Intracerebral hemorrhage in pregnancy: Frequency, risk factors,

and outcome
B. T. Bateman, H. C. Schumacher, C. D. Bushnell, et al.
Neurology 2006;67;424-429
DOI 10.1212/01.wnl.0000228277.84760.a2

This information is current as of August 7, 2006

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 Intracerebral hemorrhage
CME
in pregnancy
Frequency, risk factors, and outcome
B.T. Bateman, MD; H.C. Schumacher, MD; C.D. Bushnell, MD; J. Pile-Spellman, MD;
L.L. Simpson, MD; R.L. Sacco, MD, MS; and M.F. Berman, MD, MPH

Abstract—Objective: To describe the frequency, risk factors, and outcome of intracerebral hemorrhage (ICH) in pregnancy
and the postpartum period using a large database of US inpatient hospitalizations. Methods: The authors obtained
data from an administrative dataset, the Nationwide Inpatient Sample, which includes approximately 20% of all
discharges from non-Federal hospitals, for the years 1993 through 2002. Women aged 15 to 44 years with a diagnosis
of ICH were selected from the database for analysis, and within this group patients coded as pregnant or postpartum
were identified. Using US Census data, estimates were made of the rates of ICH in pregnant/postpartum and
non-pregnant women. Rates of various comorbidities in patients with pregnancy-related ICH were compared to the
rates found in the general population of delivering patients using multivariate logistic regression to identify indepen-
dent risk factors for pregnancy-related ICH. Results: The authors identified 423 patients with pregnancy-related ICH,
which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000
at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the age range considered).
The increased risk of ICH associated with pregnancy was largely attributable to ICH occurring in the postpartum
period. The in-hospital mortality rate for pregnancy-related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-
related mortality recorded in this database. Significant independent risk factors for pregnancy-related ICH included
advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64), African American race (OR 1.83, 95% CI 1.39 to 2.41),
preexisting hypertension (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to 3.59),
preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting hypertension with superimposed preeclampsia/
eclampsia (OR 9.23, 95% CI 5.26 to 16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR
1.95, 95% CI 1.11 to 3.42). Conclusion: Intracerebral hemorrhage (ICH) accounts for a substantial portion of
pregnancy-related mortality. The risk of ICH associated with pregnancy is greatest in the postpartum period.
Advanced maternal age, African American race, hypertensive diseases, coagulopathy, and tobacco abuse were all
independent risk factors for pregnancy-related ICH.
NEUROLOGY 2006;67:424–429

Several studies have reported an increased rate of
intracerebral hemorrhage (ICH) associated with
pregnancy.1,2 As this is rare in women, even rela-
tively large, population-based studies on stroke in
pregnancy have had few patients with ICH upon
which to make estimates of frequency, risk factors,
and outcome. In an attempt to further define the
epidemiology of ICH in pregnancy, we undertook an
analysis of this disease using the largest discharge
database available in the United States, the Nation-
wide Inpatient Sample.
Methods. Data for this study were derived from the Nationwide
Inpatient Sample (NIS), the largest all-payer inpatient care data-
base in the United States, and were collected for the years 1993
through 2002. The database represents an approximately 20%
stratified sample of all discharges from non-Federal, acute care
hospitals in the United States. Five hospital characteristics,
geographic region, ownership, location (urban or rural), teach-
ing status, and bed size, are used to create a sample that is
optimized to be representative of hospitalizations in the United
States. For the years 1993 through 2002, between 913 and 995
hospitals from between 17 and 35 states contributed discharges
to the database. The annual number of total discharges con-
tained in the database ranged from 6,538,976 to 7,853,982 for

