Parents in the Driver's Seat-Experiences of Parent-Delivered Baby-mCIMT Coached Remotely.

Background/Objectives: Recent guidelines on early intervention in children at high risk of cerebral palsy (CP) recommend parental involvement and family-centered home-based interventions with parents as primary trainers. Therapist coaching by home visitation is resource demanding, and telerehabilitation is a viable option for remote intervention and coaching. This study aims to describe parents' experiences of engaging in Baby-mCIMT coached remotely. Their infants are at high risk of unilateral cerebral palsy and the parents have been the primary trainers in regard to home-based intervention, optimizing the use of the affected hand. Methods: A qualitative approach involving semi-structured interviews with eight parents was employed. Data were analyzed using qualitative content analysis. Results: The overarching theme "Parents in the driver's seat-learning through remote coaching to create conditions to enhance the child's motor skills" describes parents' experiences as primary training providers. The following three underlying categories with subcategories were identified: (1) Baby-mCIMT coached remotely in an everyday context-practical and technical prerequisites; (2) the child's response and the therapists' coaching supports active parental learning; (3) capability and sense of control-strengthening and demanding aspects. Conclusions: Our findings revealed that Baby-mCIMT coached remotely empowered the parents as primary trainers, which provided them with opportunities for understanding and learning about their child and their development. The findings underscore the importance of responsive professional guidance and a strong therapist-parent relationship to succeed with the Baby-mCIMT program coached remotely and to manage the digital coaching format.

'We did everything by phone': a qualitative study of mothers' experience of smartphone-aided screening of cerebral palsy in Kathmandu, Nepal.

BACKGROUND: International guidelines recommend early intervention to all children at risk of cerebral palsy, but targeted screening programs are often lacking in low- and middle-income settings with the highest burden of disease. Smartphone applications have the potential to improve access to early diagnostics by empowering parents to film their children at home followed by centralized evaluation of videos with General Movements Assessment. We explored mothers' perceptions about participating in a smartphone aided cerebral palsy screening program in Kathmandu, Nepal. METHODS: This is an explorative qualitative study that used focus group discussions (n = 2) and individual interviews (n = 4) with mothers of term-born infants surviving birth asphyxia or neonatal seizures. Parents used the NeuroMotion™ smartphone app to film their children at home and the videos were analysed using Precthl's General Movements Assessment. Sekhon et al.'s framework on the acceptability of health care interventions guided the design of the group discussions and interviews, and the deductive qualitative content analysis. RESULTS: Mothers were interested in engaging with the programme and expressed hope it would benefit their children. Most felt using the app was intuitive. They were, however, unclear about the way the analysis was performed. Support from the research team was often needed to overcome an initial lack of self-confidence in using the technology, and to reduce anxiety related to the follow-up. The intervention was overall perceived as recommendable but should be supplemented by a face-to-face consultation. CONCLUSION: Smartphone aided remote screening of cerebral palsy is acceptable in a lower middle-income population but requires additional technical support.

NeuroMotion smartphone application for remote General Movements Assessment: a feasibility study in Nepal.

OBJECTIVES: To evaluate the feasibility of using the NeuroMotion smartphone application for remote General Movements Assessment for screening infants for cerebral palsy in Kathmandu, Nepal. METHOD: Thirty-one term-born infants at risk of cerebral palsy due to birth asphyxia or neonatal seizures were recruited for the follow-up at Paropakar Maternity and Women's Hospital, 1 October 2021 to 7 January 2022. Parents filmed their children at home using the application at 3 months' age and the videos were assessed for technical quality using a standardised form and for fidgety movements by Prechtl's General Movements Assessment. The usability of the application was evaluated through a parental survey. RESULTS: Twenty families sent in altogether 46 videos out of which 35 had approved technical quality. Sixteen children had at least one video with approved technical quality. Three infants lacked fidgety movements. The level of agreement between assessors was acceptable (Krippendorf alpha 0.781). Parental answers to the usability survey were in general positive. INTERPRETATION: Engaging parents in screening of cerebral palsy with the help of a smartphone-aided remote General Movements Assessment is possible in the urban area of a South Asian lower middle-income country.

