Dataset Information

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

ABSTRACT:

Background

Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment.

Objectives

To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy.

Methods

We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits.

Results

We included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5-8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34).

Conclusions

In this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.

SUBMITTER: Nilsen Husebye ES

PROVIDER: S-EPMC10375495 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Nilsen Husebye Elisabeth Synnøve ES Romanowska Julia J Bjørke-Monsen Anne-Lise AL Gilhus Nils Erik NE Selmer Kaja K Gervin Kristina K Riedel Bettina B Bjørk Marte Helene MH

The American journal of clinical nutrition 20230520 1

<h4>Background</h4>Prenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment.<h4>Objectives</h4>To examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy.<h4>Methods</h4>We included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, ...[more]

PMID: 37217097

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Project description:ObjectiveTo gather real-world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug-resistant focal epilepsy.MethodsMedical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes.ResultsStudy cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first-encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study-confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first-year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure-free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug-resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure-free were 21.32 and 3.65, respectively. Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment.SignificanceOverall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug-resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.

Project description:ObjectiveThis study was undertaken to characterize antiseizure medication (ASM) treatment pathways in Medicare beneficiaries with newly treated epilepsy.MethodsThis was a retrospective cohort study using Medicare claims. Medicare is the United States' federal health insurance program for people aged 65 years and older plus younger people with disabilities or end-stage renal disease. We included beneficiaries with newly treated epilepsy (International Classification of Diseases codes for epilepsy/convulsions 2014-2017, no ASM in the previous 2 years). We displayed the sequence of ASM fills using sunburst plots overall, then stratified by mood disorder, age, and neurologist prescriber. We tabulated drug costs for each pathway.ResultsWe included 21 458 beneficiaries. Levetiracetam comprised the greatest number of pill days (56%), followed by gabapentin (11%) and valproate (8%). There were 22 288 unique treatment pathways. The most common pathways were levetiracetam monotherapy (43%), gabapentin monotherapy (10%), and valproate monotherapy (5%). Gabapentin was the most common second- and third-line ASM. Whereas only 2% of pathways involved first-line lacosamide, those pathways accounted for 19% of cost. Gabapentin and valproate use was increased and levetiracetam use was decreased in beneficiaries with mood disorders compared to beneficiaries without mood disorders. Levetiracetam use was increased and gabapentin, valproate, lamotrigine, and topiramate use was decreased in beneficiaries aged >65 years compared with those aged 65 years or less. Lamotrigine, levetiracetam, and lacosamide use was increased and gabapentin use was decreased in beneficiaries whose initial prescriber was a neurologist compared to those whose prescriber was not a neurologist.SignificanceLevetiracetam monotherapy was the most common pathway, although substantial heterogeneity existed. Lacosamide accounted for a small percentage of ASMs but a disproportionately large share of cost. Neurologists were more likely to prescribe lamotrigine compared with nonneurologists, and lamotrigine was prescribed far less frequently than may be endorsed by guidelines. Future work may explore patient- and physician-driven factors underlying ASM choices.

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Project description:ObjectivesThe network mechanism underlying the initial response to antiseizure medication in epilepsy has not been revealed yet. Given the central role of the thalamus in the brain network, we conducted a case-control study to investigate the association between thalamic connectivity and medication response.MethodsWe recruited 39 patients with newly diagnosed and medication-naïve epilepsy of genetic or unknown etiology, including 26 with a good response (GR group) and 13 with a poor response (PR group), and 26 matched healthy participants (control group). We measured the gray matter density (GMD) and the amplitude of low-frequency fluctuation (ALFF) of bilateral thalami. We then set each thalamus as the seed region of interest (ROI) to calculate voxel-wise functional connectivity (FC) and assessed ROI-wise effective connectivity (EC) between the thalamus and targeted regions.ResultsWe found no significant difference between groups in the GMD or ALFF of bilateral thalami. However, we observed that the FC values of several circuits connecting the left thalamus and the cortical areas, including the bilateral Rolandic operculum, the left insula, the left postcentral gyrus, the left supramarginal gyrus, and the left superior temporal gyrus, differed among groups (False Discovery Rate correction, P < 0.05), with a higher value in the PR group than in the GR group and/or the control group (Bonferroni correction, P < 0.05). Similarly, both the outflow and the inflow EC in each thalamocortical circuit were higher in the PR group than in the GR group and the control group, although these differences did not remain statistically significant after applying the Bonferroni correction (P < 0.05). The FC showed a positive correlation with the corresponding outflow and inflow ECs for each circuit.ConclusionOur finding suggested that patients with stronger thalamocortical connectivity, potentially driven by both thalamic outflowing and inflowing information, may be more likely to respond poorly to initial antiseizure medication.

Project description:BackgroundComplaints of fatigue and poor sleep quality are common in patients with epilepsy. Fatigue may precipitate seizures, and patients with poor sleep quality have higher frequency of seizures and are more likely to have symptoms of depression.ObjectivesThis study aims to determine the association of baseline fatigue and sleep quality with antiseizure medication (ASM) resistance in patients with newly diagnosed epilepsy (PWNDE). We also evaluate whether the association is mediated by depression symptoms.MethodsWe performed a prospective cohort study of PWNDE at comprehensive epilepsy center in Northeast China between June 2020 and May 2024. Fatigue, sleep quality, and depression symptoms were assessed at baseline. All patients were followed for 24 months for ASM-resistant epilepsy. Cox proportional hazard regression models were used to estimate the hazard ratios (HRs) of ASM resistance. Models fitted with restricted cubic spline were performed to test for linear and nonlinear shapes of each association. Mediation analysis was used to estimate the mediating effects of depression severity on association between fatigue, sleep quality, and ASM resistance.ResultsA total of 189 patients (59 ASM-resistant cases and 130 ASM-responsive controls) were included in the final analysis. Baseline fatigue (HR, 1.98; 95% confidence interval (CI), 1.094-3.583, p = 0.024) and poor sleep quality (HR, 2.193; 95% CI, 1.29-3.729, p = 0.004) were associated with an increased hazard of ASM resistance in PWNDE after full adjustments. There exists a nonlinear association between Fatigue Severity Scale score and the hazard of ASM resistance (P for nonlinear = 0.012). Depression severity partly mediated the effect of fatigue and sleep quality on ASM resistance, with mediated proportions of 18.5% for the fatigue and 23.7% for the sleep quality.ConclusionBaseline fatigue and poor sleep quality were associated with an increased risk of ASM resistance. The association between fatigue, sleep quality, and ASM resistance were partly mediated by depression severity. These findings emphasize that patients with ASM-resistant epilepsy are more likely to have fatigue, depression, and poor sleep quality at baseline and this may be unrelated to ASM intake.

Dataset Information

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Background

Objectives

Methods

Results

Conclusions

Publications

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

Similar Datasets

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