Parental rheumatoid arthritis and childhood epilepsy: A nationwide cohort study.
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ABSTRACT: Objective
To assess the influence of parental rheumatoid arthritis (RA) on risk of epilepsy.Methods
We performed a nationwide cohort study including all singletons born in Denmark from 1977 to 2008 (n = 1,917,723) through individual linkage to nationwide Danish registries. The children were followed for an average of 16 years. Main outcome measures were adjusted hazard ratios (HRs) for epilepsy with onset in early childhood (29 days-4 years), late childhood (5-15 years), adolescence/adulthood (≥15 years), and at any age until the end of follow-up (December 31, 2010).Results
Compared to unexposed children, children exposed to maternal RA had an increased risk of early and late childhood epilepsy (adjusted HRs 1.34 [95% confidence interval (CI) 1.13-1.60] and 1.26 [95% CI 1.13-1.41]), while children exposed to maternal RA had no increased risk of epilepsy in adolescence/adulthood (HR 1.15 [95% CI 0.92-1.45]). Paternal RA was not associated with an overall risk of epilepsy in the offspring (HR 0.96 [95% CI 0.81-1.15]) or at any age. Children exposed to maternal RA in utero had a more pronounced increased risk of early childhood epilepsy than children exposed to mothers who were diagnosed with RA after childbirth (HR 1.90 [95% CI 1.26-2.86] vs HR 1.26 [95% CI 1.03-1.52], respectively [p = 0.16]).Conclusions
Exposure to maternal RA was associated with an increased risk of childhood epilepsy, while exposure to paternal RA was not, which indicates that changes in the intrauterine environment may play a role.
SUBMITTER: Rom AL
PROVIDER: S-EPMC5206999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:To estimate the influence of parental rheumatoid arthritis (RA) on child morbidity.Nationwide cohort study.Individual linkage to nationwide Danish registries.All singletons born in Denmark during 1977-2008 (n=1?917?723) were followed for an average of 16?years.Adjusted HRs for child morbidity; that is, 11 main diagnostic groups and specific autoimmune diseases within the International Classification of Diseases 8th and 10th versions.Compared with unexposed children, children exposed to maternal RA ('clinical' and 'preclinical') (n=13?566) had up to 26% higher morbidity in 8 of 11 main diagnostic groups. Similar tendencies were found in children exposed to paternal RA ('clinical' and 'preclinical') (n=6330), with statistically significantly higher morbidity in 6 of 11 diagnostic groups. HRs were highest for autoimmune diseases with up to three times increased risk of juvenile idiopathic arthritis (HR, 95% CI 3.30, 2.71 to 4.03 and 2.97, 2.20 to 4.01) and increased risk of up to 40% of diabetes mellitus type 1 (HR, 95% CI 1.37, 1.12 to 1.66 and 1.44, 1.09 to 1.90) and up to 30% increased HR of asthma (HR, 95% CI 1.28, 1.20 to 1.36 and 1.15, 1.04 to 1.26). Conclusions were roughly similar for children exposed to maternal clinical RA and for children only followed up to 16?years of age.Children of parents with RA had consistent excess morbidity. If the associations reflect biological mechanisms, genetic factors seem to play an important role. These findings call for attention given to children of parents with RA.
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Project description:ObjectivesTo determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.DesignLongitudinal nationwide register based cohort study.SettingInpatient and outpatient hospital care in Denmark from 1997 to 2009.ParticipantsEntire Danish population aged over 15 years without rheumatoid arthritis, atrial fibrillation, or stroke before 1997. Participants with rheumatoid arthritis were identified by individual level linkage of diagnoses and rheumatoid arthritis treatment.Main outcome measuresRates of atrial fibrillation and stroke.ResultsOf 4,182,335 participants included in the cohort, 18,247 were identified as having rheumatoid arthritis during follow-up, with a mean age at disease onset of 59.2 years and a median follow-up of 4.8 years. A total of 156,484 people, including 774 with rheumatoid arthritis, were diagnosed as having atrial fibrillation (age and sex matched event rates of 8.2 per 1000 person years in rheumatoid arthritis patients and 6.0 per 1000 person years in the general population), with an adjusted incidence rate ratio of 1.41 (95% confidence interval 1.31 to 1.51). In addition, 165,343 people, including 718 with rheumatoid arthritis, had a stroke (7.6 per 1000 person years in rheumatoid arthritis and 5.7 per 1000 person years in the general population), with a resultant rate ratio of 1.32 (1.22 to 1.42). For both atrial fibrillation and stroke, relative risks were increased in all strata based on thirds of sex and age, with higher relative risks in younger patients but higher absolute risk differences in older patients.ConclusionsRheumatoid arthritis was associated with an increased incidence of atrial fibrillation and stroke. The novel finding of increased risk of atrial fibrillation in rheumatoid arthritis suggests that this arrhythmia is relevant in cardiovascular risk assessment of these patients.
