Transcript Slide 1

UOG Journal Club: July 2012
Maternal hemodynamics at 11–13 weeks’ gestation and risk
of pre-eclampsia
A. Khalil, R. Akolekar, A. Syngelaki, M. Elkhouli and K. H. Nicolaides
Volume 40, Issue 1, Date: July 2012, pages 28–34
Journal Club slides prepared by Dr Asma Khalil
(UOG Editor for Trainees)
Forward flow from cardiac action
Pressure Wave
Reflection
Blood
vessel
Reflected flow from peripheral resistance
Incident pressure wave is generated by the heart.
When the wavefront encounters resistance → Reflected wave
Incident and Reflected waves → Combined waveform
Pressure Wave Reflection
Vasodilatation:
Vasoconstriction:
 Amplitude of Reflected wave
And delays its return
 Amplitude of Reflected wave
Pressure Wave Reflection
Vasodilatation
Vasoconstriction
Central Blood Pressure
Artery occluded due to
suprasternal cuff pressure
Forward wave
1
2
Pressure in
Pressure waves
the aorta is travel to the artery
generated by are transferred to
the heart
the cuff
3
The cuff
pressure is
measured
• Aortic blood pressure (BP)  brachial BP
• Better prediction of vascular disease/outcome than brachial BP
• Distinguishes between the effects of different antihypertensive
drugs when brachial BP does not
Augmentation index (AIx) and pulse wave velocity
(PWV) are increased in pre-eclampsia (PE)
Author
AIx
PWV
PE; History of PE; PE vs
gestational hypertension (GH)
Hausvater et al 2012 (meta-analysis)
PE prediction
Khalil et al 2009, Khalil et al 2011
Savvidou et al 2011
Hausvater A et al., J Hypertens 2012
Khalil A et al., BJOG 2009
Khalil A et al., Obstet Gynecol 2010
Savvidou MD et al., Am J Obstet Gynecol 2010
Maternal hemodynamics at 11–13 weeks’ gestation
and risk of pre-eclampsia
Khalil et al., UOG 2012
Prospective; 7,084 singleton pregnancies at 11+0 – 13+6 weeks;
2009 – 2011
Objective
To examine the value of maternal hemodynamics measured at
11–13 weeks in the early prediction of PE
Maternal hemodynamics at 11–13 weeks’ gestation
and risk of pre-eclampsia
Khalil et al., UOG 2012
Methodology
• Screening for PE at 11 – 13 weeks
• Comparison of history / maternal characteristics, uterine
artery Doppler, PAPP-A and AIx, PWV and central systolic
blood pressure (SBPAo)
n
• Pre-eclampsia
181 (2.6%)
• Gestational hypertension
137 (1.9%)
• Unaffected controls
6,766
Methodology
Inclusion criteria
• Singleton pregnancy and a live
fetus identified at 11+0 – 13+6
week scan
Exclusion criteria
1)
2)
3)
4)
Major fetal abnormalities
Termination of pregnancy
Miscarriage
Fetal death before 24 weeks
Outcomes
•
•
PE (ISSHP definition)
GH
Vascular measurements
• Arteriograph® was used for
recording SBPAo (mmHg), PWV
(m/s) and AIx (%)
• Results did not influence the
subsequent management
Statistical Analysis
• Multivariate logistic regression
analysis → variables that
provided a significant
contribution in predicting PE
• Receiver–operating characteristics
(ROC) analysis to determine the
performance of screening
Maternal hemodynamics and the risk of PE
Results
1.6
1.5
P<0.0001 P<0.0001
P=0.051
P<0.0001
Pulse wave velocity (MoM)
Augmentation index-75 (MoM)
1.4
1.5
1.0
0.5
1.2
1.0
0.8
0.6
0.4
0.0
Normal PE
GH
Central aortic systolic blood pressure (MoM)
2.0
P<0.0001
P<0.0001
1.25
1.0
0.75
0.5
Normal PE
GH
Normal PE
GH
Maternal hemodynamics and the risk of PE
Performance of screening
100
Area under
ROC curve
Detection rate at FPR 10%
90
80
70
60
61.9%
56.9%
50
40
P-value
History
0.80 (0.79–0.81)
History + vascularderived risk
0.84 (0.83–0.84)
0.005*
History + vascularderived risk + uterine
artery PI + PAPP-A
0.85 (0.84–0.86)
0.001*
47.0%
30
20
10
0
History + vascular + uterine PI
risk
+ PAPP-A
* Comparison with performance of screening based on maternal factors only
Maternal hemodynamics and the risk of PE
Early-onset versus late-onset PE
[History + vascular-derived risk + uterine artery PI
+ PAPP-A] compared to [History + vascular risk]
Early-onset PE
Late-onset PE
Improvement
No significant
improvement
No significant association between the vascular-derived risk for PE
(combination log10 MoM of AIx-75, PVW and SBPAo) and gestational age at
delivery of the PE group.
Whereas high uterine artery PI and low PAPP-A were more marked in earlyPE compared to late-PE.
Maternal hemodynamics and the risk of PE
Women with chronic hypertension
Superimposed PE
MoMs (n=21)
No PE
MoMs(n=47)
SBPAo
1.29
1.15*
PWV
1.02
1.00
AIx-75
1.37
1.21
uterine artery PI
1.04
1.07
PAPP-A
0.92
0.84
Even after exclusion of women with chronic hypertension, no significant
change in the results seen in those who developed PE [increased AIx-75,
PWV, SBPao and uterine artery PI, and decrease in PAPP-A].
* p<0.05
Maternal hemodynamics and the risk of PE
Discussion
Strengths
•Large number
•Narrow gestational range of 1113 weeks, which is emerging as
the first clinical visit in pregnancy
for assessment of patient-specific
risks for a wide range of
pregnancy complications
Limitations
• Lack of longitudinal data during
pregnancy and assessment of
the patients with PE after
pregnancy to document
whether in those with increased
arterial stiffness and SBPao
there was persistence of these
abnormalities
Maternal hemodynamics and the risk of PE
Discussion
PE: common phenotypic expression of two distinct processes
Predisposition for
cardiovascular disease
Late-PE
Impaired trophoblastic
invasion
Early-PE
Maternal hemodynamics at 11–13 weeks’ gestation
and risk of pre-eclampsia
Khalil et al., UOG 2012
Conclusion
 Women who develop PE have higher aortic systolic blood
pressure and arterial stiffness.
 These findings are apparent from the first trimester of
pregnancy
 The mechanism of association with PE does not appear to
be mediated by impaired placental perfusion and function
 Arterial stiffness appears promising in predicting late-PE
Maternal hemodynamics at 11–13 weeks’ gestation and risk of preeclampsia
Khalil et al., UOG 2012
Discussion points
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What is the best screening test for identifying women at high risk of pre
eclampsia?
Is this test different if the screening is performed in the first trimester or second
trimester?
Is it justified to screen for pre-eclampsia?
What are the recommended indications for low-dose aspirin for prevention of
pre-eclampsia?
How does screening for pre-eclampsia compare to screening for Down
syndrome?
Discuss whether early-onset and late-onset pre-eclampsia have different
pathologies or simply different degrees of severity of the same pathology.
Why do most of the screening markers perform better for early-onset than lateonset pre-eclampsia?
What are the potential uses of arterial stiffness in obstetrics?