title: Parental rheumatoid arthritis and childhood epilepsy: A nationwide cohort study.
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.
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark. ane.lilleoere.rom@regionh.dk.
authors.forename: Ane Lilleøre
authors.initials: AL
authors.lastname: Rom
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Chun Sen
authors.initials: CS
authors.lastname: Wu
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Damini
authors.initials: D
authors.lastname: Jawaheer
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Christensen
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Bent
authors.initials: B
authors.lastname: Ottesen
authors.affiliation: From the Research Unit, Women's and Children's Health (A.L.R.), and Department of Obstetrics and Gynecology (B.O.), The Juliane Marie Centre, and Gynaecological Clinic (L.S.M.), Copenhagen University Hospital Rigshospitalet; Section for Epidemiology, Department of Public Health (C.S.W.), and Departments of Clinical Epidemiology (J.O.) and Neurology (J.C.), University of Aarhus; Research Unit of Gynecology and Obstetrics (C.S.W.), Institute of Clinical Research, University of Southern Denmark, Odense; Department of Obstetrics and Gynecology (C.S.W.), Odense University Hospital, Denmark; Department of Epidemiology (J.O.), School of Public Health, University of California Los Angeles; Children's Hospital Oakland Research Institute (D.J.), CA; Copenhagen Center for Arthritis Research (M.L.H.), Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup; Department of Clinical Medicine (M.L.H.), Faculty of Health and Medical Sciences, University of Copenhagen; and Danish Cancer Society Research Centre (L.S.M.), Virus, Lifestyle and Genes Unit, Copenhagen, Denmark.
authors.forename: Lina Steinrud
authors.initials: LS
authors.lastname: Mørch
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000150:complications*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000175:diagnosis* / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D010290:Parents; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors