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December 13, 2016; 87 (24) Article

Parental rheumatoid arthritis and childhood epilepsy

A nationwide cohort study

Ane Lilleøre Rom, Chun Sen Wu, Jørn Olsen, Damini Jawaheer, Merete Lund Hetland, Jakob Christensen, Bent Ottesen, Lina Steinrud Mørch
First published November 16, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003424
Ane Lilleøre Rom
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.
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Chun Sen Wu
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.
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Jørn Olsen
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.
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Damini Jawaheer
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.
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Merete Lund Hetland
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.
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Jakob Christensen
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.
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Bent Ottesen
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.
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Lina Steinrud Mørch
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.
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Citation
Parental rheumatoid arthritis and childhood epilepsy
A nationwide cohort study
Ane Lilleøre Rom, Chun Sen Wu, Jørn Olsen, Damini Jawaheer, Merete Lund Hetland, Jakob Christensen, Bent Ottesen, Lina Steinrud Mørch
Neurology Dec 2016, 87 (24) 2510-2516; DOI: 10.1212/WNL.0000000000003424

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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.

GLOSSARY

CI=
confidence interval;
HR=
hazard ratio;
ICD-8=
International Classification of Diseases, 8th revision;
ICD-10=
International Classification of Diseases, 10th revision;
RA=
rheumatoid arthritis

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 2502

  • Received March 13, 2016.
  • Accepted in final form August 10, 2016.
  • © 2016 American Academy of Neurology
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