Outcomes of a Parent-Delivered Baby-mCIMT Model for Infants at High Risk of Unilateral Cerebral Palsy Using Remote Coaching in Telerehabilitation.

There is growing evidence of the positive effects of constraint-induced movement therapy (CIMT) for infants at high risk of unilateral cerebral palsy (UCP) when provided by parents with in-person coaching/supervision from occupational therapists during home visits. The aim of this study is to investigate whether Baby-mCIMT (modifiedCIMT) can be as effective if parents are coached/supervised remotely. In this case-control study, we recruited 20 infants and re-used 18 controls, 4-8-month-old infants in both groups at high risk of UCP. The same protocol regarding inclusion criteria, data collection, and training volume was used in both groups. The training was conducted for two 6-week periods, separated by a 6-week break, consisting of daily 30 min sessions conducted by parents, supported by therapist coaching once a week. The primary outcome was measured using the Hand Assessment for Infants (HAI). There was no difference in the change of HAI units (p = 0.803) or that of the affected-hand raw score (p = 0.942) between the two groups. The remote coaching method was well received by parents. In conclusion, this demonstrates that remote coaching/supervision is as effective as the in-person approach, requiring less time and effort for both families and healthcare providers.

Association of Perinatal and Childhood Ischemic Stroke With Attention-Deficit/Hyperactivity Disorder.

Importance: Early detection of attention-deficit/hyperactivity disorder (ADHD) plays a crucial role in reducing negative effects on everyday life, including academic failure and poor social functioning. Children who survive ischemic strokes risk major disabilities, but their risk of ADHD has not been studied in nationwide cohorts. Objective: To assess the risk of ADHD in children after pediatric ischemic stroke. Design, Setting, and Participants: Participants in this Swedish nationwide cohort study included 1320 children diagnosed with ischemic stroke recorded in linked Swedish national registers from January 1, 1969, to December 31, 2016, without prior ADHD diagnosis. Ten matched controls were identified for each index case, and first-degree relatives were identified for index individuals and controls. Analyses were stratified by perinatal and childhood strokes and presence of comorbid adverse motor outcomes and/or epilepsy. End of follow-up was the date of ADHD diagnosis, death, or December 31, 2016, whichever occurred first. Data analyses were performed August 1 to 28, 2021. Exposures: Pediatric ischemic stroke. Main Outcomes and Measures: Attention-deficit/hyperactivity disorder identified using codes from the International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and/or prescribed ADHD medication recorded in the Medical Birth Register, National Patient Register, or Prescribed Drug Register after stroke. Cox proportional hazards regression was used to assess adjusted hazard ratios (aHRs) for ADHD after pediatric stroke, adjusting for parental age and ADHD in first-degree relatives. Results: Of 1320 children with stroke included in the analysis (701 boys [53.1%]), 75 (45 boys [60.0%]) were diagnosed with ADHD after stroke compared with 376 (252 boys [67.0%]) among the controls (aHR, 2.00 [95% CI, 1.54-2.60]). The risk was increased after both perinatal (aHR, 2.75 [95% CI ,1.65-4.60]) and childhood (aHR, 1.82 [95% CI, 1.34-2.48]) strokes and were similar if children born preterm or small for gestational age were excluded. Compared with controls, risks of ADHD were higher among children with perinatal stroke and adverse motor outcomes and/or epilepsy (aHR, 6.17 [95% CI, 2.80-13.62]) than among those without these comorbidities (aHR, 1.65 [95% CI, 0.80-3.42]). However, findings were similar in childhood stroke for children with adverse motor outcomes and/or epilepsy (aHR, 1.80 [95% CI, 1.12-2.89]) and among those without these comorbidities (aHR, 1.92 [95% CI, 1.28-2.90]). Conclusions and Relevance: This cohort study of 1320 children with pediatric ischemic stroke suggests that there is an increased risk of ADHD, particularly in children with adverse motor outcomes and/or epilepsy, compared with controls. The risk increases after childhood strokes regardless of comorbidities.

