DOI: 10.4274/tjod.galenos.2020.

87300
CLINICAL INVESTIGATION / ARAŞTIRMA Turk J Obstet Gynecol 2020;17:161-9

Obstetric outcomes in pregnant women with

seizure disorder: A hospital-based, longitudinal
study
Nöbet bozukluğu OLAN gebe KADINLARDA OBSTETRIK sonuç: HASTANE
temelli, UZUNLAMASINA bir ÇALIŞMA
Tarang Preet Kaur1, Latika Sahu2, Asmita M. Rathore2, Sangeeta Bhasin2
1All INDIA Institute
of MEDICAL Sciences, DEPARTMENT of Obstetrics AND GYNAECology, New Delhi, INDIA
2MAULANA AZAD MEDICAL College, DEPARTMENT of Obstetrics AND GYNAECOLOGY, New Delhi, INDIA

Abstract
Objective: To study the association of seizure disorder with adverse obstetric outcome in terms of maternal and perinatal complications.
Materials and Methods: This longitudinal study was conducted at Maulana Azad Medical College, New Delhi over 15 months among women
attending the antenatal clinic (ANC) outpatient department. Fifty pregnant women with seizure disorder with their first ANC visit before 28 weeks
were recruited as the case group, excluding patients with eclampsia. The control group included 120 matched healthy pregnant women. After
obtaining informed consent, subjects were recruited and followed till one week postpartum and obstetric outcomes were analyzed.
Results: Women with seizure disorder had significantly increased incidence of severe preeclampsia (cases =8%, controls =0%, p<0.001),
antepartum hemorrhage (cases =4%, controls =0%, p<0.001), babies with early neonatal complications such as asphyxia (cases =4.1%, controls
=0.5%, p=0.04), respiratory distress (cases =14.5%, controls =5.1%, p=0.02), necrotizing enterocolitis (cases =2.0%, controls =0%, p=0.04), early
neonatal death (cases
=2.0%, controls =0%, p=0.04) and Neonatal Intensive Care Unit admission (cases =20.8%, controls =8.6%, p<0.001) when compared with women without
seizure disorder. No significant difference was observed in rates of induction of labor, cesarean section, abortion, congenital anomalies in babies, still
births. Conclusion: Women with seizure disorder are at higher risk of hypertensive disorders, antepartum hemorrhage, and early neonatal
complications. Appropriate obstetric, pediatric and neurology care is required during preconception, pregnancy, labor, delivery, and
postpartum.
Keywords: Seizure disorder, anti-epileptic drugs, maternal and perinatal complications

Öz
Amaç: Nöbet bozukluğunun olumsuz obstetrik sonuçla ilişkisini maternal ve perinatal komplikasyonlar açısından incelemektir.
Gereç ve Yöntemler: Bu uzunlamasına çalışma doğum öncesi kliniğine (ANC) katılan kadınlar arasında 15 ay boyunca Yeni Delhi Maulana Azad
Tıp Koleji’nde gerçekleştirildi. Yirmi sekiz haftadan önce ilk ANC ziyareti ile nöbet bozukluğu olan 50 gebe kadın, eklampsi hastaları hariç olgu
grubu olarak alındı. Kontrol grubuna 200 sağlıklı hamile kadın dahil edildi. Bilgilendirilmiş onam alındıktan sonra denekler işe alındı ve doğum
sonrası 1 haftaya kadar takip edildi ve obstetrik sonuçlar analiz edildi.
Bulgular: Nöbet bozukluğu olan kadınlarda şiddetli preeklampsi insidansı (olgular =%8, kontroller =%0, p<0,001), doğum öncesi kanama (olgular
=%4, kontroller =%0, p<0,0001), erken neonatal komplikasyonları olan bebekler asfiksi ile ilişkili (olgular =%4,1, kontroller =%0,5, p=0,04),
solunum sıkıntısı (olgular =%14,5, kontroller =%5,1, p=0,02), nekrotizan enterokolit (olgular =%2,0, kontroller =%0, p=0,04), erken neonatal ölüm
(olgular
=%2,0, kontroller =%0, p=0,04) ve yenidoğan yoğun bakım ünitesi kabulü (olgular =%20,8, kontroller =%8,6, p<0,001) nöbet bozukluğu olmayan
kadınlarla karşılaştırıldığında doğum indüksiyon oranları, sezaryen, kürtaj, bebeklerde doğuştan anomaliler, hala doğum oranları arasında anlamlı bir fark
gözlenmemiştir.
Sonuç: Nöbet bozukluğu olan kadınlar hipertansif bozukluklar, antepartum hemoraji ve erken neonatal komplikasyon riski altındadır. Gebelik
öncesi, gebelik, doğum ve doğum sonrası dönemde uygun obstetrik, pediatrik ve nöroloji bakımı gereklidir.
Anahtar Kelimeler: Nöbet bozukluğu, anti-epileptik ilaçlar, anne ve perinatal komplikasyonlar

PRECIS: Women with seizure disorder are at higher risk of hypertensive disorders, antepartum haemorrhage and early neonatal complications.

