| | |

Received: 7 June 2016    Revised: 17 August 2016    Accepted: 27 October 2016    First published online: 16 November 2016

DOI: 10.1002/ijgo.12029

CLINICAL ARTICLE
Obstetrics

Association of biochemical markers with the severity of

pre-­eclampsia

Ahmed M. Maged* | Gamal Aid | Nehal Bassiouny | Doaa S. Eldin | Sherif Dahab | 

Nevein K. Ghamry

Department of Obstetrics and

Gynecology, Kasr AlAiny Hospital, Cairo
University, Cairo, Egypt
*Correspondence
Ahmed M. Maged, Haram, Giza, Egypt.
Email: prof.ahmedmaged@gmail.com
Abstract
Objective: To assess the association between pre-­eclampsia severity and biochemical
and ultrasonography markers.
Methods: A retrospective study was undertaken of women with severe pre-­eclampsia
(group 1, n=90), mild pre-­eclampsia (group 2, n=90), or a normal pregnancy (group 3,
n=90) who attended a hospital in Egypt in October 2013–April 2015. Associations
between pre-­eclampsia and biochemical, cardiotocography, and ultrasonography
markers were investigated.
Results: There were significant differences between the groups in C-­reactive protein
(331.44±112.38, 251.43±59.05, and 23.81±16.19 nmol/L; P≤0.05 for all), platelet
count (113.40±36.72, 172.93±57.60, and 212.68±70.00×109/L; P≤0.05 for group 1
comparisons), alanine transaminase (52.24±14.83, 38.34±13.12, and 23.11±6.92 U/L;
P≤0.05 for group 1 comparisons), and serum uric acid (600.80±117.19, 481.83±118.97,
and 243.89±53.54 μmol/L; P=0.050 for group 3 comparisons). Cardiotocography
score was worse among women with severe pre-­eclampsia than among those in the
other two groups (P=0.039 for both comparisons). Biophysical profile score and
­umbilical artery resistance index differed by group (P≤0.05 for all). Middle cerebral
artery resistance index was lower among women with severe pre-­eclampsia (P≤0.05).
Conclusion: The levels of C-­reactive protein, blood urea nitrogen, serum uric acid, and
alanine transaminase, and the platelet count were linked with the presence and severity
of pre-­eclampsia.

KEYWORDS
Biochemical markers; C-reactive protein; Maternal complications; Neonatal complications;
Severe pre-eclampsia

1 | INTRODUCTION a leading cause of perinatal mortality and morbidity worldwide.3 The

Pre-­eclampsia is a disorder of pregnancy that can affect nearly every
1
organ system. Its pathogenesis is uncertain, but the initial step is
widely thought to be placental ischemia resulting from inadequate
trophoblast invasion because of insufficiently remodeled uterine spiral
arteries.2 The syndrome affects 2%–8% of pregnancies and remains
prevalence of pre-­eclampsia in nulliparous populations ranges from 3%
to 10%.4 The frequency in multiparas is lower than that in nulliparas.4
The diagnosis of pre-­eclampsia is difficult. The symptoms in-
clude hypertension and signs of multiple organ disease.5 Severe pre-­
eclampsia is characterized by any one of six signs: a systolic blood
pressure of 160 mm Hg or higher, or a diastolic blood pressure of

