This consensus position statement of the American Academy of Neurology, American Epilepsy Society, and Epilepsy Foundation of America updates prior 1994 and 2007 position statements on seizures, driver licensure, and medical reporting. Key consensus positions include the following: (1) in the United States, national driving standards promulgated through a system such as the Uniform Law Commission would reduce confusion and improve adherence with state driving standards; (2) state licensing criteria for medical conditions should be promulgated by regulations and guidelines based on enabling legislation rather than in statutes themselves and should be developed by medical advisory boards working in collaboration with departments of motor vehicles; (3) licensing criteria should be equitable, nondiscriminatory, objective, and compatible with comparable risks in other populations; (4) a minimum seizure-free interval of 3 months should ordinarily be required before driving in all cases and should be extended in individual cases based on review of favorable and unfavorable features by medical advisory boards; (5) individuals with exclusively provoked seizures attributable to provoking factors that are unlikely to reoccur in the future may not require a seizure-free interval before resuming driving; (6) individuals with previously well-controlled epilepsy who experience seizures due to short-term interruptions of antiseizure medications in the setting of hospitalization or practitioner-directed medication-titration may not require a seizure-free interval before driving once previously effective levels of antiseizure medications have been resumed; (7) patients and practitioners should pause driving during tapering and following discontinuation of an antiseizure medication if another such medication is not introduced; (8) individuals whose cognition or coordination is impaired due to medications used to prevent seizures should refrain from driving; (9) health care practitioners should be allowed but not mandated to report drivers who pose an elevated risk; but (10) neither a decision to report a patient suspected of being at elevated risk nor a decision declining to report a patient suspected of being at elevated risk should be subject to legal liability; (11) nations, states, and municipalities should provide alternative methods of transportation and accommodations for individuals whose driving privileges are restricted due to medical conditions.

Background and ObjectivesCisgender women with epilepsy (WWE) have distinct reproductive health needs. It is unknown to what extent WWE and their health care providers (HCPs) are aware of recent research advances regarding the reproductive health of WWE. This study aimed to survey US health care providers and WWE about their knowledge, attitudes, and decision-making pertaining to reproductive health; their awareness of key findings from recent relevant research; and whether learning of these findings would change their decision-making.MethodsA market research firm conducted an online survey of US health care providers and WWE using a proprietary nationally representative panel. Eligible HCPs included physicians and advance practice providers in neurology, obstetrics-gynecology, and primary care, who treat WWE. Eligible WWE were 18-45 years old and reported an epilepsy diagnosis and taking antiseizure medication. Data were analyzed through descriptive statistics and logistic regression.ResultsFour hundred one HCPs and 199 WWE completed the full survey. Among HCPs, 38% reported being very or extremely comfortable treating pregnant WWE. Seventy-nine percent of HCPs reported that recent relevant research findings were new to them, with 65% reporting that the findings seemed plausible and 49% reporting that the findings would probably or definitely change their management of pregnancy for WWE.Thirty percent of WWE reported that pregnancy is very or extremely safe for WWE, while 50% reported that it is somewhat safe, and 21% not at all or not very safe. Ninety-one percent of WWE reported that research findings were new to them, 37% reported that the findings seemed plausible, and 64% reported that the findings would probably or definitely influence their reproductive decision-making.ResultsFour hundred one HCPs and 199 WWE completed the full survey. Among HCPs, 38% reported being very or extremely comfortable treating pregnant WWE. Seventy-nine percent of HCPs reported that recent relevant research findings were new to them, with 65% reporting that the findings seemed plausible and 49% reporting that the findings would probably or definitely change their management of pregnancy for WWE.Thirty percent of WWE reported that pregnancy is very or extremely safe for WWE, while 50% reported that it is somewhat safe, and 21% not at all or not very safe. Ninety-one percent of WWE reported that research findings were new to them, 37% reported that the findings seemed plausible, and 64% reported that the findings would probably or definitely influence their reproductive decision-making.DiscussionSurvey findings suggest suboptimal awareness of recent research advances pertaining to the reproductive health of WWE among WWE and their HCPs. Findings also suggest that dissemination and implementation of such findings may be impactful on the medical decision-making of both HCPs and WWE. Findings may guide future initiatives to ensure prompt dissemination and implementation of research advances in epilepsy and reproductive health.

