Maternal plasma inhibin A at 11-13 weeks of gestation in hypertensive disorders of pregnancy.

Abstract

To investigate the potential value of maternal plasma inhibin A in first-trimester screening for preeclampsia (PE).
The concentration of inhibin A at 11-13 weeks was measured in samples from 121 pregnancies that developed PE, 87 cases of gestational hypertension (GH) and 208 normal controls. The distributions of inhibin A multiple of median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders.
The maternal plasma inhibin A MoM was significantly higher in the early and late PE groups (1.55 MoM and 1.24 MoM, respectively; p < 0.0083), compared to the controls (0.98 MoM), but not in GH. Significant contributions for the prediction of PE were provided by maternal factors, plasma inhibin A and uterine artery pulsatility index (PI) and with combined screening the detection rates for early and late PE were 88% and 42%, respectively, for a false positive rate of 10%.
The proposed combined screening test could be used to identify women at high risk for PE and intensive monitoring in such patients would lead to earlier identification of the disease which could potentially improve pregnancy outcome.

Full text

Page 1

PRENATAL DIAGNOSIS
Prenat Diagn 2009; 29: 753–760.
Published online 1 May 2009 in Wiley InterScience
(www.interscience.wiley.com) DOI: 10.1002/pd.2279
Maternal plasma inhibin A at 11–13 weeks of gestation
in hypertensive disorders of pregnancy
Ranjit Akolekar, Ryoko Minekawa, Alina Veduta, Ximena C. Romero and Kypros H. Nicolaides*
Harris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK
Objective
preeclampsia (PE).
To investigate the potential value of maternal plasma inhibin A in first-trimester screening for
Method
developed PE, 87 cases of gestational hypertension (GH) and 208 normal controls. The distributions of inhibin
A multiple of median (MoM) in the control and hypertensive groups were compared. Logistic regression
analysis was used to derive algorithms for the prediction of hypertensive disorders.
The concentration of inhibin A at 11–13 weeks was measured in samples from 121 pregnancies that
Results
(1.55 MoM and 1.24 MoM, respectively; p < 0.0083), compared to the controls (0.98 MoM), but not in GH.
Significant contributions for the prediction of PE were provided by maternal factors, plasma inhibin A and
uterine artery pulsatility index (PI) and with combined screening the detection rates for early and late PE were
88% and 42%, respectively, for a false positive rate of 10%.
The maternal plasma inhibin A MoM was significantly higher in the early and late PE groups
Conclusion
intensive monitoring in such patients would lead to earlier identification of the disease which could potentially
improve pregnancy outcome. Copyright  2009 John Wiley & Sons, Ltd.
The proposed combined screening test could be used to identify women at high risk for PE and
KEY WORDS: inhibin A; first trimester screening; preeclampsia; uterine artery Doppler
INTRODUCTION
Inhibin A is a dimeric glycoprotein hormone produced
by many tissues but in normal pregnancy the main
source of circulating inhibin A is the placenta (Muttukr-
ishna et al., 1997a; Petraglia et al., 1997; Florio et al.,
2001). Several studies have reported that in patients with
established preeclampsia (PE) there is a 1.5- to 8.5-fold
increase in the maternal plasma inhibin A concentration
(Table 1). There is also evidence that increased levels of
inhibin A precede the clinical onset of PE and may be
evident from the first trimester of pregnancy (Table 1).
The underlying mechanism for PE is thought to be
impaired placentation due to inadequate trophoblastic
invasion of maternal spiral arteries, documented by the
findings of both histological and Doppler ultrasound
studies of uterine arteries (Khong et al., 1986; Pijnen-
borg et al., 1991; Yu et al., 2005; Plasencia et al., 2007).
The resulting placental hypoxia leads to the release of
inflammatory factors which cause endothelial cell acti-
vation and damage (Redman 1991; Roberts et al., 1993;
Granger et al., 2001). The exact function of inhibin
A in pregnancy and its role in the pathogenesis of
PE are uncertain but there is evidence that inhibin
A has autocrine and paracrine roles in the placenta
thereby affecting trophoblastic function (Muttukrishna
et al., 1997b; Petraglia et al., 1997).
*Correspondence to: Kypros H. Nicolaides, Harris Birthright
Research Centre for Fetal Medicine, King’s College Hospital,
Denmark Hill, London SE5 9RS, UK.
