Seizures In Pregnancy Research Articles

Epilepsy or Eclampsia in Differential Diagnosis of Recurrent Seizures in Pregnancy Aisyiyah Bojonegoro Hospital: A Diagnostic Dilemma? A Case Report

Seizures in pregnancy can lead to adverse maternal and perinatal outcomes, often arising from various factors necessitating clear diagnosis for effective therapy. Concurrent occurrence of multiple causative factors can complicate diagnostic and therapeutic decisions. We present a case of a 32-week pregnant woman with poorly managed epilepsy who experienced eclampsia and recurrent seizures. Treatment involved multiple medications and emergency cesarean delivery with meticulous blood pressure control. Close monitoring and therapy adjustment were crucial. Managing seizures in such cases poses a dilemma, necessitating initial focus on airway, breathing, and circulation stabilization. Immediate delivery of a viable fetus and maternal health maintenance are paramount. Anesthetic goals encompass seizure and blood pressure control, hemodynamic stability, and intensive care support for potential complications. While eclampsia is a significant factor, seizures in pregnancy may arise from diverse causes, demanding early diagnosis and tailored treatment for optimal patient outcomes.

Neuroimaging Features in Eclamptic Encephalopathy and their Correlation with Clinical and Laboratory Parameters: a Prospective Observational Study.

New onset seizures in pregnancy and postpartum are considered eclampsia as the default diagnosis. Other causes, such as intracranial haemorrhage, subarachnoid haemorrhage, cerebral venous sinus thrombosis or acute ischaemic stroke, have a similar mode of presentation, but need prompt diagnosis and institution of specific measures to decrease the risk of mortality and morbidity. Neuroimaging plays an important role in providing a specific diagnosis and hence aids in proper management. We hypothesised to find any correlation of laboratory parameters with neuroimaging abnormalities along with providing an insight to specific diagnoses in patients of new onset seizures in pregnancy with a presumptive diagnosis of eclampsia. This was a hospital-based descriptive observational study conducted in SCB Medical College, Odisha, in the year 2018-2020 with a total of 70 clinically confirmed cases of eclampsia. They were subjected to cranial MR imaging along with routine investigations with no change in the emergency treatment protocol followed in the department. Data was compiled using Microsoft Excel 2016 and IBM SPSS statistics for Windows, version 27, and comparisons among MRI normal and abnormal group were stated. 58 (82.86%) were MR imaging positive or abnormal, while 12 (17.14%) were MR imaging negative or normal. Cortical venous thrombosis without infarction was diagnosed in 25 (43.1%) patients, 6 (10.34%) had infarction, posterior reversible encephalopathy syndrome was seen in 19 (32.76%) cases, and 8 (13.79%) had hypertensive leukoencephalopathy. The mean gestational age at the time of presentation was significantly lower in the MRI abnormal group (p = 0.012). The AST and LDH values were found to be significantly higher in the MRI abnormal group, with p = 0.02 and 0.01, respectively. Patients with imaging abnormalities have a severe form of disease in eclampsia. Neuroimaging in provisionally diagnosed cases of eclampsia will modify the management and hence prognosis in these patients.

Electronic field protocols for prehospital care quality improvement in Lithuania: a randomized simulation-based study

BackgroundPrehospital emergency care is complex and influenced by various factors, leading to the need for decision-support tools. Studies suggest that cognitive aids improve provider performance and patient outcomes in clinical emergencies. Electronic cognitive aids have rarely been investigated in prehospital care. Therefore, this study aimed to evaluate the effects of the electronic field protocol (eFP) module on performance, adherence to the standard of care, and satisfaction of prehospital care providers in a simulated environment.MethodsThis randomised simulation-based study was conducted at the Lithuanian University of Health Sciences in Kaunas, Lithuania. The simulation scenarios were developed to test 12 eFPs: adult resuscitation, pediatric resuscitation, delivery and postpartum care, seizures in pregnancy, stroke, anaphylaxis, acute chest pain, acute abdominal pain, respiratory distress in children, severe trauma, severe infection and sepsis, and initial neonatal evaluation and resuscitation. Sixteen prehospital practitioners with at least 3 years of clinical experience were randomly assigned to either use the eFP module or perform without it in each of the 12 simulated scenarios. Participant scores and adherence to standardised checklists were compared between the two performance modes. Participant satisfaction was measured through a post-simulation survey.ResultsA total of 190 simulation sessions were conducted. Compared to the use of memory alone, the use of the eFP module significantly improved participants’ performance in 10 out of the 12 simulation scenarios. Adherence to the standardised checklist increased from 60 to 85% (p < 0.001). Post-simulation survey results indicate that participants found the eFP module easy to use and relevant to prehospital clinical practice.ConclusionsThe study findings suggest that the eFP module as a cognitive aid can enhance prehospital practitioners’ performance and adherence to the standard of care in simulated scenarios. These results highlight the potential of standardised eFPs as a quality improvement step in prehospital care in Lithuania.

Increased hippocampal cannabinoid 1 receptor expression is associated with protection from severe seizures in pregnant mice with reduced uterine perfusion pressure.

Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a hypertensive pregnancy disorder. The mechanisms contributing to increased risk of seizures in preeclampsia are not fully known. One mechanism could be abnormal endocannabinoid system (ECS) activity and impaired neuromodulation. Indeed, increased placental cannabinoid receptor 1 (CB1R) expression and reduced serum anandamide, a CB1R ligand, have been reported in preeclampsia patients. We hypothesized that reduced uterine perfusion pressure (RUPP), used to mimic preeclampsia, leads to changes in hippocampal CB1R expression, and that manipulating CB1R activity will change seizure severity in RUPP mice. Pregnant mice underwent sham or RUPP surgery on gestational day (GD)13.5. On GD18.5, mice received: no drug treatment, pentylenetetrazol (PTZ, 40 mg/kg), Rimonabant (10 mg/kg) + PTZ, or 2-AG (1 mg/kg) + PTZ. Behaviors were video recorded (15 min for Rimonabant and 2-AG, followed by 30 min for PTZ), and the hippocampus was harvested. The expression of CB1R and ECS proteins was measured in hippocampal homogenates, synaptosomes, and cytosol. Hippocampal CB1R increased in homogenates and cytosolic fraction, and was unchanged in synaptosomes of RUPP mice. Increased CB1R colocalization on glutamate-releasing neurons within hippocampal CA1 was observed in RUPP mice. Rimonabant modestly increased seizure scores over time in RUPP mice. PTZ after rimonabant pretreatment increased seizure scores and duration, while reducing latency in sham mice, with little to no change in RUPP mice. Furthermore, RUPP mice had lower seizure scores over time than sham following CB1R blockade and activation. These data suggest that RUPP modifies CB1R activity prior to seizure induction, which protects mice from worse seizure outcomes.

Managing Antiseizure Medications in Pregnancy: Is Earlier and More Frequent Monitoring Better?

Medication management in pregnant women with epilepsy (PWWE) poses challenges, and understanding the effects of metabolic changes on antiseizure medications (ASMs) is important in planning care for PWWE. The possible teratogenic effects and risks of poorly controlled seizures have to be weighed. There are data in the literature on clinical management of ASMs including the effects of drug levels on seizures and factors that predict seizure frequency, but timing and frequency of monitoring and dose adjustment paradigms have not been well studied. This retrospective study was approved by the Institutional Review Board at Johns Hopkins University. We retrospectively identified adult PWWE evaluated during pregnancy at the Johns Hopkins Bayview Medical Center epilepsy clinic, between January 1, 2007, and January 1, 2021. We reviewed charts for information regarding demographics, medical and epilepsy history, medications, serum drug levels, and dosing paradigms. We assessed risk factors for breakthrough seizures with a focus on frequency and timing of laboratory testing. We calculated the dose-normalized concentration (DNC) for analysis with levetiracetam and lamotrigine, assessing changes in DNC over time by half trimesters, and analyzed DNC and effects on seizures in pregnancy. We also compared preemptive vs clinically based lamotrigine dose adjustments in managing epilepsy in pregnancy. A total of 45 pregnancies in 39 patients were included in this study, 8 generalized, 28 focal epilepsy, and 3 unclassified. 31 PWWE (36 pregnancies) were on lamotrigine and/or levetiracetam, and 14 of these pregnancies experienced breakthrough seizures, 77% in the first trimester. Seizures led to the diagnosis of pregnancy in 5 patients. The DNC for levetiracetam decreased significantly compared with prepregnancy levels by the second half of the first trimester and demonstrated variable but frequently significant or near significant reduction throughout pregnancy. DNC for lamotrigine decreased significantly in the first half of the first trimester and remained significant throughout pregnancy. Age of mother at conception, week of first ASM serum level and number of levels obtained during pregnancy, and epilepsy type were not associated with breakthrough/increase in seizures. The history of drug resistance (p = 0.038) was associated with a higher odds of seizures. In those on lamotrigine, preemptive dose adjustments demonstrated similar results regarding seizure control when compared with clinical-based or laboratory-based dose management (p = 0.531). This study demonstrates that frequency and timing of ASM level monitoring may not affect overall seizure outcomes during pregnancy in those on lamotrigine or levetiracetam. Furthermore, one can consider preemptive dose adjustments or a laboratory-based/clinical-based approach in managing lamotrigine as both seem safe and feasible. However, in those with drug-resistant epilepsy before pregnancy, earlier and closer monitoring is warranted given the risk of seizures early during pregnancy. Larger prospective studies are needed to confirm these results.

P85 A new diagnosis of neuropsychiatric lupus in an acute presentation of coma and seizure in pregnancy

P85 A new diagnosis of neuropsychiatric lupus in an acute presentation of coma and seizure in pregnancy

Association of Prenatal Exposure to Antiseizure Medication With Risk of Autism and Intellectual Disability

Women with epilepsy frequently need antiseizure medication (ASM) to prevent seizures in pregnancy. Risk of neurodevelopmental disorders after prenatal exposure to AMSs is uncertain. To determine whether children exposed prenatally to ASMs in monotherapy and duotherapy have increased risk of neurodevelopmental disorders. The Nordic register-based study of antiepileptic drugs in pregnancy (SCAN-AED) is a population-based cohort study using health register and social register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2017; analysis performed February 2022). From 4 702 774 alive-born children with available mother-child identities and maternal prescription data, this study included 4 494 926 participants. Children from a multiple pregnancy or with chromosomal disorders or uncertain pregnancy length were excluded (n = 207 848). Prenatal exposure to ASM determined from maternal prescription fills between last menstrual period and birth. We estimated cumulative incidence at age 8 years in exposed and unexposed children. Cox regression adjusted for potential confounders yielded adjusted hazard ratios (aHRs) with 95% CIs for autism spectrum disorder (ASD), intellectual disability (ID), or any neurodevelopmental disorder (ASD and/or ID). A total of 4 494 926 children were included; 2 306 993 (51.3%) were male, and the median (IQR) age at end of follow-up was 8 (4.0-12.1) years. Among 21 634 unexposed children of mothers with epilepsy, 1.5% had a diagnosis of ASD and 0.8% (numerators were not available because of personal data regulations in Denmark) of ID by age 8 years. In same-aged children of mothers with epilepsy exposed to topiramate and valproate monotherapy, 4.3% and 2.7%, respectively, had ASD, and 3.1% and 2.4% had ID. The aHRs for ASD and ID after topiramate exposure were 2.8 (95% CI, 1.4-5.7) and 3.5 (95% CI, 1.4-8.6), respectively, and after valproate exposure were 2.4 (95% CI, 1.7-3.3) and 2.5 (95% CI, 1.7-3.7). The aHRs were elevated with higher ASM doses compared with children from the general population. The duotherapies levetiracetam with carbamazepine and lamotrigine with topiramate were associated with increased risks of neurodevelopmental disorders in children of women with epilepsy: levetiracetam with carbamazepine: 8-year cumulative incidence, 5.7%; aHR, 3.5; 95% CI, 1.5-8.2; lamotrigine with topiramate: 8-year cumulative incidence, 7.5%; aHR, 2.4; 95% CI, 1.1-4.9. No increased risk was associated with levetiracetam with lamotrigine (8-year cumulative incidence, 1.6%; aHR, 0.9; 95% CI, 0.3-2.5). No consistently increased risks were observed for neurodevelopmental disorders after prenatal exposure to monotherapy with lamotrigine, levetiracetam, carbamazepin, oxcarbazepine, gapapentin, pregabalin, clonazepam, or phenobarbital. In this cohort study, prenatal exposure to topiramate, valproate, and several duotherapies were associated with increased risks of neurodevelopmental disorders.