ImportanceAntiseizure medications (ASMs) are potential teratogens commonly prescribed for multiple indications. ASM fetal exposure can impair neurodevelopment. Folate improves pregnancy outcomes, but higher doses may pose risks.ObjectivesTo compare the outcomes of 6-year-old children of women with epilepsy (WWE) vs those of healthy women (HW), and assess the association of outcomes to third-trimester ASM exposures.Design, Setting, and ParticipantsAfter informed consent, pregnant WWE and HW were enrolled from 2012 through 2016 in this prospective, multicenter, nonrandomized clinical trial. Children were assessed at 6 years of age (2019-2022). Participants were recruited from 20 US epilepsy centers. Study data were analyzed from August 2023 to August 2024.ExposuresFetal ASM exposures.Main Outcomes and MeasuresThe a priori main neurodevelopmental outcome was the blindly assessed Verbal Index Score in 6-year-old children. The Verbal Index Score is calculated as the mean of the scores from the Word Definitions and Verbal Similarities subtests from the Differential Ability Scales, Expressive One-Word Picture Vocabulary Test, Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests from the Neuropsychological Assessment and Peabody Picture Vocabulary Test. The 2 primary analyses (1) compared children of WWE and HW using linear regression and (2) examined the outcomes of fetal exposure via ASM blood concentrations. Analyses were adjusted for multiple potential confounding factors. Other outcomes and folate exposure-related outcomes were assessed.ResultsA total of 1123 pregnant women were screened, and 456 were enrolled (426 did not meet criteria, and 241 chose not to participate). A total of 298 children of WWE (mean [SD] age, 6.4 [4.2] years; 158 female [53.0%]; 140 male [47.0%]) vs 89 children of HW (mean [SD] age, 6.4 [4.2] years; 41 female [46.1%]; 48 male [53.9%]) did not differ on Verbal Index Score (parameter estimate, −0.6; 95% CI, −3.2 to 1.9; P = .64). Exposure-dependent outcomes differed across ASMs. Assessment of other ASMs was limited because 232 of 298 WWE (78%) were taking lamotrigine or levetiracetam alone or in combination. Folate supplementation during the first 12 weeks of pregnancy had positive associations with cognition and behavior with no signal for risks at higher folate doses.Conclusions and RelevanceResults of this prospective nonrandomized clinical trial suggest that verbal abilities in children of WWE vs HW did not differ. Exposure-dependent outcomes of ASMs highlight the importance of dosing high enough to protect the mother and fetus from seizures but low enough to protect the fetus. Folate supplementation early in pregnancy including higher doses was associated with improved cognitive and behavioral outcomes. Additional research is needed for ASMs with inadequate information on fetal exposure risks.Trial RegistrationClinicalTrials.gov Identifier: NCT01730170

Compare sex steroid hormone (SSH) serum concentrations in pregnant women with epilepsy (PWWE) on enzyme-inducing (EI) antiseizure medications (ASMs) to PWWE on non-EIASMs or no ASM.

Background and Objectives:Cisgender women with epilepsy (WWE) have distinct reproductive health needs. It is unknown to what extent WWE and their health care providers (HCPs) are aware of recent research advances regarding the reproductive health of WWE. This study aimed to survey US health care providers and WWE about their knowledge, attitudes, and decision-making pertaining to reproductive health; their awareness of key findings from recent relevant research; and whether learning of these findings would change their decision-making. Methods:A market research firm conducted an online survey of US health care providers and WWE using a proprietary nationally representative panel. Eligible HCPs included physicians and advance practice providers in neurology, obstetrics-gynecology, and primary care, who treat WWE. Eligible WWE were 18-45 years old and reported an epilepsy diagnosis and taking antiseizure medication. Data were analyzed through descriptive statistics and logistic regression. Results:Four hundred one HCPs and 199 WWE completed the full survey. Among HCPs, 38% reported being very or extremely comfortable treating pregnant WWE. Seventy-nine percent of HCPs reported that recent relevant research findings were new to them, with 65% reporting that the findings seemed plausible and 49% reporting that the findings would probably or definitely change their management of pregnancy for WWE.Thirty percent of WWE reported that pregnancy is very or extremely safe for WWE, while 50% reported that it is somewhat safe, and 21% not at all or not very safe. Ninety-one percent of WWE reported that research findings were new to them, 37% reported that the findings seemed plausible, and 64% reported that the findings would probably or definitely influence their reproductive decision-making. Discussion:Survey findings suggest suboptimal awareness of recent research advances pertaining to the reproductive health of WWE among WWE and their HCPs. Findings also suggest that dissemination and implementation of such findings may be impactful on the medical decision-making of both HCPs and WWE. Findings may guide future initiatives to ensure prompt dissemination and implementation of research advances in epilepsy and reproductive health.

