Population-based Longitudinal Follow-up Study Research Articles

Physical activity and the risk of chronic obstructive pulmonary disease: A longitudinal follow-up study in Taiwan

BackgroundThis study aimed to investigate whether physical activity (PA) is associated with a lower risk of subsequently developing chronic obstructive pulmonary disease (COPD). MethodsWe conducted this population-based longitudinal follow-up study in a community in Taiwan. This study recruited 61,446 subjects who had participated in the Keelung Community-based Integrated Screening Program (KCIS) between 2005 and 2012. During their participation in KCIS, they were provided with structured questionnaires to collect their baseline characteristics, including weekly PA time. After excluding subjects diagnosed with COPD before they joined KCIS and/or who provided incomplete lifestyle data, 59,457 subjects remained, and were classified into three groups based on their weekly PA time: i.e., as NPA (no regular PA), LPA (low PA, <90 min/week) and HPA (high PA, ≥90 min/week). The primary outcome was a new diagnosis of COPD, followed up until the end of 2015 or their death. Cox proportional-hazard regression was used to assess the impact of PA on the risk of COPD. ResultsThe risk of COPD was more than 20% lower in the LPA and HPA groups than in the NPA group. Specifically, the adjusted hazard ratio for the risk of COPD was 0.72 in the LPA group (95% CI, 0.61-0.85, p < 0.001) and 0.79 in the HPA group (95% CI, 0.69-0.90, p < 0.001). ConclusionsOur research uncovered an inverse relationship between PA and COPD. The findings suggest that PA might be useful as a strategy for the primary prevention of COPD.

Physical activity and the risk of ischemic stroke: A population-based longitudinal follow-up study in Taiwan (KCIS no. 43)

Lack of exercise is a leading risk factor for stroke, and it has been demonstrated that increasing physical activity (PA) can prevent ischemic stroke. However, there has been limited research on the relationship between ischemic stroke and PA, especially among Asian populations. This study therefore investigates whether the level of PA in the Taiwanese population affects its risk of first-ever ischemic stroke, utilizing screening data on 58,857 individuals collected by the Keelung Health Bureau between 2005 and 2012. These subjects were divided into three groups based on their weekly exercise frequency and duration, i.e., 1) a no PA (NPA) group, 2) a low PA (LPA) group (less than 90 min of exercise per week), and 3) a high PA (HPA) group (90 min or more of exercise per week). The results showed that, as compared to the NPA group, the adjusted hazard ratio for ischemic stroke in the LPA group was 0.86 (95 % CI, 0.78–0.95, p < 0.0001); and that in the HPA group, it was also 0.86 (95 % CI, 0.79–0.94, p < 0.0001). In other words, even engaging in PA for less than 90 min per week may lower the risk of first-ever ischemic stroke. Importantly, LPA is more accessible, more sustainable, and easier to promote for the general population than the 150 min per week recommended by the World Health Organization.

Incidence Rates and Risk Ratios of Normal Tension Glaucoma in Patients with Chronic Rhinosinusitis: A Population-Based Longitudinal Follow-Up Study.

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.

Adhesive capsulitis of the shoulder is associated with an increased risk for Parkinson's disease: a population-based longitudinal follow-up study.

Previous studies have suggested a positive association between adhesive capsulitis of the shoulder (ACS) and Parkinson's disease (PD), but longitudinal data were lacking. The present population-based longitudinal follow-up study therefore investigated the risk of developing PD in patients with ACS. This study utilized data from Taiwan's Longitudinal Health Insurance Database 2005 (LHID 2005). We defined our ACS group as the 19,920 patients aged between 40 and 79 who had been diagnosed with ACS between 2002 and 2006. The non-ACS group consisted of an age- and sex-matched but otherwise random selection of 19,920 patients without a diagnosis of ACS. The Kaplan-Meier method was then used to examine inter-group differences in PD-free survival rates, and Cox proportional-hazard regression modeling was used to evaluate the impact of ACS on PD risk. During a median follow-up period of 105 months, 242 subjects in the ACS group and 208 subjects in the non-ACS group developed PD. The adjusted hazard ratio (HR) of 1.53 (1.26-1.86) indicated that ACS patients had a significantly higher risk of developing PD than their non-ACS counterparts, regardless of sex and age. Landmark analysis that excluded PD cases detected within the first 2 years after an ACS diagnosis showed that the HR was almost unchanged, at 1.56 (1.26-1.95). Patients with ACS are at a high risk of developing PD. • This population-based study showed that adhesive capsulitis of the shoulder (ACS) is associated with a higher risk of Parkinson's disease (PD). • This study broke new ground by using a longitudinal follow-up design and a nationally representative sample. • Our findings suggest that clinicians who care for ACS patients need to be aware of this increased risk of developing PD.