Pre-pregnancy and antenatal care of women with epilepsy

BackgroundEpileptic seizures in pregnancy pose a significant risk to both the mother and fetus. There is little evidence of the impact of pre-pregnancy counselling (PPC) and specialist multi-disciplinary antenatal care on a pregnancy.ObjectivesTo determine critical components of care in preventing seizures and adverse outcomes in pregnancies of women with epilepsy.MethodA retrospective cohort study of pregnant women with epilepsy. Participants were seen in the Neuro-Obstetrics multidisciplinary clinic based in West London from 2012 to 2020.ResultsA total of 150 patients; including 242 pregnancies, were analysed. Of these pregnancies, 69 were reported to have had at least 1 seizure. The anti-epileptic drug profiles and dosages were recorded in each group; 71.5% of pregnancies involved anti-epileptic drugs (AEDs), 68.8% of these patients were on mono-therapy and 22.5% were on dual-therapy. Patients without access to PPC or specialist antenatal care had less frequent monitoring of AED levels, fewer dosage adjustments and a higher seizure frequency during the pregnancy. In 9.1% of pregnancies a new AED was started.ConclusionThese data support the use of PPC in preventing seizures in early pregnancy. The data also shows a reduction in seizure frequency following specialist multidisciplinary antenatal care.mtm116@ic.ac.uk

Seizure Worsening During Pregnancy: Who Is at Risk?

In all people with epilepsy, the goal of treatment is to stop seizures. In pregnant people, control of seizures in pregnancy protects the baby against injury and reduces the risk of premature labor and delivery. This being said, it has long been recognized that in general, women with epilepsy can have a worsening of seizures during their pregnancy.1 Less is known about the connection between the type of epilepsy and seizure worsening in pregnancy. In an article featured in this issue, “Variations in Seizure Frequency During Pregnancy and Postpartum by Epilepsy Type,” Dr. Voinescu and colleagues2 studied a group of pregnant women with epilepsy to better understand this connection.

Characteristics of Seizures in Pregnancy at RSUD dr. Soetomo Surabaya in 2016-2019

Backgrounds: Three causes of maternal death worldwide are bleeding, preeclampsia-eclampsia, and infection. Increased risk of seizures by 15-30% during pregnancy. Structural and metabolic changes can trigger the new onset of seizures while pregnant. Neurovascular adaptation during pregnancy includes decreased brain size and volume during pregnancy, increased after childbirth, lateral ventricular size increases, but this hypothesis is still unknown. Objectives : Explaining the Characteristics of Seizures in Pregnancy at dr. Soetomo Hospital Surabaya in 2016-2019 Methods : This study is a retrospective descriptive study on seizures in pregnancy treated at dr. Soetomo Hospital Surabaya during January 2016 - December 2019. The data was obtained from the hospital's medical records. Results: In this study, there were 281 cases of seizures in pregnancy reported at dr. Soetomo Hospital Surabaya in 2016-2019. A total of 32 maternal deaths were related to this case. Most of the patients were caused by eclampsia (81.49%). The onset of seizures occurs most while pregnant (75%). The majority of childbirth, in this case, is carried out by cesarean section (74.4%). Based on CT-Scan, the most results were obtained with normal results (28.8%). Conclusion: Seizures in pregnancy that we found at dr. Soetomo Hospital Surabaya in 2016-2019, where most cases were caused by eclampsia, one of the highest maternal causes of death in Indonesia.

Diagnostic challenges in cerebral tuberculoma presenting with seizures in pregnancy.

Tuberculoma is an uncommon presentation of tuberculosis and is found in regions with a high prevalence of tuberculosis. This is rarely diagnosed during pregnancy. The presentation can mimic other etiologies such as eclampsia or cerebral venous sinus thrombosis so the diagnosis can be challenging, particularly when presenting with seizures in pregnancy. Described here is a woman in her first pregnancy who presented with seizures mimicking eclampsia and was suspected to have a brain tumour on neuroimaging. She was diagnosed to have a intracerebral tuberculoma on histopathological examination following surgical decompression after delivery.

Maternal and fetal outcomes in women with cerebrovascular malformations in pregnancy: A multicentre retrospective cohort study.

