Posts Tagged pregnancy

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



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.


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.


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.


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



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.


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.


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).


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.


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.



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


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.

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


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


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.


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.


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.


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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[Abstract] Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy


Objective To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.


Methods Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1–3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample t test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.


Results AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC (p < 0.05).


Conclusion AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.


via Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy | Neurology

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[Abstract] The use of antidepressant drugs in pregnant women with epilepsy: A study from the Australian Pregnancy Register



To study interactions between first‐trimester exposure to antidepressant drugs (ADDs) and antiepileptic drugs (AEDs), and a history of clinical depression and/or anxiety, on pregnancy outcomes and seizure control in pregnant women with epilepsy (WWE).


We examined data from the Australian Pregnancy Register of Antiepileptic Drugs in Pregnancy, collected from 1999 to 2016. The register is an observational, prospective database, from which this study retrospectively analyzed a cohort. Among the AED‐exposed outcomes, comparisons were made among 3 exposure groups: (1) pregnancy outcomes with first‐trimester exposure to ADDs; (2) outcomes with mothers diagnosed with depression and/or anxiety but who were not medicated with an ADD; and (3) those with mothers who were not diagnosed with depression and/or anxiety and were not medicating with ADD. Prevalence data was analyzed using Fisher’s exact test.


A total of 2124 pregnancy outcomes were included in the analysis; 1954 outcomes were exposed to AEDs in utero, whereas 170 were unexposed. Within the group of WWE taking AEDs, there was no significant difference in the prevalence of malformations in infants who were additionally exposed to ADDs (10.2%, 95% confidence interval [CI] 3.9‐16.6), compared to individuals in the non–ADD‐medicated depression and/or anxiety group (7.7%, 95% CI 1.2‐14.2), or those without depression or anxiety (6.9%, 95% CI 5.7‐8.1; = 0.45). The malformation rates in pregnancy outcomes unexposed to AEDs were also similar in the above groups (= 0.27). In WWE medicated with AEDs and ADDs, the frequency of convulsive seizures (= 0.78), or nonconvulsive seizures (= 0.45) throughout pregnancy, did not differ across comparative groups.


Co‐medicating with ADDs in WWE taking AEDs does not appear to confer a significant added teratogenic risk, and it does not affect seizure control.


via The use of antidepressant drugs in pregnant women with epilepsy: A study from the Australian Pregnancy Register – Sivathamboo – – Epilepsia – Wiley Online Library

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[WEB SITE] Rates of Pregnancy, Live Births Similar Among Women With and Without Epilepsy

Sexual activity and rates of ovulation were also similar among women with epilepsy and those without the disorder.

Sexual activity and rates of ovulation were also similar among women with epilepsy and those without the disorder.

Women with epilepsy who are seeking to become pregnant and have no known infertility or related disorders have a similar probability of achieving pregnancy, time to pregnancy, and live birth rates as do women without epilepsy, according to the results of the observational Women With Epilepsy Pregnancy Outcomes and Deliveries prospective cohort study ( identifier: NCT01259310), which was published in JAMA Neurology.

The investigators sought to examine whether women with epilepsy with no prior diagnosis of infertility or a related disorder were as likely to become pregnant within 12 months as their peers without epilepsy. A cohort of women with epilepsy and healthy controls who were seeking pregnancy were enrolled at 4 academic medical centers in the United States and were followed for up to 21 months. Participants between 18 and 40 years of age who were seeking pregnancy were enrolled within 6 months of having discontinued contraception. Data were evaluated from November 2015 to June 2017.

The primary study outcome was the proportion of women who attained pregnancy within 12 months after enrollment. Secondary outcomes included time to pregnancy, pregnancy outcomes, sexual activity, rates of ovulation, and analysis of disease-related factors in women with epilepsy.

A total of 197 women were included in the study — 89 with epilepsy and 108 controls. Overall, 72.1% of the participants were white. The mean age of the women was 31.9±3.5 years in those with epilepsy and 31.1±4.2 years in the controls. Among the women with epilepsy, 60.7% (54 of 89) achieved pregnancy compared with 60.2% (65 of 108) of those without epilepsy. The median time to attaining pregnancy did not differ significantly between the groups (women with epilepsy: 6.0 months; 95% CI, 3.8-10.1; controls: 9.0 months; 95% CI, 6.5-11.2; =.30).

Sexual activity and rates of ovulation were also similar among women with epilepsy and those without the disorder. Overall, 81.5% (44 of 54) of pregnancies in women with epilepsy and 81.5% (53 of 65) of pregnancies in women without epilepsy resulted in live births.

The investigators concluded that the results of this study should help reassure and encourage women with epilepsy without a prior diagnosis of infertility or an associated disorder, as well as their clinicians, when planning to become pregnant, based on the similar times to achieving pregnancy and similar pregnancy outcomes reported.


Pennell PB, French JA, Harden CL, et al. Fertility and birth outcomes in women with epilepsy seeking pregnancy [published online April 30, 2018]. JAMA Neurol. doi: 10.1001/jamaneurol.2018.0646

via Rates of Pregnancy, Live Births Similar Among Women With and Without Epilepsy

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