GYNEtOLoGY

& OBSTETRICS
InternationalJournal of Gynecology& Obstetrics54 (1996)17-22

Article

Pregnancy with epilepsy -

a retrospective analysis

H. Sawhney* a, K. Vasishtaa, V. Suria, B. Khunnua, P. Gael, I.M.S. Sawhneyb

DDeprtment of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigcuh, In&
bDepartment of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Received17October1995;revised18March 1996;accepted20 March 1996

Objectives: To study the course of epilepsy in pregnancy and to assessthe perinatal outcome. Method: A retrospective analysis of 219 pregnant patients with epilepsy. The type of epilepsy, drug therapy and seizure frequency were
documented. The perinatal outcome of 157 pregnancies with epilepsy was analyzed and compared with that of 471
normal gravidas of similar age and parity. Results: Generalized seizures occurred in 203 patients, partial seizures in
13 patients and complex partial seizures in three patients. One hundred fifty-two patients (69.41%) were on
monotherapy. Carbamazepine was the most common drug (56.58%) used. Ninety-five patients (43.38%)had seizures
in the current pregnancy, five of whom had status epilepticus. There was no maternal mortality in status epilepticus.
There was no difference in perinatal outcome between the study and control groups. The incidence of congenital malformations was higher in the control group (51476,1.05%)than in the study group (l/160, 0.63%). The incidence of
low-birth-weight babies was higher in the study group in patients with gestational seizures. Conclusion: The course of
pregnancy and perinatal outcome was not altered by epilepsy. There was no increase in the incidence of congenital
malformations with the use of monotherapy.
Keywordr: Pregnancy; Epilepsy; Anticonvulsants; Status epilepticus

1. Introductioo

Epilepsy is one of the most common pre-existing

neurologic disorders encountered by the obstetrician and affects approximately 1 in 200 pregnancies [l]. Pregnancy in women with epilepsy is still
considered to be high risk becauseof the possible
increase in frequency of seizures during pregnancy, labor and delivery [2-41, and because of
* Correspondingauthor, Fax: +91 172540401.

the possible high number of complications during

labor and adverse outcome [5-71. Higher rates of
prematurity [5,8,9], low birth weight (LBW)
[lo-131 and neonatal and perinatal deaths [8,9]
have been reported among infants of mothers with
epilepsy. Despite the availability of a vast literature on the subject of the risk of pregnancy in
women with epilepsy, no complete agreement has
been reached about the real incidence of these
events and the possible influence of other factors
in their production.

0020-7292196B.15.00
0 1996International Federationof Gynecologyand Obstetrics
PII: SOOZO-7292(96)02683-S

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H. Sawhney et al. /International

Journal of Gynecology di Obstetrics 54 (19%) 17-22

In the developing countries epilepsy is still considered taboo and drug compliance is poor. The
patient often only seekstreatment for epilepsy for
the first time during pregnancy. Data on the
course of epilepsy during pregnancy and perinatal
outcome from the developing countries are sparse.
The present study was undertaken in a developing
country to study the effect of pregnancy on epilepsy and pregnancy outcome.

3. Results

2. Materials aml methods

3.1. Diseasecharacteristics
Generalized seizures occurred in 203 patients,
partial seizuresin 13 patients and complex partial
seizures in three patients. One hundred fifty-two
patients (69.41%) were on monotherapy - carbamazepine in 56.58%, phenytoin in 34.21% and
phenobarbital in 8.55%. Sixty-two patients
(28.31%)were on combination therapy, phenobarbital and phenytoin being the most frequent combination used. Five patients were not receiving any
treatment (Table 1). The duration of epilepsy was
55 years in 120 patients (54.79%), 25 of whom
had onset of epilepsy in the current pregnancy.
Epilepsy was of long-standing duration (> 5 years)
in 99 patients (45.21%).

A retrospective analysis was carried out of pregnancies with epilepsy over a period of 8 years
(1987-1994). Two hundred nineteen pregnant patients with epilepsy, registered at the Medical Surgical Disorder Antenatal Clinic of the Department
of Obstetrics and Gynaecology of Nehru Hospital,
Chandigarh, were studied. During this period a
total of 26 767 deliveries took place at the hospital.
All patients were placed under the supervision of
a neurologist and an obstetrician. Epileptic mothers were not given antenatal vitamin K supplementation. All the newborns received vitamin K
injection and were examined by trained neonatologists. Sixty-one patients were lost to follow-up
and did not deliver at our hospital. One patient
had a missed abortion.
For each case who delivered at our hospital,
three age- and parity-matched healthy gravidas
(n = 471) who had delivered at the hospital within
48 h of the study case, were chosen as controls.
Documentation of type and duration of epilepsy,
details of antiepileptic drugs, tit frequency during
pregnancy and antenatal complications such as
abortions, pregnancy-induced hypertension and
antepartum hemorrhage was done. Intrapartum
events, mode of delivery and perinatal outcome
were noted in all patients. All neonatesless than 1
standard deviation from the mean birth weight for
gestational age according to our institutes reference intrauterine growth curve, were classified as
small for gestational age (SGA). Neonates with a
birth weight ~2.5 kg were considered to be of
LBW. Statistical analysis was carried out using the
x2-test, and Yates correction was applied
wherever indicated.

