Research

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OBSTETRICS

Diagnostic utility of soluble fms-like tyrosine kinase 1 and

soluble endoglin in hypertensive diseases of pregnancy
Saira Salahuddin, MD; Young Lee, MD; Mary Vadnais, MD; Benjamin P. Sachs, MB, BS, DPH; S. Ananth Karumanchi, MD;
Kee-Hak Lim, MD
OBJECTIVE: The objective of this pilot study was to evaluate the clinical utility of soluble fms-like tyrosine kinase 1 (sFlt 1) and soluble
endoglin (sEng) in the differential diagnosis of hypertension in late
pregnancy.
STUDY DESIGN: We analyzed serum levels of sFlt 1 and sEng in

women with gestational hypertension (GHTN; n 17), chronic hypertension (CHTN; n 19), preeclampsia (n 19), and normal pregnancy (n 20) in the third trimester. We calculated the sensitivity,
specificity, and positive and negative likelihood ratio (LR) for each factor in diagnosing preeclampsia.
RESULTS: The sensitivity and specificity of sFlt 1 in differentiating pre-

eclampsia from normal pregnancy were 90% and 90%, respectively,

and 90% and 95% for sEng. In women with GHTN, they were 79% and

88% for sFlt 1; 84% and 88% for sEng; 90% and 63% for uric acid. In
women with CHTN, they were 84% and 95% for sFlt 1; 84% and 79%
for sEng; 68%; and 78% for uric acid. The positive LR for preeclampsia was 9 for sFlt 1 and 7 for sEng in women with normal pregnancy; in
women with GHTN; 6.7 for sFlt 1 and 7.2 for sEng; in CHTN, 16 for sFlt
1 and 4 for sEng. Serum uric acid had a positive LR of only 2.4 in
women with GHTN and 3.1 in women with CHTN.
CONCLUSION: Both sFlt 1 and sEng may prove useful in differentiating
preeclampsia from other hypertensive diseases of pregnancy. A prospective cohort study should be performed determine the clinical utility
of measuring these proteins.

Key words: hypertension in pregnancy, preeclampsia, soluble

endoglin, soluble fms-like tyrosine kinase 1

Cite this article as: Salahuddin S, Lee Y, Vadnais M, et al. Diagnostic utility of soluble fms-like tyrosine kinase 1 and soluble endoglin in hypertensive diseases
of pregnancy. Am J Obstet Gynecol 2007;197;28.e1-28.e6.

reeclampsia occurs in 2-7% of pregnancies1,2 and is a leading cause of

maternal and neonatal morbidity and
mortality.3,4 The diagnosis is based on
the onset of hypertension and proteinuria, usually after 20 weeks gestation as
well as a sudden rise in blood pressure
and the appearance or aggravation of
proteinuria in women with known
chronic hypertension.5,6 However, be-

cause the onset of hypertension and proteinuria can be variable and the disorder
may present without the pathognomonic signs and symptoms, differentiating preeclampsia from other forms of
hypertensive diseases of pregnancy can
be challenging and time consuming, often delaying appropriate care.

From the Departments of Obstetrics, Gynecology, and Reproductive Biology (Drs

Salahuddin, Vadnais, Sachs, Karumanchi, and Lim) and Medicine (Dr Karumanchi), Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, and the
Department of Obstetrics and Gynecology, St. Marys Hospital, College of Medicine, The
Catholic University of Korea, Seoul, Korea (Dr Lee).
Received Aug. 28, 2006; revised Dec. 9, 2006; accepted April 12, 2007.
Reprints not available from the authors.
This work was supported in part by the Obstetrics and Gynecology Foundation, Beth Israel
Deaconess Medical Center (Boston, MA).
S.A.K. is a coinventor on multiple patents filed by the Beth Israel Deaconess Medical Center for
the diagnosis of preeclampsia. S.A.K. is also a consultant to Abbott Diagnostics, Beckman
Center, and Johnson & Johnson.
0002-9378/$32.00
2007 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2007.04.010

