Heritability estimates are essential for understanding genetic and environmental contributions to disease, yet large-scale studies remain scarce. In this study, we leverage the Danish national health registers, including medical records for more than 10 million individuals, to estimate heritability for more than 1000 health outcomes. We estimate heritability using both twins and siblings born in Denmark between 1955-2021, providing insight into the influence of shared sibling environment with estimates that show strong concordance with published twin studies and meta-analyses. We consider the impact of left-truncation by conducting analyses in both the full cohort and in individuals born after 1977. In a nested genotype case-cohort sample, we contrasted twin- and sibling-based heritabilities for psychiatric and neurological disorders with single-nucleotide polymorphism (SNP)-heritability, revealing disorder-specific "missing heritability" gaps. Together, these results map disease heritability in a single population, providing comprehensive insights for future genetic studies and preventive strategies using population health registers.

BACKGROUND:Regulatory authorities have raised concerns about potential teratogenic and neurodevelopmental disorders (NDDs) risks associated with paternal valproate use during spermatogenesis, leading to restrictions. We aimed to investigate the association between paternal valproate exposure during spermatogenesis and the risk of NDDs in offspring in Sweden and Norway. METHODS:We conducted a population-based cohort study of two nationwide cohorts from Sweden and Norway, including all singleton live births (≥22 gestational weeks) from 2007 to 2020. Paternal monotherapy exposure to valproate, lamotrigine or levetiracetam was defined as ≥1 prescription filled for only one of these medications during the 3 months prior to conception. NDDs were identified from health registers from age 1 through 2022. Cox proportional hazards models were used to estimate adjusted HRs (aHRs), accounting for relevant confounders. A random-effects meta-analysis combined results from both countries. RESULTS:The Swedish cohort included 1588 children with paternal valproate and 3093 with lamotrigine/levetiracetam monotherapy, while the Norwegian cohort included 463 and 1109, respectively. Compared with paternal lamotrigine/levetiracetam monotherapy, paternal valproate exposure was not associated with increased pooled risk of any NDD (aHR, 1.06; 95% CI 0.81 to 1.22), including autism spectrum disorder (aHR, 1.29; 95% CI 0.89 to 1.85), attention-deficit/hyperactivity disorder (aHR, 0.98; 95% CI 0.76 to 1.25), intellectual disability (aHR, 1.20; 95% CI 0.65 to 2.21; Sweden only) or psychological development disorders (aHR, 1.28; 95% CI 0.84 to 1.97). Findings remained consistent in dose-response analyses and when restricted to fathers with epilepsy. CONCLUSIONS:In this large Nordic study, paternal valproate use during spermatogenesis was not associated with increased risk of NDDs in offspring, suggesting current regulatory restrictions may warrant re-evaluation.

Background We quantify the loss of working years for people with epilepsy according to underlying aetiology and compare to the general population. Methods This population-based cohort study included all individuals aged 18–65 years living in Denmark from 1995 to 2018. Using nationwide registers from 1977 onward, we identified people with epilepsy and grouped them by presumed aetiology (secondary: infection, perinatal insult, congenital malformation, brain tumour, traumatic brain injury, stroke or unknown) and obtained annual data on primary income source during 1995–2020. The main outcome was working years lost comparing people with epilepsy to the general population, reflecting losses of working life from permanent (death, disability pension, early retirement) and temporary (unemployment, sick leave) factors. Results The study included 5 466 144 individuals, with 48 223 (0.9%) having epilepsy of unknown aetiology and 26 754 (0.5%) with secondary epilepsy. Compared with the general population, post-traumatic epilepsy was associated with the greatest average loss of working life (10.2 years, 95% CI 9.9 to 10.4), whereas brain tumour-related epilepsy was associated with a reduction of 9.1 years (95% CI 8.8 to 9.4) and post-stroke epilepsy with a reduction of 6.6 years (95% CI 6.4 to 6.8). Epilepsy of unknown aetiology was associated with a 5.4-year loss (95% CI 5.2 to 5.5). Across all epilepsy types, most reductions in working life resulted from higher rates of disability pension and premature death. Conclusions Epilepsy, especially when secondary to an underlying brain insult, was associated with significant loss of working life from both disability and premature death. More support is needed to help people with epilepsy secure and retain employment.