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Project description:ObjectivesThe objectives of this study were to examine changes in the incidence and prevalence of RA between 1990 and 2014 and to explore if there is any geographic variation in the incidence and prevalence of RA in the UK.MethodsThis was a primary care-based prospective cohort study. People contributing acceptable data to Clinical Practice Research Datalink between 1 January 1990 and 31 December 2014 were included. Read codes were used to identify RA cases ?18 years of age. The prevalence and incidence rates for each year were standardized to the 2014 population and the regional incidence and prevalence of RA for the year 2014 were standardized to the overall population.ResultsThe incidence and prevalence of RA was 3.81/10 000 person-years and 0.67%, respectively, in 2014. The annual incidence of RA decreased by 1.6% (95% CI 0.8, 2.5) between 1990 and 2014, with significant joinpoints at 1994 and 2002. The prevalence of RA increased by 3.7%/year (95% CI 3.2, 4.1) from 1990 to 2005 and decreased by 1.1%/year (95% CI 2.0, 0.2) between 2005 and 2014. There were significant differences in the occurrence of RA throughout different regions of the UK, with the highest incidence in East Midlands, Yorkshire and Humber and the highest prevalence in North East, Yorkshire and Humber.ConclusionThe incidence of RA is decreasing, with a reduction in prevalence in recent years. There is significant geographic variation in the occurrence of RA in the UK. Further research is required to identify the reasons underlying this phenomenon so that public health interventions can be designed to further reduce the incidence of RA.
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Project description:The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan-Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02-1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07-1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05-1.97) and 1.66 (95% CI, 1.16-2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11-1.95) and 1.43 (95% CI, 1.07-1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.
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Project description:Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31-0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44-1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.
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Project description:ObjectiveTo investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology.MethodsThrough the Swedish Patient Register, we identified 85,201 individuals with epilepsy, as well as all their siblings (n = 80,511) and offspring (n = 98,534). Each individual with epilepsy was compared with 5 controls, matched for age, sex, calendar period, and county, while siblings and offspring were compared with siblings and offspring of controls. We excluded siblings and offspring with epilepsy. Using Cox regression, we calculated hazard ratios (HRs) for future diagnosis of ASD. Logistic regression was applied to calculate odds ratios (ORs) for prior diagnosis of ASD.ResultsDuring follow-up, 1,381 (1.6%) individuals with epilepsy and 700 (0.2%) controls were diagnosed with ASD. Individuals with epilepsy were therefore at increased risk of future ASD (HR 10.49, 95% confidence interval [CI] 9.55-11.53), with the highest risk seen in individuals diagnosed with epilepsy in childhood. Both siblings (HR 1.62, 95% CI 1.43-1.83) and offspring (HR 1.64, 95% CI 1.46-1.84) of epilepsy patients were at increased risk of ASD. The risk in the offspring was particularly high in mothers with epilepsy (HR 1.91; 95% CI 1.63-2.23). Epilepsy was also associated with a prior diagnosis of ASD (OR 4.56, 95% CI 4.02-5.18).ConclusionsIndividuals with epilepsy are at increased risk of ASD, especially if epilepsy appears in childhood. Further, ASD is more common in the siblings and offspring of individuals with epilepsy, suggesting shared etiology.
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