American Journal of Obstetrics and Gynecology (2004) 190, 1331e4

www.elsevier.com/locate/ajog

Maternal and perinatal outcome in women with

a history of stroke
Kristin H. Coppage, MD,a Andrea C. Hinton, MD,a Julie Moldenhauer, MD,b
Oormila Kovilam, MD,a John R. Barton, MD,c Baha M. Sibai, MDa,*

Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, Ohioa; Wayne State University,
Detroit, Michb; and Central Baptist Hospital, Lexington, Kyc

Received for publication August 25, 2003; revised October 28, 2003; accepted November 4, 2003

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KEY WORDS Objective: The purpose of this study was to determine recurrence risk and pregnancy outcome in
Stroke 23 women with a history of stroke.
Pregnancy Study design: We conducted a descriptive study of 23 women (35 pregnancies) with a history of
Recurrence stroke. Charts were reviewed from 1990 through 2002. The data were analyzed for the antenatal
treatment strategies, recurrence risk for stroke, and pregnancy outcome.
Results: There were 23 study patients with 35 subsequent pregnancies. Associated risk factors of
the stroke were thrombophilia (5 women), sickle cell disease (3 women), maternal cardiac malfor-
mations (3 women), hypertension (3 women), oral contraceptive use (2 women), cerebral arterio-
venous malformations (2 women), head trauma (1 woman), meningitis (1 woman), endocarditis
(1 woman), and idiopathic reason (2 women). Four women with 9 subsequent pregnancies had
a stroke that was associated with a previous pregnancy or postpartum incident. Two of these 9
pregnancies received anticoagulation (heparin, 1 pregnancy; heparin plus aspirin, 1 pregnancy).
Nineteen women with 26 subsequent pregnancies had a stroke before pregnancy. Nine of these
26 pregnancies received anticoagulation (heparin, 5 pregnancies; aspirin, 3 pregnancies; heparin
plus aspirin, 1 pregnancy). The remaining pregnancies did not receive prophylactic anticoagula-
tion. Overall, there were 21 term deliveries, 8 preterm deliveries, 5 miscarriages, and 1 fetal death.
Three of 34 pregnancies (9%) were small for gestational age infants. There were no recurrent
thrombotic episodes during pregnancy or after delivery. Maternal complications included admis-
sion to the intensive care unit for uncontrolled hypertension in 1 patient.
Conclusion: Women with a history of stroke have a low risk of recurrent stroke (0%). This infor-
mation is useful for the prepregnancy counseling of such individuals. The need for prophylactic
anticoagulation in patients with a previous stroke cannot be answered by this study.
Ó 2004 Elsevier Inc. All rights reserved.
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The incidence of stroke in women of childbearing age

averages 10.7 in 100,000 women.1-3 Pregnancy has been
* Reprint requests: Baha M. Sibai, MD, Department of Obstetrics
and Gynecology, University of Cincinnati, 231 Albert Sabin Way, ML
postulated to increase the risk of stroke because of
0526, Cincinnati, OH 45267-0526. its hypercoagulable state and the increase in venous
E-mail: baha.sibai@uc.edu stasis. Cerebrovascular disorders in pregnancy have been