Risk of Autism After Pediatric Ischemic Stroke: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Ischemic stroke increases the risk of neurodevelopmental disorders; however, the risk of autism is not thoroughly explored. Our aim was to evaluate risk of autism and risk factors for autism in children with pediatric ischemic stroke and in their first-degree relatives. METHODS: In this cohort study, individuals with ischemic stroke from 1969 to 2016, <18 years of age, alive 1 week after stroke, and without prior autism were identified in Swedish national registers. Ten matched controls per index individual and all first-degree relatives of index individuals and controls were identified. Conditional Cox regression was used to calculate the risk of autism. Unconditional logistic regression was performed to analyze sex, gestational age, age at stroke diagnoses, comorbid adverse motor outcome, comorbid epilepsy, and a sibling with autism as risk factors for autism in children with ischemic stroke. RESULTS: Of the 1,322 index individuals, 46 (3.5%) were diagnosed with autism compared to 161 (1.2%) controls (adjusted hazard ratio [aHR] 3.02, 95% CI 2.15-4.25). There was no significant difference in risk of autism according to age at stroke: perinatal (aHR 2.69, 95% CI 1.44-5.03) and childhood stroke (aHR 3.18, 95% CI 2.12-4.78). The increased risk remained after exclusion of children born preterm or small for gestational age (aHR 3.78, 95% CI 2.55-5.60) and when children with stroke diagnosed from 1997 to 2014 were analyzed (aHR 2.91, 95% CI = 1.95-4.35). Compared to controls, the risk of autism was increased in individuals with ischemic stroke and comorbid epilepsy (aHR 7.05, 95% CI 3.74-13.30), as well as adverse motor outcome (aHR 4.28, 95% CI 2.44-7.51). When individuals with adverse motor outcome and epilepsy were censored, the risk of autism was still increased (aHR 2.37, 95% CI 1.45-3.85). Sex, gestational age, and having a sibling with autism were not associated with autism in individuals with pediatric ischemic stroke. DISCUSSION: An increased risk of autism was seen after pediatric ischemic stroke, particularly in individuals with comorbid epilepsy, and could not be explained by being born preterm or small for gestational age. The risk was increased also in individuals free from epilepsy and adverse motor outcome, implying that all children with ischemic stroke should be readily screened for autism if the disorder is suspected.

Adverse motor outcome after paediatric ischaemic stroke: A nationwide cohort study.

BACKGROUND: Various frequencies of adverse motor outcomes (cerebral palsy and hemiplegia) after paediatric ischaemic stroke have been reported. Few reports on the risks of adverse motor outcomes in nationwide cohorts and contributing risk factors are available. OBJECTIVES: To assess risk of adverse motor outcome and potential risk factors thereof after paediatric ischaemic stroke in a nationwide cohort. METHODS: This nationwide matched cohort study identified 877 children <18 years of age diagnosed with ischaemic stroke through the Swedish national health registers from 1997 to 2016. These children, exposed to ischaemic stroke, alive 1 week after stroke, were matched for age, sex and county of residence with 10 unexposed children. Using Cox regression, we estimated the risk of adverse motor outcomes in children with stroke compared to that in unexposed children. Logistic regression was applied to compare the characteristics of children with and without adverse motor outcomes after stroke. RESULTS: Out of the 877 children with ischaemic stroke, 280 (31.9%) suffered adverse motor outcomes compared with 21 (0.2%) of the 8770 unexposed: adjusted hazard ratio (aHR) 167.78 (95% confidence interval (CI) 107.58, 261.66). There were no differences between risk estimates of adverse motor outcome according to age at stroke: perinatal stroke (aHR 124.11, 95% CI 30.45, 505.84) and childhood stroke (aHR 182.37, 95% CI 113.65, 292.64). An association between adverse motor outcome and childhood stroke aOR 1.56 (95% CI 1.05, 2.31) was found when analysing only children with ischaemic stroke. No associations were found between adverse motor outcome and sex, gestational age or parental age at birth. CONCLUSIONS: The risk of adverse motor outcome is substantial after paediatric ischaemic stroke, especially childhood stroke, confirming results of previous smaller studies. This study found no associations between sex, gestational age or parental age and adverse motor outcome after paediatric ischaemic stroke.