138  |  wileyonlinelibrary.com/journal/ijgo

© 2016 International Federation of Int J Gynecol Obstet 2017; 136: 138–144
Gynecology and Obstetrics
Maged ET AL.
110 mm Hg or higher on two occasions at least 4 hours apart (with
the woman on bed rest and before the initiation of antihypertensive
therapy); thrombocytopenia; impaired liver function; progressive
renal insufficiency; pulmonary edema; or new-­onset cerebral or visual
disturbances.6
The pathophysiology of pre-­eclampsia involves endothelial
cell dysfunction and inflammation. For example, pre-­eclampsia is
­associated with generalized activation of circulating leukocytes and
­increased concentrations of C-­reactive protein (CRP).7 Therefore, the
current study was designed to assess the association between serum
biochemical markers and the severity of pre-­eclampsia.
2 | MATERIALS AND METHODS
The present retrospective study included 270 women with a singleton
pregnancy of 34–40 weeks and a viable fetus who were seen at the
outpatient clinic, casualty department, or high-­risk department at Kasr
AlAiny Hospital in Cairo, Egypt, between October 1, 2013, and April
30, 2015. The study included 90 women with severe pre-­eclampsia (as
defined by the American College of Obstetricians and Gynecologists6),
90 with mild pre-­eclampsia, and 90 who were normotensive and had
no medical disorders (control group). Pre-­eclampsia was diagnosed
as the development of hypertension—defined as a persistent systolic
blood pressure of 140 mm Hg or higher or a diastolic blood pressure
of 90 mm Hg or higher—after 20 weeks of pregnancy in a woman
with previously normal blood pressure, alongside additional diagnostic
6
signs such as new-­onset proteinuria. Women with a multiple preg-
nancy, chronic hypertension, diabetes mellitus, or a history of cardiac,
liver, or renal disease were excluded from the study. Further exclusion
criteria were intrauterine fetal death, an apparent congenital anomaly,
and a history of rupture of membranes. The study was approved by
the local ethics committee. All participants had provided consent for
the inclusion of their data.
The 90 women in each group were randomly selected from the
overall pool of eligible women who attended the study center in the
study period. Random numbers in sealed envelopes were used for ran-
dom selection.
Data were recorded for age, gravidity, parity, date of the last nor-
mal menstrual period (to estimate the pregnancy duration), medical
history, and symptoms such as headache and visual disturbances. All
women had undergone a general and obstetric physical examination.
Blood pressure had been measured in a semi-­sitting position with the
woman’s arm supported and positioned at the level of the heart using
the first (systolic) and fifth (diastolic) Korotkoff sounds. Urine samples
were tested for proteinuria by the dipstick method. Mild proteinuria
was defined as a dipstick reading of 1+ or more in at least two mid-
stream samples 6 hours apart, and severe proteinuria was defined as
a dipstick reading of 2+ on at least two midstream samples 6 hours
apart.
Additionally, 5-­mL venous blood samples had been drawn on
­admission (before any magnesium sulfate administration) and analyzed
at Kasr AlAini Hospital laboratory. A complete blood count (hemoglobin
|
      139
level, total leukocyte count, platelet count) had been obtained using
a CELL-­Dyn 3700 analyzer (Abbott, St Paul, MN, USA) and kits sup-
plied by Spectra Group (Mannheim, Germany). The prothrombin time,
prothrombin concentration, and international normalized ratio (INR)
had been assayed on an STA Compact CT analyzer (Diagnostica Stago,
Parsippany, NJ, USA) using kits supplied by Etico (Dokki, Giza, Egypt).
Blood urea nitrogen, creatinine, aspartate transaminase (AST), alanine
transaminase (ALT), alkaline phosphatase (ALP), electrolytes (sodium,
potassium), uric acid, and CRP had been assayed on an Dimension
Xpand Plus system (Siemens Healthcare, Erlangen, Germany) using
kits supplied by Siemens Medical Solutions Diagnostics (Los Angeles,
CA, USA). The results were compared between the three groups for
the present study.
All women had also undergone transabdominal obstetric ultra-
sonography examination using a SonoAce X6 machine (Samsung
Medison, Seoul, South Korea) equipped with a 4–7-­MHz transabdom-
inal 3D4-­7EK probe (also from Samsung Medison). The examination
was performed in the supine position with a slight left lateral tilt to
avoid supine hypotension. The aims of the examination were to con-
firm the pregnancy duration (originally estimated by matching the
dates obtained from the last menstrual period and the first-­trimester
ultrasonography scan), to evaluate the fetal viability, to estimate the
fetal weight, to assess for placental separation, to measure the volume
and turbidity of the amniotic fluid, to perform a detailed anomaly scan,
and to assess fetal well-­being (biophysical profile test; measurement of
the resistance indices of the umbilical artery [UA] and middle cerebral
artery [MCA]).8
Doppler studies of the UA and MCA had been conducted in color
mode with a curvilinear transabdominal probe and at a Doppler angle
close to 0 degrees (with the Doppler ultrasound beam being parallel to
the direction of blood flow). The UA was visualized in a segment of the
cord where it was possible to keep the beam parallel to the blood flow;
the MCA was visualized near its separation from the ­internal ­carotid
artery. The measurements were obtained during periods of fetal
­inactivity and apnea. Average readings from at least three ­consecutive
waveforms were used to calculate the resistance index of the UA and
the resistance index of the MCA.
Cardiotocography (CTG) had been performed to assess the fetal
heart rate; the tracings were classified as normal, suspicious, of
pathologic as per Royal College of Obstetricians and Gynecologists
criteria.9 Normal tracings indicated good fetal well-­being and led to
a conservative approach to delivery; suspicious tracings resulted in
continuous observation and additional tests including vibroacoustic
stimulation; and pathological tracings were an indication for urgent
delivery.
The primary outcomes were the associations between the pres-
ence and severity of pre-­eclampsia and abnormal serum CRP, hemo-
globin, platelet count, blood urea nitrogen, creatinine, AST, ALT, and
ALP.
The sample size was calculated on the basis of the assumption of a
type-­1 error of 5%, a power of 90%, and a prevalence of pre-­eclampsia
of 3%–10%,4 and was estimated to be 87 women per group using an
uncorrected χ2 test.
 |
140       Maged ET AL.