Tea consumption and the risks of osteoporosis and hip fracture: a population-based longitudinal follow-up study

SummaryThis population-based longitudinal follow-up study showed a protective effect of tea consumption against osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture.IntroductionTo investigate the association of tea consumption with the risks of osteoporosis and hip fracture.MethodsThis study used the Keelung Community-based Integrated Screening database and Taiwan’s National Health Insurance Research Database. A total of 42,742 subjects aged 45 to 74 years were enrolled. Each was classified as no tea consumption, low tea consumption, and high tea consumption, according to the results of an eating habits questionnaire. The diagnosis of osteoporosis and hip fracture was based on BMD measured by dual-energy X-ray absorptiometry and the X-ray findings. The median follow-up time was 8.5 years.ResultsAs compared with the no tea consumption group, the osteoporosis HRs for the low tea consumption and high tea consumption groups were 0.88 (95% confidence interval (CI) 0.80–0.96) and 0.87 (95% CI 0.80–0.94), respectively. Among those participants aged 59 or below, the osteoporosis HRs for low tea consumption and high tea consumption (vs. no tea consumption) were 0.85 (95% CI 0.74–0.96) and 0.79 (95% CI 0.69–0.90). The HRs of hip fracture for the low tea consumption and high tea consumption groups (vs. no tea consumption) were 0.85 (95% CI 0.67–1.08) and 0.69 (95% CI 0.55–0.86), respectively.ConclusionTea consumption was linked to a lower risk of osteoporosis, particularly among women and middle-aged people. High tea consumption was also associated with a reduced risk of hip fracture.

The Association between Osteoporosis and Peripheral Artery Disease: A Population-Based Longitudinal Follow-Up Study in Taiwan.

Background: There are several possible links that have been used to claim that osteoporosis and peripheral artery disease (PAD) are associated; however, the solid evidence is not sufficient. This study aimed to use the Taiwan National Health Insurance Research Database (NHIRD) to determine if osteoporosis is associated with peripheral artery disease (PAD). Method: NHIRD records from 23 million patients were collected to recruit two matched cohort groups: 64,562 patients with and 64,562 patients without osteoporosis. To compare the crude hazard ratio (HR) and the incidence rate ratio between the two cohort groups for PAD, the Cox model was used. Result: With an adjusted HR of 1.18 (95% CI, 1.08–1.29), the osteoporosis cohort group had a significantly greater risk for PAD than the group without osteoporosis. The cumulative incidence of PAD in the cohort group was also statistically higher than it was in the group without osteoporosis (1.71% and 1.39%; p ≤ 0.0001, log-rank) over the 10-year follow-up period. In addition, the osteoporotic patients with ischemic stroke, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF) had a significantly increased risk of PAD based on subgroup analysis. Conclusions: There was a positive association between osteoporosis and the development of PAD, as patients with osteoporosis had an increased incidence of PAD over time.

Osteoarthritis Is Associated With an Increased Risk of Age-Related Macular Degeneration: A Population-Based Longitudinal Follow-Up Study.

AimsTo investigate the long-term risk of age-related macular degeneration (AMD) in persons with osteoarthritis (OA).MethodsThis retrospective cohort study first enrolled 71,609 subjects diagnosed with OA, and 236,169 without such a diagnosis between January 1, 2002 and December 31, 2005, from the Longitudinal Health Insurance Database 2005. All were aged 40–69. After excluding subjects who had pre-existing AMD and/or who had missing socioeconomic data, frequency matching by sex and age was performed. This resulted in there being 60,274 subjects in each of the final matched OA and non-OA groups. The study participants were followed up to the occurrence of AMD, death, or the end of 2011. We used Cox proportional-hazards regression to estimate the impact of OA on the risk of developing AMD, and performed subgroup analyses stratified by sex and age.ResultsThe median follow-up time was 8.9 years, with an interquartile range of 1.4 years. The incidence rate of AMD in the OA group was 2.77 per 1,000 person-years [95% confidence interval (CI), 2.62–2.92], and in the non-OA group, 2.06 per 1,000 person-years (95% CI, 1.94–2.19). The adjusted hazard ratio (HR) of AMD for the OA group was therefore 1.30 (95% CI, 1.20–1.41). In the subgroup analysis stratified by sex for the OA group, the adjusted HRs of AMD were 1.29 in the women's stratum and 1.31 in the men's. When stratified by age, the adjusted HRs of AMD for the younger (40–54 years) and older (55–69 years) strata were 1.28 and 1.31, respectively.ConclusionsPersons with OA have an increased risk of developing AMD, regardless of age and sex.