Long-Term Mortality in Children With Ischemic Stroke: A Nationwide Register-Based Cohort Study.

BACKGROUND AND PURPOSE: Ischemic stroke is a common cause of death in adults, however, mortality after pediatric ischemic stroke is not well explored. We investigate long-term and cause-specific mortality in children with ischemic stroke and their first-degree relatives. METHODS: Through nationwide Swedish registers, we identified 1606 individuals <18 years old with ischemic stroke between 1969 and 2016 and their first-degree relatives (n=5714). Each individual with ischemic stroke was compared with 10 reference individuals (controls) matched for age, sex, and county of residence. Our main analysis examined 1327 children with ischemic stroke still alive 1 week after the event. First-degree relatives to children with ischemic stroke were compared with first-degree relatives to the reference individuals. Using a Cox proportional hazard regression model, the risk of overall and cause-specific mortality was computed in individuals with pediatric ischemic stroke and their first-degree relatives. RESULTS: The mortality rate in the first 6 months was 40.1 (95% CI, 24.7-55.6) per 1000 person-years compared with 1.1/1000 in controls (95% CI, 0.3-1.9). The overall mortality risk was hazard ratio (HR)=10.8 (95% CI, 8.1-14.3) and remained elevated beyond 20 years (HR=3.9 [95% CI, 2.1-7.1]). Children with ischemic stroke were at increased risk of death from neurological diseases (HR=29.9 [95% CI, 12.7-70.3]), cardiovascular diseases (HR=6.2 [95% CI, 1.8-22.2]), cancers (HR=6.5 [95% CI, 2.6-15.9]) and endocrine, nutritional and metabolic diseases (HR=49.2 [95% CI, 5.7-420.8]). First-degree relatives to children with ischemic stroke had an increased mortality risk (HR=1.21 [95% CI, 1.05-1.39]), with the highest risk among siblings (HR=1.52 [95% CI, 1.09-2.11]) and relatives to individuals with ischemic stroke >28 days of age (HR=1.23 [95% CI, 1.06-1.42]) compared with the relatives of the controls. CONCLUSIONS: Long-term mortality increased after pediatric ischemic stroke, even 20 years later, with neurological diseases as the most frequent cause of death.

Pediatric Ischemic Stroke and Epilepsy: A Nationwide Cohort Study.

Background and Purpose: The risk of epilepsy after stroke has not been thoroughly explored in pediatric ischemic stroke. We examined the risk of epilepsy in children with ischemic stroke as well as in their first-degree relatives. Methods: In Swedish National Registers, we identified 1220 children <18 years with pediatric ischemic stroke diagnosed 1969 to 2016, alive 7 days after stroke and with no prior epilepsy. We used 12 155 age- and sex-matched individuals as comparators. All first-degree relatives to index individuals and comparators were also identified. The risk of epilepsy was estimated in children with ischemic stroke and in their first-degree relatives using Cox proportional hazard regression model. Results: Through this nationwide population-based study, 219 (18.0%) children with ischemic stroke and 91 (0.7%) comparators were diagnosed with epilepsy during follow-up corresponding to a 27.8-fold increased risk of future epilepsy (95% CI, 21.5­36.0). The risk of epilepsy was still elevated after 20 years (hazard ratio [HR], 7.9 [95% CI, 3.3­19.0]), although the highest HR was seen in the first 6 months (HR, 119.4 [95% CI, 48.0­297.4]). The overall incidence rate of epilepsy was 27.0 per 100 000 person-years (95% CI, 21.1­32.8) after ischemic stroke diagnosed ≤day 28 after birth (perinatal) and 11.6 per 100 000 person-years (95% CI, 9.6­13.5) after ischemic stroke diagnosed ≥day 29 after birth (childhood). Siblings and parents, but not offspring, to children with ischemic stroke were at increased risk of epilepsy (siblings: HR, 1.64 [95% CI, 1.08­2.48] and parents: HR, 1.41 [95% CI, 1.01­1.98]). Conclusions: The risk of epilepsy after ischemic stroke in children is increased, especially after perinatal ischemic stroke. The risk of epilepsy was highest during the first 6 months but remained elevated even 20 years after stroke which should be taken into account in future planning for children affected by stroke.