All statistical calculations were performed using SPSS version 17
(SPSS Inc, Chicago, IL, USA) for Microsoft Windows. One-­way ANOVA
was used to compare the three study groups. Spearman rank correla-
tion was used to evaluate the correlation between serum levels of CRP
and blood pressure. P≤0.05 was considered statistically significant.
3 |  RESULTS
The three study groups did not differ significantly in terms of age
and body mass index (Table 1). Nulliparity was more common among
women with severe or mild pre-­eclampsia than among ­controls
(Table 1). The pregnancy duration at delivery among women with
­severe pre-­eclampsia was significantly shorter than that among
women with mild pre-­eclampsia or controls (Table 1). The mode of
­delivery also differed significantly between the three study groups:
vaginal delivery was most common in the control group and least
­common among women with severe pre-­eclampsia (Table 1). There
were also significant differences in the indication for cesarean
­delivery, with ­deterioration of the general condition being the most
­common ­indication among women with severe or mild pre-­eclampsia,
but not in the control group (Table 1).
With regard to the biochemical variables, there were no significant
differences between the three study groups in the hemoglobin level,
the total leukocyte count, the creatinine level, the prothrombin time
and concentration, the INR, and the levels of AST, ALP, total bilirubin,
and serum sodium and potassium (Table 2). The platelet count was sig-
nificantly lower and the ALT level significantly higher among women
with severe pre-­eclampsia compared with the other two groups,
whereas blood urea nitrogen and serum uric acid were significantly
lower in the control group than among women with mild or severe pre-­
eclampsia. There were also significant differences between the three
study groups regarding the CRP level.
Ultrasonography revealed differences between the three study
groups regarding the biophysical profile, the UA resistance index,
and the MCA resistance index; the differences were significant for
all comparisons between the two pre-­eclampsia groups and between
the group with severe pre-­eclampsia and the control group (Table 3).
Cardiotocography scores were significantly higher among women with
severe pre-­eclampsia than among those with mild disease or healthy
controls (Table 3).
The CRP level was significantly correlated with the systolic blood
pressure among women with severe pre-­eclampsia, but not in any of
the other groups (Table 4).

T A B L E   1   Characteristics of the study population.a

P values
Group 1: severe Group 2: mild Group 3:
Characteristic pre-­eclampsia (n=90) ­pre-­eclampsia (n=90) control (n=90) 1 vs 2 1 vs 3 2 vs 3