See related editorial, page 1

28.e1

American Journal of Obstetrics & Gynecology JULY 2007

Recently, it has been shown that 2 antiangiogenic peptides produced by the

placenta, soluble fms-like tyrosine kinase 1 (sFlt 1) and soluble endoglin
(sEng), contribute to the pathogenesis of
preeclampsia.7-11 By sequestering the
proangiogenic proteins, vascular endothelial growth factor, and placental
growth factor, sFlt-1 has been shown to
cause hypertension, proteinuria, and
glomerular endotheliosis in rats.7 Endoglin, a coreceptor for transforming
growth factor (TGF)-1 and TGF-3,
has been shown to be upregulated in the
placenta in preeclampsia, leading to increased secretion of the soluble form into
maternal circulation.8 We have shown
that the serum level of sEng is increased
in patients with preeclampsia and correlates with the disease severity. In addition, sEng, in the presence of elevated
sFlt 1, has been shown to cause hemolysis, hepatic ischemia, and necrosis, and
extensive vascular damage of the placenta, including infarction at the maternalfetal junction as well as signs of severe maternal vascular damage in rats.8
In humans, the rise in serum levels of

Obstetrics

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Research

TABLE 1

Admission demographics
Control (n 20)
Age (y)

33.7 5.3

GHTN (n 17)
31.2 5.5

CHTN (n 19)
35.2 6.3

Preeclampsia
(n 19)
30.6 5.6

P (by ANOVA)
.05

................................................................................................................................................................................................................................................................................................................................................................................

26.9 6.0

27.6 12

31.8 10

28.1 5.4

.40

SBP (mm Hg)

118.4 9.5

145.4 8.0

142.2 17

146.0 16.5

.001*

DBP (mm Hg)

74.7 8.2

93.0 9.4

92.6 26

91.8 10

.001*

GA (wks)

39.1 1.3

36.4 1.9

35.7 3.2

34.6 3.3

.05

Hematocrit (%)

34.8 3.0

34.2 4.2

34.6 3.0

35.1 3.3

.9

BMI

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

BMI, body mass index; CHTN, chronic hypertension; DBP, diastolic blood pressure; GA, gestational age; GHTN, gestational hypertension; SBP, systolic blood pressure.
* Compared with control.

these 2 peptides seems to precede the onset of hypertension and proteinuria by a

few weeks9,11 and correlates with severity
of the disease.
Elevated serum levels of both sFlt 1
and sEng have been documented in preeclampsia and gestational hypertension
retrospectively in samples stored for
more than a decade,9,11 and the clinical
utility of these 2 factors in differentiating
the 2 forms of hypertensive diseases in
pregnancy has not been examined. Furthermore, we could not locate reports of
serum levels of these peptides in women
with chronic hypertension in the third
trimester. Therefore, we performed this
pilot study in advance of larger ones to
evaluate the sensitivity, specificity, and
positive and negative likelihood ratios
(LRs) of sFlt1 and sEng in patients with
various hypertensive diseases in
pregnancy.

M ATERIALS AND M ETHODS

We performed a prevalence case-control
study measuring serum sFlt 1 and sEng
in consenting pregnant women presenting to labor and delivery at Beth Israel
Deaconess Medical Center (Boston,
MA) from 2004-2006 with hypertension
in the third trimester. The Committee on
Clinical Investigations at Beth Israel
Deaconess Medical Center approved the
study (protocol 2003-P-000342/5; Oct.
14, 2004). The pregnancy outcomes were
analyzed by reviewing each case and
were categorized as gestational hypertension, chronic hypertension, or preeclampsia, according to the diagnostic
criteria outlined by the American Col-

lege of Obstetrics and Gynecology

(ACOG) practice bulletin (Jan. 2002).5
For proteinuria, 0.3 g protein or higher
in a 24-hour urine specimen was used as
much as possible. When the 24-hour
urine was not available, either a dipstick
of 1 or greater or a protein/creatinine
ratio of 0.3 or greater was used. We used
the criteria outlined by ACOG rather
than more stringent criteria of 2 dipstick because we were interested in the
performance of these peptides in a typical clinical setting.
Severe preeclampsia was diagnosed if 1
or more of the following was present: (1)
blood pressure of 160 mm Hg or greater
systolic or greater than 110 mm Hg diastolic on 2 occasions at least 6 hours
apart while on bed rest; (2) proteinuria
of 5 g or higher in a 24-hour urine collection or greater than positive 3 on 2
random urine samples collected at least 4
hours apart; (3) oliguria of less than 500
mL in 24 hours; (4) cerebral or visual disturbances; (5) pulmonary edema or cyanosis; (6) epigastric or right upper-quadrant pain; (7) impaired liver function;
(8) thrombocytopenia; or (9) fetal
growth restriction.5 Pregnant women
without hypertension, proteinuria, or
underlying medical conditions were recruited as controls.
The serum samples were stored at
70oC in a freezer before use. Assays
were performed by personnel who were
unaware of the outcome of the pregnancy. Enzyme-linked immunosorbent
assays (ELISAs) for sFlt 1 and endoglin
were performed with commercially
available kits, as previously described

(R&D Systems Inc, Minneapolis, MN).