To determine maternal, obstetric and neonatal outcomes in a cohort of women with cerebrovascular malformations (CVMs) that include arterial venous malformations (AVMs) and cavernomas. Retrospective cohort study. Six specialist centres managing pregnant women with neurological disorders. Sixty-three women with CVMs in 83 pregnancies of ≥20 completed weeks' gestation. Retrospective case notes review. Neurological outcomes including rates of acute cerebral bleeding in pregnancy and reported seizures during pregnancy. Maternal outcomes included number of women with a livebirth and the proportion of women being delivered by caesarean section. Most women had a good pregnancy outcome with high rates of vaginal delivery (73%) at term. There were no maternal deaths. Six women had an acute cerebral bleed, all of whom were delivered by planned caesarean section. In total, tenwomen had seizures in pregnancy (of whom four also had a bleed). Six (7%) babies were admitted to a neonatal unit. There was no significant difference in outcomes between women with AVMs and those with cavernomas. In the majority of cases, pregnancy outcomes were favourable, with most women having a vaginal delivery. All cases of cerebral bleeds that occurred were at a remove from the peripartum period. Women with cerebrovascular malformations have high rates of vaginal delivery.

The control of treated generalized and focal epilepsies during pregnancy

ObjectivesTo examine factors contributing to failure to achieve full seizure control during pregnancy in women with anti-seizure medication (ASM) treated generalized epilepsy compared with focal epilepsy. ResultsFull seizure control was not attained in 51.4% of 1223 pregnancies of women with focal epilepsies in the Australian Pregnancy Register, and in 38.7% of 1026 pregnancies in women with generalized epilepsy (P < 0.05). For convulsive seizures only, the corresponding figures of 20.8% and 22.9% were reasonably similar. Where seizures had occurred in the pre-pregnancy year, 82.5% of the focal epilepsy pregnancies were seizure affected, and 70.1% of the generalized epilepsy ones (P < 0.05). Where the pre-pregnancy year was seizure free, the corresponding figures were 22.6% and 16.4% (P < 0.05), a roughly four-fold lower rate. Maternal age, epilepsy onset age, and epilepsy duration also differed between the focal and generalized epilepsy pregnancies. Multivariate regression analysis showed that generalized epilepsy and younger maternal age were associated with statistically significant decreased risks of seizure-affected pregnancy, and having seizure-affected pre-pregnancy years with an increased risk. However, for convulsive seizures only, the risk of seizure-affected pregnancy appeared increased in generalized epilepsy. ConclusionsThe risk of seizure-affected pregnancy appears lower in women with generalized epilepsy, independently of pre-pregnancy seizure control, itself a major determinant of the risk. The risk of having only convulsive seizures in pregnancy was not lower in generalized epilepsy than in focal epilepsy. ASM therapy seemed less effective in controlling focal than generalized epileptic seizures during pregnancy.

Diagnostic Dilemma: Neurocysticercosis—A Differential Diagnosis for Seizures in Pregnancy and Early Postpartum Period

Diagnostic Dilemma: Neurocysticercosis—A Differential Diagnosis for Seizures in Pregnancy and Early Postpartum Period

The evolving definition of pre-eclampsia.

Pre-eclampsia is a nebulous term. Literally meaning 'prior to a seizure in pregnancy', the name of the syndrome does not accurately depict the clinical reality. The disease rarely leads to eclampsia even if untreated, and this is a rare neurological complication. The definition has been equally imprecise; it has been recognised for many years there is a lack of consistency, even in research papers (Chappell et al. BJOG 1999;106(9)983-5). Original definitions were pragmatic, usually based on consensus, and constructed on blood pressure thresholds known to equate to increased perinatal mortality.