E-mail: kypros@fetalmedicine.com
Previous studies reported that at 11–13 weeks of
gestation in pregnancies that subsequently develop PE
the uterine artery pulsatility index (PI), assessed by
Doppler ultrasound, is increased (Plasencia et al., 2007)
and the maternal serum concentration of pregnancy-
associated plasma protein A (PAPP-A), which is thought
to be involved in placental growth and development, is
reduced (Poon et al., 2009). The differences between
pregnancies developing PE from controls in uterine
artery PI and serum PAPP-A are particularly marked
in severe early onset disease requiring delivery before
34 weeks (early PE) (Plasencia et al., 2007; Poon et al.,
2009). The individual risk for the development of early
and late PE can be calculated from a combination
of maternal demographic characteristics and obstetric
history, the uterine artery PI and maternal serum PAPP-
A (Poon et al., 2009).
The aim of this study was to first investigate further
the maternal plasma concentration of inhibin A in the
first trimester of pregnancy in cases that subsequently
developed hypertensive disorders and secondly to esti-
mate the potential performance of screening for PE by
a combination of maternal factors, uterine artery PI and
maternal serum PAPP-A and inhibin A.
METHODS
Study population
This was a prospective screening study for hyperten-
sive complications of pregnancy in women attending for
Copyright  2009 John Wiley & Sons, Ltd.
Received: 2 January 2009
Revised: 12 February 2009
Accepted: 8 March 2009
Published online: 1 May 2009

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754
R. AKOLEKAR ET AL.
Table 1—Studies reporting on the association between maternal serum inhibin A concentration and preeclampsia
PreeclampsiaControls
Gestation
(w)
Kit used for
analysisAuthor
n
Inhibin A
n
Inhibin A
p value
During preeclampsia
Muttukrishna et al., 1997b
Silver et al., 1999
Gratacos et al., 2000
Keelan et al., 2002
Zeeman et al., 2002
Florio et al., 2002
Bersinger et al., 2003
Hanisch et al., 2004
Hamar et al., 2006
Paiwattananupant et al., 2008
Before preeclampsia
Cuckle et al., 1998
R¨ aty et al., 1999
Sebire et al., 2000
Grobman et al., 2000
D’Anna et al., 2002
Davidson et al., 2003
Florio et al., 2003
Ay et al., 2005
Wald et al., 2006
Spencer et al., 2006
Kim et al., 2006
Zwahlen et al., 2007
Kang et al., 2008
Spencer et al., 2008a
25–33
25–42
30–37
30–38
34–40
25–38
25–39
29–35
26–38
33–39
Not stated
Serotec
Serotec
Not stated
Serotec
Serotec
Not stated
Serotec
DSL
DSL
20
60
20
22
77
21
19
21
31
30
3.05 ng/mLa
2.6 MoM
2.18 ng/mLa
15.1 ng/mLb
1806.3 pg/mLb
2.46 MoM
3080.0 pg/mLa
1325.5 pg/mLa
1863.7 pg/mLa
1229.7 pg/mLa
20
60
60
22
83
42
19
11
16
30
0.36 ng/mL
1.00 MoM
0.50 ng/mL
5.3 ng/mL
936.0 pg/mL
1.00 MoM
1510.0 pg/mL
346.1 pg/mL
572.6 pg/mL
839.1 pg/mL
<0.001
<0.0001
<0.001
<0.001
<0.001
<0.001
<0.01
<0.05
<0.05
<0.01
13–18
12–20
10–14
14–28
15–18
15–20
24
16–18
15–20
22–24
14–23
11–13
10–21
11–14
Serotec
Biosource
Not stated
Serotec
Serotec
Not stated
Serotec
Serotec
DSL
Serotec
DSL
Serotec
Not stated
DSL
28
22
9
12
20
39
18
14
96
24
40
52
32
64
2.01 MoM
1.09 U/mLa
233 pg/mLa
700.0 pg/mLa
1.43 MoM
206 pg/mLb
131.2 pg/mLa
3.36 MoM
1.39 MoM
2.03 MoM
414 pg/mLb
0.46 mg/mLb
1.73 MoM
1.24 MoM
701 1.00 MoM
0.85 U/mL
167 pg/mL
613.0 pg/mL
1.03 MoM
188 pg/mL
91.9 pg/mL
0.99 MoM
1.00 MoM
1.05 MoM
280 pg/mL
0.28 mg/mL
1.00 MoM
1.00 MoM
<0.001
NS
<0.05
NS
NS
NS
<0.05
<0.001
<0.05
<0.001
<0.001
<0.05
<0.001
<0.001
7
759
24
40
155
40
164
480
144
80
104
3044
240
amean values;
bmedian values;
MoM, multiple of the median.
their routine first hospital visit in pregnancy at King’s
College Hospital, London, UK. In this visit, which is
held at 11+0–13+6weeks of gestation, first, all women
have an ultrasound scan to confirm gestational age from
the measurement of the fetal crown-rump length (CRL),
secondly, diagnose any major fetal abnormalities and
thirdly, measure fetal nuchal translucency (NT) thick-
ness as part of screening for chromosomal abnormalities.