Address for Correspondence/Yazışma Adresi: Tarang Preet Kaur, MD,

All India Institute of Medical Sciences, Department of Obstetrics and Gynaecology, New Delhi, India

1
Phone: +91 997 177 9382 E-mail: tarang.preet@gmail.com ORCID ID: orcid.org/0000-0003-3630-675X
Received/Geliş Tarihi: 25.03.2020 Accepted/Kabul Tarihi: 24.04.2020
©Copyright 2020 by Turkish Society of Obstetrics and Gynecology
Turkish Journal of Obstetrics and Gynecology published by Galenos Publishing House.

2
Kaur et al. Pregnancy and seizure disorder: Obstetric Turk J Obstet Gynecol 2020;17:161-
outcome 9

Introduction disorder is conflicting, we aimed to study the obstetric outcomes

of women with seizure disorder and establish whether pregnant
Seizure disorder is characterized by an episode of abnormal,
such women had an increased risk of complications
uncontrolled neuronal activity in the brain resulting in
compared with a control group of matched healthy
various manifestations ranging from dramatic convulsive
pregnant women.
activity, altered consciousness, abnormal sensations to
experiential phenomena not readily discernible by an
observer(1). Epilepsy as described by International League
Against Epilepsy (ILAE) 2014 includes at least 2
unprovoked (or reflex) seizures occurring more than 24
hours apart(2). It is the second most common neurologic
problem encountered in pregnancy after headaches with a
prevalence of 0.3-0.7%(3).
Women with Epilepsy (WWE) are considered at high risk
in pregnancy with maternal mortality 10 times higher
than women without seizure disorder(4). Although 90% of
WWE have uneventful pregnancies, many studies have
shown its association with increased complications(5).
Individual studies provide inconclusive estimates of the
association between seizure disorder and pregnancy
complications such as antenatal [miscarriage, gestational
hypertension, preeclampsia, gestational diabetes mellitus
(GDM), antepartum hemorrhage (APH), preterm delivery,
fetal growth restriction (FGR)], intranatal (need for
induction of labor, cesarean section), postnatal
[postpartum hemorrhage (PPH)], fetal [low-birth- weight
(LBW) babies, need for Neonatal Intensive Care Unit
(NICU) admission, congenital fetal anomalies, still births](6-
9)
. Newborns exposed to anti-epileptic drugs (AEDs) in utero
have been shown to have 2-3-fold increased (3.3-9%)
prevalence of major congenital abnormalities compared
with unexposed newborns(10).
Commonly seen congenital malformations include cleft
lip and palate, cardiac defects, neural tube defects,
skeletal abnormalities, and hypospadias. These
malformations are observed more frequently with increased
doses of AEDs, higher serum levels of AEDs, and
polytherapeutic approaches(6). Folic acid deficiency may
also be responsible for the occurrence of major
complications to some degree as folic acid supplementation
in women under anticonvulsant medications has been shown
to decrease malformation rates(11).
Approximately two-thirds of patients experience no change
or decrease in the frequency of seizure episodes, whereas
the remaining one-third have an increase in frequency.
Some of the changes can be attributed to pregnancy-
associated physiologic changes and psychological stress.
Deliberate patient noncompliance secondary to the fear of
the effect of AEDs on the fetus is more likely to be blamed
for the increased seizure frequency. It has been seen that
lower the number of seizures occurring in the 9 months
before conception, the lower the risk of experiencing
seizure episodes during pregnancy(12).
Therefore, as the outcomes of pregnant women with seizure
Turk J Obstet Gynecol 2020;17:161- Kaur et al. Pregnancy and seizure disorder: Obstetric
9 outcome
Aims and Objectives type as per the ILAE 2017 classification by a neurologist,
1. To study the profile of pregnant women with seizure underlying cause, date of last seizure prior to pregnancy,
disorder. seizure episodes
2. To study the obstetric outcome in women with seizure
disorder in terms of maternal and perinatal outcomes.
3. Compare the outcomes with a control group
comprising healthy pregnant women.