BACKGROUND:Seizure disorders, including epilepsy and febrile seizures, affect around 5% of all children in Western countries. Although these conditions may be associated with psychosocial challenges, their impact on school well-being remains unclear. We examined the association of childhood epilepsy and febrile seizures with school well-being. METHODS:We conducted a register-based cohort study including children born in Denmark (2000-2014) who participated in the Danish National Well-being Survey (2015-2022) [a survey mandated by law in all public mainstream schools in Denmark]. Children with epilepsy and febrile seizures were matched (1:10) by age and sex to unaffected children. Children with epilepsy and febrile seizures were identified from hospital contacts and antiseizure medication use. Poor school well-being was defined using systematic survey data. Adjusted odds ratios (aORs) with 95% CIs were estimated using logistic regression. RESULTS:Among 770,988 eligible children, 6,862 (0.9%) had epilepsy and 30,851 (4.0%) had febrile seizures, matched to 68,620 and 308,510 unaffected peers, respectively. Among children with epilepsy, 7% of assessments in grades 0-3 indicated poor overall well-being versus 6% in matched peers (aOR, 1.12; 95% CI, 0.99-1.28). In grades 4-9, 10% versus 8% indicated poor well-being (aOR, 1.18; 95% CI, 1.10-1.27), and the association was strongest for academic well-being (aOR, 1.35; 95% CI, 1.27-1.43). Children with febrile seizures had odds of poor well-being similar to their matched peers. CONCLUSION:Childhood epilepsy was associated with marginally poorer school well-being, although more pronounced in later grades and academic domains, underscoring the need for educational and psychosocial support. Febrile seizures were not associated with poor well-being, providing reassurance for affected children and their families.

BACKGROUND:Both bipolar disorder (BD) and epilepsy (ES) have been linked to polycystic ovary syndrome (PCOS) that is one of the most common endocrine disorders in women of reproductive age. The antiseizures medication valproate is widely used in the treatment of both disorders but has been suspected to increase the risk of PCOS. Previous studies have been limited by small sample sizes and heterogeneous definitions. We aimed to investigate the association between valproate exposure and incident PCOS in females with BS and ES. METHODS:We conducted a register-based cohort study including all females in Denmark with a first diagnosis of BD (ICD-10: F30.x-F31.x) or ES (ICD-10: G40.x) between January 1, 2000, and July 31, 2022. Women with BD, ES, valproate exposure, or PCOS prior to January 1, 2000, were excluded. Exposure to valproate was primarily modeled as current cumulative exposure. We also included a never/ever analysis and an overall cumulative analysis, accumulating dosages over the entire study period. The outcome was incident PCOS (ICD-10: E28.2). Cox regression models adjusted for age at diagnosis and calendar year were applied. RESULTS:The cohort comprised of 20,967 women, 8,003 diagnosed with BD and 12,964 diagnosed with ES. In total, 266 females developed PCOS during follow-up, of whom 160 had been exposed to valproate. In the main analysis, current cumulative exposure was strongly associated with PCOS, with HRRs rising from 4.43, 95%CI:3.42-5.73 (0-90 DDDs) to 7.08, 95%CI:3.85-13.03 (> 365 DDDs), P < 0.001. In the never/ever analysis, valproate exposure was also associated with increased PCOS risk (HRR 1.55, 95%CI:1.20-2.00). By contrast, overall cumulative exposure showed a less consistent pattern, with risk most clearly elevated in the highest dosage category (> 365 DDDs, HRR 2.04, 95%:CI 1.28-3.20), p < 0.01. CONCLUSIONS:Valproate exposure was associated with an increased risk of PCOS. The risk was especially pronounced during current and cumulative exposure, whereas overall cumulative exposure suggested increased risk at higher thresholds. These findings suggest that PCOS risk may be driven by acute pharmacological effects, although long-term cumulative use may also contribute. The results reinforce recommendations to avoid valproate in women of reproductive age when possible.