From the Department of Anesthesiology (M.F.B.), College for Physicians & Surgeons (B.T.B.), Columbia University, New York; Doris and Stanley Tanan-
baum Stroke Center, Neurological Institute (H.C.S., R.L.S.), and Interventional Neuroradiology, Departments of Radiology, Neurology, and Neurosurgery
(J.P.-S.), New York-Presbyterian Hospital, College of Physicians & Surgeons, Columbia University, New York; Duke Center for Cerebrovascular Disease
(C.D.B.), Department of Medicine (Neurology), Duke University Medical Center, Durham, NC; Department of Obstetrics and Gynecology (L.L.S.), Division of
Maternal Fetal Medicine, New York Presbyterian Medical Center, College of Physicians and Surgeons, Columbia University, New York; and Department of
Epidemiology (R.L.S.), Mailman School of Public Health, Columbia University, New York, NY.
B.T.B. was supported by the Doris Duke Charitable Foundation. J.P.S. was supported in part by a grant from NYSTAR. C.D.B. receives research support
from the NIH and from Bristol Myers Squibb/Sanofi Partnership. R.L.S. is supported by grants from NINDS (Specialized Program on Translational Research
in Acute Stroke, P50 049060).
Disclosure: The authors report no conflicts of interest.
Received December 20, 2005. Accepted in final form April 4, 2006.
Address correspondence and reprint requests to Dr. H. Christian Schumacher, Doris & Stanley Tananbaum Stroke Center, Neurological Institute, New York
Presbyterian Hospital, College of Physicians & Surgeons, Columbia University, 710 West 168th Street, Box 163, New York, NY 10032; e-mail:
hs775@columbia.edu

