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Comorbidity and complications in neurological diseases
Örebro University, School of Medical Sciences.ORCID iD: 0000-0003-0898-9418
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Neurological diseases are complex and many share etiology as well as comorbidities. Epilepsy, a brain disorder characterized by an enduring predisposition to generate epileptic seizures and autism spectrum disorder (ASD), are considered to be associated, but the connection is still not fully uncovered. Cerebral palsy (CP), a lifelong, nonspecific, non-progressive disorder of posture and movement control, and Ehlers-Danlos Syndrome (EDS), a connective tissue disorder, both have many consequences for health and wellbeing throughout life.

Aims: The aim of this thesis was to explore the impact of comorbidity and complications in neurological diseases and EDS. The objective was to gain information on the nature of the connection between epilepsy and ASD, if EDS, ASD and CP have consequences for pregnancy outcome, and the risk of traffic accidents in individuals with epilepsy.

Materials and methods: The studies are all historical observational population- based cohort studies with prospectively collected data from national registers. The risk of ASD was analysed in 85,201 individuals with epilepsy and compared with 425,760 controls as well as for their firstdegree relatives. In a cohort of 1,248,178 singleton births, 314 births to women with EDS, 2,072 births to women with ASD, and 770 births to women with CP, pregnancy outcome was explored. The risk of traffic accidents was estimated in 29,220 individuals with epilepsy and 267,637 matched controls.

Results: There is an increased risk of; ASD in individuals with epilepsy and their relatives, moderately preterm birth and pre-eclampsia in maternal ASD, of preterm birth in maternal CP and transport accidents in individuals with epilepsy. There is no increased risk of adverse pregnancy outcome in women with EDS.

Conclusions: This thesis found proofs of a bidirectional association between epilepsy and ASD, that ASD and CP have consequences for pregnancy outcome and epilepsy is a risk factor for traffic accidents.

Place, publisher, year, edition, pages
Örebro: Örebro University , 2017. , 81 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 163
Keyword [en]
antiepileptic drugs, autism, cerebral palsy, child, Ehlers-Danlos Syndrome, epilepsy, obstetric, pregnancy, traffic accidents
National Category
Family Medicine
Identifiers
URN: urn:nbn:se:oru:diva-58056ISBN: 978-91-7529-199-4 (print)OAI: oai:DiVA.org:oru-58056DiVA: diva2:1110034
Public defence
2017-09-08, Örebro universitet, Campus USÖ, Hörsal C3, Södra Grev Rosengatan 32, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2017-06-15 Created: 2017-06-15 Last updated: 2017-10-02Bibliographically approved
List of papers
1. Autism and epilepsy: A population-based nationwide cohort study
Open this publication in new window or tab >>Autism and epilepsy: A population-based nationwide cohort study
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2016 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 87, no 2, 192-197 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate the risk of autism spectrum disorder (ASD) in individuals with epilepsy and in their first-degree relatives to determine shared etiology.

Methods: Through 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.

Results: During 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).

Conclusions: Individuals 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.

Place, publisher, year, edition, pages
Philadelphia, USA: Lippincott Williams & Wilkins, 2016
National Category
Medical and Health Sciences Neurosciences
Identifiers
urn:nbn:se:oru:diva-54630 (URN)10.1212/WNL.0000000000002836 (DOI)000381470700039 ()27306624 (PubMedID)2-s2.0-84979000396 (Scopus ID)
Funder
Swedish Research Council
Note

Funding Agencies:

Swedish Initiative for research on Microdata in the Social and Medical Sciences (SIMSAM) 

Swedish Research Council for Health, Working Life and Welfare 

Available from: 2017-01-12 Created: 2017-01-12 Last updated: 2017-10-18Bibliographically approved
2. Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome
Open this publication in new window or tab >>Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome
2017 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 1, 114-119 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected.

MATERIAL AND METHODS: In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes.

RESULTS: Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome.

CONCLUSION: Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keyword
Ehlers-Danlos syndrome, Joint hypermobility syndrome, child, obstetric - cohort study, pregnancy
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-59089 (URN)10.1111/aogs.13043 (DOI)000391980100014 ()27743500 (PubMedID)2-s2.0-85006078185 (Scopus ID)
Funder
Swedish Research Council, 2013-2429Forte, Swedish Research Council for Health, Working Life and Welfare, 2015-01369Stockholm County Council, 20130156
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-10-18Bibliographically approved
3. Pregnancy outcomes in women with autism: A Nationwide populationbased cohort study
Open this publication in new window or tab >>Pregnancy outcomes in women with autism: A Nationwide populationbased cohort study
(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-59093 (URN)
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-10-18Bibliographically approved
4. Pregnancy outcome in women with cerebral palsy: A nationwide population-based cohort study
Open this publication in new window or tab >>Pregnancy outcome in women with cerebral palsy: A nationwide population-based cohort study
(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-59096 (URN)
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-10-18Bibliographically approved
5. Epilepsy, anti-epileptic drugs, and serious transport accidents: A nationwide cohort study
Open this publication in new window or tab >>Epilepsy, anti-epileptic drugs, and serious transport accidents: A nationwide cohort study
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Family Medicine
Identifiers
urn:nbn:se:oru:diva-59097 (URN)
Available from: 2017-08-15 Created: 2017-08-15 Last updated: 2017-10-18Bibliographically approved

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