Impact of Reduced ASIC2 and Pregnancy on Seizure Susceptibility in Mice

RationalePreeclampsia, a hypertensive disorder of pregnancy, can advance to eclampsia with the occurrence of new‐onset seizures in the mother. What induces this progression is unknown. Previous research found that utero‐placental ischemia, modeled by reducing uterine perfusion pressure (RUPP) in the rat, reduced latency to drug‐induced seizures. While acid sensing ion channels (ASICs) have been implicated in reducing seizure longevity and severity, the role ASICs have in seizure susceptibility in the context of pregnancy or placental ischemia has not been investigated.HypothesisIn this study, we tested the hypothesis that placental ischemia reduces hippocampal ASIC2 expression and that reduced ASIC2 increases seizure severity and longevity in pregnancy.MethodsUtero‐placental ischemia was induced in female C57BL/6 mice by ligating the uterine arteries between the ovaries and the first pup at day 13.5 post coitus. Hippocampi (SHAM=6, RUPP=5) were harvested on day 18.5 and processed for Western blot analysis to assess ASIC2a expression. Using Image Lab software, ASIC2a expression was normalized to total protein on the Western blot. The role of ASIC2 in seizure activity was assessed by inducing seizures using pentylenetetrazol (PTZ, 40mg/kg, i.p.) in pregnant and non‐pregnant ASIC2 wild type (WT) and heterozygous (HET) transgenic mice (n=4–11). After injection, mice were video monitored for 30 minutes. Using Observer XT software, seizure behavior was scored using a modified Racine Scale with scores ranging from 0 to 7, where 0 indicates normal behavior and 7 indicates respiratory arrest. Seizure activity was determined based on the following: latency to first seizure behavior, duration of all seizures, highest seizure severity score, and duration of seizure behavior associated with grand mal seizures (scores 4–7). Unpaired t‐test was used to analyze ASIC2a expression, and 2‐way ANOVA using a Sidak’s multiple comparison test was used to assess seizure behavior (factors: genotype and pregnancy status).ResultsHippocampal ASIC2a expression was reduced in RUPP (0.47±0.088) compared to SHAM (1±0.19; p= 0.021) mice. In WT mice, pregnancy increased latency to first seizure (116±43.3 vs 50±10.5s; p=0.057), decreased seizure duration (1026±142 vs.1643±44s; p=0.053), and decreased duration of grand‐mal associated seizure scores (23.5±23.5 vs1092±205s; p=0.018) compared to non‐pregnant mice. There was no effect of pregnancy on any of the seizure activity measures within the HET mice (p&gt;0.05). However, there was a significant increase in duration of grand‐mal associated seizures in HET (1065±238s) vs WT pregnant mice (23.5±23.5; p=0.038). No significant difference in highest seizure severity score or survival was observed with pregnancy or reduced ASIC2.ConclusionOur finding of reduced hippocampal ASIC2 in placental ischemic mice and the absence of improved seizure latency and severity with pregnancy in HET mice, support the hypothesis that reduced ASIC2 contributes to increased seizure severity and longevity in placental ischemia.SignificanceASIC2a is a potential novel therapeutic target for the treatment of seizures in pregnancy as occurs in eclampsia.Support or Funding InformationNIH R00HL129192 and R00HL129192‐S1

English

English

Self-reported maternal morbidity: Results from the community level interventions for pre-eclampsia (CLIP) baseline survey in Sindh, Pakistan.

Community-based data regarding maternal and perinatal morbidity and mortality are scarce in less-developed countries. The aim of the study was to collect representative community-level demographic health information to provide socio-demographic and health outcome data. A retrospective household survey of women of reproductive age (15-49 years) living in two districts of Sindh Province, Pakistan was conducted. Pregnancy incidence over the past 12 months and during each woman's lifetime; maternal, fetal, infant and child deaths in the past 12 months; and rates of hypertension and seizures in pregnancy were calculated. From June to September 2013, 88,410 households were surveyed with 1.2 (±0.6) women of reproductive age per household. 19,584 women (11.9%) reported pregnancies in the preceding 12 months; 83.0% had live births, 3.5% resulting in stillbirths and 13.6% in miscarriages. 34.2% of deliveries occurred at home. Out of all women who reported a pregnancy in past 12 months, 62.1% reported high blood pressure and 11.9% reported seizures complicating her most recent pregnancy. Blood pressure was not measured during survey to confirm hypertension. The perinatal, neonatal and maternal mortality ratios were 64.7/1000, 39/1000 and 166/100,000 livebirths, respectively. This study estimated population-level mortality ratios that can be used for the planning of health interventions in these regions. Self-reported pregnancy hypertension and seizures was inaccurate, reflecting limited community understanding of these disorders. Mortality estimates are comparable to those reported by the World Health Organization for maternal mortality ratio and neonatal mortality rate of 170/100,000 and 36/1000 live births, respectively.

Predicting seizures in pregnant women with epilepsy: Development and external validation of a prognostic model.

