-8.3%) of pregnancies exposed only to IFN-beta 6 months before or during pregnancy and in 2.7% (95%CI: 1.2-5.0%) of unexposed pregnancies. The confounder adjusted analyses did not support the hypothesis that MS treatment duration before pregnancy would modify the risk of adverse pregnancy outcomes after exposure to IFN-beta 6 months before or during pregnancy., Conclusion: The prevalence of adverse pregnancy outcomes was not increased after IFN-beta exposure, when pregnancies of women with MS were stratified by maternal and newborn characteristics. The stratified results were similar to the unstratified results in the same population., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Variation in testicular cancer incidence can be used to assist in identification of risks. Finland has a significantly lower germ-cell testicular cancer risk than Sweden. Finns who immigrate to Sweden maintain their lower risk irrespective of age at immigration. We investigated difference in risk between Finland and Sweden by examining germ-cell testicular cancer incidence in males born in Sweden to Finnish immigrant parents. Swedish general population registers were used to identify 11,662 males born in Sweden where both Finnish parents immigrated to Sweden from Finland from 1969 or afterward. All of these offspring were at least 15 years old by final follow-up in 2001. Some six offspring (all diagnosed between ages 20 and 24 years) had a diagnosis of germ-cell testicular cancer. Comparison with the Swedish population rate produced standardized incidence ratios [SIR (95% confidence interval)] of 0.85 (0.31-1.84) for all the men and 1.75 (0.64-3.81) for the 20- to 24-year age group. SIRs calculated using the Finnish population rates produced an overall SIR (95% confidence interval) of 1.11 (0.41-2.41) and 2.95 (1.08-6.42) for the 20- to 24-year age group. Although the substantially reduced risk of testicular cancer previously observed in Finnish immigrant to Sweden was not found, this study had insufficient statistical power to conclude that environmental exposures explain the difference in germ-cell testicular cancer risk between Finland and Sweden.

Although the incidence of testicular cancer is increasing, substantial differences in incidence between countries and populations exist. These differences cannot be explained solely by genetic differences, but environmental exposures, particularly early exposures, have been implicated in the etiology of testicular cancer. To assess whether early exposures contribute to the incidence of testicular cancer, we identified 93 172 Finnish men who immigrated to Sweden between 1969 and 1996 and followed them for the occurrence of testicular cancer. The risk of testicular cancer was lower for Finnish immigrants to Sweden than for the Swedish general population (standardized incidence ratio [SIR] = 0.34, 95% confidence interval [CI] = 0.21 to 0.53). The reduced risk was associated with both seminomas and non-seminomas. Neither age at immigration nor duration of stay in Sweden had any impact on the reduced risk. Although the type of environmental exposures remains unknown, the results strongly indicate that early exposures are major determinants for testicular cancer.