Background: Frontotemporal dementia (FTD) is a common form of early-onset dementia, and little is known about potential modifiable FTD risk factors. We sought to determine if exposure to ambient particulate matter with a diameter less than 2·5 μm (PM2·5) and exposure to nitrogen dioxide (NO2) was associated with risk of FTD diagnosis. Methods: We conducted a population-based, nested case-control study within a source population of all individuals aged 35-95 years residing in Denmark between January 1, 2001, and December 31, 2021. Cases were identified from hospital diagnoses with FTD and matched on sex and birth date with 10 controls randomly selected using risk-set sampling. We used conditional logistic regression to estimate incidence rate ratios (IRRs) for the associations of exposure to PM2·5 or NO2. Each matched case-control set formed a separate stratum. Models were adjusted for confounding factors and stratified by age and sex. Findings: There were 3,572 incident cases of FTD identified with 35,720 matched controls (median, interquartile range [IQR] age at FTD diagnosis: 74 years [67-80];50·4% females). In adjusted models, each 5 µg/m³ increase in PM2·5 was associated with a greater rate of FTD (IRR=1·80; 95%CI:1·42–2·27). The association was stronger in females (IRR=2·24; 95%CI:1·63-3·07) compared to males (IRR=1·42; 95%CI:1·03-1·96)(p=0·040). Each 10 µg/m³ increase in NO₂ was associated with 1·14-times greater rate of FTD (95%CI:1·02–1·28) with no significant difference between females (IRR=1·22; 95%-CI:1·05-1·41) and males (IRR=1·07;95%CI:0·92-1·24)(p=0·171). Interpretation: Exposure to PM2·5 and NO2 were each associated with a higher risk of FTD. These findings strengthen the evidence supporting an association of air pollution with neurodegeneration and specifically with FTD.

OBJECTIVE:To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS:Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES:the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95% CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS:We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS:In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

BACKGROUND:High-dose folic acid supplementation is recommended for women using antiseizure medication (ASMs) to reduce risk of major congenital anomalies (MCAs) in offspring, but evidence is lacking. METHODS:We conducted a sequential target trial emulation using nationwide register data from Denmark, Iceland, Norway, and Sweden (1997-2020). Eligible women using ASMs were included and classified as initiators or non-initiators based on whether they filled prescription for high-dose folic acid within one week of inclusion. Risk difference (RD) and risk ratio (RR) for MCAs diagnosed before one year of age in offspring were estimated for initiators of high-dose folic acid (4 or 5 mg/day) supplementation in three periconceptional periods (13-52 weeks before, 1-12 weeks before, and 1-12 weeks after pregnancy onset) compared with non-initiators. RESULTS:We included 18 255, 13 619, and 12 365 eligible pregnancies and identified 1047 (5.7%), 521 (3.8%) and 1778 (14.4%) initiators of high-dose folic acid in the three periods, respectively. Initiation of high-dose folic acid 1-12 weeks before pregnancy was associated with a lower prevalence of MCA in offspring (2.6% vs 4.8% among non-initiators), corresponding to an absolute risk reduction of 2.2 percentage points (95% CI 0.5 to 3.5) and a 45% relative risk reduction (RR=0.55, 95% CI 0.25 to 0.91). No risk reduction was observed with initiation 1-12 weeks after (RR=1.27, 95% CI 0.94 to 1.64) or 13-52 weeks before (RR=0.99, 95% CI 0.65 to 1.36) pregnancy onset. CONCLUSIONS:Initiation of high-dose folic acid in the 12 weeks before pregnancy was associated with a reduced risk of MCA in offspring of women using ASMs while initiation in the 12 weeks after pregnancy onset was not. RESEARCH PROTOCOL REGISTRATION: https://osf.io/vph2n/?view_only=c9361e4996eb4c4da32fc878f2fbf5b9.

