THE ROLE OF ULTRASOUND

IN EARLY PREDICTION OF PREECLAMPSIA

HERMAN KRISTANTO
Ultrasound Working Group
Indonesian Society of Obstetrics & Gynecology
The normal pregnancy is a result of a complex series of changes in
the vascular anatomy of the mother, principally in the uterine
perfusion that is fundamental for the pregnancy success.
With the implantation of the fertilized ovum in the uterine cavity, the
arterial system that irrigates the endometrium and the subjacent
myometrium undergoes a series of changes which lead to the
uteroplacental circulation.
Such changes in the arterial system are a result of the decidua
invasion by the trophoblast.
Carrera, et al. Doppler en Obstetricia 1992

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
One believes that the trophoblastic invasion occurs in two waves :
The first wave extends from the 6th to the 10th week of gestation
and affects the spiral arteries from the distal end, up to the border
between the basal decidua and the myometrium.
The second wave starts between the 14th and 16th weeks and
develops during 4-6 weeks, reaching the myometrial segment of
the spiral arteries, including the most distal portions of the radial
arteries.
Pijnenborg R, et al. Placenta 1980 ; 1

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
These morphologic changes in the uterine vascularization can be
demonstrated by the color and pulsed Doppler with detection and
analysis of main uterine arteries and their ramifications into arcuate and
radial arteries up to their spiral artery terminal branches. The blood flow
velocity increases in the uteroplacental circulation, while its impedance
decreases as the gestation develops.
Kurjak A, et al. Early Hum Dev 1992 ; 29

The impedance index decreased with the gestation evolution in both

uterine arteries, but this decrease was lower in the arteries contralateral
to the placenta.
Valentin L, et al. Am J Obstet Gynecol 1996 ;174

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The Role of Ultrasound in Early Prediction of Preeclampsia
Herman Kristanto
 Trudinger, et al. Br J Obstet Gynecol 1985 ; 92

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Jauniaux, et al. Am J Obstet Gynecol 1992 ; 166

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Jurkovic, et al. Obstet Gynecol 1991 ; 77

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Bower & Campbell. 1993

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Stages of Preeclampsia

Suppo, et al. NeoReviews 2011 ; 12 (4)

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Stages of Preeclampsia

Redman & Sargent. Am J Reprod Immun 2010 ; 63

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Stages of Preeclampsia

Rabaglino, et al. Hypertension 2015 ; 65

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Normal

Preeclampsia

Lam, et al. Hypertension ; Nov 2005

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Kingdom & Drewlo. Blood 2011 : 118

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Kingdom & Drewlo. Blood 2011 : 118

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Normal Pregnancy Preeclampsia

Brossens, et al. Obstet Gynecol Annu 1972 ; 1

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Prefumo, et al. Human Reproduction 2004 ; 19

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Ultrasound in Early Prediction of PE

• Doppler Studies :
• Uterine artery
• Ophtalmic artery
• Middle cerebral artery
• 3D power doppler placental vascularity

• Placental Studies :
• Location
• Volume

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Ultrasound in Early Prediction of PE

• Doppler Studies :
• Uterine artery
• Ophtalmic artery
• Middle cerebral artery
• 3D power doppler placental vascularity

• Placental Studies :
• Location
• Volume

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The Role of Ultrasound in Early Prediction of Preeclampsia
Herman Kristanto
Transabdominal Transvaginal

Costa SF

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Uterine artery

Uterine artery

Evaluation of UtA-PI at 11–13 weeks can be achieved at the level of the

internal cervical os in a greater proportion of women than at the level of
the apparent crossover with the external iliac vessels, and the
measurements obtained correlate better with second-trimester UtA-PI
Levebre, et al. Ultrasound Obstet Gynecol 2012 ; 40

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
“How To” record uterine artery Doppler at 11–13 weeks