We created a simulation-based educational tool for adult neurology residents focused on work-up of first-of-lifetime seizure, diagnosis of epilepsy, and key components of treatment plans and counseling. Primary outcomes were six-month embedded learning and confidence in a subgroup of residents who had participated in the simulation compared to those who had not.

BACKGROUND AND OBJECTIVES:Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). METHODS:The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. RESULTS:The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. DISCUSSION:Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. TRIAL REGISTRATION INFORMATION:The study is registered at ClinicalTrials.gov as NCT01730170.

There is a reciprocal relationship between epilepsy and reproductive endocrine disorders. Seizures and anti-seizure medications (ASMs) can contribute to reproductive and endocrine dysfunction and reproductive dysfunction may exacerbate seizures. Epilepsy via neuroendocrine mechanisms affects the hypothalamic-pituitary-ovarian (HPO) axis, disrupting the regulation of gonadotropin secretion, and resulting in dystrophic effects on the ovaries and early menopause. Anti-seizure medications have endocrine-related side effects on sexual function and bone health. Long-term use of ASMs may result in menstrual irregularities, sexual dysfunction, anovulatory cycles, polycystic ovaries, and reduced fertility. Some ASMs also interfere with bone metabolism. Epilepsy patients treated with ASMs are at risk for bone loss and fractures. This article explores the endocrine and hormonal effects of seizures and ASMs.

Importance:The association of fetal exposure to antiseizure medications (ASMs) with outcomes in childhood are not well delineated. Objective:To examine the association of fetal ASM exposure with subsequent adaptive, behavioral or emotional, and neurodevelopmental disorder outcomes at 2, 3, and 4.5 years of age. Design, Setting, and Participants:The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational cohort study conducted at 20 epilepsy centers in the US. A total of 456 pregnant women with epilepsy or without epilepsy were enrolled from December 19, 2012, to January 13, 2016. Children of enrolled women were followed up with formal assessments at 2, 3, 4.5, and 6 years of age. Statistical analysis took place from August 2022 to May 2023. Exposures:Exposures included mother's epilepsy status as well as mother's ASM blood concentration in the third trimester (for children of women with epilepsy). Women with epilepsy were enrolled regardless of ASM regimen. Main Outcomes and Measures:The primary outcome was the Adaptive Behavior Assessment System, Third Edition (ABAS-3) General Adaptive Composite (GAC) score among children at 4.5 years of age. Children of women with epilepsy and children of women without epilepsy were compared, and the associations of ASM exposures with outcomes among exposed children were assessed. Secondary outcomes involved similar analyses of other related measures. Results:Primary analysis included 302 children of women with epilepsy (143 boys [47.4%]) and 84 children of women without epilepsy (45 boys [53.6%]). Overall adaptive functioning (ABAS-3 GAC score at 4.5 years) did not significantly differ between children of women with epilepsy and children of women without epilepsy (parameter estimate [PE], 0.4 [95% CI, -2.5 to 3.4]; P = .77). However, in adjusted analyses, a significant decrease in functioning was seen with increasing third-trimester maximum ASM blood concentrations (PE, -7.8 [95% CI, -12.6 to -3.1]; P = .001). This decrease in functioning was evident for levetiracetam (PE, -18.9 [95% CI, -26.8 to -10.9]; P < .001) and lamotrigine (PE, -12.0 [95% CI, -23.7 to -0.3]; P = .04), the ASMs with sample sizes large enough for analysis. Results were similar with third-trimester maximum daily dose. Conclusions and Relevance:This study suggests that adaptive functioning of children of women with epilepsy taking commonly used ASMs did not significantly differ from that of children of women without epilepsy, but there was an exposure-dependent association of ASMs with functioning. Thus, psychiatric or psychological screening and referral of women with epilepsy and their offspring are recommended when appropriate. Additional research is needed to confirm these findings.