Usability and inter-rater reliability of the NeuroMotion app: A tool in General Movements Assessments.

BACKGROUND: Early intervention after perinatal brain insults requires early detection of infants with cerebral palsy (CP). General Movements Assessments (GMA) in the fidgety movement period has a high predictive value for CP. AIM: To investigate the NeuroMotion™ app's usability regarding film quality and user experience and to assess the inter-rater reliability of GMA in a neonatal risk group. METHODS: GMA, inter-rater reliability and film quality was assessed in a cohort consisting of 37 infants enrolled in a multicentre study of GMA as part of the Swedish neonatal follow-up program for high-risk infants. Some of these infants were filmed twice. For evaluation of user experience 95 parents of 52 infants were addressed with a web-based questionnaire. A GMA expert assessed film quality and performed GMA and three on-site assessors, individually performed GMA. Inter-rater reliability was computed using Krippendorff's alpha (k-alpha). RESULTS: In all, 45 films showed good or excellent quality. The response rate of the questionnaire survey was 40% and revealed predominantly positive perceptions of the NeuroMotion™ app. GMA in 36 infants resulted in substantial agreement (k-alpha = 0.72, 95%CI = 0.3-1.0) between the three on-site assessors' consensus and the GMA expert. Inter-rater reliability for GMA between the on-site assessors was moderate (k-alpha = 0.48, 0.18-0.74). CONCLUSION: The NeuroMotion™ app produces good technical quality films and the app user experience was overall positive. High agreement was observed between the on-site assessors and the GMA expert. The study design is feasible for more extensive GMA studies in cohorts of infants at risk of CP.

Paediatric ischaemic stroke is a valid diagnosis in the Swedish National Patient Register.

AIM: The Swedish National Patient Register offers unique opportunities for epidemiological research of paediatric ischaemic stroke. We aimed to validate the diagnosis of paediatric ischaemic stroke in the National Patient Register to ensure the quality of future research. METHODS: The PedStroke cohort consists of 1606 individuals aged <18 years with a diagnosis of paediatric ischaemic stroke (ICD-10: I63, I64; ICD-8 and 9: 433, 434, 436) in Swedish national health registers between 1969 and 2016. We selected 292 cases for validation by reviewing medical charts. RESULTS: In all, 277 of the 292 medical charts were received, of which 273 had enough information to qualify for review. The diagnosis was correct in 242/273 cases, yielding a positive predictive value (PPV) of 89% (95% confidence interval (CI): 0.85-0.92) for paediatric ischaemic stroke in the National Patient Register. After validation, seven cases of 222 with childhood stroke were re-categorised to perinatal stroke, resulting in a total of 56 perinatal stroke cases. In the Medical Birth Register, 38 stroke cases were identified of which 37 had correct diagnosis, generating a PPV of 97% (95% CI: 0.92-1.0). Incorrect diagnoses decreased over time and the number of diagnoses confirmed by radiology increased correspondingly. CONCLUSION: The National Patient Register is reliable for epidemiological research of paediatric ischaemic stroke because of its high PPV for this diagnosis.

Adaptation of the Charlson Comorbidity Index for Register-Based Research in Sweden.

PURPOSE: Comorbidity indices are often used to measure comorbidities in register-based research. We aimed to adapt the Charlson comorbidity index (CCI) to a Swedish setting. METHODS: Four versions of the CCI were compared and evaluated by disease-specific experts. RESULTS: We created a cohesive coding system for CCI to 1) harmonize the content between different international classification of disease codes (ICD-7,8,9,10), 2) delete incorrect codes, 3) enhance the distinction between mild, moderate or severe disease (and between diabetes with and without end-organ damage), 4) minimize duplication of codes, and 5) briefly explain the meaning of individual codes in writing. CONCLUSION: This work may provide an integrated and efficient coding algorithm for CCI to be used in medical register-based research in Sweden.