0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajog.2003.11.002
1332
Table I Demographic variables
Variable Mean Range
Age at time of stroke (y) 22 2-36
Age during index pregnancy (y) 26 16-37
Interval between stroke and 4 1-19
index pregnancy (y)
Stroke during pregnancy/postpartum 4 (17%)
period (n)
Black race (n) 8 (35%)
History of substance abuse (n) 0 in women with pregnancy-related strokes (n = 4 woman)
Tobacco use (n) 5 (22%)
Chronic hypertension (n) 3 (13%)
associated with increased maternal morbidity and in-
creased perinatal morbidity and morality rates.2-9 Most
studies, however, have evaluated pregnancy outcomes
in women who had a stroke in pregnancy or in the
peripartum period; therefore, little information exists
regarding the recurrence, counseling, and treatment of
the patient with a history of a stroke.10,11 The objective
of this study was to determine the recurrence risk, ther-
apeutic interventions, and pregnancy outcomes in
women with a history of stroke.
Material and methods
This was a retrospective case series of pregnant women
with a history of stroke. The 3 centers that were involved
in data collection were the University of Cincinnati,
Central Baptist Hospital, and Wayne State University.
The years from 1990 through 2002 were reviewed in each
center. Charts were selected by International Classifica-
tion of Diseasese9 codes and a perinatal database. In-
clusion criteria were a history of nonobstetric stroke
or a stroke that was documented during the preg-
nancy/postpartum period before the index pregnancy.
Demographic data that included maternal age, race, ges-
tational age, associated medical conditions, and sub-
stance abuse were collected. The pregnancy course was
reviewed for prenatal care, anticoagulation treatment,
hospitalizations, and outcomes. Delivery data and neo-
natal outcome data were also collected. The data were
analyzed regarding antenatal treatment strategies, preg-
nancy outcomes, and recurrence risks.
Results
During the study period, there were a total of 164,689 de-
liveries at the participating institutions. There were 23
women with a total of 35 subsequent pregnancies that
were analyzed. Associated risk factors of the initial stroke
Coppage et al
were thrombophilia (5 women), sickle cell disease (3
women), maternal cardiac malformations (3 women), hy-
pertension (3 women), oral contraceptive use (2 women),
cerebral arteriovenous malformations (2 women), head
trauma (1 woman), meningitis (1 woman), endocarditis
(1 woman), and idiopathic factors (2 women). The demo-
graphic variables are listed in Table I. Eleven pregnancies
(8 pregnancies with associated thrombophilia) received
prophylactic anticoagulation. Two of the 9 pregnancies
received anticoagulation (heparin, 1 woman; heparin plus
aspirin, 1 woman). Nine of the 26 pregnancies in women
with stroke that was unrelated to pregnancy (n = 19
woman) received anticoagulation (heparin, 5 women; as-
pirin, 3 women; heparin plus aspirin, 1 woman). The re-
maining 24 pregnancies did not receive prophylactic
anticoagulation.
Overall, there were 21 term deliveries, 8 preterm de-
liveries, 5 miscarriages, and 1 fetal death. Nine deliveries
(26%) were by cesarean delivery; 1 delivery (2.8 %) was
a forceps-assisted delivery, and the remainder of the de-
liveries (25-71.2%) were spontaneous vaginal deliver-
ies. The 8 preterm deliveries were due to premature
rupture of the membranes or preterm labor (5 deliver-
ies); 1 delivery was due to preeclampsia; 1 delivery was
due to maternal congestive heart failure; and 1 delivery
was a repeat cesarean delivery.
There were no recurrent cerebrovascular episodes
during pregnancy or in the postpartum period. Maternal
complications included admission to the intensive care
unit because of uncontrolled hypertension (1 patient),
endomyometritis (1 patient), and postpartum seizure in
1 woman with a history of seizures. Neonatal complica-
tions included small for gestational age (3 infants) and
transient tachypnea of the newborn (2 infants: 1 infant
was delivered at 34 weeks of gestation because of pre-
eclampsia, and 1 twin delivered at 36 weeks of gestation
because preterm labor). Detailed pregnancy outcomes
are found in Table II.
Comment
Over the past decades, there has been significant im-
provement in the treatment of individuals with stroke.
As a result, most of these women are recovering without
residual neurologic deficits. Consequently, some of these
women will seek counseling regarding future pregnan-
cies. In reviewing the literature, we were surprised about
the paucity of data about this subject. Our study is
unique because of its sample size and because it included
information that was collected from medical records and
that the authors followed many of these women. In this
large case series, women with a history of stroke were
found to have a low risk of recurrent stroke (0%) or
other pregnancy complications. These findings are in
Coppage et al 1333

