Psychiatric disorders among survivors of childhood acute lymphoblastic leukemia in Denmark and Sweden.

BACKGROUND: The diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) may impact mental health. We investigated the long-term risk of psychiatric disorders among survivors of ALL in a population-based cohort study. METHODS: We identified patients diagnosed with ALL in Denmark and Sweden before age 20 during 1982-2008. Survivors of ALL (n = 2026), their siblings (n = 3027), and population comparison subjects (n = 9713) were followed for hospital contacts for psychiatric disorders from 5 years after ALL diagnosis (or corresponding index date) until 2017. RESULTS: By age 30, the absolute risk of psychiatric hospital contacts was 19.9% (95% confidence interval [CI]: 17.9-22.1) for ALL survivors, 18.5% (95% CI: 16.9-20.2) for siblings, and 18.3% (95% CI: 17.3-19.2) for population comparison subjects. Overall, survivors were at higher risk of any psychiatric disorders than siblings (hazard ratio [HR] = 1.25; 95% CI: 1.04-1.50), and population comparison subjects (HR = 1.20; 95% CI: 1.06-1.35). The subgroup of survivors (n = 332) who received a hematopoietic stem cell transplantation (HSCT) and/or had a relapse were at highest risk of psychiatric disorders (HR = 2.07; 95% CI: 1.26-3.41 compared to siblings; HR = 1.67; 95% CI: 1.25-2.23 compared to population comparison subjects). CONCLUSIONS: The overall absolute risk of psychiatric hospital contacts among ALL survivors was close to that in siblings and population comparison subjects. The modestly increased relative risk was mainly driven by the subgroup of survivors who received HSCT and/or had a relapse. Our findings are reassuring for the large subgroup of ALL survivors without HSCT or relapse, and provide novel insight on both absolute and relative risk of hospital contacts for psychiatric disorders.

Pregnancy outcomes in women with neurofibromatosis 1: a Danish population-based cohort study.

BACKGROUND: The probability of a pregnancy, live birth, stillbirth and abortion has never been assessed in women with neurofibromatosis 1 (NF1) in a large population-based study. METHODS: We included 1006 women (15-49 years) registered with NF1 in the Danish National Patient Registry or followed in two national Centers for Rare Diseases and 10 020 women from the Danish population. Information on pregnancy outcomes was ascertained from health registries. Cumulative incidence, mean cumulative count, hazard ratios (HRs) and proportion ratios (PRs) with 95% CIs were calculated. RESULTS: The cumulative incidence of a first pregnancy at age 50 years was slightly lower in women with NF1 (74%; 95% CI 70 to 77) than in population comparisons (78%; 95% CI 77 to 79). When all pregnancies were included, two pregnancies were expected per woman at age of 50 years, irrespective of a NF1 diagnosis. The hazard of a pregnancy did not differ between women with NF1 (HR 1.03; 95% CI 0.95 to 1.11) and the comparisons after adjustment for somatic and psychiatric disease. The proportion of pregnancies that resulted in a live birth was 63% (783/1252) among women NF1 and 68% (8432/12 465) among the comparisons, yielding a PR of 0.95 (95% CI 0.90 to 1.00). The proportions of stillbirths (PR 2.83; 95% CI 1.63 to 4.93) and spontaneous abortions (PR 1.40; 95% CI 1.09 to 1.79) were increased in women with NF1. CONCLUSIONS: A similar hazard for pregnancy was observed for women with NF1 and population comparisons after adjustment for potential medical consequences of NF1. However, women with NF1 experienced more spontaneous abortions and stillbirths.

Temporal changes in the probability of live birth among female survivors of childhood cancer: A population-based Adult Life After Childhood Cancer in Scandinavia (ALiCCS) study in five nordic countries.