Briefly, various samples for ELISA measurement were diluted in respective calibrator diluent. After adding assay diluent and the diluted sample in a 96-well
plate precoated with captured antibodies
directed against human sFlt-1 or human
endoglin, the plates were incubated for 2
hours. The wells were washed 4 times in
wash buffer and incubated with secondary polyclonal antibody against sFlt-1
and endoglin conjugated to horseradish
peroxidase for an additional 2 hours.
The plates were then washed 4 times in
wash buffer.
Substrate solution containing hydrogen peroxide and tetramethylbenzadine
were added to each well and incubated
for 30 minutes under protection from
light. Stop solution was added to each
well. The optical density was then determined by subtracting readings at 540 nm
from the reading at 450 nm. All assays
were performed in duplicate, and the
protein levels were calculated using a
standard curve derived from a known
concentration of respective recombinant
proteins. The minimum detectable doses
in the assay for sFlt-1 and endoglin were
3.5 and 7 pg/mL, respectively, with intraassay and interassay coefficients of
variation of 3.5% and 5.5%, respectively,
for sFlt-1 and 3.2% and 6.5%, respectively, for endoglin.
The data were analyzed using analysis of
variance (ANOVA) and Student t test as
appropriate using the Systat 8.0 program
(SPSS Inc, Chicago, IL). Receiver operator
characteristic (ROC) curves were drawn
and a full analysis performed to detect the

JULY 2007 American Journal of Obstetrics & Gynecology

28.e2

Research

Obstetrics

highest sensitivity, specificity, positive

(sensitivity/[1-specificity]) and negative
([1-sensitivity]/specificity) likelihood ratios using MedCalc software (Broekstraat,
Mariakerke, Belgium).

www.AJOG.org

FIGURE 1

Serum levels of sFlt 1 in various hypertensive diseases of pregnancy

1000

**

gHTN
(n=17)

Preeclampsia
(n=19)

R ESULTS

28.e3

100
sFlt 1 (ng/ml)

Nineteen women with preeclampsia, 17

women with gestational hypertension,
and 19 women with chronic hypertension were recruited for the study. In addition, 20 women with normal pregnancy were enrolled as controls. Basic
clinical and demographic information is
shown in Table 1. We enrolled both multiparous and nulliparous women in the
study. There were no significant differences between the groups in terms of
maternal age, body mass index, or gestational age. The women with preeclampsia, gestational hypertension, and
chronic hypertension had significantly
higher systolic (P .001) and diastolic
(P .001) blood pressure than the control group. Five of 19 patients with preeclampsia met the criteria for severe disease as defined by ACOG.5 Two of the 5
patients had HELLP (hemolysis, elevated liver enzymes, and low platelet
count) syndrome, and the remaining 3
met only the blood pressure criteria.
Three women in the preeclampsia group
had small-for-gestational-age babies as
defined by birthweight less then 10% for
gestational age.
The serum values of sFlt 1 in women
with different hypertensive diseases of
pregnancy are shown in Figure 1. The
mean serum value of sFlt 1 was significantly higher in women with preeclampsia (74.7 83.3 ng/mL) than in women
with gestational hypertension (23.5
14.9 ng/mL), chronic hypertension (15.4
12.7 ng/mL), or normal pregnancy
(16.6 11.0 ng/mL, P .01 by
ANOVA). Unlike women with chronic
hypertension, the mean serum level of
sFlt 1 in women with gestational hypertension was statistically higher than the
control group (23.5 14.9 ng/mL vs
16.6 11.0 ng/mL, P .04 by t test).
Similarly, the mean serum level of
sEng was significantly higher in women
with preeclampsia (69.2 42.5 ng/mL)
than in women with gestational hyper-

10

1
Control
(n=19)

cHTN
(n=20)