Materials and Methods

This was a longitudinal study conducted after obtaining
clearance from the Institutional Ethics Committee
among women attending the antenatal outpatient department
(OPD)/ high-risk OPD/gyne casualty in the department of
Obstetrics and Gynecology, Maulana Azad Medical College and
associated Lok Nayak Hospital, Govind Ballabh Pant Institute
of Postgraduate Medical Education and Research (GIPMER)
hospital, New Delhi, from November 2016 to January
2017 (15 months) (approval number: 113, date:
04/11/2016). It included 250 pregnant women, out of
which 50 women were cases and 200 controls as per the
following criteria:
Selection of Cases
Inclusion criteria: Pregnant women with known case of
seizure disorder with first antenatal clinic (ANC) visit
between 18 to 28 weeks of gestation.
Exclusion criteria: Pregnant women with eclampsia at the
time of enrolment.
- Selection of controls: Age, body mass index (BMI),
and gestational age-matched healthy pregnant women.
Pregnant women with known medical problems (e.g.
chronic hypertension, pre-existing diabetes, asthma,
pre-existing hypothyroidism) were excluded.
- Primary outcome: To study obstetric outcomes in women
with seizure disorder when compared with women
without seizure disorder in terms of maternal
complications such as antenatal (abortion, gestational
hypertension, preeclampsia, GDM, hypothyroidism,
intrahepatic cholestasis of pregnancy, APH, preterm
delivery), intranatal (need for induction of labor, caesarean
section), postnatal (PPH), fetal (FGR, LBW babies, NICU
admissions, congenital fetal anomalies, still births, early
neonatal complications such as respiratory distress related,
asphyxia related, intraventricular hemorrhage, necrotizing
enterocolitis, neonatal hypoglycemia, and 1 and 5-
minute Apgar scores).
After obtaining written informed consent from the
subjects, data were collected and recorded on a
questionnaire. It included baseline demographic details
such as age, education status, weight at first visit, height,
BMI, significant obstetric history, menstrual history,
significant past and family history, pre-pregnancy and
trimester-wise intake of folic acid, and preconception
counselling.
Detailed history of seizure was recorded in known cases
such as time since diagnosis of seizure disorder, seizure
during pregnancy and postpartum period, AED intake prior social or cosmetic consequences for the affected individual,
to pregnancy, AEDs consumed during pregnancy, any
change in the antiepileptic medication.
For quantifying change in seizure episodes, the frequency in
the pre-pregnancy year was taken as the baseline. Increased
seizure frequency was defined as a ≥50% increase in the
number of seizure episodes from baseline during pregnancy
and postpartum period. Decreased seizure frequency was
defined as a ≥50% decrease in the number of seizure
episodes from baseline during pregnancy and the
postpartum period. Any change in seizure frequency
between these was defined as unchanged. Abortion is
defined as a clinically recognized pregnancy loss before the
20th week of gestation. The World Health Organization
defines abortion as expulsion or extraction of an embryo or
fetus weighing 500 g or less. Different countries have their
own laws for defining criteria for abortion(13). In India,
this has been fixed administratively at 28 weeks, when the
fetus weighs approximately 1000 g(14). So, any delivery
before 28 weeks was categorized as abortion.
Subjects were diagnosed as having gestational hypertension
when either systolic blood pressure (BP) was 140 mm Hg
or greater or diastolic BP was 90 mm Hg or greater or both,
in at least two recordings, at least 4 hours apart(15).
Preeclampsia was also defined using criteria by the Task
Force on Hypertension in Pregnancy under the American
College of Obstetrician and Gynecologists.
To screen and diagnose GDM, the 75 g oral glucose
tolerance test as was performed recommended by American
Diabetic Association and International Association of
Diabetes and Pregnancy Study Groups at first ANC visit for
high-risk women or at 24-28 weeks. The cut-offs were taken
as follows: fasting blood glucose ≥92 mg/dL, postprandial 1
hour ≥180 mg/dL, postprandial 2 hours ≥153 mg/dL. One
or more abnormal values lead to the diagnosis of
GDM(16).
Hypothyroidism was defined as per the gestational age
specific cut-off for thyroid stimulating hormone, as
recommended by American Thyroid Association(17).
FGR was defined as a baby with estimated fetal weight
(EFW) or abdominal circumference (AC) less than 10th
centile, and severe FGR as EFW AC less than 3 rd centile.
Fetuses with growth restriction were identified using
INTERGROWTH-21st charts(18).
Fetal birth weight was recorded and was further classified as
normal (2.5-4.2 kg), LBW (less than 2.5 kg) or large baby
(more than 4.2 kg)(19). Apgar scores at 1 and 5 minutes
were recorded by a pediatrician.
As per the protocol, all newborns received a 1 mg
injection of vitamin K at delivery(20).
Fetal malformations and early neonatal problems were
recorded by a pediatrician. They were classified as major
or minor malformations. Major congenital anomalies were
defined as structural changes that had significant medical,
163
and typically require medical intervention. Examples pregnancy (p=0.26).
include cleft lip, spina bifida, gastroschisis, meningocele. The cause of seizure disorder was unknown in 66% (n=33)
Minor congenital anomalies were defined as structural of the cases. The various causes found are shown in
changes that posed no significant health problems in the Figure 1.
neonatal period and tended to have limited social or
cosmetic consequences for the affected individual. Examples
include single palmar crease and clinodactyly(21).
Follow-up: Patients were followed up from their first ANC
visit till 1 week after delivery to look for early neonatal
complications and postpartum seizure episodes.
Statistical Analysis
Data were analyzed and statistically evaluated using the
Statistical Package for the Social Sciences version- Personal
Computer (SPSS-PC-17) software.
Quantitative data are expressed in mean, standard
deviation, and differences between two comparable groups
were tested using Student’s t-test (unpaired) or the
Mann-Whitney U test. Qualitative data are expressed as
percentages. Statistical differences between the
proportions were tested using the chi- square test or
Fisher’s Exact test. P-values less than 0.05 were considered
statistically significant. Further, odds ratio (OR) and 95%
confidence intervals (CI) were used to quantify the risk
factors. Univariate analysis was performed, and factors that
were found to be significant with p-values ≤0.1 were
entered in multivariate analysis.