BACKGROUND: During the past 4 decades, there has been a growing focus on preserving the fertility of patients with childhood cancer; however, no large studies have been conducted of live births across treatment decades during this period. Therefore, the authors estimated the potential birth deficit in female childhood cancer survivors and the probability of live births. METHODS: In total, 8886 women were identified in the 5 Nordic cancer registries in whom a childhood cancer had been diagnosed during 1954 through 2006. A population comparison cohort of 62,903 women was randomly selected from the central population registries matched by age and country. All women were followed for live births recorded in medical birth registries. The cumulative probability and the risk ratio (RR) with 95% confidence intervals (CIs) of a live birth were calculated by maternal age across treatment decades. RESULTS: The probability of a live birth increased with treatment decade, and, at age 30 years, the rate for survivors most recently diagnosed was close to the rate among the general population (1954-1969: RR, 0.65 [95% CI, 0.54-0.78]; 1970s: RR, 0.67 [95% CI, 0.60-0.74]; 1980s: RR, 0.69 [95% CI, 0.64-0.74]; 1990s: RR, 0.91 [95% CI, 0.87-0.95]; 2000s: RR, 0.94 [95% CI, 0.91-0.97]). CONCLUSIONS: Female childhood cancer survivors had a lower probability of a live birth than women in the general population, although, in survivors diagnosed after 1989, the probability was close to that of the general population. Because the pattern of live births differs by cancer type, continuous efforts must be made to preserve fertility, counsel survivors, and refer them rapidly to fertility treatment if necessary. LAY SUMMARY: The purpose of this study was to compare the probability of giving birth to a liveborn child in female survivors of childhood cancer with that of women in the general population. Survivors of childhood cancer had a lower probability of live births than women in the general population, although survivors diagnosed after 1989 had a probability close to that of the general population. Continuing focus on how to preserve the potential for fertility among female patients with childhood cancer during treatment is important to increase their chances of having a child.

The impact of childhood cancer on parental working status and income in Denmark: Patterns over time and determinants of adverse changes.

Having a child with cancer may affect the socioeconomic situation of the parents. We aimed to assess the impact of childhood cancer on parental working status and income and to identify determinants of adverse changes after the child's cancer diagnosis by calendar period. We conducted a nationwide cohort study using Danish registry data. Parents of children diagnosed with cancer in 1982-2014 (n = 12,418) were matched with comparison parents of cancer-free children (n = 125,014). We analysed annual working status (working/not working) and annual disposable income (lowest quintile/not lowest quintile) of case and comparison parents over a period of 10 years after diagnosis by calendar period (1982-1999 vs. 2000-2014). Logistic regression models were used to identify determinants of adverse changes after diagnosis. Mothers of children diagnosed in 1982-1999 were more likely not working or having a low income than comparison mothers up to 10 years after diagnosis. This risk of not working or low income was lower in mothers of children diagnosed in 2000-2014 compared to 1982-1999 in the first years after diagnosis (pinteraction < 0.05). We observed no consistent patterns among fathers. Low parental education, diagnosis of lymphoid leukaemia and younger age of the child at diagnosis were the main determinants of adverse changes in working status or income after diagnosis. Childhood cancer adversely interfered with parents' socioeconomic situation in the earlier calendar period, particularly among mothers. The absence of such an effect in more recent years emphasises the supportive role of a countries' welfare system alongside the general advances in childhood cancer treatment.

Risk factors for cardiovascular disease in 5-year survivors of adolescent and young adult cancer: A Danish population-based cohort study.

BACKGROUND: An increased risk of metabolic syndrome has been reported for childhood cancer survivors and for adult survivors with certain cancer types. One previous study reported on the risk for diseases in the metabolic syndrome specifically among survivors of adolescent and young adult cancers. METHODS: The study comprised 11,822 five-year survivors of adolescent and young adult cancer (ages 15-39 years at diagnosis) who were diagnosed during the period from 1994 through 2009 in Denmark and a population-based comparison cohort of 76,024 individuals. The cohorts were linked to Danish nationwide registries for information on hospital contacts and purchase of prescription drugs related to metabolic syndrome, respectively. Standardized rate ratios (RRs) for hospital contacts (SHRRs) and prescriptions (SPRRs) with 95% CIs were calculated for diabetes, hyperlipidemia, and hypertension. RESULTS: Survivors had increased risks for hospital contacts and prescriptions for diabetes (SHRR, 1.21; 95% CI, 1.03-1.43; SPRR, 1.08; 95% CI, 0.96-1.23), hyperlipidemia (SHRR, 1.18; 95% CI, 1.00-1.40; SPRR, 1.16; 95% CI, 1.08-1.25), and hypertension (SHRR, 1.27; 95% CI, 1.15-1.41; SPRR, 1.25; 95% CI, 1.20-1.31). The highest risks for hospitalizations were among survivors of brain cancer (RR, 2.94 for diabetes) and Hodgkin lymphoma (RR, 2.40 for diabetes). Survivors of brain cancer and Hodgkin lymphoma were most likely to purchase prescription drugs for diseases in metabolic syndrome. CONCLUSIONS: Survivors of adolescent and young adult cancer are at increased risk of hospital contacts and purchase of prescription drugs for diseases in metabolic syndrome. Survivors at high risk should be followed closely to improve prevention, early detection, and management of these diseases to ultimately minimize the risk of cardiovascular diseases.