Importance:Evidence on the association of exposure to ambient particulate matter with a diameter less than 2.5 µm (PM2.5) and nitrogen dioxide (NO2) and the later development of dementia with Lewy bodies (DLB) or Parkinson disease-related dementia (PDD) is limited. Objective:To determine whether exposures to ambient PM2.5 or NO2 are associated with risk of incident DLB or PDD. Design, Setting, and Participants:This population-based case-control study used linked Danish nationwide registry data to identify individuals with DLB and PDD diagnosed between January 1, 2001, through December 31, 2021. Each individual with dementia was matched with 10 controls on age, sex, and time. Data were analyzed from June 2025 through February 2026. Exposures:A 10-year time-weighted mean concentration of PM2.5 or NO2 prior to DLB or PDD diagnosis. Main Outcomes and Measures:A conditional logistic regression model was used to examine the associations of exposure to PM2.5 or NO2 with risk of DLB or PDD. The models were sequentially adjusted for age, sex, and calendar period, then individual-level socioeconomic characteristics, then medical and psychiatric comorbidity, and finally area-level socioeconomic factors. Results:Among 2 184 847 Danish citizens aged between 65 and 95 years, there were 3024 individuals with DLB (mean [SD] age, 78 [6], 1894 [62.6%] male) and 3808 with PDD (mean [SD] age, 78 [6], 2400 [63.0%] male) who were matched with 30 240 and 38 080 controls, respectively. PM2.5 and NO2 exposure were each associated with increased risk of DLB or PDD after controlling for age, sex, and calendar period. In fully adjusted models, each 5 µg/m3 increase in PM2.5 exposure was associated with nearly 4-fold greater risk of DLB (adjusted odds ratio [aOR], 3.70; 95% CI, 2.69-5.10) and more than 2-fold greater risk of PDD (aOR, 2.41; 95% CI, 1.88-3.08), while each 10 µg/m3 increase in NO2 exposure was associated with 95% greater risk of DLB (aOR, 1.95; 95% CI, 1.69-2.27) and 14% greater risk of PDD (aOR, 1.14; 95% CI, 1.01-1.29). Conclusions and Relevance:In this case-control study, exposures to ambient PM2.5 or NO2 were each associated with increased risks of DLB and PDD, with a greater magnitude of association for risk of DLB. These findings warrant concern about the impact of air pollution on brain health.

BACKGROUND:Childhood-onset epilepsy has been linked to poor school performance but limited evidence exists for long-term educational achievement. We examined educational achievement from adolescence into adulthood in individuals with childhood-onset epilepsy compared with the general population. METHODS:In this nationwide population-based cohort study using Danish registers, we included 1 195 138 individuals born between 1987 and 2005 and followed through 2023. Epilepsy before age 15 years was identified from hospital diagnoses and antiseizure medication prescriptions (n=11 758). Individuals with epilepsy were matched on sex and age to reference individuals without epilepsy, with additional propensity score matching on perinatal and parental factors. Outcomes included completion of primary school, ninth grade mean grades and attainment of higher educational levels. Adjusted ORs (aORs), mean grade differences and adjusted incidence rate ratios were estimated using multivariable regression models. Educational trajectories were assessed from age 15 to 35 years. RESULTS:Compared with reference individuals, those with epilepsy had higher odds of not completing primary school (aOR 3.0, 95% CI 2.8 to 3.1) and lower grades in mathematics (-0.9, 95% CI -0.9 to -0.8) and language (-0.6, 95% CI -0.6 to -0.5). Educational attainment rates were reduced by 50%-56% across all higher levels, and only 9.3% of individuals with epilepsy attained the highest educational level versus 19.5% of matched reference individuals by age 35 years. CONCLUSIONS:Childhood-onset epilepsy was associated with significantly lower primary school completion rates, grades and long-term educational attainment. Targeted assessment of academic capacity, interventions and support are needed to optimise outcomes for young people with epilepsy.