Osteoporosis and the long-term risk of peripheral artery disease: a population-based longitudinal follow-up study in Taiwan.

Osteoporosis has been linked to atherosclerotic diseases such as coronary heart disease and ischemic stroke. However, the relationship between osteoporosis and peripheral artery disease (PAD) has not been investigated. This study aims to evaluate the risk of PAD in patients with osteoporosis and the impact of sex on this association. This population-based study used the Longitudinal Health Insurance Database 2005, a subset of Taiwan's National Health Insurance research database. A total of 54,324 individuals between 40 and 79 years old were included in this study. The osteoporosis group (n = 27,162) consisted of patients with a diagnosis of osteoporosis between January 1, 2002, and December 31, 2006, while the non-osteoporosis group were patients without osteoporosis selected by stratified random sampling (n = 27,162). The primary outcome was the occurrence of newly diagnosed PAD. Cox proportional hazard regression modeling was used to evaluate the association between osteoporosis and the risk of PAD, with adjustment for the baseline characteristics. The risk of PAD for the osteoporosis group was 28% higher than for the non-osteoporosis group (adjusted hazard ratio (HR) 1.28, 95% confidence interval [CI] 1.20-1.36, p < 0.001), and the PAD-free survival rate was lower in the osteoporosis group (p < 0.001). Sex-stratified analysis revealed a similar HR magnitude between osteoporotic men (HR 1.36; 95% CI 1.19-1.57) and women (HR 1.25; 95% CI 1.17-1.35), compared with their non-osteoporotic counterparts. This study found an increased long-term risk of PAD in both men and women with osteoporosis. Osteoporosis has been associated with increased risks of atherosclerotic diseases. However, the relationship between osteoporosis and peripheral artery disease remains uncertain. The present population-based longitudinal follow-up study showed that patients with osteoporosis are at an increased risk of developing peripheral artery disease.

Physical Activity and the Risk of Hemorrhagic Stroke: A Population-Based Longitudinal Follow-Up Study in Taiwan.

Background: Data on the relationship between physical activity (PA) and hemorrhagic stroke (HS) are limited in Asian populations. This population-based longitudinal follow-up study therefore investigates whether PA is associated with a reduced risk of HS in Taiwan.Methods: A total of 58,857 subjects who had participated in the Keelung Community-based Integrated Screening Program between 2005 and 2012 were enrolled. Information about their PA, obtained using questionnaires, was used to categorize them into three groups according to their average weekly time engaged in it: (1) no PA, (2) low PA (<90 min weekly), and (3) high PA (90 min per week or more). Cox proportional hazard regression was used to evaluate the effect of PA on HS. Stratified analysis by sex and comorbidities (diabetes mellitus, hypertension, and hyperlipidemia) were conducted to evaluate their impact on the relationship between PA and HS.Results: Compared to the no-PA group, the adjusted hazard ratio of HS for the low-PA group was 0.74 (95% CI, 0.57–0.96, p = 0.0219), and for the high-PA group, 0.72 (95% CI, 0.58–0.90, p = 0.004). The stratified analyses showed that, for the non-comorbidity strata, the beneficial effect of PA on reducing HS risk became stronger as PA increased. However, in the diabetes and hypertension strata, high PA did not appear to have any greater protective effect than low PA.Conclusions: Our findings suggested that even <90 min of PA per week might be beneficial to reduce HS risk. Such a low level of PA is likely to be more achievable and easier to maintain for the general population. Additionally, personalized recommendations based on pre-existing comorbidities may help optimize the beneficial effects of PA on HS prevention.

Reduced Risk of Atrial Fibrillation Following Cholecystectomy: A Nationwide Population-Based Study.