Results
The baseline demographic data of the study population
are shown in Table 1. Preconception counselling was
attended by a significantly (p<0.01) greater number of
women with seizure disorder (24%) as compared with
the controls (2%). Periconception folic acid intake was
also observed to be significantly higher (p<0.01) among
cases as compared with controls as depicted in the Table
1.
It was also seen that the women with seizure disorder
(63%) had a significant (p<0.01) history of abortions in the
past when compared with healthy pregnant women
(28.5%).
As depicted in Table 2, generalized onset seizure
disorder (n=44, 88%) was the most common type seen.
Most of the WWE (n=48, 96%) had motor type of seizures
and tonic-clonic was the commonest (n=42, 84%)
subtype.
Around 46% (n=23) had a seizure disorder of duration
between 1-5 years. Among the 30 (60%) women who
experienced seizure episodes during pregnancy, the highest
number (n=8, 26.6%) had it during the third trimester.
Out of these, one woman was not on any AEDs, seven
(24.1%) were not compliant with AED intake, and 22
(75.9%) were regularly taking their medication. History
of seizure in previous pregnancy had no significant
impact on the occurrence of seizure in the current

164
Out of the 50 women enrolled with seizure disorder, 49 were delivered by cesarean section, two (14.3%) had
(98%) were taking AEDs. Out of these, six (12%) were APH, one (7.1%) had cephalopelvic disproportion, three
started on AEDs during the pregnancy. Most of the women (21.4%) had failed induction, six (42.8%) had fetal
(n=24, 48.9%) were taking second-generation AEDs. distress, and two (14.3%) had malpresentation.
Monotherapy was given to 33 (67.2%) women with None of the women with seizure disorder who crossed
levetiracetam being the most commonly prescribed AED the period of viability (n=48) had still birth.
(n=19, 38.7%). Overall, congenital anomalies were observed in three (6.2%)
The most commonly observed change in therapy was the cases and five (2.5%) controls, the difference was not
addition of a drug to the pre-existing treatment as seen statistically significant. However, minor congenital
in 8 (16.3%) women (Table 3). malformations were significantly (p<0.01) more frequent
Women with seizure disorder had a higher incidence of among the cases (n=2%) than in the controls (0%), as
preeclampsia (case n=6, control n=4, p<0.01) and APH depicted in Table 5. The major congenital malformations
(case n=2, control n=0, p<0.01) with no significant among the cases included posterior urethral valve with
difference in the rate of other antenatal complications, as bilateral hydronephrosis, cleft palate, and polydactyly.
detailed in Table 4. A higher number of women with Babies with posterior urethral valves had early neonatal
seizure disorder underwent instrumental vaginal delivery demise. Babies born to mothers with seizure disorder had a
[adjusted odds ratio (aOR)=3.68, CI=1.07-9.64] when significantly increased incidence of early neonatal
compared with the controls. Among the 14 women with complications (Table 5).
seizure disorder who