424 Copyright © 2006 by AAN Enterprises, Inc.

the years considered. The database includes patient informa-
tion, coded at the time of discharge, including age, up to 15
diagnoses, up to 15 procedures, and discharge destination. The
database is maintained by the Healthcare Utilization Project
(HCUP) of the Agency for Healthcare Quality and Research
(AHRQ). Information on the database is available at
http://www.hcup-us.ahrq.gov/nisoverview.jsp.
All women in the database, ages 15 to 44 years, with a diagno-
sis of intracerebral hemorrhage (ICD-9 code 431, from the Inter-
national Classification of Disease–Clinical Modification, 9th
revision) were identified.3 From this group, we selected patients
who had also been coded for an antepartum condition, childbirth
or fetal demise, or postpartum condition (ICD-9 codes 640-677,
V22-V24, V27-V28)—these patients were designated as having a
pregnancy-related ICH.
Some women with pregnancy-related ICH receive a specific
code for “cerebrovascular disorders in the puerperium” (ICD-9
code 674.0). This diagnostic code specifies cerebrovascular dis-
orders occurring during pregnancy, childbirth, or the puerpe-
rium, and has a modifier that identifies whether the
complication is antepartum or postpartum, and whether the
admission included childbirth. For ICH patients carrying
the diagnostic code 674.0, a determination was made for each
age group of the proportion of pregnancy-related ICH that oc-
curred during the antepartum and postpartum periods. There is
no specific modifier denoting cerebrovascular accidents occur-
ring during labor or delivery; thus it is likely that the majority
of ICH occurring during labor and delivery will be coded as
postpartum events, the period during which the diagnosis is
likely to be confirmed. For purposes of calculating the relative
frequency of antepartum and postpartum ICH, it was assumed
that the calculated proportion for a particular age group ap-
plied to all cases of pregnancy-related ICH, even if the patient
was not coded with 674.0.
The overall number of pregnancies in the cohort was deter-
mined by searching the database for the ICD-9 codes for live-
birth (ICD-9 V27.0, V27.2, V27.3, V27.5, V27.6) and stillbirths
(ICD-9 V27.1, V27.4, or V27.7). Births of unknown outcome
(ICD-9 V27.9) were imputed to be live births. National esti-
mates of the number of livebirths and stillbirths were made
using the weighting factor supplied by the NIS. Because gesta-
tional length is not coded in the NIS database, gestational
length was computed according to the method described by
Kittner et al.2 Live births were assumed to last 38 weeks and
stillbirths were assumed to last 28 weeks. In addition, there
was assumed to be a 6-week postpartum period of risk following
both stillbirths and livebirths. The total number of antepartum
at-risk person-years for the cohort was thus determined by
multiplying the number of livebirths by 38/52 years and the
number of stillbirths by 28/52 years, and then summing these
two figures; the postpartum at-risk person-years was calculated
by summing the number of livebirths and stillbirths and multi-
plying it by 6/52 years. The number of antepartum or postpar-
tum ICH cases (calculated using the NIS weighting factor to
create national estimates) was then divided by the relevant
at-risk person-years to calculate the frequency.
Pregnancies resulting in either spontaneous or induced
abortions were not included in the calculation of pregnancy-
related at-risk person years as 1) previous studies have shown
that most pregnancy-related ICH occurs after the first trimes-
ter (after the vast majority of both spontaneous and induced
abortions have occurred), and 2) we believe that cases of ICH
that may occur after miscarriage or induced abortion are un-
likely to be coded as pregnancy-related (particularly as there
are specific ICD-9 codes for spontaneous and induced abortion-
related complications).
The rate of non-pregnancy-related ICH was calculated using
estimates of the non-pregnant female population. The number of
non-pregnant person-years was determined by multiplying the
mean total female US population during the study period for each
age group, as obtained from the yearly estimates of the United
States Census Bureau, by the length of the study period and then
subtracting the national estimate of antepartum and postpartum
person-years. The number of non-pregnancy-related ICH (calcu-
lated using the NIS weighting factor to create national estimates)
was then divided by the non-pregnant person-years.
The rate of ICH relating to cerebrovascular malformations was
calculated for pregnant and non-pregnant women by identifying
the subgroup of patients with ICH who were also coded with
ICD-9 747.81 (cerebrovascular anomaly). The numbers of preg-
nant and non-pregnant women with cerebrovascular malforma-
tion related ICH were divided by the pregnant and non-pregnant
female at-risk person-years to arrive at rates for the subgroup
with cerebrovascular malformation.
Morbidity and mortality related to ICH during pregnancy were
estimated using the discharge status of the cases identified. The
Nationwide Inpatient Sample specifies in-hospital mortality, and
discharge to home, as well as discharge with home health care,
transfer to long- and intermediate-care facilities, and transfer to
another short-term hospital.
We identified risk factors for pregnancy-related and non-
pregnancy-related ICH from published reviews and case series on
ICH1-15 and compared the rates of various comorbid conditions for
patients with pregnancy-related ICH and for a control group of
patients aged 15 to 44 years hospitalized for delivery without a
diagnosis of ICH. These comorbidities included multiple gesta-
tions (ICD-9 651), preexisting hypertension (ICD-9 642.0 – 642.2),
gestational hypertension (ICD-9 642.3, 642.9), preeclampsia/
eclampsia (ICD-9 642.4 – 642.6), preeclampsia/eclampsia compli-
cating preexisting hypertension (ICD-9 642.7), diabetes mellitus
(ICD-9 250, 648.0, 648.8), coagulopathy (ICD-9 286, 641.3, 666.3),
thrombocytopenia (ICD-9 287.3–287.5), cocaine abuse/dependence
(ICD-9 304.2 or 305.6), alcohol abuse/dependence (ICD-9 303, and
305.0), tobacco abuse (ICD-9 305.1).
Statistical analysis utilized the two-tailed t test for continuous
variables and the ␹2 test for categorical variables. Multivariable
logistic regression analysis was performed with all the patient
demographic characteristics (including advanced age and race)
and the various comorbidities (defined above) entered simulta-
neously into the model, in order to identify independent predictors
of the outcomes of interest. Statistical procedures were performed
using SPSS (version 11; SPSS, Inc., Chicago, IL).
Results. We identified 423 patients aged 15 to 44 years
with a pregnancy-related ICH in the National Inpatient
Sample (NIS) for the years 1993 through 2002, and a
total of 6,969,553 deliveries in the survey during this
period (table 1). This corresponds to 6.1 patients with
pregnancy-related ICH per 100,000 deliveries and 7.1
pregnancy-related ICH per 100,000 at-risk person-years.
We also identified 5,729 female patients aged 15 to 44
years in the database with non-pregnancy-related ICH,
corresponding to 5.0 non-pregnancy-related ICH per
100,000 person-years.
Table 1 compares maternal age and the rates of various
patient characteristics and medical conditions for women
with pregnancy-related ICH to women hospitalized for de-
livery without the diagnosis of ICH. The mean age was
significantly higher for women with ICH, and a higher
percentage of these women were 35 years or older. African
Americans were over-represented among patients with
ICH. Women with ICH also had significantly higher rates
of hypertensive disorders, coagulopathy, thrombocytope-
nia, and cocaine and tobacco use. Following entry of all
relevant patient characteristics and medical conditions
into a multivariable logistic regression model, age greater
than 35, African American race, hypertensive conditions
(including preeclampsia/eclampsia), coagulopathy, and to-
bacco abuse/dependence were independent predictors of
pregnancy-related ICH.
The presence of a cerebrovascular malformation was
noted in 30 (7.1%) patients with pregnancy-related ICH
and 169 (0.002%) patients in the general delivering popu-
lation. The rate of ICH related to cerebrovascular malfor-
mations per 100,000 person-years was similar in pregnant
(0.50) and non-pregnant women (0.33).
August (1 of 2) 2006 NEUROLOGY 67 425
Table 1 Patient characteristics, comparing pregnant or postpartum patients with ICH and patients hospitalized for delivery without ICH

