Posts Tagged pregnancy

[ARTICLE] Principles of Epilepsy Management for Women in Their Reproductive Years – Full Text

In the United States, there are over one million women with epilepsy (WWE) in their childbearing years. Pregnancy can be challenging for this population. A number of international registries have documented that children born to these women are at increased risk for major congenital malformations (MCM), lower intelligence quotient scores and neurodevelopmental disorders, when the mother is managed on antiseizure medications (ASMs). To prevent poor neonatal outcomes for this population, safe and thoughtful management strategies are necessary. We propose to divide these management strategies into five principles. These include (I) choosing suitable ASMs for the patient’s seizure type, (II) choosing an ASM with the least teratogenic and cognitive side effects, (III) dosing at the lowest possible effective dosage, (IV) selecting the best ASM regimen as promptly as possible, even before a woman has her first menses, and (V) supplementing these patients with folic acid in order to try to enhance cognition and reduce neural tube defects.

Introduction

In the United States, there are over one million WWE in their childbearing years (1). Because of the reproductive potential of these women their management can often differ from males and post-menopausal women.

Management of seizures is traditionally guided by the classification of seizures as focal or generalized in onset. Thankfully, there are ASMs that can treat seizures in each classification. That selection is then narrowed down further in WWE based on the teratogenicity potential of these ASMs that is available from the various pregnancy registries. These registries include the North American Pregnancy Registry, The UK & Ireland Epilepsy and Pregnancy Register, EURAP Registry (includes 44 countries all around the world) and the Australian Registry.

Along with an increase of MCM some ASMs can also lead to lower intelligence quotient scores, and neurodevelopmental disorders (1). Unintended pregnancies further complicate this risk as they often lead to inadequate or delayed initiation of prenatal care and an increased risk for fetal exposure teratogenic substances such as alcohol and nicotine (2). In 2011, there were 45 unintended pregnancies for every 1,000 women aged 15–44 years (3). Similar rates are reflected worldwide in other developed countries, but are substantially higher in developing countries at 65 unintended pregnancies for every 1,000 women age 15–44 years (4). It is thus evident that WWE in their reproductive years require different management strategies to improve their healthcare outcomes as well as the health of their potential offspring.[…]

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[Abstract + References] Therapeutic Drug Monitoring of Antiepileptic Drugs in Women with Epilepsy Before, During, and After Pregnancy – Review

Abstract

During pregnancy, the pharmacokinetics of an antiepileptic drug is altered because of changes in the clearance capacity and volume of distribution. These changes may have consequences for the frequency of seizures during pregnancy and fetal exposure to antiepileptic drugs. In 2009, a review was published providing guidance for the dosing and therapeutic drug monitoring of antiepileptic drugs during pregnancy. Since that review, new drugs have been licensed and new information about existing drugs has been published. With this review, we aim to provide an updated narrative overview of changes in the pharmacokinetics of antiepileptic drugs in women during pregnancy. In addition, we aim to formulate advice for dose modification and therapeutic drug monitoring of antiepileptic drugs. We searched PubMed and the available literature on the pharmacokinetic changes of antiepileptic drugs and seizure frequency during pregnancy published between January 2007 and September 2018. During pregnancy, an increase in clearance and a decrease in the concentrations of lamotrigine, levetiracetam, oxcarbazepine’s active metabolite licarbazepine, topiramate, and zonisamide were observed. Carbamazepine clearance remains unchanged during pregnancy. There is inadequate or no evidence for changes in the clearance or concentrations of clobazam and its active metabolite N-desmethylclobazam, gabapentin, lacosamide, perampanel, and valproate. Postpartum elimination rates of lamotrigine, levetiracetam, and licarbazepine resumed to pre-pregnancy values within the first few weeks after pregnancy. We advise monitoring of antiepileptic drug trough concentrations twice before pregnancy. This is the reference concentration. We also advise to consider dose adjustments guided by therapeutic drug monitoring during pregnancy if the antiepileptic drug concentration decreases 15–25% from the pre-pregnancy reference concentration, in the presence of risk factors for convulsions. If the antiepileptic drug concentration changes more than 25% compared with the reference concentration, dose adjustment is advised. Monitoring of levetiracetam, licarbazepine, lamotrigine, and topiramate is recommended during and after pregnancy. Monitoring of clobazam, N-desmethylclobazam, gabapentin, lacosamide, perampanel, and zonisamide during and after pregnancy should be considered. Because of the risk of teratogenic effects, valproate should be avoided during pregnancy. If that is impossible, monitoring of both total and unbound valproate is recommended. More research is needed on the large number of unclear pregnancy-related effects on the pharmacokinetics of antiepileptic drugs.