Figure 1. Causes of seizure disorder in cases

Table 1. Demographic parameters of subjects

Parameter Case (n=50) Control (n=200) p
Age (years) (mean ± SD) 25.38±4.32 25.02±3.07 0.36
Illiterate, % (n) 16 (8) 7.5 (15) 0.06
Weight (kg) mean ± SD 54.48±8.85 55.23±10.37 0.63
Height (cm) 152.49±5.61 154.95±12.04 0.16
Gestational age at recruitment (weeks) (mean ± SD) 22 weeks 6 days ±3 weeks 2 22 weeks ±3 weeks 0.11
days
Nulliparous, % (n) 56 (28) 44 (88) 0.12
Previous cesarean section, % (n) 10 (3) 21.8 (29) 0.20
History of abortion, % (n) 63 (19) 28.5 (38) <0.01
Preconception counselling %, (n) 24 (12) 2 (4) <0.01
Preconception folic acid intake, % (n) 30 (15) 1 (2) <0.01
First-trimester folic acid intake, % (n) 76 (38) 64 (128) 0.03
SD: Standard deviation
Discussion avoid valproate in women of reproductive age group
Preconceptional counselling holds an important place in the wherever possible. In the study by Mawer et al.(22),
planning of pregnancy in women with seizure disorder monotherapy was prescribed to 66.8% of the women,
because a careful balance is required between the type, and carbamazepine was the most commonly prescribed
number, and doses of AEDs for the best possible maternal drug (26.7%), followed by valproate in 20.6% of subjects.
and fetal outcome, thus challenging both the obstetrician Also, in the study by Ozdemir et al.(23), carbamazepine was
and the neurologist. the most commonly prescribed AED (27.5%)(23).
A significantly higher number of women with seizure The occurrence of seizure episodes was found higher in
disorder went for preconception counselling (case =24%, women with unknown etiology (63.6%) than in women
control =1%, p<0.01) and consumed periconception folic with known etiology (52.9%), but the results did not
acid (case =30%, control =1%, p<0.01). This reflected reach the level of significance (p=0.54) as observed by
increased the awareness created among women with seizure Chawla and Subbaiah (24). It was observed that out of the
disorder by the referring neurologists at the associated 30 (60%) women who experienced seizure episodes during
GIPMER hospital regarding preconception counselling pregnancy, 16 (53.3%) had a history of seizure episodes
and the advantage of intake of folic acid in the prenatal within the 9-month period prior to pregnancy. No
period. Folic acid intake was also documented by Borthen significant association (p=0.9) was found between a 9-month
et al.(3) to be significantly greater in WWE than in women seizure-free interval and the prediction of
without epilepsy (case =43.6%, control
=28.5%, p<0.001). Table 3. Antiepileptic drug profile of cases
The majority of the cases were on monotherapy (67.3%) Parameters n %
with levetiracetam being the most commonly prescribed
Patients not on AED in current pregnancy 1 2.0
newer AED (38.7%). Carbamazepine was the second
most commonly used AED (14.2%), and the most Antiepileptic drugs started in current pregnancy 6 12.0
commonly used old antiepileptic drug. Despite the Patient not compliant to AED therapy 13 26.5
established risk of teratogenicity with valproate(10). it was
AEDs taken during pregnancy
consumed by 16.3% of the subjects, either as monotherapy
or a part of polytherapy. This could be because our First generation 18 36.7
hospital serves as a referral center and most of the time we Second generation 24 48.9
receive late referrals when women have already taken First and second generation 7 14.3
valproate in periconceptionally and in the early weeks of
Others
pregnancy. Here, lies the importance of awareness of
preconception counselling and the need for neurologists to -Clonazepam 2 4.0

Table 2. Seizure disorder profile of cases

Parameter n=50 % -Clobazam 6 12.0
Type of seizure Monotherapy 33 67.3
disorders
Focal 5 19 10.0
-Levetiracetam 38.7
-Aware 4 8
-Carbamazepine 7 14.2
-Impaired 1 2
awareness -Valproate 3 6.1
Generalized 44 88.0 -Phenytoin 2 4.1
Focal to generalized
-Oxcarbamazepine 11 2.0
2.0
Up to 1 year 7 14.0 -Phenobarbital 1 2.0
Duration of seizure 1-5 year 23 46.0 -Lamotrigine 0 0
disorders 6-10 year 9 18.0 Polytherapy (2 drugs) 16 32.6
>10 year 11 22.0 -Valproate containing 5 10.2