Importance Antiseizure medications (ASMs) are potential teratogens commonly prescribed for multiple indications. ASM fetal exposure can impair neurodevelopment. Folate improves pregnancy outcomes, but higher doses may pose risks. Objectives To compare the outcomes of 6-year-old children of women with epilepsy (WWE) vs those of healthy women (HW), and assess the association of outcomes to third-trimester ASM exposures. Design, Setting, and Participants After informed consent, pregnant WWE and HW were enrolled from 2012 through 2016 in this prospective, multicenter, nonrandomized clinical trial. Children were assessed at 6 years of age (2019-2022). Participants were recruited from 20 US epilepsy centers. Study data were analyzed from August 2023 to August 2024. Exposures Fetal ASM exposures. Main Outcomes and Measures The a priori main neurodevelopmental outcome was the blindly assessed Verbal Index Score in 6-year-old children. The Verbal Index Score is calculated as the mean of the scores from the Word Definitions and Verbal Similarities subtests from the Differential Ability Scales, Expressive One-Word Picture Vocabulary Test, Phonological Processing, Comprehension of Instructions, and Sentence Repetition subtests from the Neuropsychological Assessment and Peabody Picture Vocabulary Test. The 2 primary analyses (1) compared children of WWE and HW using linear regression and (2) examined the outcomes of fetal exposure via ASM blood concentrations. Analyses were adjusted for multiple potential confounding factors. Other outcomes and folate exposure-related outcomes were assessed. Results A total of 1123 pregnant women were screened, and 456 were enrolled (426 did not meet criteria, and 241 chose not to participate). A total of 298 children of WWE (mean [SD] age, 6.4 [4.2] years; 158 female [53.0%]; 140 male [47.0%]) vs 89 children of HW (mean [SD] age, 6.4 [4.2] years; 41 female [46.1%]; 48 male [53.9%]) did not differ on Verbal Index Score (parameter estimate, -0.6; 95% CI, -3.2 to 1.9; P = .64). Exposure-dependent outcomes differed across ASMs. Assessment of other ASMs was limited because 232 of 298 WWE (78%) were taking lamotrigine or levetiracetam alone or in combination. Folate supplementation during the first 12 weeks of pregnancy had positive associations with cognition and behavior with no signal for risks at higher folate doses. Conclusions and Relevance Results of this prospective nonrandomized clinical trial suggest that verbal abilities in children of WWE vs HW did not differ. Exposure-dependent outcomes of ASMs highlight the importance of dosing high enough to protect the mother and fetus from seizures but low enough to protect the fetus. Folate supplementation early in pregnancy including higher doses was associated with improved cognitive and behavioral outcomes. Additional research is needed for ASMs with inadequate information on fetal exposure risks. Trial Registration ClinicalTrials.gov Identifier: NCT01730170