CHTN, chronic hypertension; GHTN, gestational hypertension; sFlt 1, soluble

fms-like tyrosine kinase 1
*P = .04 compared with control
**P < .01 compared with control
The mean serum level of sFlt 1 in women with preeclampsia was significantly higher than that of
the control group (P .01 by t test). Interestingly, the mean serum level of women with gestational
hypertension was significantly higher than the control group as well (P .04 by t test). ANOVA
showed that the mean serum value in women with preeclampsia (74.7 83.3 ng/mL) was
significantly higher than those seen in control (16.6 11.0 ng/mL), gestational hypertension (23.5
14.9 ng/mL), or chronic hypertension (15.4 12.7 ng/mL) (P .01).

tension (23.6 15.3 ng/mL) or chronic

hypertension (22.7 19.9 ng/mL) or the
control group (15.5 6.9 ng/mL; P
.01 by ANOVA) (Figure 2). Similar to
sFlt 1, the mean value of sEng was significantly higher in women with gestational
hypertension when compared with that
of the control group (23.6 15.3 ng/mL
vs 15.5 6.9 ng/mL; P .03 by t test) but
not in women with chronic hypertension
(23.6 15.3 ng/mL vs 22.7 19.9 ng/
mL; P .13 by t test).
The sensitivity, specificity, positive LR,
negative LR, and area under the ROC
curve for sFlt 1, sEng, and uric acid in
various hypertensive diseases in pregnancy are shown in Table 2. According to
the ROC curve analysis, the serum sFlt 1
level of 23.5 ng/mL had the best sensitiv-

American Journal of Obstetrics & Gynecology JULY 2007

ity (90%) and specificity (90%) with the

highest positive LR (9.0) and the lowest
negative LR (0.1) in differentiating
women with preeclampsia from normal
pregnancy. The area under the ROC
curve was 0.94 with SE of 0.04 (P .01).
For differentiating women with preeclampsia from those with gestational
hypertension, the serum sFlt-1 level of
41.8 ng/mL had the highest sensitivity
(79%) and specificity (88%) with positive LR and negative LR of 6.7 and 0.2,
respectively. The area under the ROC
curve was 0.89 with SE of 0.06 (P .01).
For diagnosing preeclampsia in women
with chronic hypertension, the sFlt-1
level of 35.8 ng/mL showed the best sensitivity (84%) and specificity (95%) with
positive LR of 16 and negative LR of 0.2.

Obstetrics

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FIGURE 2

The serum levels of sEng in various hypertensive diseases of

pregnancy

sEndoglin (ng/ml)

1000

**

100

10

1
Control

CHTN

GHTN

Preeclampsia

(n=19)

(n=20)

(n=17)

(n=19)

CHTN, chronic hypertension; GHTN, gestational hypertension; sEndoglin, soluble

endoglin.
*P = .03 compared with control
**P < .01 compared with control
The mean serum levels of sEng in women with preeclampsia was significantly higher than that of
the control group (P .01, t test). Similar to sFlt 1, the mean serum level of sEng in women with
gestational hypertension was statistically higher than that of the control group (P .03, t test).
ANOVA showed that the mean serum value in preeclampsia (69.2 42.5 ng/mL) was higher than
those noted in control (15.5 6.9 ng/mL), gestational hypertension (23.6 15.3 ng/mL), or
chronic hypertension (22.7 19.9 ng/mL) (P .01).

Research

The area under the curve (AUC) was

0.94 with SE of 0.04 (P .01).
Similarly, sEng had high sensitivity
and specificity in differentiating women
with preeclampsia from those with normal pregnancy as well as various hypertensive diseases of pregnancy. Analysis of
the ROC curve showed that the serum
level of 24.8 ng/mL had the highest sensitivity (90%) and specificity (95%) with
a positive LR of 18 and negative LR of 0.1
in differentiating women with preeclampsia from those with normal pregnancy. The AUC was 0.93 with SE of 0.04
(P .01). For diagnosing preeclampsia
in women with gestational hypertension,
the serum sEng level of 33 ng/mL showed
a sensitivity of 84% and specificity of
88% with a positive LR of 7.2 and negative LR of 0.2. The AUC was 0.87 with SE
of 0.06 (P .01). For diagnosing preeclampsia in women with chronic hypertension, the serum level of 31.5 ng/mL
had a sensitivity of 79% and specificity of
99% with a positive LR of 4 and negative
LR of 0.2. The AUC was 0.87 with SE of
0.6 (P 0.01).
Consistent with previously published
reports,12 we found the mean serum
level of uric acid to be significantly
higher in women with preeclampsia (6.4
1.1 mg/dL, P .02) than that of
women with gestational hypertension
(5.0 1.4 mg/dL). However, the mean
serum uric acid value in women with
chronic hypertension (5.7 1.5 mg/dL;
P .2) was not statistically different
from that noted in women with preeclampsia (Figure 3). The ROC curve
showed that the serum level of 4.9 mg/dL
has 90% sensitivity and 62.5% specificity
in diagnosing preeclampsia from those