In addition, the maternal serum PAPP-A and free beta-
human chorionic gonadotropin (ß-hCG) are determined
and the results are combined with the fetal NT to cal-
culate the patient-specific risk for trisomy 21 (Snijders
et al., 1998; Kagan et al., 2008a). We recorded maternal
characteristics and medical history, measured the uter-
ine artery PI by transabdominal color Doppler (Plasencia
et al., 2007) and stored serum and plasma at −80◦C
for subsequent biochemical analysis. A written informed
consent was obtained from the women agreeing to par-
ticipate in the study, which was approved by King’s
College Hospital Ethics Committee.
We prospectively examined 8234 singleton pregnan-
cies between March 2006 and March 2007. In 147
(1.8%) cases there was subsequent development of PE,
135 (1.6%) cases developed gestational hypertension
(GH) and 7922 cases were unaffected by PE or GH. In
this study we measured maternal plasma inhibin A in a
case-control population of 121 PE, 87 GH and 208 con-
trols. The selection of the specific samples from each
group of hypertensive disorders was simply based on
availability. The cases and controls were matched for
length of storage of their blood samples and none of the
samples were previously thawed and refrozen.
This study is part of a research program on the early
prediction of pregnancy complications and the data from
these patients on serum PAPP-A were included in a
previous publication (Poon et al., 2009).
Maternal factors
Patients were asked to complete a questionnaire on
maternal age, racial origin, cigarette smoking during
pregnancy, method of conception, medical history, med-
ication, parity, obstetric history and family history of PE
in the mother. The questionnaire was then reviewed by
a doctor together with the patient. The maternal weight
and height were measured and the body mass index
(BMI) was calculated in kg/m2.
Outcome measures
The definitions of PE and GH were those of the
International Society for the Study of Hypertension in
Pregnancy (Davey et al., 1988). In GH the diastolic
blood pressure should be 90 mmHg or more on at
Copyright  2009 John Wiley & Sons, Ltd.
Prenat Diagn 2009; 29: 753–760.
DOI: 10.1002/pd

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INHIBIN A AND HYPERTENSIVE DISORDERS
755
least two occasions 4 h apart developing after 20 weeks
of gestation in previously normotensive women in the
absence of significant proteinuria. In PE there should
be GH with proteinuria of 300 mg or more in 24 h
or two readings of at least ++ on dipstick analysis
of midstream or catheter urine specimens, if no 24-h
collection is available.
Sample analysis
Duplicate plasma samples of 50 µL were used to mea-
sure inhibin A concentration by a quantitative enzyme-
linked immunoassay (ELISA) technique using DSL-10-
28100 inhibin A immunoassay (Diagnostic systems lab-
oratories, Inc. Webster, Texas, USA). The assays were
performed on an automated ELISA processor (Dade-
Behring BEP 2000, Liederbach, Germany). Absorbance
readings were taken on a VICTOR3plate reader
(PerkinElmer Life and Analytical Sciences, Turku, Fin-
land) and inhibin A concentrations were determined
using MultiCalc software (PerkinElmer Life and Analyt-
ical Sciences, Turku, Finland). The lower limit of detec-
tion of the assay was 1.0 pg/mL and the between-batch
imprecision was 15.4% at an inhibin A concentration
of 94.5 pg/mL and 8.2% at 361.0 pg/mL. All samples
were analyzed in duplicate and those with a coefficient
of variation exceeding 10% were reanalyzed.
Maternal serum PAPP-A was measured using the
DELFIA XPRESS analyzer (PerkinElmer Life and Ana-
lytical Sciences, Waltham, USA). The variation of the
DELFIA XPRESS PAPP-A assay was determined in 20
runs with two replicates using this system. The cali-
bration curve of the first run was used as a reference
curve during the 14-day-period. The intra- and interas-
say variations were 1.2% and 2.1%, respectively, at a
PAPP-A concentration of 462 mU/L, 1.4% and 2.3% at
2124 mU/L and 1.3% and 2.5% at 5543 mU/L.