Patients with Patients

pregnancy-related delivering Univariate OR Multivariate OR
ICH, n (%) without ICH, n (%) (95% CI) p (95% CI) p

Total 423 6,969,553

Age, years

Mean 29 ⫾ 7 27 ⫾ 6 — ⬍0.01

Median 29 27 — —

Advanced maternal age (ⱖ35 y) 103 (24.3) 902,990 (13.0) 2.16 (1.73–2.70) ⬍0.01 2.11 (1.69–2.64) ⬍0.01

Race

White 153 (36.2) 3,086,763 (44.3) Ref Ref

African American 79 (18.7) 769,687 (11.0) 2.07 (1.58–2.72) ⬍0.01 1.83 (1.39–2.41) ⬍0.01

Hispanic 59 (13.9) 1,014,775 (14.6) 1.17 (0.87–1.58) 0.30 1.23 (0.91–1.67) 0.18

Asian or Pacific Islander 15 (3.5) 205,386 (2.9) 1.47 (0.87–2.50) 0.15 1.56 (0.92–2.66) 0.10

Native American <10 22,461 (0.3) 0.90 (0.13–6.42) 0.92 0.87 (0.12–6.23) 0.89

Other <10 200,835 (2.9) 0.80 (0.40–1.64) 0.55 0.84 (0.41–1.70) 0.62

Missing 108 (25.5) 1,669,646 (24.0) 1.31 (1.02–1.67) 0.03 1.32 (1.03–1.69) 0.03

Multiple gestation <10 78607 (1.1) 0.84 (0.31–2.24) 0.72 0.46 (0.17–1.22) 0.12

Preexisting HTN <10 50059 (0.7) 3.01 (1.55–5.82) ⬍0.01 2.61 (1.34–5.07) 0.01

Transient HTN of pregnancy 26 (6.1) 202,688 (2.9) 2.19 (1.47–3.25) ⬍0.01 2.41 (1.62–3.59) ⬍0.01

Preeclampsia/eclampsia 117 (27.7) 215,580 (3.1) 11.98 (9.68–14.82) ⬍0.01 10.39 (8.32–12.98) ⬍0.01

Preexisting HTN with superimposed 13 (3.1) 16,635 (0.2) 13.25 (7.63–23.02) ⬍0.01 9.23 (5.26–16.19) ⬍0.01
preeclampsia/eclampsia

Coagulopathy 36 (8.5) 14,545 (0.2) 44.48 (31.60–62.61) ⬍0.01 20.66 (13.67–31.23) ⬍0.01

Thrombocytopenia 16 (3.8) 27,338 (0.4) 9.98 (6.06–16.45) ⬍0.01 0.96 (0.53–1.74) 0.90

Cocaine abuse/dependence <10 30,256 (0.4) 3.30 (1.47–7.39) 0.01 2.03 (0.84–4.87) 0.11

Alcohol abuse/dependence <10 8,185 (0.1) 4.04 (1.01–16.21) 0.09 1.69 (0.37–7.64) 0.50

Tobacco abuse/dependence 13 (3.1) 119,412 (1.7) 1.82 (1.05–3.16) 0.04 1.95 (1.11–3.42) 0.02

For cells that contain less than 10 observations, the exact number of patients cannot be shown due to the regulations of the Agency for
Healthcare Research and Quality (AHRQ) designed to protect individual personal patient information.