TABLE 2

Test performance of serum sFlt 1, sEng, and uric acid in diagnosing preeclampsia
Control/PRE

Gest HTN/PRE

Chronic HTN/PRE

sFlt 1

sEng

sFlt 1

sEng

Uric acid

sFlt 1

sEng

Uric acid

Sens (%)

90

90

79

84

90

84

84

68

Spec (%)

90

95

88

88

63

95

79

78

16

3.1

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

LR (positive)

17.9

6.7

7.2

2.4

LR (negative)

0.1

0.1

0.2

0.2

0.2

0.2

0.2

0.4

ROC

0.93

0.93

0.88

0.87

0.75

0.94

0.87

0.70

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

Chronic HTN, chronic hypertension; gest HTN, gestational hypertension; PRE, preeclampsia; Sens, sensitivity; Spec, specificity.

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28.e4

Obstetrics

with gestational hypertension. However,

the positive LR was only 2.4 with negative LR or 0.2. In the setting of chronic
hypertension, the serum level of 5.9
mg/dL was associated with a sensitivity
of 68% and specificity of 78% with positive LR of 3.1 and negative LR of 0.4 in
diagnosing preeclampsia.

C OMMENT
Our data show that the serum levels of
sFlt 1 and sEng are significantly higher in
women with preeclampsia than women
with normal pregnancy, gestational hypertension, and chronic hypertension.
Interestingly, consistent with previously
published reports our data show that, although to a lesser degree, the mean serum level of these peptides in women
with gestational hypertension is higher
than in the control group.8-11 Because it
is estimated that approximately 25% of
patients with gestational hypertension
will develop preeclampsia, it is possible
that some of the patients with gestational
hypertension in our study may have had
preeclampsia without proteinuria. It will
be interesting to determine whether
there is a correlation between perinatal
outcome and serum levels of these factors in women with gestational hypertension in a larger study.
Furthermore, our findings suggest
that the serum levels of these antiangiogenic factors may be sensitive and specific markers for preeclampsia. More importantly, the positive LRs of these
serum markers can increase the pretest
probability of having preeclampsia
enough to alter clinical decision making.13 Because these angiogenic factors
have been shown to cause glomerular endotheliosis in rats,7 to date, they may be
the best serologic indicators of glomerular endotheliosis. In fact, the AUC comparison showed that serum sFlt 1 is a significantly better test than serum uric acid
in differentiating preeclampsia from
chronic hypertension (AUC 0.94 vs. 0.7,
P .02). For differentiating preeclampsia from gestational hypertension, the
ROC curve for sFlt-1 was also better,
compared with that of uric acid (AUC of
0.88 vs 0.75), but the difference was statistically not significant (P .13).
28.e5

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FIGURE 3

The serum levels of uric acid

11
10

9
Uric Acid (mg/dl)

Research

8
7
6
5
4
3
CHTN

GHTN

(n=18)

(n=16)

Preeclampsia
(n=19)

CHTN, chronic hypertension; GHTN, gestational hypertension; UA, uric acid.

* P=.02 compared to GHTN

The mean serum level in patients with preeclampsia was statistically higher than that of the women
with gestational hypertension (P .02, ANOVA) but not with chronic hypertension.