Background: Gallstone disease (GD) is associated with a high risk of cardiovascular disease. However, it is unknown whether GD contributes to atrial fibrillation (AF). We aimed to investigate the association between GD and AF.Methods: We performed a population-based cohort study using data from the Taiwan National Health Insurance Research Database between 2001 and 2011. A GD cohort of 230,076 patients was compared with a control cohort consisting of an equal number of patients matched for age, sex, cardiovascular and gastrointestinal comorbidities.Results: In total, 5,992 (49.8/10,000 person-years) patients with GD and 5,804 (44.5/10,000 person-years) controls developed AF. GD increased AF risk with a hazard ratio (HR) of 1.20 [95% confidence interval (CI), 1.16–1.25]. In patients with GD but without cholecystectomy, the HR of AF reached 1.57 (95% CI = 1.50–1.63). After cholecystectomy, the HR of AF significantly decreased to 0.85 (95% CI = 0.81–0.90). Among the three age groups with GD (<45, 45–64, and ≥65 years), the adjusted HRs of AF were 1.59 (95% CI = 1.08–2.33), 1.31 (95% CI = 1.18–1.45), and 1.18 (95% CI = 1.13–1.22), respectively. Compared with patients with a CHA2DS2-VASc score equal to 0, the HRs of AF risk among total cohort patients and a score equal to 1, 2, 3, and ≥ 4 were 1.28 (95% CI = 1.15–1.43), 2.26 (95% CI = 2.00–2.56), 3.81 (95% CI = 3.35–4.34), and 5.09 (95% CI = 4.42–5.87), respectively.Conclusion: This population-based longitudinal follow-up study showed that patients with GD had an increased AF risk. Moreover, cholecystectomy was related to reduced AF risk. Cardiovascular checkups may be necessary for patients with GD, especially those who are young and have other typical risk factors.

Increased risk of acute pancreatitis in persons with spinal cord injury: a population-based, propensity score-matched longitudinal follow-up study

Retrospective cohort study. To evaluate the risk of acute pancreatitis (AP) in persons with spinal cord injury (SCI) based on a nationally representative sample. A retrospective cohort study using Taiwan's National Health Insurance Research Database. Drawing on Taiwan's Longitudinal Health Insurance Database 2005, the researchers created an SCI group consisting of 2280 persons with SCI aged 20-74 years. Propensity-score matching was then used to generate a non-SCI group of 9120 participants with similar baseline characteristics to the SCI group. These two groups' respective cumulative incidence of AP was compared, and the effect of SCI on AP risk was then assessed using stratified Cox proportional-hazards regression. For the SCI and non-SCI groups, the respective incidence rates of AP were 1.34 per 1000 person-years (95% confidence interval [CI], 0.83-2.05) and 0.79 per 1000 person-years (95% CI, 0.61-1.01). Compared with the non-SCI group, the hazard ratio of AP for the SCI group was 1.96 (95% CI 1.19-3.25, p = 0.0088); and the SCI group's cumulative incidence of AP was significantly higher than that of the non-SCI group (p = 0.0227). This population-based longitudinal follow-up study indicates that there is an increased long-term risk of AP in persons with SCI.

Parkinson disease and risk of acute myocardial infarction: A population-based, propensity score–matched, longitudinal follow-up study

Previous studies on the risk of acute myocardial infarction (AMI) in patients with Parkinson disease (PD) have generated inconsistent results. The purpose of this population-based longitudinal follow-up study was to investigate whether incident PD is associated with an increased risk of AMI. A total of 3,211 subjects with at least 2 ambulatory visits with the principal diagnosis of PD in 2001 were enrolled in the PD group. The non-PD group consisted of 3,211 propensity score-matched subjects without PD. The propensity scores were computed using a logistic regression model that included age, sex, preexisting comorbidities, and socioeconomic status. The 3-year AMI-free survival rates of the 2 groups were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression with patients matched by propensity score was used to estimate the effect of PD on subsequent occurrence of AMI. During the 3-year follow-up period, 83 subjects in the PD group and 53 in the non-PD group developed AMI (either fatal or nonfatal) events. The hazard ratio of AMI for the PD group compared with the non-PD group was 1.67 (95% CI 1.15-2.41, P = .0067). The AMI-free survival rate of the PD group was significantly lower than that of the non-PD group (P = .0032). The hazard ratios associated with PD for the combined end point 1 (AMI or cardiovascular death) and combined end point 2 (AMI or all-cause death) were 1.46 (95% CI 1.14-1.88, P = .0029) and 1.42 (95% CI 1.24-1.64, P < .0001), respectively. This study shows that PD is related to an increased risk of AMI. Further studies are required to investigate the mechanism underlying this association.