ICH ⫽ intracerebral hemorrhage; HTN ⫽ hypertension.

The timing of pregnancy-related ICH was examined us- period from all causes. Of these, 86 (7.1%) carried the
ing the 293 patients (69.3%) who had the ICD-9 code, diagnosis of ICH. The results of the multivariable re-
which specified whether their cerebrovascular incident oc- gression analysis revealed that advanced maternal age,
curred during the antepartum or postpartum periods. Of Hispanic race, and coagulopathy were significant inde-
these, 171 (58.4%) were listed as postpartum hemorrhages.
The figure details the rate of ICH per 100,000 person-years
for the antepartum and postpartum periods, and compares
these rates with those for non-pregnant women. For all age
groups, the postpartum rate of ICH was higher than that
of the antepartum period and higher than that for the
control group. The difference was especially marked at the
extremes of maternal age.
Preeclampsia or eclampsia accounted for 129 (30.5%) of
the pregnancy-related ICH cases. Of the patients with
preeclampsia- or eclampsia-related ICH, 98 were given an
ICD-9 code that specified when the hemorrhage occurred;
of these patients 61 (62.2%) had a hemorrhage in the post-
partum period.
Approximately one-fifth of women with pregnancy-
related ICH died (table 2). Another half was discharged
home, and the balance was discharged to a medical facil-
ity. For the entire 10-year study period, 1,205 patients Figure. Incidence of non-pregnancy, antepartum, and post-
age 15 to 44 died during pregnancy or the postpartum partum ICH for women age 15 to 44.
426 NEUROLOGY 67 August (1 of 2) 2006
Table 2 Disposition of pregnant or postpartum patients with
intracerebral hemorrhage
Died
Routine
Home health care
Transfer to short term hospital
Other transfers
pendent predictors for in-hospital death in pregnancy-
related ICH (table 3).
Discussion. Using a 10-year representative sam-
ple of the entire US obstetrical population, our re-
sults show that pregnancy increases the risk for
intracerebral hemorrhage and that the risk is pri-
marily related to the postpartum period. Further,
hypertensive disease in pregnancy, coagulopathy,
maternal age of 35 or older, African American race,
and tobacco dependence are associated with
pregnancy-related ICH, suggesting that they are im-
portant risk factors.
The rate of 6.1 per 100,000 deliveries for
pregnancy-related ICH based on the data from NIS
N (%) falls within the range of rates reported in previous
studies (range: 3.8 to 18.1 per 100,000 deliver-
86 (20.3) ies).1-3,5,7,16,17 Although rare, we found that the diag-
187 (44.2) nosis of ICH accounted for 7.1% of all pregnancy-
24 (5.7) related maternal deaths, making this an issue of
50 (11.8) importance to the obstetrical community.
Three different studies have investigated
75 (17.7)
pregnancy-related ICH in varying populations. One
study compared the incidence of ICH associated with
pregnancy to the incidence in an age-matched popu-
lation of women who were not pregnant using a
hospital-based registry that encompassed Washing-
ton, DC, and central Maryland for the years 1988
and 1991.2 Another study analyzed data from 63
public maternities in the region of Ile de France for
the years 1989 through 1992.1 Both studies found
that ICH was highest in the postpartum period, a
finding similar to our study. In contrast, a study
from Taiwan in Chinese women reported that 58%
of pregnancy-related ICH occurred prepartum. A
possible explanation for this discrepancy may be the
higher incidence of hemorrhagic stroke in Asian13,18-21
compared to white patients.

