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)

2. Pressure Wave Reflection
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

3. Pressure Wave Reflection
Vasodilatation:
Amplitude of Reflected wave
And delays its return
Vasoconstriction:
 Amplitude of Reflected wave

4. Pressure Wave Reflection
Vasodilatation
Vasoconstriction

5. Central Blood Pressure
Forward wave
Artery occluded due to suprasternal cuff pressure
Pressure in the aorta is generated by the heart
Pressure waves travel to the artery are transferred to the cuff
The cuff pressure is measured 1 2 3
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

6. 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

7. 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

8. 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 (2.6%)
Gestational hypertension (1.9%)
Unaffected controls ,766

9. Vascular measurements
Methodology
Inclusion criteria
Singleton pregnancy and a live fetus identified at 11+0 – 13+6 week scan
Exclusion criteria
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

10. Maternal hemodynamics and the risk of PE
Results PE GH
Normal
Augmentation index-75 (MoM)
0.0
0.5
1.0
1.5
2.0
P<0.0001
0.75
1.25
Central aortic systolic blood pressure (MoM)
0.4
0.6
0.8
1.2
1.4
1.6
Pulse wave velocity (MoM)
P=0.051

11. Maternal hemodynamics and the risk of PE Performance of screening10 20 30 40 50 60 70 80 90
100
History
+ vascular risk
+ uterine PI
+ PAPP-A
47.0%
56.9%
61.9%
Detection rate at FPR 10%
History + vascular-derived risk
0.84 (0.83–0.84)
0.005*
History
0.80 (0.79–0.81)
P-value
Area under ROC curve
History + vascular-derived risk + uterine artery PI + PAPP-A
0.85 (0.84–0.86)
0.001*
* Comparison with performance of screening based on maternal factors only

12. 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]
Improvement
No significant improvement
Early-onset PE
Late-onset PE
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 early-PE compared to late-PE.

13. Maternal hemodynamics and the risk of PE
Women with chronic hypertension
PWV
1.02
1.00
1.15*
SBPAo
1.29
No PE MoMs(n=47)
Superimposed PE MoMs (n=21)
uterine artery PI
1.04
1.07
1.21
AIx-75
1.37
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

14. Maternal hemodynamics and the risk of PE
Discussion
Strengths
Large number
Narrow gestational range of 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

15. Maternal hemodynamics and the risk of PE
Discussion
PE: common phenotypic expression of two distinct processes
Predisposition for cardiovascular disease
Impaired trophoblastic invasion
Late-PE
Early-PE

16. 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

17. Maternal hemodynamics at 11–13 weeks’ gestation and risk of pre-eclampsia
Khalil et al., UOG 2012
Discussion points
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 late-onset pre-eclampsia?
What are the potential uses of arterial stiffness in obstetrics?