Background The neurodevelopmental effects of fetal exposure to most antiseizure medications are unclear. We aimed to investigate the effects of fetal exposure to commonly used antiseizure medications on neuropsychological outcomes at age 3 years. Methods The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. We have investigated pregnancy outcomes in women (aged 14-45 years) with and without epilepsy who were enrolled during pregnancy (<= 20 weeks' gestational age), and their children. The primary outcome for children at age 3 years was a blindly assessed Verbal Index score, which was calculated by averaging scores on the Naming Vocabulary and Verbal Comprehension subtests of Differential Ability Scales-II, Expressive Communication and Auditory Comprehension subscales of Preschool Language Scale-5, and Peabody Picture Vocabulary Test-4. Children of women with and without epilepsy were compared, and the associations of medication exposures to outcomes in exposed children were assessed. The MONEAD study is registered with ClinicalTrials.gov, NCT0730170, and is ongoing. Findings Between Dec 19, 2012, and Jan 13, 2016, 456 pregnant women (351 with epilepsy and 105 without epilepsy) were enrolled into the study. 345 children were born to women with epilepsy and 106 children were born to women without epilepsy. Verbal Index scores at age 3 years did not differ for children of women with epilepsy (n=284; adjusted least-square mean 102 center dot 7, 95% CI 101 center dot 4 to 103 center dot 9) versus those without epilepsy (n=87; 102 center dot 3, 99 center dot 8 to 104 center dot 7). Significant risk factors for reduced Verbal Index scores included maternal intelligence quotient, maternal education, post-birth anxiety, gestational age at enrolment, child's sex, and child's ethnicity. For Verbal Index scores, antiseizure medication exposure effects were not seen for maximum third trimester blood concentrations (n=258; adjusted parameter estimate -2 center dot 9, 95% CI -6 center dot 7 to 1 center dot 0). However, in secondary analyses, exposure-dependent effects were present on multiple cognitive measures, which varied by medication. Interpretation We found no difference in neurodevelopmental outcomes between children with fetal exposure to newer antiseizure medications compared with unexposed children. However, some exposure-dependent antiseizure medication effects were seen in secondary analyses. The adverse effects of maternal post-birth anxiety emphasise the importance of screening mothers during pregnancy and postpartum and implementing interventions. Additional studies are needed to clarify the exposure-dependent effects. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke, and National Institute of Child Health and Development. Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Background and ObjectivesBreastfeeding has important health benefits for both mother and child. We characterize breastfeeding initiation and duration in mothers with epilepsy relative to control mothers in a large prospective cohort.MethodsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a prospective, multicenter observational, US cohort study. Pregnant individuals with and without epilepsy, aged 14-45 years, were enrolled between December 19, 2012, and February 11, 2016. Exclusion criteria included intelligence quotient (IQ) <70, and gestational age >20 weeks at enrollment. Breastfeeding was assessed through electronic diary and at study visits until 2 years postpartum. Odds of initiating breastfeeding was compared between cohorts using unadjusted and adjusted logistic regression models. Duration of breastfeeding was compared between cohorts using the log-rank test.ResultsThree hundred fifty-one pregnant individuals with epilepsy and 105 pregnant controls were enrolled. Breastfeeding data were available for 325 mothers with epilepsy and 98 controls. Study cohorts were similar demographically except race (p = 0.008); 84.9% of mothers with epilepsy and 71.4% of controls were White. The mean IQ was lower in mothers with epilepsy compared with that in controls (97.7 vs 104.2, p < 0.001). Breastfeeding was initiated by 74.8% mothers with epilepsy and 88.8% controls; this difference was significant in unadjusted logistic regression (odds ratio [OR] 0.4 [95% CI 0.2, 0.7], p = 0.004), but not in adjusted model (OR 0.5 [95% CI 0.2, 1.0], p = 0.051). Factors associated with breastfeeding were higher maternal education and IQ. There was no difference in duration of breastfeeding between mothers with and without epilepsy (median duration 8.5 months vs 9.9 months, p = 0.793). Among mothers with epilepsy, both convulsive seizures and all seizures that impair awareness during pregnancy were associated with lower breastfeeding initiation (OR 0.4 [95% CI 0.2, 0.8], p = 0.013) and (OR 0.4 [95% CI 0.2, 0.8], p = 0.003, respectively). Any peripartum seizures were associated with shorter breastfeeding duration (median 6 months vs 9.7 months, [p = 0.040]).DiscussionMothers with epilepsy were less likely to initiate breastfeeding compared with controls; however, this difference was not significant when controlling for maternal IQ and education level. Continuation of breastfeeding once initiated was not different between mothers with and without epilepsy. Seizure control was associated with breastfeeding initiation and duration in mothers with epilepsy.

On June 24, 2022, Dobbs vs Jackson Women's Health Organization was decided by the Supreme Court effectively overturning the former precedent of Roe v. Wade. This ruling has direct consequences for the care of persons with epilepsy of childbearing potential. Now more than ever we need to provide informed and comprehensive care to our patients with epilepsy who are particularly vulnerable to the impact of this legislation on their reproductive decision-making. Important areas to understand include (1) the current state of affairs on abortion in the United States; (2) contraception options, their effectiveness, and interactions with anti-seizure medications (ASM); (3) teratogenic effects and adverse neurocognitive outcomes of ASMs; (4) folic acid supplementation; (5) the effect on perinatal and pediatric care; and (6) unique issues related to people of color.