Table 3 Patient characteristics that predict mortality after a pregnancy-related ICH

No. of patients Mortality, by

with pregnancy- patient group, Univariate Multivariate
related ICH n (%) OR (95% CI) p OR (95% CI) p

Total 423 86 (20.3)

Advanced maternal age (ⱖ35 years) 103 28 (27.2) 1.68 (1.00–2.82) 0.05 1.88 (1.07–3.29) 0.03

Race

White 153 21 (13.7) Ref Ref

African American 79 16 (20.3) 1.60 (0.78–3.27) 0.20 1.10 (0.50–2.43) 0.82

Hispanic 59 19 (32.2) 2.99 (1.46–6.10) ⬍0.01 2.20 (1.01–4.79) 0.05

Asian or Pacific Islander 15 <10 0.97 (0.20–4.59) 0.97 0.99 (0.20–4.95) 0.99

Native American <10 <10 N/A N/A N/A N/A

Other <10 <10 2.10 (0.40–11.08) 0.38 2.06 (0.36–11.85) 0.42

Missing 108 25 (23.4) 1.92 (1.01–3.64) 0.05 1.58 (0.80–3.11) 0.19

Multiple gestation <10 <10 1.31 (0.13–12.71) 0.82 0.63 (0.04–9.92) 0.74

Preexisting HTN <10 <10 1.99 (0.49–8.12) 0.34 2.31 (0.52–10.26) 0.27

Transient HTN of pregnancy 26 <10 1.19 (0.46–3.05) 0.73 1.62 (0.58–4.54) 0.36

Preeclampsia/eclampsia 117 36 (30.8) 2.27 (1.38–3.72) ⬍0.01 1.69 (0.95–3.03) 0.08

Preexisting HTN with superimposed 13 <10 1.77 (0.53–5.90) 0.35 1.06 (0.27–4.23) 0.94
preeclampsia/eclampsia

Coagulopathy 36 21 (58.3) 6.91 (3.39–14.12) ⬍0.01 5.95 (2.72–13.00) ⬍0.01

Thrombocytopenia <10 <10 2.45 (0.86–6.93) 0.09 1.42 (0.44–4.61) 0.56

Cocaine abuse/dependence <10 <10 1.98 (0.36–10.97) 0.44 5.97 (0.75–47.37) 0.09

Alcohol abuse/dependence <10 <10 N/A N/A N/A N/A

Tobacco abuse/dependence 13 <10 0.32 (0.04–2.48) 0.27 0.52 (0.06–4.27) 0.54

For cells that contain less than 10 observations, the exact number of patients cannot be shown due to the regulations of the Agency for
Healthcare Research and Quality (AHRQ) designed to protect individual personal patient information.

ICH ⫽ intracerebral hemorrhage; HTN ⫽ hypertension.