Date of last seizure prior to ≤9 27 54.0 Drug added 8 16.3

months
pregnancy >9 months 23 46.0 Drug deducted 4 8.2
History of seizure in previous pregnancies 11 36.3 Change in Dose increased 4 8.2
treatment
Seizure episodes in Dose decreased 1 2.0
30 60
current pregnancy Drug changed 2 4.1
Seizure episodes in postpartum period 3 6 AED: Anti-epileptic drugs
 Table 4. Antenatal complications and delivery outcomes among subjects
Cases (n=50) Controls (n=200)
Antenatal complications p-value Adjusted OR (95% CI)#
No (%) No (%)
GDM 3 (6) 11 (5.5) 0.92 1.06 (0.31-1.89)
Hypertensive disorders 9 (18) 15 (7.5) 0.02 -
Gestational hypertension 3 (6) 11 (5.5) 0.92 1.11 (0.69-2.11)
Mild PE 2 (4) 4 (2) 0.4 2.24 (0.39-8.65)
Severe PE 4 (8) 0 (0) <0.001 3.16 (1.67-6.43)*
FGR 11 (22) 38 (19) 0.63 1.24 (0.57-2.69)
Threatened abortion 2 (4) 6 (3) 0.66 1.37 (0.26-7.02)
Hypothyroidism 1 (2) 9 (4.5) 0.69 0.39 (0.04-3.23)
IHCP 2 (4) 7 (3.5) 0.86 1.17 (0.23-5.86)
Abortion 2 (4) 4 (2) 0.34 -
Antepartum haemorrhage 2 (4) 0 (0) <0.001
Delivery outcomes Cases (n=48) Controls (n=196)
Preterm delivery 13 (26) 30 (15) 0.066
Operative vaginal delivery 5 (10.4) 6 (3.1) 0.13 3.68* (1.07-9.64)
Caesarean section 14 (29.10) 39 (19.8) 0.06 1.66 (0.81-3.40)
Induction of labor 19 (39.5) 52 (26.5) 0.1 1.73 (0.92-3.34)
#Adjusted forage, education, previous LSCS (lower segment caesarean section), past history of TB and history of abortion, *Significant at <0.01 level, OR: Odds ratio, CI: Confidence
intervals, GDM: Gestational diabetes mellitus