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[Abstract] Do Women with epilepsy benefit from epilepsy specific pre-conception care?

Abstract

BACKGROUND

To determine how pre-conception care (PCC) influenced the outcome of epilepsy, pregnancy and malformation risk in women with epilepsy (WWE)

METHODS

All primigravida in the Kerala registry of epilepsy and pregnancy (KREP) with the final outcome of pregnancy known who were enrolled prospectively in pre-conception stage (PCC group) or first trimester of pregnancy (PRG group) were included. The two groups were compared for fetal and maternal outcomes including seizure control and complications of pregnancy.

RESULTS

There were 320 (30.4%) in PCC group and 732 in PRG group. Both groups were comparable for epilepsy classification, maternal birth defects and family history of epilepsy but the PCC group had significantly higher education (48.9%, p = .027) and employment (22.1%, p < .001). They had higher usage of folate in pre-pregnancy month (87.5%, p < .001) and first trimester (96.3%, p < .001) than PRG group. Fewer women in the PCC group were off AEDs in first trimester (5% vs 9.3%, p = .018). Within monotherapy group, use of levetiracetam (10.8%, p = .017), valproate ( 34%, p = .002) in PCC group and carbamazepine (39.1%, p = .04), phenobarbitone (13.3%, p = .001) in PRG group was significantly high. More women in this group were seizure free during pregnancy (62.8%, p = .005) than PRG group. Early fetal loss was better captured in PCC (90.6%,p = .025) than in the PRG. There was no difference in malformation rate between PCC (7.2%) and PRG groups (6.1%, p = .3).

CONCLUSION

PCC reduced the risk of seizures during pregnancy and improved the periconceptional use of folate but did not influence the fetal malformation risk.

 

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[Abstract + References] The impact of maternal epilepsy on delivery and neonatal outcomes

Abstract

Purpose

Epilepsy is a common neurological disorder that may complicate reproductive health. Our aim in this study was to provide prospective ascertainment of obstetric and neonatal outcomes in women with epilepsy and investigate whether the risk of pregnancy, delivery, and neonatal complications differed between women with epilepsy and women without epilepsy.

Methods

Pregnant women with epilepsy and women without epilepsy (control group) were prospectively evaluated during the years 2013–2018. They were regularly followed by a neurologist and obstetrician until the end of pregnancy.

Results

Delivery and perinatal outcomes were compared between 112 women diagnosed with epilepsy and 277 women without epilepsy. Epilepsy was a significant risk factor for preterm delivery, cesarean section, fetal hypoxia, and Apgar score ≤ 7 at 5 min in offspring (odds ratio (OR) = 2.83, 95% confidence interval (CI) 1.03–7.76; OR = 5.61, 95% CI 3.44–9.14; OR = 1.81, 95% CI 1.08–3.04; OR = 8.12, 95% CI 4.04–16.35, respectively). Seizures during pregnancy had influence on the preference of cesarean section as a mode of delivery (ОR = 3.39; 95% CI 1.40–8.17). The rate of perinatal hypoxia was significantly higher in children born by cesarean section (ОR = 2.84; 95% CI 1.04–7.76). There was no significant difference between women with epilepsy and controls in malformation rate.