Gallstone Disease and the Risk of Stroke: A Nationwide Population-based Study

Gallstone disease (GD) and stroke share a number of risk factors including diabetes and hyperlipidemia. This nationwide population-based study was designed to estimate the risk of stroke after a diagnosis of GD. Data were obtained from the Taiwan National Health Insurance Research Database. A total of 135,512 patients with a diagnosis of GD and 271,024 age- and gender-matched non-GD control patients were included to assess the risk of stroke using Cox proportional hazard regression. During the study period (2000-2003), 12,234 (153.67/10,000 person-years) strokes occurred among the GD patients, and 20,680 (114.83/10,000 person-years) among the controls. The diagnosis of GD carried a higher risk of developing ischemic and hemorrhagic stroke, with a hazard ratio (HR) of 1.28 and 1.33 (95% confidence interval [CI], 1.25-1.31 and 1.25-1.41, both P<.0001), respectively. Stroke risk was increased in both genders but at a higher rate in younger age. The GD group had significantly higher prevalence rate of comorbidities that are known stroke risk factors, including hypertension, diabetes, and coronary artery disease. Stroke risk was higher in the GD group with or without any of these comorbidities. In this population-based longitudinal follow-up study, GD carried a significantly higher stroke risk, particularly for younger age with or without stroke risk factors. Stroke preventive measures maybe needed for patients with GD, especially those of younger age and with stroke risk factor(s).

Increased Risk of Ischemic Stroke in Young Patients with Ankylosing Spondylitis: A Population-Based Longitudinal Follow-Up Study

BackgroundProspective data on the association between ischemic stroke and ankylosing spondylitis (AS) in the young are sparse. The purpose of this population-based, age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in young patients with AS.MethodsA total of 4562 patients aged 18- to 45-year-old with at least two ambulatory visits in 2001 with a principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 22810 age- and sex-matched, randomly sampled subjects without AS. The two-year ischemic stroke-free survival rate for each group were calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke after adjusting for demographic and clinical covariates.ResultsDuring follow-up, 21 patients in the AS group and 53 in the non-AS group developed ischemic stroke. The ischemic stroke-free survival rate over the 2 year follow-up was lower in the AS group than the non-AS group (p = 0.0021). The crude hazard ratio of ischemic stroke for the AS group was 1.98 (95% CI, 1.20–3.29; p = 0.0079) and the adjusted hazard ratio after controlling for demographic and comorbid medical disorders was 1.93 (95% CI, 1.16–3.20; p = 0.0110).ConclusionOur study showed an increased risk of developing ischemic stroke in young patients with AS.

Increased Risk of Ischemic Heart Disease in Young Patients with Newly Diagnosed Ankylosing Spondylitis – A Population-Based Longitudinal Follow-Up Study

BackgroundProspective data is sparse on the association between ischemic heart disease (IHD) and ankylosing spondylitis (AS) in the young. The purpose of this population-based, age- and sex- matched follow-up study was to investigate the risk of IHD in young patients with newly diagnosed AS.MethodsA total of 4794 persons aged 18 to 45 years with at least two ambulatory visits in 2001 with the principal diagnosis of AS were enrolled in the AS group. The non-AS group consisted of 23970 age- and sex-matched, randomly sampled subjects without AS. The three-year IHD-free survival rate and cumulative incidence of IHD were calculated using the Kaplan-Meier method. The Cox proportional hazards regression model was used to estimate the hazard ratio of IHD after controlling for demographic and cardiovascular co-morbidities.ResultsDuring follow-up, 70 patients in the AS group and 253 subjects in the non-AS group developed IHD. The cumulative incidence rate of IHD over time was higher in the AS group than the non-AS group. The crude hazard ratio of IHD for the AS group was 1.47 (95% CI, 1.13 to 1.92; p = 0.0043) and the adjusted hazard ratio after controlling for demographic characteristics and comorbid medical disorders was 1.47 (95% CI, 1.13 to 1.92; p = 0.0045).ConclusionsThis study showed an increased risk of developing IHD in young patients with newly diagnosed AS.