The mean age of the patients in the study group

was 25.14 * 3.47 years and 93 patients (42.47%)
were primigravidas. The occurrence of pregnancyinduced hypertension was slightly higher in the
study group (9.55O/, than in the control group
(8.06%). There were three twin pregnancies in the
study group and five in the control group.

3.2. Effe of pregnancy on epilepsy (Tables 2-4)

Ninety-five patients (43.48%)had seizuresin the

Table 1
Treatment protocol
Drug therapy

Monotherapy
Carbamazepine
Phenytoin
Phenobarbital
Valproic acid
Combination therapy
Phenytoin + phenobarbital
Phenytoin + carbamazepine
Carbamazepine + phenobarbital
Phenytoin + valproic acid
Phenobarbitone + valproic acid
No therapy

No. of patients
(n = 219)
No.

152
86
52
13
1
62
33
16
11
1
1
5

69.41
56.58
34.21
8.55
0.66
28.31
53.23
25.81
17.74
1.61
1.61
2.28

H. Sawhney et al. /lnrernational

Journal of Gynecology & Obstetrics 54 (19%) 17-22

Table 2
Effect of pregnancy on seizures
Gestational seizures

Table 4
Duration of epilepsy and occurrence of gestational seizures
No. of patients
(n = 95)

Duration of epilepsy

Gestational seirures
Present

No. of seizures
l-2
2-5
>5
Gestational age at seizures
1st trimester
2nd trimester
3rd trimester
All trimesters

19

No.

16
12
7

80
12.63
1.37

24
32
35
4

25.26
33.68
36.84
4.21

Onset during pregnancy

(n = 25)
s5 Years
(n = 95)
>5 Years
(n=99)

(n = 95)

Absent
(n = 124)

25

24/95
(25.26%);

71195
(74.74%))+
53l99
(53.54%)**

;6%%)*

P < 0.05, l *P > 0.05.

index pregnancy, 19 (20%) of whom had more

than two; five of these patients had status epilepticus. The most common time for recurrence of seizures was the third trimester. The seizures were
terminated in casesof status epilepticus with intravenous diazepam bolus and an intravenous
loading dose of phenytoin. Seizures could not be
controlled in one patient and she required a thiopental drip and ventilation.
Seventy-onepatients (74.74%) with epilepsy I 5
years duration remained seizure-free in the current pregnancy, whilst in long-standing epilepsy
(>5 years), 53.54% had no seizures.
3.3. Delivery characteristics and perinatal outcome
(Tables 5 and 6)

In the study group one patient had a missed

abortion.
The mean gestational age was similar in both

groups (study group 38.06 A 1.42 weeks, control

group 38.17 * 3.58 weeks).
The incidence of cesareansection was higher in
the study group (26.75OA)than in the control group
(14.23%) although in the control group the incidence of cesarean section for fetal distress was
higher.
The mean birth weight was 2823.55 f 564.43 g
in the study group and 2770.77 f 551.89 g in the
control group. The incidence of LBW babies was
higher in the control group although the difference
betweenthe two groups was not statistically significant. In the study group one baby was congenitally malformed having hydrocephalus with spina
bilida. This was a twin pregnancy with a normal
co-twin and the mother had not received any treatment during pregnancy. There were five congenitally malformed babies (four neural tube
defects, one penile hypospadias) in the control
group.

Table 3
Outcome of pregnancies with status epilepticus
Patient
no.

Duration of epilepsy

1
2
3
4
5

3.5 Years
Onset during pregnancy
6 Years
Onset during pregnancy
2 Years

Gestational age (weeks)

At status

At delivery

34
28
23
33
35

37
37
38
34.5
37.5

NVD, normal vaginal delivery; LB, liveborn; SB, stillborn.

Ventilation.

Interval to
delivery

Type of delivery

Outcome

3 Weeks
9 Weeks
15 Weeks
11 Days
18 Days

NVD
Cesarean section
NVD
NVD
NVD

LB 3.6 kg
LB 2.5 kg
LB 2.8 kg
SB 1.2 kg
LB 2.4 kg

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H. Sawhney er al. /International

Journal of Gynecology & Obstetrics 54 (1996) 17-22

Table 5
Delivery characteristics
Study group (n = 157)
No.
Gestational age (weeks)
(mean i S.D.)
Type of delivery
Vaginal
Spontaneous
Assisted (forceps/ventouse)
Cesarean section
Fetal distress
Cephalo-pelvic disproportion
Cervical dystocia
Placenta previa
Malpresentation

38.06 f 1.42

115
101
14
42
16
14
7
3
2

Control group (n = 471)

No.