Age, y 26.1±51.0 26.2±4.4 25.4±4.7 0.132 0.173 0.451

Body mass indexb 32.9±2.8 31.8±2.9 29.4±2.1 0.942 0.361 0.122
c c
Pregnancy duration at delivery, wk 35.5±1 37.4±1 38.3±1.6 0.050 0.040 0.364
Parity 0.443 0.018c 0.026c
Nulliparous 54 (60.0) 53 (58.9) 40 (44.4)
Multiparous 36 (40.0) 37 (41.1) 50 (55.6)
Mode of delivery 0.007c 0.001c 0.001c
Normal vaginal 20 (22.2) 35 (38.9) 58 (64.4)
Cesarean 70 (77.8) 55 (61.1) 32 (35.6)
Indication
Deterioration of 38 (54.3) 22 (40.0) 6 (18.8) 0.263 0.004c 0.020c
maternal conditiond
Abnormal BPP scoree 18 (25.7) 12 (21.8) 2 (6.3) 0.311 0.010c 0.029c
Previous cesarean 10 (14.3) 15 (27.3) 12 (37.5) 0.036c 0.004c 0.162
f c
Other 4 (5.7) 6 (10.9) 12 (37.5) 0.145 0.001 0.173
Blood pressure, mm Hg
Systolic 175±14 143±6 120±3 0.030c <0.001c 0.030c
Diastolic 116±14 92±5 70±4 0.021c <0.001c 0.030c

Abbreviation: BPP, biophysical profile.

a
Values are given as mean±SD or number (percentage), unless indicated otherwise.
b
Calculated as weight in kilograms divided by the square of height in meters.
c
Statistically significant (P≤0.05).
d
Worsening of the signs and symptoms of pre-­eclampsia.
e
<6/10.
f
Malpresentation or infertility.
Maged ET AL. |
      141

T A B L E   2   Hematological, biochemical, and coagulation measures.a

P values
Group 1: severe Group 2: mild Group 3: control
Measure pre-­eclampsia (n=90) pre-­eclampsia (n=90) (n=90) 1 vs 2 1 vs 3 2 vs 3

Hematological
Hemoglobin, g/L 130.30±19.10 123.01±13.10 112.01±11.10 0.372 0.171 0.501
9 b b
Platelets, ×10 /L 113.40±36.72 172.93±57.60 212.68±70.00 0.050 0.001 0.061
Total leukocyte count, ×109/L 6.96±1.82 6.85±1.43 6.61±1.29 0.562 0.442 0.521
Biochemical
Creatinine, μmol/L 97.24±35.36 97.24±35.36 79.56±17.68 >0.99 0.891 0.891
b
Blood urea nitrogen, mmol/L 9.25±3.75 7.71±3.96 5.68±2.31 0.124 0.001 0.050b
b
Aspartate transaminase, U/L 45.62±14.43 35.54±13.03 28.31±11.02 0.061 0.050 0.071
b b
Alanine transaminase, U/L 52.24±14.83 38.34±13.12 23.11±6.92 0.050 0.001 0.062
C-­reactive protein, nmol/L 331.44±112.38 251.43±59.05 23.81±16.19 0.050b 0.001b 0.001b
Alkaline phosphatase, U/L 280.21±96.60 255.41±73.22 245.50±48.01 0.122 0.091 0.343
Total bilirubin, μmol/L 5.34±2.74 5.64±1.71 5.13±1.71 0.873 0.562 0.882
b
Uric acid, μmol/L 600.80±117.19 481.83±118.97 243.89±53.54 0.453 0.050 0.050b
Sodium, mEq/L 135.00±3.52 137.11±3.02 139.41±3.74 0.782 0.664 0.673
Potassium, mmol/L 2.91±0.28 3.42±0.72 4.22±0.44 0.442 0.062 0.091
Coagulation profile
Prothrombin time, s 20.23±6.14 15.31±3.01 12.53±0.53 0.063 0.050b 0.542
Prothrombin concentration, % 72.24±10.04 86.12±6.12 98.34±4.03 0.114 0.050b 0.492
b
International normalized ratio 1.81±0.62 1.22±0.38 0.96±0.14 0.062 0.050 0.323
a
Values are given as mean±SD unless indicated otherwise.
b
Statistically significant (P≤0.05).