Pregnancy outcome in women with cerebral palsy: A nationwide population-based cohort study.

INTRODUCTION: Cerebral palsy (CP) is a lifelong disorder with a high rate of comorbidities and complications. We hypothesized that women with CP are at increased risk of adverse pregnancy outcome. MATERIAL AND METHODS: In this nationwide population-based cohort study 1997-2011, we examined the outcome of 770 births in women with CP vs 1 247 408 births in women without a CP diagnosis using the Swedish Medical Birth Register. We used unconditional logistic regression, adjusting for maternal age, smoking, parity, year of birth and epilepsy, to calculate adjusted odds ratios for adverse pregnancy outcome. Main adverse outcome was preterm birth. Secondary outcomes were cesarean section, induction of labor, low 5-min Apgar score, small for gestational age, large for gestational age, and stillbirth. RESULTS: After adjusting for potential confounders, maternal CP was associated with increased risk of preterm birth (12.9% vs 4.9%; adjusted odds ratio [aOR] 2.8, 95% CI 2.3-3.5), cesarean delivery (aOR 1.9, 95% CI 1.6-2.2), induced delivery (aOR 1.4, 95% CI 1.1-1.6), low 5-min Apgar score (aOR 1.8, 95% CI 1.1-2.9) and small of gestational age birth (aOR 1.6, 95% CI 1.2-2.3). We found no increased risk of large for gestational age or stillbirth. CONCLUSIONS: Women with CP are at increased risk of preterm birth and other adverse pregnancy outcomes, suggesting that they deserve extra surveillance during antenatal care. Further studies, with information on type of CP and gross motor function, are warranted to better understand the association between CP and pregnancy outcome.

Pregnancy outcomes in women with autism: a nationwide population-based cohort study.

BACKGROUND: The consequences of autism in pregnancy outcomes have not been explored before, although it is of crucial importance because of the frequent comorbidities and medication in this group of women. OBJECTIVES: To estimate the risk of adverse pregnancy outcomes in women diagnosed with autism. DESIGN: Nationwide population-based cohort study. SETTING: Sweden. PARTICIPANTS: Singleton births identified in the Swedish Medical Birth Registry, 2006-2014. A total of 2,198 births to women diagnosed with autism registered in the Swedish National Patient Registry were compared to 877,742 singleton births to women without such a diagnosis. MAIN OUTCOME AND MEASURES: Preterm delivery. Secondary measures were cesarean delivery (emergency and elective), Apgar score <7 at 5 minutes, small for gestational age, large for gestational age, stillbirth, gestational diabetes, and preeclampsia. ORs were calculated through logistic regression, adjusted for maternal age at delivery, maternal country of birth, smoking, maternal body mass index, parity, calendar year of birth, and psychotropic and antiepileptic medication during pregnancy. RESULTS: Women with autism were at increased risk of preterm birth (OR=1.30; 95% CI=1.10-1.54), especially medically indicated preterm birth (OR=1.41; 95% CI=1.08-1.82), but not with spontaneous preterm birth. Maternal autism was also associated with an increased risk of elective cesarean delivery (OR=1.44; 95% CI=1.25-1.66) and preeclampsia (OR=1.34; 95% CI=1.08-1.66), but not with emergency cesarean delivery, low Apgar score (<7), large for gestational age, gestational diabetes, and stillbirth. In women with medication during pregnancy, there was no increased risk of adverse pregnancy outcome except for induction of delivery (OR=1.33; 95% CI=1.14-1.55). CONCLUSION AND RELEVANCE: Maternal autism is associated with preterm birth, likely due to an increased frequency of medically indicated preterm births, but also with other adverse pregnancy outcomes, suggesting a need for extra surveillance during prenatal care.

[Epilepsy: incidens, prevalens and causes]. / Epilepsins orsaker, förekomst och prognos.