How To: Record uterine artery Doppler pulsatility index (PI) at

11+0 to 13+6 weeks’ gestation

Indication: To screen in the first trimester for pre-eclampsia

and/or fetal growth restriction

Machine settings: Routine first-trimester scan preset with

color Doppler velocity 30–40 cm/s, pulsed wave Doppler
velocity 80–100 cm/s, low filter (50–100 Hz) and pulsed
Doppler sample volume 2 mm
Uterine artery Doppler: identifying the cervix
• Obtain a mid-sagittal section of the
uterus and cervix

• Use HD zoom to enlarge the view of the

cervix
Uterine artery Doppler: identifying the uterine artery

• Apply color flow mapping

• Slide the transducer to view the para-
cervical region
• Gently move the transducer from side
Mid-sagittal view
to side to identify the uterine artery
Bladder
• The uterine arteries are at the level of
the internal cervical os

Cervix

Paramedian view
Uterine artery Doppler: obtaining a spectral Doppler signal
Color Doppler of uterine arteries
• Set the sampling gate to 2 mm so as
to cover whole vessel
• Angle of insonation should be less
than 30º
• The peak systolic velocity should be
more than 60 cm/s in the uterine artery
• Obtain three similar consecutive
waveforms
Uterine artery waveform
• The mean PI is obtained as the
average of the left PI and right PI
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The Role of Ultrasound in Early Prediction of Preeclampsia
Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 DeVore GR. Fetal Diagnostic Centers. www.fetal.com

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Everett & Lees, Placenta 2012 ; 33

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Gomez, et al. Ultrasound Obstet Gynecol 2008; 32

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Preeclampsia and early preeclampsia were present 9.4% and 3.1%
of pregnancies respectively. Mean UtA PI was 2.5 ± 0.9 in group
who developed preeclampsia and 1.7 ± 0.5 in non-preeclamptic
group (p<0.001).

Uterine artery Doppler at 11-14 weeks of gestation identifies about

65% of women who develop early preeclampsia.
Erdogdu, et al. Perinatal Journal 2014 ; 22

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The sensitivity and specificity of abnormal uterine artery flow velocity
waveform (FVW) in the prediction of early-onset pre-eclampsia were 47.8%
(95% CI: 39.0–56.8) and 92.1% (95% CI: 88.6–94.6), and in the prediction of
early-onset fetal growth restriction were 39.2% (95% CI: 26.3–53.8) and
93.1% (95% CI: 90.6–95.0), respectively. The sensitivities for predicting any
pre-eclampsia and fetal growth restriction were 26.4% (95% CI: 22.5–30.8)
and 15.4% (95% CI: 12.4–18.9), respectively, and the specificities were
93.4% (95% CI: 90.4–95.5%) and 93.3% (95% CI: 90.9–95.1), respectively

Velauthar, et al. Ultrasound Obstet Gynecol 2014 ; 43

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
First-trimester uterine artery Doppler is a useful tool for predicting
early-onset pre-eclampsia, as well as other adverse pregnancy
outcomes. Based on the NNT, abnormal uterine artery Doppler in
low-risk women achieves a sufficiently high performance to justify
aspirin prophylaxis in those who test positive.

Velauthar, et al. Ultrasound Obstet Gynecol 2014 ; 43

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
In the normal outcome group, UtA-PI decreased with gestational
age and MAP decreased between 12 and 24 weeks and then
increased. In the preterm PE group, as compared to the normal
group, UtA-PI and MAP were higher from early pregnancy onward
and the difference for both increased with gestational age. In the
term PE group, UtA-PI was significantly increased only from 33
weeks onward and MAP was increased from 12 weeks onward but
the difference from normal did not increase with gestation.