There were significant differences between women with se-

vere pre-­eclampsia and women in the other two groups in terms
of maternal complications such as HELLP syndrome (hemolysis,
elevated liver enzyme levels, and low platelet levels) and eclamp-
sia than women in the other two groups, but not in terms of intra-
cranial hemorrhage (Table 5). Regarding neonatal complications,
the pre-­eclampsia groups had significantly lower Apgar scores
than the control group, and admission to the neonatal intensive
care unit was more likely than in the control group (Table 5).
Moreover, severe pre-­e clampsia was associated with perinatal
death (Table 5).
4 | DISCUSSION
Increasing evidence indicates that pre-­eclampsia is primarily caused
by a disturbance of normal endothelial cell function10 that results
from persistent systemic inflammation during early pregnancy.11
Consistent with this hypothesis, the present study found a significant
positive correlation between the level of CRP and the presence and
severity of pre-­eclampsia.
Previously, a US study12 found that women with a CRP level
of more than 4.1 mg/L had a three-­ to five-­times higher risk of

T A B L E   3   Ultrasonography assessment of fetal well-­being, and Doppler measures.a

P values
Group 1: severe Group 2: mild Group 3: control
Parameter pre-­eclampsia (n=90) pre-­eclampsia (n=90) (n=90) 1 vs 2 1 vs 3 2 vs 3
b c c
Cardiotocography score 2 (1–3) 1 (1–3) 1 (1–2) 0.039 0.039 0.925
d c c
Biophysical profile score 6 (10–4) 8 (10–6) 10 (10–6) 0.050 0.001 0.050c
c c
Umbilical artery resistance index 0.87±0.10 0.71±0.14 0.66±0.11 0.039 0.010 0.050c
Middle cerebral artery resistance 0.77±0.07 0.81±0.08 0.90±0.07 0.050c 0.021c 0.061
index
a
Values are given as median (range) or mean±SD.
b
1=normal; 2=suspicious; 3=pathologic.
c
Statistically significant (P≤0.05).
d
0–4=fetal asphyxia; 6=possible fetal asphyxia; 8–10=normal.
 |
142       Maged ET AL.

T A B L E   4   Correlation between C-­reactive protein level and blood pressure.

Group 1: severe pre-­eclampsia (n=90) Group 2: mild pre-­eclampsia (n=90) Group 3: control (n=90)

Statistic SBP DBP SBP DBP SBP DBP

r value 0.352 0.612 0.593 0.563 0.053 0.193

P value 0.001 0.021 0.042 0.332 0.617 0.072

Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.

pre-­eclampsia than did women whose CRP level was lower than
13
1.1 mg/L. Hwang et al. reported that the serum CRP level was
higher in women with pre-­eclampsia than in healthy pregnant women,
and both the systolic and the diastolic blood pressure were positively
correlated with the serum CRP level in the group with pre-­eclampsia.
Another study14 of 506 pregnant women found that women who
developed pre-­eclampsia had significantly higher concentrations of
CRP than did normotensive women (8.7±5.5 mg/L vs 5.3±4.3 mg/L;
P=0.02).
The platelet count in the present study was significantly lower
among women with severe pre-­eclampsia than in the other two
groups. Mohapatra et al.15 reported an inverse relationship ­between

T A B L E   5   Maternal and neonatal outcomes.a

P values
Group 1: severe Group 2: mild Group 3: control
Outcome pre-­eclampsia (n=90) pre-­eclampsia (n=90) (n=90) 1 vs 2 1 vs 3 2 vs 3

Maternal complications
Eclampsia 12 (13.3) 0 0 <0.001b 0.001b NA
c b b
HELLP syndrome 8 (8.9) 0 0 <0.001 0.001 NA
Intracranial hemorrhage 1 (1.1) 0 0 0.159 0.159 NA
Neonatal outcomes
Apgar score
1 min 4 (2–6) 6 (4–8) 8 (4–8) 0.041b 0.001b 0.040b
5 min 6 (2–10) 8 (4–10) 10 (4–10) 0.051b 0.001b 0.050b
b
Admission to neonatal intensive care unit 16 (17.8) 9 (10.0) 2 (22.2) 0.062 0.001 0.010b
Reason for admission
Low birth weight 11 (68.8) 6 (66.7) 0 0.451 0.031b 0.050b
Infection 2 (12.5) 1 (11.1) 1 (50.0) 0.114 0.174 0.315
Prematurity 2 (12.5) 1 (11.1) 0 0.324 0.267 0.336
d
Other 1 (6.3) 1 (11.1) 1 (50.0) 0.465 0.101 0.124
>24 h 11 (68.8) 2 (22.2) 0 0.012b 0.031b 0.254
b b
Perinatal death 7 (7.8) 2 (2.2) 2 (22.2) 0.044 0.044 0.511
Cause
Prematurity 5 (71.4) 1 (50.0) 0 0.313 0.044b 0.213
Stillbirth 1 (14.3) 0 1 (50.0) 0.314 0.174 0.213
e
Other 1 (14.3) 1 (50.0) 1 (50.0) 0.173 0.174 0.501
Timing
Stillbirth 1 (14.3) 1 (50.0) 0 0.175 0.314 0.215
First day 2 (28.6) 1 (50.0) 0 0.316 0.235 0.216
First 3 days 3 (42.9) 0 1 (50.0) 0.237 0.316 0.213
First week 1 (14.3) 0 1 (50.0) 0.316 0.177 0.213