Objective: To understand the experiences and attitudes of persons with epilepsy of gestational capacity (PWEGC) regarding pregnancy and breastfeeding. Background: NA Design/Methods: A market research firm recruited PWEGC ages 18–45 years old currently taking an antiseizure medication (ASM) from a nationally representative panel to complete a survey. Respondent groups were compared by chi-square analysis. Results: Of 199 respondents, 62 recently had a child, 30 were pregnant, 91 were considering pregnancy, and 16 decided not to have a child. Over two-thirds of respondents believe that pregnancy is at least somewhat safe for PWEGC. A higher proportion of respondents who recently had a child or are pregnant/considering pregnancy believe that pregnancy planning is important compared to those who decided not to have a child (p<0.05). The most prevalent concerns cited by participants who were currently pregnant/considering pregnancy were prenatal exposure to ASMs (50%) and pregnancy impacting seizure control (50%). The most prevalent concern of participants who recently had a child was heritability of epilepsy (58%). Seventy-five percent of participants who recently had a child, or who are pregnant/considering pregnancy, report that reassurance from their physician is the leading factor in deciding to have a child. Forty-eight percent of these respondents were prescribed a different ASM once considering pregnancy, with adjustments <3 months for most. Among participants who chose to breastfeed, 53% were told by physicians that breastfeeding is safe while taking ASMs. Among participants who chose not to breastfeed, 61% had concerns about transmission of ASMs to the baby and 21% reported that they were told by physicians not to breastfeed because of their ASMs. Conclusions: Findings illuminate concerns of PWEGC regarding reproductive health and highlight the provider's important role in shared decision-making. Results may inform best practices for providers counseling and educational initiatives for patients and providers. Disclosure: The institution of Dr. Kirkpatrick has received research support from American Academy of Neurology. The institution of Dr. Kirkpatrick has received research support from Academic Pediatric Association. The institution of Dr. Kirkpatrick has received research support from American Academy of Pediatrics. The institution of Dr. Kirkpatrick has received research support from Society of Family Planning. The institution of Dr. Kirkpatrick has received research support from North American Society for Pediatric and Adolescent Gynecology. Dr. Gerard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Pharmaceuticals. The institution of Dr. Gerard has received research support from NIH/NINDS. The institution of Dr. Gerard has received research support from Xenon Pharmaceuticals. The institution of an immediate family member of Dr. Gerard has received research support from NIH. The institution of an immediate family member of Dr. Gerard has received research support from Novo Nordisk. The institution of Dr. Gerard has received research support from Eisai, Inc. (via Stanford University). The institution of Dr. Voinescu has received research support from NIH. Dr. Voinescu has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Neurodiem. Dr. Voinescu has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Physicians' Education Resouce. Dr. Voinescu has received personal compensation in the range of $500-$4,999 for serving as a Speaker with American Epilepsy Society. Dr. Voinescu has a non-compensated relationship as a Board Member and Chair with My Epilepsy Story that is relevant to AAN interests or activities. Dr. Voinescu has a non-compensated relationship as a Speaker with Epilepsy Foundation that is relevant to AAN interests or activities. Dr. Voinescu has a non-compensated relationship as a Grant Reviewer with Epilepsy Ireland that is relevant to AAN interests or activities. Dr. Voinescu has a non-compensated relationship as a Grant Reviewer with American Epilepsy Society that is relevant to AAN interests or activities. Dr. Voinescu has a non-compensated relationship as a Member of Scientific Advisory Committee with North American AED Pregnancy Registry that is relevant to AAN interests or activities. An immediate family member of Dr. Pack has received personal compensation for serving as an employee of REGENEXBIO. The institution of Dr. Pack has received research support from National Institutes of Health. Dr. Pack has received publishing royalties from a publication relating to health care. Dr. Li has nothing to disclose. Ms. Kemp has nothing to disclose. Dr. Pennell has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for American Epilepsy Society. The institution of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Department of Defense. The institution of an immediate family member of Dr. Pennell has received research support from Environmental Protection Agency. The institution of an immediate family member of Dr. Pennell has received research support from NIH. The institution of an immediate family member of Dr. Pennell has received research support from Advanced Energy Consortium. Dr. Pennell has received publishing royalties from a publication relating to health care.