Statistical analysis
The following steps were taken. First, the distributions
of uterine artery PI, PAPP-A and inhibin A were made
Gaussian after logarithmic transformation. Distributions
were confirmed to be Gaussian using the probability
plots and Kolmogorov–Smirnov test. Second, multiple
regression analysis was used to determine which of the
factors amongst the maternal characteristics and gesta-
tion were significant predictors of log inhibin A in the
unaffected group. Then the distribution of log inhibin A
expressed as multiples of the median (MoM) of the unaf-
fected group, were determined in the PE and GH groups
of the case-control population. Third, the measured uter-
ine artery PI was converted into MoM after adjustment
for gestation, maternal age, BMI and racial origin, as
described earlier (Plasencia et al., 2007). Fourth, the
measured PAPP-A was converted into MoM after adjust-
ment for gestation, maternal age, racial origin, weight,
parity, cigarette smoking status and method of concep-
tion as described earlier (Kagan et al., 2008b). Fifth,
Kruskall–Wallis test with Dunn’s procedure and Bon-
ferroni correction was used to compare median MoM
of inhibin A, uterine artery PI and PAPP-A between the
outcome groups. Sixth, regression analysis was used to
determine the significance of association between log
inhibin A MoM and log uterine artery PI MoM in the
different outcome groups. Seventh, logistic regression
analysis was used to determine which of the factors
amongst the maternal characteristics, log uterine artery
PI MoM, log inhibin A MoM and log PAPP-A MoM had
a significant contribution in predicting early and late PE.
Eighth, the detection and false positive rates (FPR) were
calculated as the respective proportions of PE (detec-
tion rate) and unaffected pregnancies (FPR) with MoM
values above given cut-offs. Ninth, the performance of
screening was determined by receiver operating charac-
teristic (ROC) curves analysis.
The statistical software package SPSS 15.0 (SPSS
Inc.,Chicago, IL), MedCalc for windows, version 9.6.2.0
(MedCalc Software,Mariakerke,
XLSTAT-Pro 2008 (Addinsoft, USA) were used for data
analyses.
Belgium)and
RESULTS
The maternal characteristics of each of the outcome
groups are compared in Table 2.
Unaffected group
Multiple regression analysis in the unaffected group of
the case-control population demonstrated that for log
inhibin A and significant independent contributions were
provided by maternal weight and racial origin:
logexpected inhibinA = 2.596–0.003 × maternal
weight in kg + (0.127 if Black, 0 if other racial origins);
R2= 0.078, p < 0.0001.
In each patient we used this formula to derive the
expected log inhibin A and then expressed the observed
value as a MoM of the expected (Table 3). Similarly,
we used previously derived formulae for uterine artery
PI and PAPP-A to calculate the respective MoM values
(Plasencia et al., 2007; Kagan et al., 2008b).
Hypertensive disorders
Plasma inhibin A and uterine artery PI were significantly
higher in early and late PE than in controls, but not in
GH than in controls (Table 3, Figure 1). Serum PAPP-A
was significantly lower in early PE than in controls but
not in late PE or GH than in controls (Table 3). There
were no significant associations between plasma inhibin
A and uterine artery PI in either of the controls (p =
0.120) or the hypertensive groups (early PE p = 0.568,
late PE p = 0.492, GH p = 0.671).
Screening for early PE
Logistic regression analysis demonstrated that in the
prediction of early PE there were significant contribu-
tions from log MoM uterine artery PI (OR 4.442E5,
Copyright  2009 John Wiley & Sons, Ltd.
Prenat Diagn 2009; 29: 753–760.
DOI: 10.1002/pd

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R. AKOLEKAR ET AL.
