UOG Journal Club: July 2012Maternal hemodynamics at 11–13 weeks’ gestation and risk

of pre-eclampsiaA. 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)

BloodBloodvesselvessel

Forward flow from cardiac actionForward flow from cardiac action

Reflected flow from peripheral resistanceReflected flow from peripheral resistance

Incident pressure wave is generated by the heart.pressure wave is generated by the heart.

Pressure Wave Pressure Wave ReflectionReflection

When the wavefront encounters resistance When the wavefront encounters resistance →→ Reflected wavewave

Incident and Reflected waves → → Combined waveform waveform

Vasodilatation:Vasodilatation:

Amplitude of Amplitude of Reflected wavewaveAnd delays its returnAnd delays its return

Vasoconstriction:Vasoconstriction:

Amplitude of Amplitude of Reflected wavewave

Pressure Wave ReflectionPressure Wave Reflection

Pressure Wave ReflectionPressure Wave Reflection

VasodilatationVasodilatation

VasoconstrictionVasoconstriction

Central Blood PressureCentral Blood Pressure

• 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

Forward wave

Artery occluded due to suprasternal cuff pressure

Pressure in Pressure in the aorta is the aorta is

generated by generated by the heartthe heart

Pressure waves Pressure waves travel to the artery travel to the artery are transferred to are transferred to

the cuffthe cuff

The cuff The cuff pressure is pressure is measuredmeasured

1 2 3

Augmentation index (AIx) and pulse wave velocity Augmentation index (AIx) and pulse wave velocity (PWV) are increased in pre-eclampsia (PE)(PWV) are increased in pre-eclampsia (PE)

Khalil et al 2009, Khalil et al 2011Savvidou et al 2011

Hausvater et al 2012 (meta-analysis)

PE; History of PE; PE vs gestational hypertension (GH)

PWVPWVAIxAIxAuthorAuthor

PE prediction

Hausvater A et al., J Hypertens 2012Khalil A et al., BJOG 2009

Khalil A et al., Obstet Gynecol 2010Savvidou 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

ObjectiveTo examine the value of maternal hemodynamics measured at11–13 weeks in the early prediction of PE

Prospective; 7,084 singleton pregnancies at 11+0 – 13+6 weeks; 2009 – 2011

MethodologyMethodology

• 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

Maternal hemodynamics at 11–13 weeks’ gestation and risk of pre-eclampsia

Khalil et al., UOG 2012

MethodologyMethodology

Inclusion criteria

• Singleton pregnancy and a live fetus identified at 11+0 – 13+6 week scan

Exclusion criteria

1) Major fetal abnormalities2) Termination of pregnancy3) Miscarriage4) 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 PEMaternal hemodynamics and the risk of PE

ResultsResults

PE GHNormal

Au

gm

enta

tio

n in

dex

-75

(Mo

M)

0.0

0.5

1.0

1.5

2.0P<0.0001 P<0.0001

0.5

0.75

1.0

1.25

1.5

Normal PE GH

P<0.0001

P<0.0001

Cen

tral

ao

rtic

sys

tolic

blo

od

pre

ssu

re (

Mo

M)

0.4

0.6

0.8

1.0

1.2

1.4

1.6

Normal PE GH

Pu

lse

wav

e ve

loci

ty (

Mo

M)

P<0.0001P=0.051

Maternal hemodynamics and the risk of PEMaternal hemodynamics and the risk of PE

Performance of screeningPerformance of screening

0

10

20

30

40

50

60

70

80

90

100

History + vascularrisk

+ uterine PI + PAPP-A

47.0%

56.9%61.9%

Det

ecti

on

rat

e at

FP

R 1

0%

History + vascular-History + vascular-derived riskderived risk

0.84 (0.83–0.84) 0.005*

HistoryHistory 0.80 (0.79–0.81)

P-valueP-valueArea under Area under ROC curveROC curve

History + vascular-History + vascular-derived risk +derived risk + uterine uterine artery PI + PAPP-Aartery PI + PAPP-A

0.85 (0.84–0.86) 0.001*

* Comparison with performance of screening based on maternal factors only

Maternal hemodynamics and the risk of PEMaternal hemodynamics and the risk of PE

Early-onset versus late-onset PEEarly-onset versus late-onset PE

[History + vascular-derived risk +[History + vascular-derived risk + uterine artery PI uterine artery PI + PAPP-A] compared to [History + vascular risk]+ PAPP-A] compared to [History + vascular risk]

Improvement No significant improvement

Early-onset PE Early-onset PE Late-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.

Maternal hemodynamics and the risk of PEMaternal hemodynamics and the risk of PE

Women with chronic hypertensionWomen with chronic hypertension

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].

PWVPWV 1.02 1.00

1.15*SBPAoSBPAo 1.29

No PENo PEMoMs(n=47)MoMs(n=47)

Superimposed PESuperimposed PEMoMs (n=21)MoMs (n=21)

uterine artery PIuterine artery PI 1.04 1.07

1.21AIx-75AIx-75 1.37

PAPP-APAPP-A 0.92 0.84

* p<0.05

DiscussionDiscussion

StrengthsStrengths

•Large number•Narrow gestational range of 11-13 weeks, which is emerging as the first clinical visit in pregnancy for assessment of patient-specific risks for a wide range of pregnancy complications

LimitationsLimitations

• 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 PEMaternal hemodynamics and the risk of PE

DiscussionDiscussion

Maternal hemodynamics and the risk of PEMaternal hemodynamics and the risk of PE

PE: common phenotypic expression of two distinct processesPE: common phenotypic expression of two distinct processes

Predisposition for Predisposition for cardiovascular disease cardiovascular disease

Impaired trophoblastic Impaired trophoblastic invasioninvasion

Late-PELate-PE Early-PEEarly-PE

ConclusionConclusion Women who develop PE have higher aortic systolic bloodpressure 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 pre-eclampsia

Khalil et al., UOG 2012

Maternal hemodynamics at 11–13 weeks’ gestation and risk of pre-eclampsia

Khalil et al., UOG 2012

• 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?

Discussion points