During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences.To characterize pregnancy-associated concentration changes for several antiseizure medications among women with epilepsy.Enrollment in this prospective, observational cohort study, Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), occurred from December 19, 2012, to February 11, 2016, at 20 US sites. Enrolled cohorts included pregnant women with epilepsy and nonpregnant control participants with epilepsy. Inclusion criteria were women aged 14 to 45 years, an intelligence quotient greater than 70 points, and, for the cohort of pregnant women, a fetal gestational age younger than 20 weeks. A total of 1087 women were assessed for eligibility; 397 were excluded and 230 declined. Data were analyzed from May 1, 2014, to June 30, 2021.Medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications. The cohort of pregnant women was monitored through 9 months post partum, with similar time points for control participants.Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Phlebotomy was performed during 4 pregnancy study visits and 3 postpartum visits for the pregnant women and 7 visits over 18 months for control participants. The primary hypothesis was to test pregnancy changes of dose-normalized concentrations from nonpregnant postpartum samples compared with those of control participants.Of the 351 pregnant women and 109 control participants enrolled in MONEAD, 326 pregnant women (median [range] age, 29 [19-43] years) and 104 control participants (median [range] age, 29 [16-43] years) met eligibility criteria for this analysis. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine (15.60 μg/L/mg to 6.85 μg/L/mg; P < .001), 36.8% for levetiracetam (11.33 μg/L/mg to 7.16 μg/L/mg; P < .001), 17.3% for carbamazepine (11.56 μg/L/mg to 7.97 μg/L/mg; P = .03), 32.6% for oxcarbazepine (11.55 μg/L/mg to 7.79 μg/L/mg; P < .001), 30.6% for unbound oxcarbazepine (6.15 μg/L/mg to 4.27 μg/L/mg; P < .001), 39.9% for lacosamide (26.14 μg/L/mg to 15.71 μg/L/mg; P < .001), and 29.8% for zonisamide (40.12 μg/L/mg to 28.15 μg/L/mg; P < .001). No significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 μg/L/mg to 13.77 μg/L/mg; P = .18). Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) μg/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) μg/L/mg (P = .01); lacosamide, -0.23 (0.07) μg/L/mg (P < .001); lamotrigine, -0.20 (0.02) μg/L/mg (P < .001); levetiracetam, -0.06 (0.03) μg/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) μg/L/mg (P < .001); oxcarbazepine unbound, -0.11 (0.03) μg/L/mg (P < .001); and zonisamide, -0.53 (0.14) μg/L/mg (P < .001) except for topiramate (-0.35 [0.20] μg/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] μg/L/mg).Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy.

Objective To determine which antiepileptic drugs pregnant women receive by trimester. Methods This retrospective cohort study using the IBM Watson Health MarketScan Research Databases evaluated which antiepileptic drugs pregnant women with epilepsy received by trimester. Women with aged 15-54 years with a history of seizure disorder who underwent a delivery hospitalization between 2008 and 2017 were included in the analysis. Descriptive statistics were performed. Results Of 34,144 women with a seizure disorder diagnosis and a delivery hospitalization, 10,289 (30.1%) received an anti-epileptic medication during pregnancy of which more than half received lamotrigine or levetiracetam. Other antiepileptic medications used by >5% of the population during any one trimester in the study period included carbamazepine, clonazepam, and topiramate. In evaluating medication use in the 1st trimester versus the 2nd trimester, clonazepam use decreased 32.0% (95% CI 60.0%, 77.0%) from 5.6% to 3.8% of patients receiving antiepileptics from the 1st to the 2nd trimester, gabapentin deceased 22.1% (95% CI 0.68%, 0.90%) from 4.1% to 3.2%, and topiramate decreased 30.0% (95% CI 62.8%, 77.9%) from 7.2% to 5.1%. In comparison, levetiracetam increased from 22.5% to 33.3% between the 1st and 3rd trimester and lamotrigine 22.2% to 27.5% between the 1st and 3rd trimester, 48.3% and 24.0% increases respectively. Conclusion Antiepileptic drugs with less favorable fetal risk profiles such as topiramate decreased by trimester while medications with more favorable fetal risk profiles such as lamotrigine and levetiracetam increased. These findings broadly support that there are opportunities to improve pre-conceptional counseling of women with epilepsy.