Table 2—Maternal characteristics in the four outcome groups
Maternal characteristics
Control
(n = 208)
31.9 (28.7–35.3)
25.2 (23.0–29.1)
64.1 (59.7–71.0)
12.4 (12.2–13.0)
Early
preeclampsia
(n = 26)
32.7 (27.4–38.7)
27.3 (23.7–32.0)
68.8 (58.3–74.5)
12.4 (12.2–13.3)
Late
preeclampsia
(n = 95)
31.6 (26.7–36.3)
27.0 (23.7–33.3)∗
62.0 (58.0–68.9)
12.3 (12.1–12.5)
Gestational
hypertension
(n = 87)
33.4 (30.1–35.9)
26.6 (24.1–31.1)
62.2 (57.6–69.1)
12.3 (12.1–13.0)
Maternal age in years, median (IQR)
BMI in kg/m2, median (IQR)
CRL in mm, median (IQR)
GA at sampling (weeks), median (IQR)
Racial origin
White, n (%)
Black, n (%)
Indian or Pakistani, n (%)
Chinese or Japanese, n (%)
Mixed, n (%)
Parity
Nulliparous, n (%)
Parous—no previous PE, n (%)
Parous—previous PE, n (%)
Family history of PE—Mother (n, %)
Cigarette smoker, n (%)
Conception
Spontaneous, n (%)
Assisted, n (%)
Medical history
None, n (%)
Chronic hypertension, n (%)
Diabetes mellitus, n (%)
Thrombophilia, n (%)
Others, n (%)
Medication during pregnancy
None, n (%)
Antihypertensives, n (%)
Insulin, n (%)
Antiasthmatics, n (%)
Thyroxin, n (%)
Aspirin, n (%)
Antidepressant, n (%)
Antiepileptic, n (%)
Others, n (%)
146 (70.2)
41 (19.7)
14 (6.7)
2 (1.0)
5 (2.4)
11 (42.3)
11 (42.3)∗∗
2 (7.7)
0
2 (7.7)
41 (43.2)
40 (42.1)∗∗∗
7 (7.4)
2 (2.1)
5 (5.3)
66 (75.9)
16 (18.4)
0∗∗
1 (1.1)
4 (4.6)
80 (38.5)
122 (58.7)
6 (2.9)
7 (3.4)
16 (7.7)
13 (50.0)
6 (23.1)∗∗
7 (26.9)
3 (11.5)
0
61 (64.2)
22 (23.2)
12 (12.6)∗∗
11 (11.6)∗∗
6 (6.3)
48 (55.2)
29 (33.3)
10 (11.5)∗
9 (10.3)∗
7 (8.0)
201 (96.6)
7 (3.4)
23 (88.5)
3 (11.5)
91 (95.8)
4 (4.2)
84 (96.6)
3 (3.4)
201 (96.6)
1 (0.5)
2 (1.0)
3 (1.4)
1 (0.5)
21 (80.8)
4 (15.4)
0
1 (3.8)
0
89 (93.7)
4 (4.2)∗
1 (1.1)
1 (1.1)
0
84 (96.6)
0
2 (2.3)
1 (1.1)
0
188 (90.4)
0
2 (1.0)
5 (2.4)
3 (1.4)
3 (1.5)
2 (1.0)
4 (1.9)
1 (0.5)
22 (84.6)
2 (7.7)∗
0
0
1 (3.8)
1 (3.8)
0
0
0
87 (91.6)
2 (2.1)
1 (1.1)
3 (3.2)
1 (1.1)
0
1 (1.1)
0
0
75 (86.2)
0
2 (2.3)
4 (4.5)
2 (2.3)
2 (2.3)
1 (1.1)
1 (1.1)
0
BMI, body mass index; CRL, crown-rump length; GA, gestational age; IQR, interquartile range. Note: Comparisons between each outcome group
with controls (Chi-square test and Fisher’s exact test for categorical variables and Kruskall–Wallis test and Dunn’s procedure with Bonferroni
correction for continuous variables):∗p < 0.05;∗∗p < 0.01;∗∗∗p < 0.001.
95% CI 413.0–4.8E8; p < 0.0001), log MoM PAPP-
A (OR 0.099, 95% CI 0.011–0.929; p = 0.043) log
MoM inhibin A (OR 249.6, 95% CI 9.3–6.688E3; p =
0.001), history of chronic hypertension (OR 143.3, 95%
CI 8.3–2.463E3; p = 0.001), Black ethnic origin (OR
5.5, 95% CI 1.4–21.8; p = 0.016), mixed ethnic origin
(OR 16.3, 95% CI 1.3–198.1; p = 0.029) and parous
with no previous PE (OR 0.159, 95% CI 0.039–0.651;
p = 0.011) but not BMI (p = 0.190) or family history
of PE (p = 0.068); R2= 0.608, p < 0.0001.
The estimated detection rates of early PE at fixed
FPR of 5% and 10% in screening by maternal obstetric
history and characteristics, inhibin A, PAPP-A, uterine
artery PI and by their combinations are shown in
Table 4 and the areas under the ROC curves are shown
in Table 5. The estimated detection rate of screening
for early PE by inhibin A was 23.1% and 30.8% at
respective FPR of 5% and 10% and the values increased
to 84.6% and 88.5% in screening by a combination of
maternal obstetric history and characteristics, inhibin A
and uterine artery PI.