Conclusions

Women with epilepsy had an increased risk of pregnancy and delivery complications. Cesarean section was associated with an increased risk of complications in offspring.

 

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via The impact of maternal epilepsy on delivery and neonatal outcomes | SpringerLink

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[ARTICLE] Maternal complications in pregnancy and childbirth for women with epilepsy: Time trends in a nationwide cohort – Full Text

Abstract

Objective

Obstetric trends show changes in complication rates and maternal characteristics such as caesarean section, induced labour, and maternal age. To what degree such general time trends and changing patterns of antiepileptic drug use influence pregnancies of women with epilepsy (WWE) is unknown. Our aim was to describe changes in maternal characteristics and obstetric complications in WWE over time, and to assess changes in complication risks in WWE relative to women without epilepsy.

Methods

This was a nationwide cohort study of all first births in the Medical Birth Registry of Norway, 1999–2016. We estimated maternal characteristics, complication rates, and risks for WWE compared to women without epilepsy. Main maternal outcome measures were hypertensive disorders, bleeding in pregnancy, induction of labour, caesarean section, postpartum hemorrhage, preterm birth, small for gestational age, and epidural analgesia. Time trends were analyzed by logistic regression and comparisons made with interaction analyses.

Results

426 347 first births were analyzed, and 3077 (0.7%) women had epilepsy. In WWE there was an increase in proportions of induced labour (p<0.005) and use of epidural analgesia (p<0.005), and a reduction in mild preeclampsia (p = 0.006). However, the risk of these outcomes did not change over time. Only the risk of severe preeclampsia increased significantly over time relative to women without epilepsy (p = 0.006). In WWE, folic acid supplementation increased significantly over time (p<0.005), and there was a decrease in smoking during pregnancy (p<0.005), but these changes were less pronounced than for women without epilepsy (p<0.005).

Conclusions

During 1999–2016 there were important changes in maternal characteristics and complication rates among WWE. However, outcome risks for WWE relative to women without epilepsy did not change despite changes in antiepileptic drug use patterns. The relative risk of severe preeclampsia increased in women with epilepsy.

Introduction

Epilepsy is one of the most common chronic diseases during pregnancy.[14] Women with epilepsy (WWE) have been considered as high risk parturients with increased risk for maternal complications.[28] Almost half of women with ongoing or previous epilepsy use antiepileptic drugs (AEDs) in pregnancy to control seizures despite their potential adverse effects on the fetus and maternal complications.[2911] The pattern of antiepileptic drug use in pregnant WWE has changed markedly during the last two decades owing to newer antiepileptic drugs, primarily lamotrigine and levetiracetam, replacing older antiepileptic drugs, such as carbamazepine, phenytoin, and valproate. [1214] The newer antiepileptic drugs are better tolerated and believed to have less fetal and maternal adverse effects, but are associated with increased seizure risk during pregnancy.[10111519] Increasing maternal age, increasing maternal body mass index (BMI), and decrease in smoking during pregnancy over the last two decades should also affect WWE.[2023] These factors could be proportional or have a more complex interaction. Global trends show an increase in caesarean section rates and increased induction of labour.[2426] Such interventions are common in WWE.[24578] During the last decade, there has been an increasing focus on management of WWE during pregnancy and delivery and recent guidelines encourage close monitoring of pregnancies in WWE and strict indications for interventions.[252730] However, there is little data on how focused management and guidelines have affected maternal outcomes of WWE. A recent meta-analysis indicates a trend towards increasing rates of caesarean section and induction of labour in WWE.[31] However, different geographical populations with great variation in obstetric practice were compared to describe differences over time, and no reference populations were included. Therefore, it is not known how changes in population characteristics, obstetric practice and general complication rates have affected WWE. We expect that changes during the recent years in folate use, indications for operative interventions, and AEDs used have all influenced maternal complications in WWE during pregnancy and when giving birth.