BackgroundSeizures are the main cause of maternal death in women with epilepsy, but there are no tools for predicting seizures in pregnancy. We set out to develop and validate a prognostic model, using information collected during the antenatal booking visit, to predict seizure risk at any time in pregnancy and until 6 weeks postpartum in women with epilepsy on antiepileptic drugs.Methods and findingsWe used datasets of a prospective cohort study (EMPiRE) of 527 pregnant women with epilepsy on medication recruited from 50 hospitals in the UK (4 November 2011–17 August 2014). The model development cohort comprised 399 women whose antiepileptic drug doses were adjusted based on clinical features only; the validation cohort comprised 128 women whose drug dose adjustments were informed by serum drug levels. The outcome was epileptic (non-eclamptic) seizure captured using diary records. We fitted the model using LASSO (least absolute shrinkage and selection operator) regression, and reported the performance using C-statistic (scale 0–1, values > 0.5 show discrimination) and calibration slope (scale 0–1, values near 1 show accuracy) with 95% confidence intervals (CIs). We determined the net benefit (a weighted sum of true positive and false positive classifications) of using the model, with various probability thresholds, to aid clinicians in making individualised decisions regarding, for example, referral to tertiary care, frequency and intensity of monitoring, and changes in antiepileptic medication. Seizures occurred in 183 women (46%, 183/399) in the model development cohort and in 57 women (45%, 57/128) in the validation cohort. The model included age at first seizure, baseline seizure classification, history of mental health disorder or learning difficulty, occurrence of tonic-clonic and non-tonic-clonic seizures in the 3 months before pregnancy, previous admission to hospital for seizures during pregnancy, and baseline dose of lamotrigine and levetiracetam. The C-statistic was 0.79 (95% CI 0.75, 0.84). On external validation, the model showed good performance (C-statistic 0.76, 95% CI 0.66, 0.85; calibration slope 0.93, 95% CI 0.44, 1.41) but with imprecise estimates. The EMPiRE model showed the highest net proportional benefit for predicted probability thresholds between 12% and 99%. Limitations of this study include the varied gestational ages of women at recruitment, retrospective patient recall of seizure history, potential variations in seizure classification, the small number of events in the validation cohort, and the clinical utility restricted to decision-making thresholds above 12%. The model findings may not be generalisable to low- and middle-income countries, or when information on all predictors is not available.ConclusionsThe EMPiRE model showed good performance in predicting the risk of seizures in pregnant women with epilepsy who are prescribed antiepileptic drugs. Integration of the tool within the antenatal booking visit, deployed as a simple nomogram, can help to optimise care in women with epilepsy.

A randomized trial comparing the pharmacology of magnesium sulfate when used to treat severe preeclampsia with serial intravenous boluses versus a continuous intravenous infusion

BackgroundMagnesium sulfate is the preferred pharmacological intervention for the prevention and treatment of eclamptic seizures in pregnancy. Pain associated with intramuscular injections and the need for an electronic infusion pump for use intravenously represent significant barriers to broader utilization. We hypothesize that an alternative regimen based on serial intravenous (IV) boluses can produce serum concentrations comparable to those produced by a continuous infusion.MethodsAn open-label randomized trial was performed at two hospitals in Egypt. Women with severe preeclampsia were eligible and enrolled between January 2015 and February 2016. Two hundred subjects were randomized by random numbers generated centrally in distinct blocks and stratified by study site. They were assigned to a continuous infusion arm, (4 g loading dose with 1 g/hr. continuous infusion) or a serial IV bolus arm, (6 g loading dose with 2 g bolus every 2 h using a Springfusor® pump). Sparsely sampled magnesium serum concentrations were collected, nonlinear mixed effect modeling was conducted and Monte Carlo simulations were used to generate 200 simulated subjects in each treatment arm. The simulated populations were used to determine area under the concentration-time curve (AUC) as a measure of total drug exposure and compared.ResultsSimulated area under the magnesium serum concentration-time curve was significantly higher in the serial IV bolus arm than in the continuous infusion arm (1107 ± 461 mmol•min /L vs. 1010 ± 398 mmol•min /L, (P = 0.02)). Four percent of women in the serial bolus arm considered the treatment unacceptable or very unacceptable compared to 2% in the continuous infusion arm, (P = 0.68).ConclusionsSerial IV boluses achieve serum magnesium concentrations statistically significantly higher but clinically comparable to those achieved with a continuous infusion and offer a third option for the administration of MgSO4 to women with preeclampsia that may reduce barriers to utilization.Trial registrationTrial no. NCT02091401, March 17, 2014.