Screening for late PE
Logistic regression analysis demonstrated that in the
detection of late PE there were significant contributions
from log MoM uterine artery PI (OR 32.0, 95% CI
3.4–302.5; p = 0.002), log MoM inhibin A (OR 21.0,
95% CI 4.6–96.1; p < 0.0001), BMI (OR 1.1, 95%CI
1.1–1.2; p < 0.001), Black ethnic origin (OR 3.8, 95%
CI 2.0–7.3; p < 0.0001) and parous with no previous
PE (OR 0.123, 95% CI 0.062–0.243; p < 0.0001) but
not from log MoM PAPP-A (p = 0.283), history of
chronic hypertension (p = 0.266) and family history of
PE (p = 0.063) R2= 0.377, p < 0.0001.
The estimated detection rates of late PE at fixed FPR
of 5% and 10% in screening by maternal obstetric
Copyright  2009 John Wiley & Sons, Ltd.
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DOI: 10.1002/pd

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INHIBIN A AND HYPERTENSIVE DISORDERS
757
Table 3—Median (IQR) for inhibin A, uterine artery pulsatility index (PI) and PAPP-A in the four outcome groups
Serum inhibin A (median, IQR)
Uterine artery PI (median, IQR)
Serum PAPP-A (median, IQR)
MoM
pg/mL
MoM
Unit
MoM
mU/L
Unaffected
0.98 (0.72–1.43)
244.0 (171.9–341.0)
1.05 (0.83–1.30)
1.68 (1.32–2.04)
1.00 (0.69–1.45)
2.80 (1.81–4.60)
Early preeclampsia
1.55 (0.95–2.05)∗
378.8 (243.6–529.8)
1.56 (1.20–1.69)∗
2.49 (1.96–2.66)
0.62 (0.42–1.11)∗
2.63 (0.95–3.36)
Late preeclampsia
1.24 (0.89–1.65)∗
322.3 (210.3–444.5)
1.26 (0.92–1.44)∗
2.00 (1.54–2.36)
0.95 (0.58–1.31)
2.71 (1.55–4.32)
Gestational hypertension
1.07 (0.80–1.42)
253.1 (196.0–333.2)
1.12 (0.89–1.33)
1.77 (1.42–2.08)
0.87 (0.62–1.44)
2.01 (1.54–3.38)
Note: Comparisons between outcome groups by Kruskall–Wallis test and Dunn’s procedure with Bonferroni correction,
∗p < 0.0083.
history and characteristics, inhibin A, PAPP-A, uterine
artery PI and by their combinations are shown in Table 4
and the areas under the ROC curves are shown in
Table 5. The estimated detection rate of screening for
late PE by inhibin A was 13.7% and 16.8% at respective
FPR of 5% and 10% and the values increased to
36.8% and 55.8% in screening by a combination of
maternal obstetric history and characteristics and plasma
inhibin A.
DISCUSSION
The findings of this study that at 11–13 weeks of
gestation, women who subsequently develop PE have
increased maternal plasma levels of inhibin A, reduced
serum PAPP-A and increased uterine artery PI are
consistent with previous reports (Sebire et al., 2000;
Plasencia et al., 2007; Zwahlen et al., 2007; Spencer
et al., 2008a; Spencer et al., 2008b). The maternal
plasma inhibin A and uterine artery PI are significantly
higher in early and late PE but not in GH whereas
maternal serum PAPP-A is significantly lower in early
PE but not in late PE and GH.
In the unaffected controls, the measured concentration
of maternal plasma inhibin A decreased with maternal
weight and was higher in Black than in White women.
Consequently, as in the case of uterine artery PI and
serum PAPP-A the measured concentration of inhibin A
must be adjusted for these variables before comparing
with pathological pregnancies (Plasencia et al., 2007;
Kagan et al., 2008b). Most of the previous studies
did not make any adjustments for these variables,
except a few that adjusted only for gestational age
(Florio et al., 2002; Ay et al., 2005; Kim et al., 2006;
Figure 1—Box-and-whisker plot of (median, interquartile range and
range) of inhibin A multiple of median (MoM) in pregnancy outcome
groups: controls, early preeclampsia (PE), late PE and gestational
hypertension (GH)
Copyright  2009 John Wiley & Sons, Ltd.
Prenat Diagn 2009; 29: 753–760.
DOI: 10.1002/pd