In the past few years, the work done by

our group and others7-11 established the
possible pathogenic role of sFlt 1 and
sEng in preeclampsia. This work represents an attempt to determine the clinical application of these markers. Because
the serum levels of these markers rise approximately 6 weeks before the onset of
the symptoms of the disease, increased
serum levels of these factors in the setting
of labile blood pressures or equivocal
proteinuria may identify patients who
will develop the full symptoms and signs
of preeclampsia imminently. Depending
on the gestational age, this type of information may be highly valuable in developing rational management plans for
these patients. In addition, the serum
levels of these factors may correlate better with various perinatal outcomes than
blood pressure or 24-hour urine protein.
The correlation between disease severity
and serum levels of these antiangiogenic
peptides has been demonstrated.7,8 In
our study, the sample size was too small

American Journal of Obstetrics & Gynecology JULY 2007

to correlate various perinatal outcomes

with the serum levels of these peptides. A
larger study to examine the possibility of
these angiogenic factors predicting poor
perinatal outcome in women with hypertension in pregnancy will be of great
clinical interest.
A limitation of this study was the sample size. This study was conducted to assess the rationale and feasibility of designing a larger, prospective study to
determine the clinical utility of these angiogenic factors. A sample size estimation was difficult because we were not
able to locate sensitivity, specificity, and
likelihood ratios for these factors. However, based on our previous published
result of serum levels of sFlt1 and sEng in
patients with preeclampsia and control
population (sFlt1: 20 8 ng/mL [control] vs 40 10 ng/mL [preeclampsia]
and sEng: 19 5ng/mL [control] vs 38
12 ng/mL [preeclampsia]),8 we
needed less than 10 patients in each arm
to show a 50% difference in the mean

Obstetrics

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serum values between the 2 groups, with
an alpha of 0.05 and a beta of 0.2. Assuming that the mean serum levels in patients
with gestational hypertension and
chronic hypertension were similar to
control population, we estimated the
same number of patients will be needed
to show a 50% difference in the mean
values, compared with patients with
preeclampsia.
Given our findings (ie, area under the
curves of the ROC), we now estimate
that we would need approximately 34
patients to show that sFlt 1 is a better
marker than serum uric acid for distinguishing women with preeclampsia
from those with chronic hypertension
with a beta of 0.2. For sEng, we would
need 69 women. For differentiating
women with gestational hypertension
from preeclampsia, we would need 103
women for sFlt1 and 121 for sEng.
Despite its small size, however, we
were able to demonstrate and confirm
the differences in serum levels of these
peptides in various hypertensive diseases
in pregnancy. This finding was true, even
if we excluded the 5 patients with severe
preeclampsia for both sFlt 1 (83.1 95.2
ng/mL [preeclampsia] vs 16.6 11.0
ng/mL [control], 15.4 12.8 ng/mL
[chronic hypertension], 23.5 14.9
ng/mL [gestational hypertension], P by
ANOVA .01) and sEng (62.0 34.0
ng/mL [preeclampsia] vs 15.5 6.9
ng/mL [control], 22.7 19.9 ng/mL
[chronic hypertension], 23.6 15.3
ng/mL [gestational hypertension], P by
ANOVA .01). In addition, our findings were unchanged when we excluded
the highest serum value noted in sFlt 1
(60.8 27.0 ng/mL [preeclampsia] vs
16.6 11.0 ng/mL [control], 15.4 12.8
ng/mL [chronic hypertension], 23.5
14.9 ng/mL [gestational hypertension],
P by ANOVA .001).
Another limitation was that we were
not able to control for gestational age.

However, all of the deliveries took place

after 28 weeks of gestation. In addition,
the control group had the mean gestational age that is greater than that of the
study population. It is unclear whether
there is statistical difference in the serum
levels of these angiogenic factors between early third trimester and term.
Nevertheless, previously published data
suggest that the serum level of both sFlt 1
and sEng rise in normal pregnant population with increasing gestational
age.9,11,14,15 We believe that this would
have biased the data against our findings
because the serum levels of our control
group were measured later in gestation.
Despite this possibility, our data show
that the serum levels of these antiangiogenic proteins are higher in women with
preeclampsia. A larger study will allow us
to determine whether the clinical utility
of these factors will vary, depending on
gestational age.
Although preliminary, our findings
raise the possibility that measuring serum levels of sFlt 1 and sEng in women
with various hypertensive diseases of
pregnancy may be clinically useful. Having a sensitive and specific serum biomarker for preeclampsia that can be
used in conjunction with urine protein
analysis will not only improve the accuracy but also expedite the diagnosis of
preeclampsia. Our findings provide a rationale for a large prospective study to
define normal reference ranges for these
factors and to determine their clinical
utility and ability to predict perinatal
outcome in the setting of various hypertensive diseases in pregnancy.
f
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