By analyzing a stable nationwide cohort over 18 years, our aim was to describe changes in maternal characteristics and maternal complication rates in WWE over time, and to assess changes in complication risks relative to women without epilepsy. For changes in outcome risks in WWE over time, the influence of AED use and other specific factors were assessed.

Continue —->  Maternal complications in pregnancy and childbirth for women with epilepsy: Time trends in a nationwide cohort

 

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[Book Chapter] Pregnancy and Epilepsy

VD Kapadia – Medical Disorders in Pregnancy

Epilepsy is the most common neurological disorder, with 50 million people affected by it worldwide. Nearly 50% of these affected individuals are women. The burden of  epilepsy in women in India is to the tune of 2.73 million, with 52% of them being in …

Continue —> Pregnancy and Epilepsy [PDF]

 

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[NEWS] New guidance on use of valproate in women, girls of child bearing age with epilepsy published

Apr 2 2019

 

New guidance to support regulations around the use of valproate in women and girls of child bearing age with epilepsy has been published by specialists from 13 UK healthcare bodies including seven Royal Colleges.

And NICE has published a summary of updated guidance for healthcare professionals bringing together all its recommendations and other safety advice on the drug valproate.

The use of sodium valproate during pregnancy is associated with up to a 40 per cent risk of neuordevelopmental disorders and a 10 per cent risk of physical disabilities for an unborn child.

In March 2018, the Medicines and Healthcare products Regulatory Agency published guidelines which meant that valproate could no longer be prescribed for girls and women of childbearing age unless no other effective treatment was available.

Any girl or woman prescribed valproate should also be fully informed of the risks associated with the medication and the need for effective contraception.

But a year on, implementation of the guidelines have thrown up specific challenges with complex issues and individual situations where the best interests of the patient did not always appear to be met.

Claire Glazebrook, Director of Fundraising, Marketing and External Affairs at Epilepsy Society, said:

Over the last year our Helpline has received multiple calls from women, parents and healthcare professionals, all struggling to interpret the guidelines and what they mean for them as individuals. And we know that this experience is replicated across other patient organizations and clinics.

I hope this guidance will help to answer some of their questions and provide clarity in what can be a very emotional and challenging decision.

For some girls and women, they have no option but to take sodium valproate as it may be the only drug that will control their seizures. But that of course means there are some very important and potentially heartbreaking issues to consider around planning a family.

All these women and girls deserve consistency in the advice and information that they receive.”

The new pan-college guidance has been drawn up by Judy Shakespeare of the Royal College of General Practitioners and Sanjay Sisodiya of the Association of British Neurologists and Royal College of Physicians. Sanjay Sisodiya is also Director of Genomics at Epilepsy Society and Professor of Neurology at UCL.

He said: This work has come together through much valued contributions from specialists across all the national bodies involved.

“In some cases the new regulations have lead to situations where the best interests of the patients may not appear to be best served. Some of the points raised by the regulations are also complex ethical issues. We do not attempt to address all these issues in this document but hope that it will bring greater clarity for clinicians  leading to better care for women and girls with epilepsy. All women and girls have individual needs and where possible should be involved in the choices they make about their own health and plans to start a family.”

Writing in the guidance, Professor Dame Sally Davies, Chief Medical Officer for England said:

I am very pleased that the Medical Royal Colleges have come together to produce this important and helpful guidance, so that doctors and other healthcare professionals across primary and secondary care are on the same page regarding the use of sodium valproate – including around instances where its use is still appropriate.”

via New guidance on use of valproate in women, girls of child bearing age with epilepsy published

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[Abstract] Management of epilepsy in women