Table II Pregnancy outcome

Stroke during Received
Patient Cause of stroke/lesion previous pregnancy Thrombophilia Any residual anticoagulation Pregnancy outcomes
1 Sagittal sinus thrombosis During the Protein S deficiency No Therapeutic heparin Preeclampsia at 36 weeks 3
postpartum period days of gestation
2 Uncontrolled hypertension At 39 weeks Not done Right-sided weakness No Premature rupture of
membranes at 26 weeks
(pregnancy 1) and at 36 weeks
(pregnancy 2) of gestation
3 Oral contraceptive user; No Negative Right-sided weakness Baby aspirin Term: small for
smoker; left anterior gestational age
cerebral artery occlusion
4 Head trauma No Not done Right-sided weakness Baby aspirin Term
5 Oral contraceptive user; No Negative Right-sided numbness No Term
left parietal region
6 Congenital cardiac malformation No Not done No No Maternal congestive heart
occurred during the correction failure at 34 weeks of
procedure; right frontoparietal gestation
region
7 Idiopathic No Negative Left-sided weakness Prophylactic heparin Pregnancy 1, term;
pregnancy 2,
36 weeks of gestation
8 Severe sickle cell disease No Not done No No 2 pregnancies at term
9 Severe sickle cell disease/right No Not done No No Term
posterior temporal
10 Severe Sickle cell disease No Not done No No 2 pregnancies at term
11 Endocarditis; left middle No Negative Expressive aphasia; Prophylactic heparin Term
cerebral artery occlusion right-sided
hemiplegia and
hemianesthesia
12 Meningitis No Not done No No Term
13 Patent foramen ovale-uncorrected; No Negative Dysarthria Prophylactic heparin Pregnancy 1, miscarriage;
left middle cerebral artery pregnancy 2, at term
occlusion
14 Intracranial arteriovenous No Not done Right-sided weakness No Twins at 36 weeks of
malformation-corrected; left gestation
thalamic region
15 Atrial septal defect- uncorrected No Not done Left arm weakness Baby aspirin Term
16 Idiopathic; right lacunar infarct in No Negative Right-sided muscle No Term
deep white matter twitching
17 Protein S deficiency thrombosis No Protein S deficiency No Enoxaprin (Lovenox) Term
18 Factor V Leiden mutation; middle No Factor V Leiden No Heparin Term: small for gestational age
cerebral artery occlusion mutation
19 Sticky platelet syndrome No Sticky platelet Right-sided weaknessHeparin and baby Term: small for gestational age
syndrome aspirin
20 Protein C deficiency; right middle During the Protein C deficiency Left paraplegia Heparin and baby aspirin Pregnancy 1 and 2,
cerebral artery occlusion postpartum period miscarriage;
pregnancy 3,
premature rupture
of membranes at 35 weeks;
pregnancy 4, term
21 Uncontrolled hypertension At 6 weeks Not done No No Pregnancy 1, miscarriage;
pregnancy 2, intrauterine
fetal death at 26
weeks of gestation
and intensive care unit
admission for uncontrolled
hypertension
22 Intracranial arteriovenous No Not done Right-sided weakness No Pregnancy 1, miscarriage;
malformation- corrected pregnancy 2, premature
rupture of membranes at 34
weeks of gestation; pregnancy
3 and 4, term
23 Uncontrolled hypertension; right No Not done No No Term
posterior temporal infarct

agreement with the work of Lamy et al10 in France who patients from 9 neurologic centers in France from 1987
studied 125 women with a history of ischemic stroke in through 1991. In their cohort study, they noted that on-
187 subsequent pregnancies. This study consisted of ly 2 of the 13 recurrent strokes were associated with
a mailed questionnaire and a phone survey of surviving a subsequent pregnancy/postpartum period, which gives
1334
a recurrence risk of stroke of 1% (2/187 pregnancies),
which is similar to the recurrence risk of 0% found in
our study.
Our data are also reassuring for patients with throm-
bophilia. Overall, 5 of our patients with thrombophilia
who had 8 subsequent pregnancies received various
forms of anticoagulation (unfractionated heparin or
enoxaparin), and all 8 women had normal pregnancy
outcomes and no recurrent stroke in their subsequent
pregnancies. Our results differ, however, from the study
by Soriano et al,11 who studied 12 patients with a previ-
ous stroke who also had thrombophilia in 15 subsequent
pregnancies. Each patient received prophylactic low mo-
lecular weight heparin and low-dose aspirin. There were
4 episodes of recurrent thromboembolic complications
(27%), but no long-term neurologic damage was re-
ported. Currently, there is no consensus in the literature
regarding the best protocol to be used for anticoagula-
tion during pregnancy in such women; however, because
these women are at high risk for pregnancy complica-
tions, it is justified probably to use some form of antico-
agulation. We recommend low-dose aspirin plus
prophylactic doses of unfractionated heparin or low mo-
lecular weight heparin. In addition, these women require
close follow-up evaluation because they continue to be
at risk for maternal-fetal complications (eg, fetal growth
restriction, preeclampsia).
Our study does have its limitations because of its rel-
atively small sample size. However, with the rate of
stroke in reproductive aged women being so low, it
would take years to accumulate a larger cohort. In addi-
tion, because the study was retrospective, the treatment
of these women was not standardized, and many ac-
tions, interventions, or other confounding variables
could not be analyzed. For this reason, the results of this
study should be interpreted with caution.
In summary, when we combine the finding of our
work with the other 2 studies,10,11 patients with a previ-
Coppage et al
ous history of stroke should feel reassured regarding
pregnancy and the potential for a good outcome. With
all the studies combined, the overall recurrence risk for
stroke ranges from 0%(95% CI, 0-7%) in our study to
1% (2/187 women) in the study of Lamy et al.10 For pa-
tients with thrombophilia, the recurrence is as high as
20% (4/20 patients). For physicians, this information
is useful for the prepregnancy counseling of such indi-
viduals. The need for prophylactic anticoagulation,
however, cannot be answered by this study.
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