Dermatomyositis is associated with an increased risk of cardiovascular and cerebrovascular events: a Taiwanese population-based longitudinal follow-up study

While the chronic inflammation related to autoimmune diseases is known to be associated with an increased cardiovascular risk, much less is known about cerebrovascular risks. The present population-based, age- and sex-matched follow-up study was undertaken to investigate the risks of acute myocardial infarction (AMI) and ischaemic stroke in patients with dermatomyositis (DMS). In total 907 patients with DMS were enrolled and compared with a non-DMS control group consisting of 4535 age- and sex-matched, randomly sampled subjects without DMS. The AMI-free and ischaemic stroke-free survival curves were generated using the Kaplan-Meier method. Cox proportional hazard regression was used to estimate the DMS-associated risks of AMI and ischaemic stroke. During the 2-year follow-up period, 14 patients with DMS (1.5%) and 18 patients in the non-DMS control group (0.4%) suffered AMIs. The crude hazard ratio (HR) for suffering an AMI in patients with DMS compared with subjects in the non-DMS group was 3.96 [95% confidence interval (CI) 1.97-7.96, P = 0.0001], while the adjusted HR was 3.37 (95% CI 1.67-6.80, P = 0.0007), after taking into account demographic characteristics and cardiovascular comorbidities. During the same follow-up period, 46 patients (5.1%) and 133 subjects in the control group (2.9%) developed ischaemic strokes. The crude HR for developing an ischaemic stroke in patients with DMS compared with subjects in the non-DMS group was 1.78 (95% CI 1.27-2.49, P = 0.0007), and the adjusted HR was 1.67 (95% CI, 1.19-2.34, P = 0.0028). These findings suggest that DMS is associated with an increased risk of cardiovascular and cerebrovascular events.

Developmental Delay and in Utero Phenytoin Exposure

Psychomotor development was assessed in preschool children exposed to antiepileptic drugs (AED) in utero as part of a population-based longitudinal follow-up study of children born to women with meticulously treated epilepsy during pregnancy at the Karolinska Institute, Stockholm, Sweden.

Psychomotor development in preschool children exposed to antiepileptic drugs in utero

The aim of this study was to assess psychomotor development with the Griffiths' test in preschool children exposed to antiepileptic drugs (AED) in utero. The study sample consisted of 76 children exposed to AED in utero and 71 unexposed children. The children (exposed and unexposed) have since birth been included in a population-based longitudinal follow-up study of children born to women with meticulously treated epilepsy during pregnancy, initiated in 1985. In total, 67 exposed and 66 unexposed children were tested with the Griffiths' test, which consists of 6 subsets: locomotor function, personal and social behaviour, hearing and speech, eye and hand coordination, performance, and practical reasoning. There was no significant difference in the global scores of the Griffiths' test between the two groups of children. Children exposed to phenytoin in utero (n = 16) showed a significant but subtle reduction in the scores for locomotor development compared with the unexposed children (mean scores: 98 vs 106: 95% confidence interval for the difference in mean scores: -14.0 to -0.4). There was no such difference for the children exposed to carbamazepine in utero (n = 35). The exposed children had significantly fewer siblings (p < 0.01). A significant number of the mothers with AED treatment had no higher level of education than compulsory school (p < 0.01). No other differences in socioeconomic status were observed between the groups. The subtle delay in locomotor development evaluated with the Griffiths' test at 4.5-5 y of age in children exposed to phenytoin may indicate a subtle influence on psychomotor development, which may be more obvious at school age: thus, larger studies and further follow-up are warranted.

Psychomotor development in preschool children exposed to antiepileptic drugs in utero

The aim of this study was to assess psychomotor development with the Griffiths' test in preschool children exposed to antiepileptic drags (AED) in utero. The study sample consisted of 76 children exposed to AED in utero and 71 unexposed children. The children (exposed and unexposed) have since birth been included in a population‐based longitudinal follow‐up study of children born to women with meticulously treated epilepsy during pregnancy, initiated in 1985. In total, 67 exposed and 66 unexposed children were tested with the Griffiths' test, which consists of 6 subsets: locomotor function, personal and social behaviour, hearing and speech, eye and hand coordination, performance, and practical reasoning. There was no significant difference in the global scores of the Griffiths' test between the two groups of children. Children exposed to phenytoin in utero (n= 16) showed a significant but subtle reduction in the scores for locomotor development compared with the unexposed children (mean scores: 98 vs 106; 95% confidence interval for the difference in mean scores: −14.0 to −0.4). There was no such difference for the children exposed to carbamazepine in utero (n= 35). The exposed children had significantly fewer siblings (p &lt; 0.01). A significant number of the mothers with AED treatment had no higher level of education than compulsory school (p &lt; 0.01). No other differences in socioeconomic status were observed between the groups. Conclusion: The subtle delay in locomotor development evaluated with the Griffiths' test at 4.5‐5 y of age in children exposed to phenytoin may indicate a subtle influence on psychomotor development, which may be more obvious at school age; thus, larger studies and further follow‐up are warranted.