38.17 f 3.58

73.25*
64.33
8.92
26.75*

404
376
28
67
31
27
3
3
3

85.77
79.83
5.94
14.23

*P < 0.05.

3.4. Gestational seizures and perinatal outcome

(Table 7)
Of the 157 patients in the study group who
delivered at our hospital, 67 had seizures in the
present pregnancy, 65 had generalized convulsion,
one had focal seizuresand one had complex partial
seizures. Gestational seizures had no effect on
mean birth weight. There was no difference in the
incidence of cesarean section for fetal distress in
the two groups. The incidence of LBW and SGA
babies was higher in the presence of gestational
seizures.There was one stillbirth in a patient who
had status epilepticus.

4. Discnssioo
Seizure control during pregnancy and the
puerperium is influenced by a number of factors
including physiological changessuch as increased
levels of estrogens and progestogens, which alter
seizurethreshold [2,3], change in medication compliance [4], sleep deprivation [3], as well as
changes in the pharmacokinetics of antiepileptic
drugs which tend to lower drug blood levels
[14-161. The effect of pregnancy on epilepsy
varies. The reported change in seizure frequency
varies widely [lo- 12,14,17]: seizure frequency in

Table 6
Perinatal outcome
Study group (n = 160)
No.
Birth weight (g)
(mean f S.D.)
Livebom
Stillborn
LBW
SGA
Congenital malformations
l P > 0.05.

2823.55 f 564.43
159
1
25
12
1

99.38
0.63
I5.63*
7.50*
0.63

Control group (n = 476)

No.

2770.77 AZ551.89
476

100.00

86
52
5

18.07*
10.92*
1.os

H. Sawhney et al. /International

Journal of Gynecology & Obstetrics 54 (19%) 17-22

21

Table 7
Gestational seizuresand perinatal outcome
Gestational seizures
Present
(n = 68)
Gestational age (weeks)
(mean f I SD.)
Birth weight (g)
(mean f 1 S.D.)
Livebom
Stillborn
LBW
SGA
Cesarean for fetal distress

Absent
(II = 92)

37.78 f 1.50

38.16 + 1.46

2875.95 f 430.53

2766.96 f 586.94

61
1
14 (20.59%)*
7 (10.29%)2
5/14 (35.71%)

92
11 (11.96%)+
5 (5.43%).
1l/28 (39.29%)

l P > 0.05.

pregnancy has been reported to increasein 4-75%

of casesor decreasein 3-82% of cases,whilst most
recent studies report that seizure frequency does
not change significantly in 60-83% of women with
epilepsy [11,12,17].
Many investigators have concluded that the
effect of pregnancy on epilepsy is unpredictable.
However, others have found that the severity of
epilepsy prior to pregnancy is predictive of exacerbation of seizures during gestation. Knight and
Rhind [2] reported that women with more than
one seizure per month had an increased frequency
of seizuresduring pregnancy, while those with less
than one seizure every 9 months did not have any
increase in frequency. Gjerde et al. [17] observed
that there was a strong tendency for cases with
pregestational seizures to have seizures during
pregnancy. Seventy-nine percent of cases with
pregestational seizures had seizures during pregnancy, whereas in caseswithout seizures prior to
pregnancy, only 16% experienced seizures during
pregnancy.
In the present study 95 patients (43.38%) had
seizures during pregnancy and in 25 patients
(11.42%) onset of seizures was in the index pregnancy. Exact seizure frequency prior to pregnancy
was not known in the remaining 70 patients. The
incidence of gestational seizures increased with
increase in duration of epilepsy. Seventy-one patients (74.75%) with epilepsy ~5 years duration
remained seizure-free,while with increasing dura-

tion of epilepsy (> 5 years), only 53199(53.54%)remained seizure-free. However there was no
statistically significant difference in the number of
patients with or without seizureswhen duration of
epilepsy was more than 5 years.
Status epilepticus is a rare occurrence during
pregnancy and is associatedwith increased maternal and perinatal mortality [ 1,2,4]. In the present
study there was one stillbirth but no maternal mortality with status epilepticus.
An excessin almost all of the common pregnancy complications has been observed in many
studies of pregnanciesin women with epilepsy, including preeclampsia, bleeding in pregnancy and
premature labor [1,9,10,12]. The relative risk of
these complications is approximately 1.5-3 times
the risk of that in women without epilepsy [9].
However in the present study there was no difference in pregnancy complications in patients with
epilepsy compared with the control group.
A higher incidence of congenital malformations
has been reported in infants of mothers with
epilepsy with or without use of antiepileptic drugs
[ 12- 161.The reported frequency of malformations
in infants of mothers with epilepsy ranges from
1.25 to 11.5%,and trimethadione, phenytoin and
valproic acid are widely considered to be human
teratogens. Polypharmacy increasesthe incidence
of congenital malformations [l l] and in recent
studies [ 13,181it was observed that reduction or
near elimination of polypharmacy reduced the