Objective Prior research demonstrated large increased risk for maternal mortality among women with epilepsy. The objective of this study was to estimate risk for adverse maternal outcomes during delivery hospitalizations among women with epilepsy. Methods Truven Health MarketScan databases were used to compare risk for adverse maternal outcomes during delivery hospitalizations based upon whether there was diagnosis of epilepsy and receipt of anti-epileptic drugs prior to delivery. Outcomes included: (i) death during delivery hospitalization, (ii) severe maternal morbidity, (iii) cesarean delivery, (iv) postpartum hemorrhage, (v) placental abruption, (vi) preeclampsia, (vii) preterm delivery, (viii) premature rupture of membranes, and (ix) stillbirth. Adjusted models including hospital and demographic factors were performed with adjusted risk ratios (aRR) with 95% CIs as measures of effect. Results Women with epilepsy prior to delivery who received antiepileptic drugs (n = 6019) during pregnancy were not at increased risk for mortality with no deaths occurring in this group (p = .27). Risk for severe maternal morbidity in this group was approximately double (aRR 2.16, 95% CI 1.86-2.51) with risks for other outcomes including placental abruption (aRR 1.29, 95% CI 1.04-1.60), cesarean delivery (aRR 1.14, 95% CI 1.10-1.18), and preterm delivery (aRR 1.25, 95% CI 1.15-1.35) slightly increased compared to women without seizures. Conclusion No significant difference in mortality risk was found for women with epilepsy. Increased risk for other adverse maternal outcomes for women with epilepsy on antiepileptics was modest.

ImportanceThe neurodevelopmental risks of fetal exposure are uncertain for many antiseizure medications (ASMs).ObjectiveTo compare children at 2 years of age who were born to women with epilepsy (WWE) vs healthy women and assess the association of maximum ASM exposure in the third trimester and subsequent cognitive abilities among children of WWE.Design, Setting, and ParticipantsThe Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicenter investigation of pregnancy outcomes that enrolled women from December 19, 2012, to January 13, 2016, at 20 US epilepsy centers. Children are followed up from birth to 6 years of age, with assessment at 2 years of age for this study. Of 1123 pregnant women assessed, 456 were enrolled; 426 did not meet criteria, and 241 chose not to participate. Data were analyzed from February 20 to December 4, 2020.Main Outcomes and MeasuresLanguage domain score according to the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), which incorporates 5 domain scores (language, motor, cognitive, social-emotional, and general adaptive), and association between BSID-III language domain and ASM blood levels in the third trimester in children of WWE. Analyses were adjusted for multiple potential confounding factors, and measures of ASM exposure were assessed.ResultsThe BSID-III assessments were analyzed in 292 children of WWE (median age, 2.1 [range, 1.9-2.5] years; 155 female [53.1%] and 137 male [46.9%]) and 90 children of healthy women (median age, 2.1 [range, 2.0-2.4] years; 43 female [47.8%] and 47 male [52.2%]). No differences were found between groups on the primary outcome of language domain (-0.5; 95% CI, -4.1 to 3.2). None of the other 4 BSID-III domains differed between children of WWE vs healthy women. Most WWE were taking lamotrigine and/or levetiracetam. Exposure to ASMs in children of WWE showed no association with the language domain. However, secondary analyses revealed that higher maximum observed ASM levels in the third trimester were associated with lower BSID-III scores for the motor domain (-5.6; 95% CI, -10.7 to -0.5), and higher maximum ASM doses in the third trimester were associated with lower scores in the general adaptive domain (-1.4; 95% CI, -2.8 to -0.05).Conclusions and RelevanceOutcomes of children at 2 years of age did not differ between children of WWE taking ASMs and children of healthy women.Trial RegistrationClinicalTrials.gov Identifier: NCT01730170.