Respiratory syncytial virus (RSV) is a major health problem worldwide, particularly in infants and young children. The infection can progress to life-threatening lower respiratory disease and, in rare cases, involves the central nervous system. We explore the pathophysiology in a child with high fever, seizures, and encephalopathy with brain inflammation during severe RSV infection. Whole-genome sequencing revealed homozygosity for a rare loss-of-function variant in the early-onset Parkinson-related gene PARK7/DJ-1. PARK7 plays a role in immune regulation, stress responses, and cell death. The patient’s Peripheral blood mononuclear cells and fibroblasts exhibited increased inflammatory cytokine responses, impaired RSV-induced apoptosis, and dampened autophagy. Studies in PARK7-deficient neuronal cells recapitulated the patient’s cellular phenotype, which was reversed upon PARK7 reconstitution. To our knowledge, this is the first association between PARK7 deficiency and RSV-induced brain inflammation, encephalopathy, and seizures. Collectively, our results demonstrate a role for PARK7 in regulation of inflammation and cellular homeostasis and suggest that PARK7 deficiency may aggravate infectious disease and cause immunopathology.

PURPOSE:Childhood urinary incontinence (UI) is a common disorder with significant negative impact on self-esteem and quality of life, but the impact on school performance is unknown. This study investigates how UI in children is associated with school performance. MATERIALS AND METHODS:This is a nationwide matched cohort study of children born in Denmark to Danish parents between 1997 and 2008 investigating association between UI and results from standardized National School Tests from 2010 to 2018 (1- to 100-point scale). Multiple linear regression estimated difference (∆) in test scores between children with UI and matched references after adjusting for relevant confounders. Subanalyses investigated the influence of psychiatric disorders (PDs) and age at treatment onset. RESULTS:Overall, children with UI (n = 42,999) performed comparably with the matched reference children (n = 429,999; ∆ range -2.5 to +0.6 points). Children with UI co-occurring with PDs scored substantially lower than the reference population, most pronounced for attention-deficit/hyperactivity disorder (∆ range -3.7 to -11.2 points). Children with nocturnal enuresis aged 11 years and older at treatment onset had lower overall school performance than children aged 5 to 7 years at treatment onset (∆ -2.9 [95% CI, -4.0 to -1.7]). CONCLUSIONS:School performance in children with UI was normal. However, because PDs are more prevalent in UI and children with UI and co-occurring PDs had significantly lower school performance, we recommend assessing for PDs in UI. Children with late treatment onset had lower school performance than children with early treatment onset; further research is needed on the effect of delayed treatment on children with UI.

BACKGROUND AND OBJECTIVES:Reproduction is lower in male individuals compared with female individuals with epilepsy. The reason is unknown. We studied sex-specific reproduction in individuals with epilepsy and the role of epilepsy subtype and psychiatric comorbidity. METHODS:We conducted a population-based register study in Denmark, using data from January 1, 1982, to December 31, 2021. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) with 95% CIs for the chance of having ≥1 child. We followed all persons from 15 years of age until birth of live-born offspring, 45 years of age, emigration, death, or end of follow-up (December 31, 2021), whichever occurred first. Epilepsy status was identified from the Danish National Patient Register. The primary outcome was the occurrence of live-born children identified from the Danish Medical Birth Register among persons with and without epilepsy. RESULTS:We included 2,593,097 individuals (49% of female individuals), including 46,243 (1.8%) with epilepsy (mean age at diagnosis of 13.1 years [SD 9.2]). Compared with individuals without epilepsy, the aHR of having ≥1 child was reduced in both sexes with epilepsy, but lower in male individuals (0.59, 95% CI 0.57-0.60) compared with female individuals with epilepsy (0.72, 95% CI 0.71-0.74). By age 45 years, the probability of being childless was 45.9% in male individuals and 30.7% in female individuals with epilepsy, compared with 22.8% in male individuals and 14.1% in female individuals without epilepsy. Compared with persons without epilepsy, the chance of having a first child was lower in female individuals with focal epilepsy (aHR 0.61, 95% CI 0.58-0.64) than in female individuals with generalized epilepsy (aHR 0.72, 95% CI 0.69-0.75), and lower in male individuals with focal epilepsy (aHR 0.51, 95% CI 0.48-0.53) than in male individuals with generalized epilepsy (aHR 0.57, 95% CI 0.54-0.60). Reproduction was particularly low in persons with epilepsy and psychiatric comorbidity (male individuals: aHR 0.30, 95% CI 0.28-0.32; female individuals: aHR 0.51, 95% CI 0.48-0.53). DISCUSSION:Individuals with epilepsy were less likely to become parents than individuals without epilepsy, and the association was stronger in male individuals and those with psychiatric comorbidity and varied with epilepsy subtype.