Table 5. Neonatal outcomes

Cases (n=48) Control (n=197)
Neonatal outcomes p-value Adjusted OR# (95% CI)
n (%) n (%)
Still birth 0 (0) 2 (1) 0.49 -
Low birth weight (<2.5 kg) 13 (27.1) 42 (21.5) 0.41 1.39 (0.66-2.92)
APGAR at 1 minutes ≤7 3 (6.2) 6 (3.1) 0.38 2.13 (0.51-8.89)*
APGAR at 5 minutes ≤7 0 (0) 4 (2) 0.97
Congenital anomalies (n=50) (n=200)
Major (M) 2 (4) 5 (2.5) 0.57
1.44 (0.53-3.06)
Minor (m) 1 (2) 0 (0) <0.01
Early neonatal complications n=48 n=196
Respiratory distress 7 (14.5) 10 (5.1) 0.02 2.96 (1.14-6.97)
NEC 1 (2) 0 (0) 0.04 -
Asphyxia related 2 (4.1) 1 (0.5) 0.04 1.23 (0.86-1.96)
MAS 0 (0) 3 (1.5) 0.39 -
Meningitis 0 (0) 1 (0.5) 0.11 -
Diarrhea 1 (2) 1 (0.5) 0.29 -
Early neonatal death 1 (2) 0 (0) 0.04 -
NICU admission 10 (20.8) 11 (5.6) <0.001 3.47 (1.76-9.35)**
#Adjusted for age, education, previous LSCS, past history of TB and history of abortion,*Significant at 0.05 level, **Significant at 0.01 level, NEC: Necrotizing enterocolitis, NICU:
Neonatal Intensive Care Unit, MAS: Meconium aspiration syndrome
seizure during pregnancy, which was observed in a study Most of the women with seizure disorder in the present study
by Thomas(25). had a normal vaginal delivery (60.4%). However, this
The difference in findings could be attributed to their larger number
sample size.
In this study, seizure frequency was increased in 48% of
the subjects, unchanged in 34%, and decreased in 18%. The
non- compliance or discontinuation of anticonvulsants
might be explained by the women’s concerns about
teratogenic effects of these drugs. However, no significant
difference was observed in noncompliant patients who did
(24.1%) and did not (30%) have seizures during pregnancy
(p=0.2). Thus, it could mainly be due to subtherapeutic
AED levels occurring due to physiologic alterations in
pregnancy leading to increased clearance of the drug(13).
It was also observed that women with seizure disorder
had a significantly higher incidence of abortions in
previous pregnancies (p<0.001). Both spontaneous and
induced abortions were included. It could be the effect of
seizure disorder or voluntarily induction out of concern for
teratogenicity in the babies or ultrasound findings
suggestive of a congenital anomaly.
In this study, 28 (56%) women with seizure disorder
developed antenatal complications against 90 (45%) women in
the control group, but the difference was not statistically
significant (p=0.068). Overall, there was a significantly
higher incidence of hypertensive disorders in women with
seizure disorder in this study (case =18%, control =7.5%,
p=0.02). The rates of gestational hypertension were not
significant between the two groups (case =6%, control
=5.5%, p=0.92). Preeclampsia with severe features was
highly significant in women with seizure disorder in this
study (p<0.001) and it was found to be nearly three times
more common in women with seizure disorder [adjusted
relative risk (aRR)=3.16, CI: 1.67-6.43]. This is similar to
the outcome observed by a register-based study on AED-
using women where an increased risk of preeclampsia was
observed(26). However, the American Academy of Neurology
in their report concluded that the evidence was
insufficient to support or refute an increased risk of
gestational hypertension or preeclampsia in WWE-taking
AEDs(27).
APH was significantly higher in women with seizure
disorder
(p<0.001). Harden et al.(27) also concluded that there was
a moderately increased risk of late pregnancy- related
bleeding complications. On the other hand, Richmond et al.
(7)
and Katz et al.(8) reported no increased association of
placental abruption in WWE.
No increased association was established in the rates of
GDM (p=0.98, aRR=1.06, CI: 0.31-1.89), hypothyroidism
(aRR=0.39, CI: 0.04-3.23), intrahepatic cholestasis of
pregnancy (aRR=1.17, CI: 0.23-5.86) in women with seizure
disorder in this study. Chawla and Subbaiah (24) also found
similar outcomes in their study.
was significantly less than among healthy pregnant women meta-analysis by Viale et al.(29), rates of NICU admission
(73.7%, p=0.01). Risk of instrumental delivery was found to were significantly higher in WWE when compared with
be around 3.7 times higher in women with seizure heathy controls.
disorder than in healthy pregnant women. The number of Overall, the incidence of congenital anomalies in this
women with seizure disorder who underwent cesarean study population was 3.2%. Women with seizure disorder
section were 1.6 times higher than in the controls, but had an
the difference did not reach the level of significance
(p=0.06). Harden et al. (27) also concluded a moderately
increased risk of cesarean delivery in women with seizure
disorder.
LBW babies were born to around 27% mothers with
seizure disorder. This rate was slightly higher than among
the healthy mothers and was not statistically different
(aRR=1.39, CI: 0.66- 2.92). Katz et al.(8) also reported no
significant association between seizure disorder and
LBW babies (p=0.62).
Overall, the incidence of congenital anomalies in this
study population was 3.2%. Women with seizure
disorder had an incidence of 6% and healthy pregnant
women had an incidence of 2.5%. Major congenital
anomalies were found in 4% (n=2) of babies born to
mothers with seizure disorder and 2.5% (n=5) of the
healthy mothers. Out of the three babies of case group
with a congenital malformation, two (66.6%) babies
were on polytherapy and the mother of one (33.3%) baby
was receiving monotherapy with phenytoin. In the
polytherapy group, one mother with valproate-based
polytherapy gave birth to a baby with polydactyly and the
other mother who was on a carbamazepine-based
polytherapy had a baby with posterior urethral anomaly.
In the present study, the rates of congenital malformations
were
1.4 times higher than in the controls, but it was not
statistically significant (aRR=1.4, CI: 0.53-3.06). Borthen et
al.(6) found a significantly higher rate of congenital
malformations in WWE on anticonvulsive drugs,
compared with the control group (p=0.007).
Babies of mothers with seizure disorder in this study were
found to have a significantly higher incidence of respiratory
distress (p=0.02), necrotizing enterocolitis (p=0.04),
asphyxia-related complications (p=0.04), and early neonatal
death (p=0.04). The baby who died in the early neonatal
period was born preterm, had LBW and also had bilateral
posterior urethral valve and went into multiorgan failure.
Razaz et al.(28) found an increased risk of neonatal
complications in WWE when compared with controls such
as hypoglycemia (OR=1.53, CI: 1.34-1.75), infections
(OR=1.42, CI: 1.17-1.73), asphyxia-related complications
(OR=1.75, CI: 1.26-2.42), and respiratory distress
(OR=1.48, CI: 1.30-1.68).
In this present study, admission to the NICU was reported
to be
3.4 times more frequent in babies born to women with
seizure disorder than in the controls (aRR=3.4, CI: 1.76
-9.35) and was found significant (p=0.01). In a recent
incidence of 6% and healthy pregnant women had an should be managed with the least teratogenic AEDs at the
incidence of 2.5%. Major congenital anomalies were found lowest possible dose to diminish the risk of complications,
in 4% (n=2) of babies born to mothers with seizure and also maintain good seizure control. Babies born to
disorder and 2.5% (n=5) of the healthy mothers. Out of women with seizure disorder
the three babies of case group with a congenital
malformation, two (66.6%) babies were on polytherapy
and the mother of one (33.3%) baby was receiving
monotherapy with phenytoin. In the polytherapy group, one
mother with valproate-based polytherapy gave birth to a baby
with polydactyly and the other mother who was on a
carbamazepine-based polytherapy had a baby with
posterior urethral anomaly.
In the present study, the rates of congenital malformations were
1.4 times higher than in the controls, but it was not
statistically significant (aRR=1.4, CI: 0.53-3.06). Borthen et
al.(6) found a significantly higher rate of congenital
malformations in WWE on anticonvulsive drugs,
compared with the control group (p=0.007).
The risk of congenital anomalies was not increased in
women with seizure disorder. This could be attributed to
significantly higher intake of periconceptional folic acid
in women with seizure disorder and higher consumption of
least teratogenic drugs in this study such as levetiracetam
and carbamazepine as was shown by Peterson et al.(30).
Study Limitations
Large sample size studies are needed to be performed in
a prospective manner in order to assess the impact of
seizure disorder on maternal and neonatal outcomes. Also,
studies need to focus on seizure control in pregnancy,
individual AEDs and their dose, and their effect on
pregnancy complications.