Abbreviation: NA, not available.

a
Values are given as number (percentage) or median (range), unless indicated otherwise.
b
Statistically significant (P<0.05).
c
Hemolysis, elevated liver enzymes, low platelets.
d
Meconium aspiration syndrome, asphyxia, jaundice.
e
Congenital anomaly, birth asphyxia.
Maged ET AL.
the ­platelet count and the severity of pregnancy-­induced hyperten-
sion. The present findings agree with a study of 100 women with se-
vere pre-­eclampsia,16 in which 50 women had a platelet count below
150 000/μL, and 13 of these women had a prolonged prothrombin
or activated partial thromboplastin time. No patient had an abnormal
fibrinogen level or a prolonged prothrombin time ­partial thrombo-
plastin time in the absence of thrombocytopenia. The ­authors con-
cluded that thrombocytopenia is a strong indicator of the severity of
pre-­eclampsia.
There was no significant difference between the three study
groups for the hemoglobin level, the total leukocyte count, the serum
levels of creatinine, AST, ALP, total bilirubin, sodium, and potassium,
the prothrombin time and concentration, and the INR. However, the
ALT level was significantly higher among women with severe pre-­
eclampsia than in the other two groups, and blood urea nitrogen and
serum uric acid were significantly higher in the two groups of women
with pre-­eclampsia. In a previous study,17 women in the pre-­eclampsia
group (n=50) had significantly higher levels of liver enzymes (ALT,
AST, and ALP) than did women in the control group (n=50). However,
the difference in total bilirubin between these two groups was not
significant.
The present study found a significant difference between the three
study groups regarding the CTG findings, with suspicious CTG trac-
ings being more common among women with pre-­eclampsia than in
the other two groups. Some adverse maternal and neonatal outcomes
were more common among women with pre-­eclampsia, and therefore
the suspicious CTG findings could be associated with the poor out-
comes. Indeed, previous authors18 found an association between an
abnormal umbilical artery Doppler study and an abnormal perinatal
outcome.
In terms of the development of maternal complications, ­eclampsia
and HELLP syndrome were significantly more common among women
with severe pre-­eclampsia in the present study than among women
with mild pre-­eclampsia or healthy women; there was no significant
difference with regard to intracranial hemorrhage. Moreover, neonatal
complications (low Apgar score, admission to the neonatal intensive
care unit, and perinatal death) were more common among women with
pre-­eclampsia than in the control group, irrespective of the ­severity of
pre-­eclampsia.
The main limitation of the present study was the lack of a long
follow-­up for neonatal development; it was therefore not possible to
observe the long-­term effects of pre-­eclampsia and to correlate these
with the various markers studied here.
To the best of our knowledge, the present study is the first to
combine the assessment of ultrasonographic markers, fetal heart
rate tracings, and various biochemical markers in women with
pre-­eclampsia, correlating them to the development and severity
of the disease, and giving consideration to maternal and neonatal
outcomes. The levels of CRP, blood urea nitrogen, serum uric acid,
and ALT and the platelet count were shown to be linked with the
presence and severity of pre-­eclampsia. Moreover, pre-­eclampsia is
associated with significant changes in CTG tracings and UA and MCA
Doppler waveforms.
|
      143
In conclusion, the present study has shown that the plate-