Epilepsy affects people in all ages with the highest incidence in small children, particularly before age one year, and in elderly aged 65 years and older. In Sweden, between 4500-5000 persons develop epilepsy annually. Based on studies from North America and Europe, including the Nordic countries, the number of people with active epilepsy in Sweden is between 60000-70000. The lifetime risk for epilepsy up to age 85 years is 4-5 %, i.e. approximately every 25th person. The new epilepsy classification divides etiology into the following groups: structural, genetic, infectious, metabolic, immune and unknown. The majority (70%) of people with epilepsy eventually become seizure free. Epilepsy increases the risk of psychosocial problems and accidents. People with epilepsy have up to a 3-fold increase in mortality, mainly due to the underlying causes and epilepsy related deaths, e.g. status epilepticus, SUDEP and accidents. Somatic, psychiatric and neuropsychiatric comorbidities are common in epilepsy.

Epilepsy, antiepileptic drugs, and serious transport accidents: A nationwide cohort study.

OBJECTIVES: To investigate the association between epilepsy and antiepileptic drugs and serious transport accidents requiring emergency care or resulting in death. METHODS: We identified 29,220 individuals 18 years or older with epilepsy without cerebral palsy or intellectual disability and 267,637 matched controls using Swedish registers. This nationwide cohort was followed from 2006 to 2013 for serious transport accidents. We used Cox regression to analyze the risk of serious transport accidents between individuals with epilepsy and matched controls, and then stratified Cox regression to compare the risk during periods of medication with the risk during nonmedication period within the same individual with epilepsy. We adjusted for civil status, employment, education, living area, psychiatric disorders prior to the start of follow-up, and psychotropic medication. RESULTS: Compared to matched controls, individuals with epilepsy were at increased risk of serious transport accidents (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.29-1.46). There were increased risks of pedestrian accidents (HR 2.24, 95% CI 1.69-2.97), bicycle accidents (HR 1.68, 95% CI 1.49-1.89) and car accidents (HR 1.31, 95% CI 1.19-1.44). However, among patients with a diagnosis of epilepsy, use of antiepileptic drugs did not influence the risk of serious transport accidents in population-level comparisons (HR 0.97; 95% CI 0.85-1.11) or within-individual comparisons (HR 0.99; 95% CI 0.69-1.42). CONCLUSION: Serious transportation accidents were more common in individuals with epilepsy, but this risk was independent of use of antiepileptic drugs.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

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.

Autism and epilepsy: A population-based nationwide cohort study.

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.

Nationwide population-based cohort study of celiac disease and risk of Ehlers-Danlos syndrome and joint hypermobility syndrome.

BACKGROUND: Patients with celiac disease (CD) often have articular complaints, and small prior studies suggest an association with Ehlers-Danlos syndrome (EDS)/joint hypermobility syndrome (JHS). AIMS: This study examines the risks of EDS/JHS in patients with CD. METHODS: This cohort study compared all individuals in Sweden diagnosed with CD based on small intestinal biopsy between 1969-2008 (n=28,631) to 139,832 matched reference individuals, and to a second reference group undergoing biopsy without having CD (n=16,104). Rates of EDS/JHS were determined based on diagnostic codes in the Swedish Patient Register. Hazard ratios (HRs) for EDS/JHS were estimated through Cox regression. RESULTS: There are 45 and 148 cases of EDS/JHS in patients with CD and reference individuals, respectively. This corresponds to a 49% increased risk of EDS/JHS in CD (95%CI=1.07-2.07). The HR for EDS was 2.43 (95%CI=1.20-4.91) and for JHS 1.34 (95%CI=0.93-1.95). Compared to reference individuals undergoing intestinal biopsy, CD was not a risk factor for EDS/JHS. A stronger association was seen in patients initially diagnosed with EDS/JHS and subsequently diagnosed with CD (odds ratio=2.29; 95%CI=1.21-4.34). CONCLUSIONS: Individuals with CD have higher risk of EDS/JHS than the general population, which may be due to surveillance bias or factors intrinsic to celiac development.