Conclusion
Women with seizure disorder and AED use had an
increased risk of preeclampsia and APH. The risk of
induction of labor and cesarean section was not increased
but there was increased risk of instrumental vaginal
delivery. Babies of mothers with seizure disorder had an
increased risk of early neonatal complications, early
neonatal death, and NICU admissions. The risk of congenital
anomalies and LBW babies was not increased in women
with seizure disorder.
Interpretation
On the basis of findings of this study, women with
seizure disorder should be informed that there is small
but significant risk of obstetric complications. Women
with seizure disorder should be monitored regularly for
BP for the early detection of hypertensive disorders.
Attention should be given to women in labor for the early
detection and management of APH. Periconception folic
acid intake should be encouraged and these women
need expert pediatrician follow-up for the management J Matern Fetal Neonatal Med 2006;19:21-5.
of neonatal complications.
Acknowledgements
I would like to express my deepest appreciation to all those
who helped me completing this report. A special
gratitude to the patients who consented us to for this
study.
Ethics
Ethics Committee Approval: This was a longitudinal study
conducted after obtaining clearance from the Institutional
Ethics Committee among women attending the antenatal
outpatient department (OPD)/high-risk OPD/gyne casualty in the
department of Obstetrics and Gynecology, Maulana Azad
Medical College and associated Lok Nayak Hospital, Govind
Ballabh Pant Institute of Postgraduate Medical Education and
Research (GIPMER) hospital, New Delhi, from November
2016 to January 2017 (15 months) (approval number: 113,
date: 04/11/2016).
Informed Consent: Informed consent was obtained from
the participants.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Concept: T.P.K., L.S., Design: A.M.R., S.B., Data Collection
or Processing: T.P.K., L.S., Analysis or Interpretation: T.P.K.,
L.S., Literature Search: A.M.R., Writing: T.P.K., L.S.
Conflict of Interest: The authors report no conflict of
interest. Financial Disclosure: Authors have no financial
interests about the research.

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