Background The Global Burden of Disease Study (GBD) produces prevalence estimates for 'idiopathic epilepsy' (ie, of unknown aetiology) and 'secondary epilepsy' (ie, with known aetiology) but does not report prevalence by underlying aetiologies for 'secondary epilepsy'.Methods We used nationwide, population-based register data from Denmark to identify underlying causes of epilepsy and their contribution to prevalence of 'secondary epilepsy' and compared with global prevalence data from GBD 2019. We identified all persons with a hospital-based epilepsy diagnosis and a filled prescription for antiseizure medication between 1 January 2009 and 31 December 2018. Epilepsy was categorised into 'idiopathic' or 'secondary' and 'total epilepsy' as the sum of the two epilepsy categories.Results On 31 December 2018, a total of 5 784 284 individuals (49.7% males) were living in Denmark including 40 336 with epilepsy (51.5% males). Perinatal conditions, traumatic brain injury, brain tumours and stroke were prominent underlying causes of 'secondary epilepsy'. The prevalence of 'total epilepsy' in Denmark was 697 (95% CI 691 to 704) per 100 000 population (264 (95% CI 260 to 269) for 'secondary epilepsy' and 433 (95% CI 428 to 438) for 'idiopathic epilepsy'). In the GBD 2019 Study, the prevalence of 'total epilepsy' in 2018 was 682 (95% uncertainty interval (UI) 586 to 784) per 100 000 population (359 (95% UI 324-397) for 'secondary epilepsy' and 324 (95% UI 249 to 404) for 'idiopathic epilepsy').Conclusions Prevalence estimates of 'total epilepsy', 'idiopathic epilepsy' and 'secondary epilepsy' in Denmark align with the GBD 2019 estimates. In future studies, it is suggested to explicitly include all types of epilepsy, including 'secondary epilepsy', which is currently estimated as sequelae (consequences) of underlying diseases.

BackgroundWe quantify the loss of working years for people with epilepsy compared with the general population and consider variation by aetiology, psychiatric comorbidity, sex and age.MethodsThis population-based cohort study included all individuals aged 18–65 years living in Denmark from 1995 to 2018. Using nationwide registers since 1977, we identified people with epilepsy and obtained information on the main source of income or employment for each year during follow-up from 1995 to 2020. The main outcome was number of working years lost in people with epilepsy compared with the general population of same sex and age, capturing both working life lost due to permanent (death, disability pension, early retirement) and temporary (unemployment, sick leave) factors.ResultsThe study comprised 5 466 140 individuals, including 74 980 (1.4%) with epilepsy. In people with epilepsy, the number of working years was on average reduced by 6.6 (95% CI: 6.5 to 6.7) years compared with the general population, largely due to disability pension (4.8 years, 95% CI: 4.7 to 4.9) and premature death (1.6 years, 95% CI: 1.6 to 1.7). Loss of working life was more pronounced in those with a presumed underlying aetiology (9.0 years (95% CI: 8.9 to 9.2) vs 5.4 years (95% CI: 5.2 to 5.5) in those with unknown aetiology), those with psychiatric comorbidity (14.5 years (95% CI: 14.2 to 14.7) vs 5.6 years (95% CI: 5.5 to 5.7) in those without), men (7.2 years (95% CI: 7.1 to 7.3) vs 5.9 (95% CI: 5.8 to 6.0) years in women) and people with early onset of epilepsy (eg, 11.5 years (95% CI: 11.3 to 11.7) among those with onset <20 years).ConclusionsEpilepsy was associated with significant loss of working life resulting from both disability and premature death.

This cohort study assesses associations of paternal use of valproate with neurodevelopmental disorders in children.