Journal home page for The Lancet NeurologySummary

Epilepsy is a common neurological condition in women worldwide. Hormonal changes occurring throughout a woman’s life can influence and be influenced by seizure mechanisms and antiepileptic drugs, presenting unique management challenges. Effective contraception is particularly important for women with epilepsy of childbearing potential because of antiepileptic drug-related teratogenicity and hormonal interactions; although studies reveal many women do not receive contraceptive and preconceptual counselling. Management challenges in this population include the higher risk of pregnancy complications and peripartum psychiatric problems than in women without epilepsy. Research is needed to clarify the precise role of folic acid supplementation in prevention of congenital malformations in children born to women with epilepsy. To optimise treatment of low bone density in women with epilepsy, studies investigating bone densitometryfrequency and calcium and vitamin D supplements are required. Understanding of the mechanisms linking seizures and the menopause will help to develop effective therapeutic strategies, and advances in managing epilepsy could improve quality of life for women with this condition.

 

via Management of epilepsy in women – ScienceDirect

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[BLOG POST] Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children

Bromley RL, Weston J, Marson AG.

JAMA 2017; 318:1700-1701.

Abstract

CLINICAL QUESTION:

Is maternal use of antiepileptic drugs during pregnancy associated with major congenital malformations in children?

BOTTOM LINE:

Certain antiepileptic drugs were associated with increased rates of congenital malformations (eg, spina bifida, cardiac anomalies). Lamotrigine (2.31% in 4195 pregnancies) and levetiracetam (1.77% in 817 pregnancies) were associated with the lowest risk and valproate was associated with the highest risk (10.93% in 2565 pregnancies) compared with the offspring of women without epilepsy (2.51% in 2154 pregnancies).

Also see

Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 2016; 11:CD010224.

Both references are cited in the neurochecklist:

Antiepileptic drugs (AEDs): teratogenicity

Abstract link 1

Abstract link 2

Drugs firms ‘creating ills for every pill’. Publik15 on Flickr. https://www.flickr.com/photos/publik15/3415531899

via Which are the safest epilepsy drugs in pregnancy? – Neurochecklists Updates

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[Abstract] Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy – A retrospective single center study

Highlights

Pregnancies in women with epilepsy (WWE) increased significantly during our 11-year study period (41% increase).

Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015) with Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%) most commonly used.

Valproic acid use was markedly reduced comparing the years 2005-2010 (18.4%) and 2011-2015 (9.4%), a reduction of 48%.

Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Cover image Epilepsy ResearchAbstract

Purpose

Antiepileptic drugs (AED) are among the most common teratogenic drugs prescribed to women of childbearing age. During pregnancy, the risk of seizures has to be weight against the use of AED treatment. Primary goal was to observe and describe AED treatment policy and its changes during an eleven-year period at our third referral center.

Methods

We scrutinized the medical health records for all cases of female epileptic patients admitted for labor at the Rabin Medical Center during the years 2005 – 2015.

Results

A total of 296 deliveries were recorded with 136 labors occurring in the period 2005-2010 (22.7/y) and 160 in 2011-2015 (32.0/y; increase of 41%). Twelve different AEDs were prescribed to WWE during pregnancies in the 11-year period investigated (2005-2015). Most commonly used AEDs during pregnancy were Lamotrigine (36.1%), Carbamazepine (25.0%), and Valproic Acid (13.5%). Comparing their use during the years 2005-2010 and 2011-2015, Lamotrigine (35.3% vs. 36.9%) and Carbamazepine use (23.5% vs. 26.0%) increased slightly. Valproic acid use was markedly reduced in the second period: 18.4% in the years 2005-2010 lowered to 9.4% during 2011-2015, a reduction of 48%. Unfortunately, a trend towards an increase in treating WWE with more than one AED was observed.

Conclusions

The proportion of WWE treated with VPA during pregnancy was significantly reduced in the observed period (2005-2015). Change in fetal outcome during this period for WWE could not be detected.

via Antiepileptic drug treatment during pregnancy and delivery in women with epilepsy—A retrospective single center study – ScienceDirect

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