August (1 of 2) 2006 NEUROLOGY 67 427

 The role of eclampsia (or preeclampsia) in the gen-
esis of ICH remains controversial. The rates of
eclampsia or preeclampsia reported in patients with
ICH have ranged from 14% to 50%.1-3,5,16 Our study
found these diagnoses in 30.5% of patients with
pregnancy-related ICH. The wide variation in re-
ported rates may reflect true differences in study
populations, or may relate to differences in the crite-
ria used for diagnosing eclampsia or preeclampsia.
The small sample size of some earlier studies may
also play a role. Our data support the view that
eclampsia and preeclampsia are important risk fac-
tors for pregnancy-related ICH.
The percentage of pregnancy-related ICH attrib-
utable to cerebrovascular malformations has been
reported from 20% to 67%.1,2,5,6,8,9,16 In the NIS co-
hort, cerebrovascular malformations were coded in
only 7.1% of pregnancy-related ICHs. This may
reflect, in part, differences in the definition of ce-
rebrovascular malformations and in the sensitivity
of ICD-9 codes for detecting these malformations.
All of the referenced studies used chart review of
patient records, usually by neurologists or nurses
specializing in neurology. Nevertheless, a single-
center study utilized administrative discharge da-
tabases and the ICD-9 code 747.81 and reported a
sensitivity of 94% for detection of any cerebrovas-
cular malformation (including brain arteriovenous
malformations, cavernous malformations, unrup-
tured cerebral aneurysms, dural arteriovenous
malformations, and venous malformations),22 sug-
gesting that ascertainment of cases of cerebrovas-
cular malformations using this code is quite good.
However, the ICD-9 code 747.81 is the only avail-
able code for the different types of cerebrovascular
malformations. Therefore, administrative data-
bases utilizing ICD-9 codes do not allow more spe-
cific information on the frequency of ICH stratified
by the different types of cerebrovascular
malformations.
There is a related controversy regarding the ques-
tion of whether pregnancy increases the risk of rup-
ture of existing cerebrovascular malformations.8,9
The NIS data do not suggest greatly increased rate
of cerebrovascular malformation-related hemorrhage
in the pregnancy-related group compared to women
with non-pregnancy-related ICH (0.50 vs 0.33 per
100,000 person-years). However, we cannot exclude
the possibility of underestimating the risk for ICH
associated with cerebrovascular malformations dur-
ing pregnancy. Our calculation of rupture rates is
based on population-based determination of at-risk
person-years, and it may be that women with known
malformations avoid pregnancy, which would mask
an increased risk of bleeding from these lesions dur-
ing pregnancy. This question can only be answered
by prospective population-based studies, such as the
New York Island AVM study23 or the Scottish Intra-
cranial Vascular Malformation Study (SIVMS).24
Substance abuse, including cocaine,10 alcohol,11,12
and tobacco use,14,15 are well characterized risk fac-
428 NEUROLOGY 67 August (1 of 2) 2006
tors for ICH, and several studies have found one of
more of these risk factors among patients with
pregnancy-related ICH.1,2,5,6 We compared the rates
of various forms of substance abuse of patients
with pregnancy-related ICH with that for the gen-
eral population of delivering patients. The tobacco
and cocaine use rate as coded in NIS was signifi-
cantly higher among ICH patients. Focused treat-
ment of substance abuse is one intervention that
may significantly reduce the risk of pregnancy-
related ICH.
There are limitations and benefits of a study such
as ours, which uses administrative data to draw con-
clusions about disease states. Previous studies have
been limited by having relatively few patients with
pregnancy-related ICH (generally less than 20) upon
which to draw conclusions. Our study identified over
400 patients with pregnancy-related ICH in a cohort
of almost 7 million deliveries. However, administra-
tive datasets are subject to coding errors and unlike
a chart review, we cannot confirm the diagnosis of
ICH in the cases we identify. Still, studies have
shown the sensitivity and specificity of discharge
datasets to be quite high for ICH.25,26 We are also
limited in the length of our follow-up for patients
with ICH. Our mortality estimate of 20.3% for
pregnancy-related ICH is lower than the generally
reported range of 25 to 40%, and is probably an un-
derestimate, as we cannot detect patient deaths that
occur after discharge or transfer from the primary
admitting hospital.
A detailed discussion of the etiology of the in-
creased rate of ICH in the postpartum period is
beyond the scope of our study. It should be noted,
though, that the postpartum period is a time of
rapid hormonal and hemodynamic changes and
proximate causes of ICH may include effects on
coagulation and on the walls of blood vessels.2 In
our cohort, a substantial percentage of patients
with ICH had eclampsia or preeclampsia. Studies
have documented that preeclampsia is associated
with increased cerebral perfusion pressure,27 and
that eclampsia is associated with a loss of autoreg-
ulation of cerebral blood flow and subsequent cere-
bral hyperperfusion. 28-30 Further, the HELLP
variant of preeclampsia is associated with throm-
bocytopenia.31 Cerebral perfusion pressure/hyper-
perfusion and thrombocytopenia thus may
contribute to the increased risk of ICH in patients
with preeclampsia/eclampsia. Future studies will
be needed to characterize the physiologic basis of
peripartum ICH.
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August (1 of 2) 2006 NEUROLOGY 67 429
Intracerebral hemorrhage in pregnancy: Frequency, risk factors, and outcome
B. T. Bateman, H. C. Schumacher, C. D. Bushnell, et al.
Neurology 2006;67;424-429
DOI 10.1212/01.wnl.0000228277.84760.a2

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