let count and levels of CRP, blood urea nitrogen, serum uric acid,
and ALT are linked with the development and severity of pre-­
eclampsia. Therefore, these markers could be used to assess the
risk of the ­disease and its severity. CTG monitoring, and UA and
MCA Doppler assessments should be done for all patients with
pre-­eclampsia to detect changes that could be associated with fetal
compromise.
AU T HO R CO NT R I B U T I O NS
GA and NB developed the study protocol. NB, DSE, and NKG col-
lected data. DSE and NKG managed data. AMM, DSE, and SD ana-
lyzed the data. All authors participated in the writing and editing of
the manuscript.
CO NFL I C T O F I NT ER ES T
The authors have no conflict of interest.
REFERENCES
1. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Sponge
CY. Pregnancy hypertension. In: Cunningham FG, Williams JW,
eds. William’s Obstetrics. 23rd edn. New York, NY: McGraw-Hill;
2010:761–808.
2. Kang A, Struben H. Pre-­eclampsia screening in first and second tri-
mester. Ther Umsch. 2008;65:663–6.
3. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-­
eclampsia. Lancet. 2010;376:631–44.
4. Maged AM, ElNassery N, Fouad M, Abdelhafiz A, Al Mostafa W. Third-­
trimester uterine artery Doppler measurement and maternal postpar-
tum outcome among patients with severe pre-­eclampsia. Int J Gynecol
Obstet. 2015;131:49–53.
5. Duhig KE, Shennan AH. Recent advances in the diagnosis and manage-
ment of pre-­eclampsia. F1000Prime Rep. 2015;7:24. doi:10.12703/
P7-24. eCollection 2015. Review.
6. American College of Obstetricians and Gynecologists (ACOG), Task
Force on Hypertension in Pregnancy. Establishing the diagnosis of
preeclampsia and eclampsia. In: ACOG, Task Force on Hypertension
in Pregnancy. Hypertension in Pregnancy. Washington, DC: ACOG;
2013:17–20.
7. Redman CW, Sargent IL. Latest advances in understanding pre-
eclampsia. Science. 2005;308:1592–4.
8. Romero R, Hernandez-Andrade E. Doppler of the middle cerebral
artery for the assessment of fetal well-­being. Am J Obstet Gynecol.
2015;213:1. doi:10.1016/j.ajog.2015.05.064.
9. Royal College of Obstetricians and Gynaecologists (RCOG). Severe
Pre-eclampsia/Eclampsia, Management. Green-top Guideline No. 10A.
London: RCOG; 2006.
10. Sibai BM. Diagnosis, prevention, and management of eclampsia.
Obstet Gynecol. 2005;105:402.
11. Belo L, Santos-Silva A, Rumley A. Elevated tissue ­plasminogen activa-
tor as a potential marker of endothelial ­dysfunction in preeclampsia:
Correlation with proteinuria. BJOG. 2002;109:1250–1255.
12. Wolf M, Kettyle E, Sandler L. Obesity and preeclampsia: The potential
role of inflammation. Obstet Gynecol. 2001;98:757–762.
13. Hwang HS, Kwon JY, Kim MA, Park YW, Kim YH. Maternal serum
highly sensitive C-­reactive protein in normal pregnancy and pre-­
eclampsia. Int J Gynecol Obstet. 2007;98:105–109.
 |
144       Maged ET AL.

14. Ronald G, Johanna C, Jesús S. Raised C-­reactive protein and impaired
flow-­mediated vasodilationprecede the development of preeclamp-
sia. Am J Hypertens. 2007;20:98–103.
15. Mohapatra S, Pradhan BB, Satpathy UK, Mohanthy A, Pattnaik JR.
Platelet Estimation: Its prognostic value in pregnancy induced hyper-
tension. Indian J Physiol Pharmacol. 2007;51:160–164.
16. Leduce L, Wheeler JM, Kirshon B, Mitchell P, Cotton DB. Coagulation
profile in Severe Preeclampsia. J Obstet Gynaecol. 1992;79:14–18.
17. Munazza B, Raza N, Naureen A, et  al. Liver function tests in pre-
eclampsia. J Ayub Med Coll Abbottabad. 2011;23:3–5.
18. Arauz JF, León JC, Velásquez PR, Jiménez GA, Pérez CJ. Umbilical
artery Doppler velocimetry and adverse perinatal outcome in severe
pre-­eclampsia. Ginecol Obstet Mex. 2008;76:440–9.