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Journal of Gynecology & Obstetrics 54 (19%) 17-22

overall prevalence of malformations from 13.5 to

6.2%. In the present analysis, only one baby had
hydrocephalus with spina bitida and that too occurred in a pregnancy which was not exposed to
antiepileptic drugs. The majority of the patients
were on monotherapy (69.41%), carbamazepine
being the most frequently used drug.
Increased perinatal mortality (1.2- to 3-fold) has
been reported in women with epilepsy [2,10]. Intrauterine deaths after a seizure have been
reported only occasionally. Occurrence of seizure
in the index pregnancy did not make any significant difference to the birth weight of the newborns
in the present study. The incidence of LBW was
higher in patients with gestational seizures, however the results were not statistically significant.
One intrauterine death occurred in a status epilepticus patient while all other babies had good
Apgar scoresat 5 min.
This retrospective study showed that there was
a slight increase in the incidence of pregnancyinduced hypertension in epileptic mothers. However the prevalence of other complications associated with pregnancy remained the same.There was
no change in the perinatal outcome and incidence
of congenital malformations. The avoidance of
polypharmacy in a large number of patients may
have been responsible for these results.
References
[l] Yerby MS. Problems and management
of the pregnant
woman with epilepsy. Epilepsia 1987; 28 Suppl 13:
S29-36.
[2] Knight AH, Rhind EG. Epilepsy and pregnancy: a study
of 153 pregnancies in 59 patients. Epilepsia 1975; 16:
99-110.
[3] Schmidt D, Conyen R, Avanzini G et al. Change in
seizure frequency in pregnant epileptic women. J Neurol
Neurosurg Psychiatry 1983;46: 751-755.

[41 Philbert A, Dam M. The epileptic mother and her child.

Epilepsia 1982;23: 85-99.
I51 Bjerkdal T, Bahna SL. The course and outcome of pregnancy in women with epilepsy. Acta Obstet Gynecol
Stand 1973; 52: 245-248.
161Montouris GD, Feinchel GM, MclainW. The pregnant
epileptic. Arch Neurol 1979; 36: 601-603.
I71 Yerby M, Koepsell T, Daling J. Pregnancycomplications
and outcome in a cohort of women with epilepsy. Epilepsia 1985;26: 631-635.
181Hiilesmaa VK, Teramo K, Granstrom ML et al. Fetal
head growth retardation associated with maternal antiepileptic drugs. Lancet 1981;ii: 165-167.
191 Yerby MS. Pregnancy and epilepsy. Epilepsia 1991: 32
Suppl6: s51-59.
1101Hiilesmaa VK. Pregnancy and birth in women with
epilepsy. Neurology 1992;42 Suppl 5: 8- 11.
1111Tanganelli P, RagestaG. Epilepsy, pregnancy and major
birth anomalies: an Italian prospective, controlled study.
Neurology 1992;42 Suppl 5: 89-93.
1121Svigos JM. Epilepsy and pregnancy. Aust N Z J Obstet
Gynaecol 1984;24: 182-185.
1131Lindout D, Meinardi H, Meizer JWA et al. Antiepileptic
drugs and teratogenesis in two consecutive cohorts:
changes in prescription policy paralleled by changes in
pattern of malformations. Neurology 1992;42 Suppl 5:
94-l 10.
[I41 Otani K. Risk factors for the increasedseizure frequency
during pregnancy and the puerperium. Foha Psychiatry
Neurol J 1985;39: 33-42.
1151Dansky L, Andermann E, Scherwin AL, Andermann F.
Plasma levels of phenytoin during pregnancy and the
puerperium. In: Janz D, Bossil D, Dam M, Heige H,
Richens A et al, editors. Epilepsy, pregnancy and the
child. New York: Raven Press, 1982: 155-162.
It51Janz D. Antiepileptic drugs and pregnancy: altered
utilization patterns and teratogenesis.Epilepsia 1982;23
Suppl 1: S53-62.
[I71 Gjerde ID, Strandjord RE, Ulstein M. The course of
epilepsy during pregnancy: a study of 78 cases. Acta
Neurol Stand 1988;78: 198-205.
ltsl Kaneko S, Otani K, Kondo T et al. Malformations in
infants of mothers with epilepsy receiving antiepileptic
drugs. Neurology 1992;42 Suppl 5: 68-74.