Khalil, et al. Ultrasound Obstet Gynecol 2014 ; 43

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The decrease in uterine artery PI between 11 + 0 to 13 + 6 and 21 +
0 to 24 + 6 weeks is steeper in pregnancies with a normal outcome
than in those developing pre-eclampsia. Effective screening for
preeclampsia can be achieved by the Doppler measurement of
uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in PI
between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks

Plasencia, et al. Ultrasound Obstet Gynecol 2008 ; 43

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Using mUtA-PI, the detection rates of late and early PE for a false-positive
rate of 10% were 14.3% and 33.3%, respectively, at 11–13 weeks, and
19.0% and 66.7%, respectively, at 19–22 weeks. Using a semi-quantitative
approach, the group of pregnant women with mUtA-PI ≥90th percentile at
both 11–13 and 19–22 weeks had a greater risk for early PE (odds ratio,
21.4 (95% CI, 2.5–184.7)) compared with the group with mUtA-PI <90th
percentile at both periods. Using a quantitative approach, there was
relative worsening in the mUtA-PI (multiples of the median) from the first
to the second trimester in all cases of early PE.

Herraiz, et al. Ultrasound Obstet Gynecol 2012 ; 4\0

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The predictive accuracy of first-trimester uterine artery Doppler is
better in the detection of early-onset preeclampsia FGR than late-
onset disease. The sensitivities and specificities of uterine artery
Doppler indices for the prediction of preeclampsia in low risk
populations vary from 34% to 76% and 83% to 93%, respectively.
Algorithms that combine maternal characteristics, uterine artery
Doppler velocimetry, and biochemical markers in the first trimester
have the potential to improve the detection rate of early-onset
preeclampsia to over 90% at a false positive rate of 10%.

Khong, et al. Disease Makers 2015

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 Khong, et al. Disease Makers 2015

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
The uterine artery L-PI was significantly higher in early PE and late PE
than in the unaffected group (P < 0.0001), in early PE than late PE or GH
(P < 0.0001), and in GH than in the unaffected group (P = 0.014).
In screening by a combination of the maternal factor-derived apriori
risk, uterine artery L-PI and MAP, the estimated detection rate at a 10%
false-positive rate was 89.2% (95% CI, 74.6–96.9%) for early PE, 57.0%
(95% CI, 48.0–65.7%) for late PE and 50.0% (95% CI, 41.4–58.6%) for GH.

Poon, et al. Ultrasound Obstet Gynecol 2009 ; 34

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 • The mini-combined test (MAP
and PAPP-A)
Preterm Preeclampsia Term Preeclampsia
• Biophysical test (uterine artery
PI and MAP)
• Biochemical test (serum PLGF
and PAPP-A)
• The triple test (uterine artery PI,
MAP and serum PLGF)

Gorman, et al. Am J Obstet Gynecol 2016

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Combined screening by maternal factors, uterine artery pulsatility index,
mean arterial pressure, and placental growth factor predicted 75% (95%
CI, 70-80%) of preterm-preeclampsia and 47% (95% CI, 44-51%) of term-
preeclampsia, at a false positive rate of 10%; inclusion of pregnancy-
associated plasma protein-A did not improve the performance of
screening. Such detection rates are superior to the respective values of
49% (95% CI, 43-55%) and 38% (34-41%) that were achieved by screening
with maternal factors alone.

Gorman, et al. Am J Obstet Gynecol 2016

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
Screening with use of the FMF algorithm based on a combination
of maternal factors, mean arterial pressure (MAP), uterine artery
pulsatility index (UtA-PI) and serum placental growth factor (PlGF)
detected 100% (95% CI, 80–100%) of PE <32 weeks, 75% (95% CI,
62–85%) of PE <37 weeks and 43% (95% CI, 35–50%) of PE ≥37
weeks, at a 10.0% FPR.

Gorman, et al. Ultrasound Obstet Gynecol 2017 ; 49

The Role of Ultrasound in Early Prediction of Preeclampsia

Herman Kristanto
 PE Risk factors
Risk factors Frequency of occurrence
Previous preeclampsia 20-30%
Previous preeclampsia at ≤ 28 weeks 50%
Chronic hypertension 15-25%
Severe hypertension 40%
Renal disease 25%
Pregestational diabetes mellitus 20%
Class B/C diabetes 10-15%
Class F/R diabetes 35%
Thrombophilia 10-40%
Obesity/insulin resistance 10-15%
Age > 35 years 10-20%
Family history of preeclampsia 10-15%
Primiparity 6-7%
Thank You