Employment, occupation, and income in adults with neurofibromatosis 1 in Denmark: a population- and register-based cohort study.

BACKGROUND: Little is known about employment status, occupation, and disposable income in adults with NF1. METHODS: From the Danish National Patient Registry and database of two national Centers for Rare Diseases, we identified 1469 adults with NF1, who were matched to 11,991 randomly selected population comparisons on sex and birth year and month. Annual information on employment, occupation and disposable income was ascertained from national registries in 1980-2019. RESULTS: Adults with NF1 had a lower odds ratio (OR) for employment [OR 0.71, 95% confidence interval (CI) 0.61-0.83] and higher OR for health-related unemployment (OR 2.94, 95% CI 2.16-3.96) at age 30 years than population comparisons, which persisted at age 40 and 50 years. Somatic diagnoses were associated with a higher OR for health-related unemployment in adults with NF1 than in the population comparisons. Adults with NF1 had a slightly lower disposable income, with a 14% (0.82-0.89) reduction observed among the youngest birth cohort. Furthermore, adults with NF1 were less likely to be in a high skilled occupation at ages 30, 40 and 50 years. CONCLUSION: Adults with NF1 have a lower employment rate, which was mainly due to health-related reasons and a slightly lower disposable income than adults without NF1. Thus, anticipation guidance for employment should be part of the management of NF1 families.

Effects of early maternal cancer and fertility treatment on the risk of adverse birth outcomes.

Background: Early maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes. Methods: This population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994-2016) of mothers with previous cancer (<40 years) recorded in the Danish Cancer Registry (1955-2014). We randomly selected 80,262 live-born singletons of mothers with no cancer <40 years matched to mothers with cancer by birth year and month. We calculated odds ratios (ORs) for preterm birth, low birth weight (LBW) (<2500 g) and small for gestational age (SGA), mean differences in birth weight in grams, and additional cases of preterm birth (gestational age<259 days) per 100,000 person-years. Multiplicative and additive interaction of maternal cancer and fertility treatment was compared with outcomes of children conceived naturally to mothers with no maternal cancer (reference group). Findings: Among 84,332 live-born singletons, increased ORs for preterm birth were observed among children born to mothers with previous cancer (1·48, 95% confidence interval [CI] 1·33-1.65) or after fertility treatment (1·43, 95% 1·28-1-61), with 22 additional cases of preterm birth among both group of children (95% CI 15-29; 95% CI 14-30). In the joint analyses, the OR for SGA for children born after fertility treatment to mothers with previous cancer was similar to that of the reference group (OR 1·02, 95% CI 0·72-1·44, P for interaction=0·52). Children with both exposures had increased ORs for LBW (1·86, 95% CI 1·17-2·96, P for interaction=0·06) and preterm birth (2·31, 955 CI 1·66-3·20, P for interaction = 0·56), with 61 additional cases of preterm birth (95% CI 27-95, P for interaction=0.26) over that of children in the reference group. The mean birth weight was also lower in children born to mothers with both exposures (-140 g, 95% CI -215; -65) (P for interaction=0.06) but decreased to -22 g (95% CI -76; 31) after adjustment for GA. Interpretation: Although we did not find any statistically significant additive interaction between maternal cancer and fertility treatment, children born after fertility treatment of mothers with previous cancer were at increased risk for adverse birth outcomes. Thus, pregnant women with both exposures need close follow-up during pregnancy. Funding: The Danish Cancer Society and the Danish Childhood Cancer Foundation.