clinical significance of the uterine artery doppler flowmetry : state of the art
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Clinical significance of the uterine artery Doppler flowmetry : state of the art. Campbell S et al: New Doppler technique for assessing uteroplacental blood flow. Lancet 1983; 1: 675-677. Significance of pre- eclampsia (PE) - PowerPoint PPT PresentationTRANSCRIPT
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Clinical significance of the uterine artery Doppler flowmetry :
state of the art
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Campbell S et al: New Dopplertechnique for assessinguteroplacental blood flow. Lancet 1983; 1: 675-677
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Significance of pre-eclampsia (PE)
* Incidence of 3-14% worldwide* Accounts for 100.000 maternal deaths worldwide per year* Second most common cause of maternal death in the developing world*Principal cause of maternal admission to ICU* Causes 4-fold increase in perinatal mortality* Responsible for 10% of stillbirths and 15% of preterm births* Causes long term maternal and infant morbidity RCOG Maternal Mortality Report 2008
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Perinatal mortality
Fetal abnormalitiesPremature birthImpaired placentation
Account for more than 90 % of perinatal deaths
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Aetiological factors in PE
*Inadequately modelled spiral arteries ( impaired trophoblastic invasion )* Restriction of placental perfusion (hypoxemia in placental bed )* Early placental ischaemia* Up-regulation of anti- angiogenesis factors(endoglyn and sflt-1) * Down-regulation of angiogenic factors (VEGF, PIGF )* Increase in oxygen free radicals* Widespread maternal vascular endothelial dysfunction* Reduced vascular endothelial nitric oxide production (key factor in symptomatology of PE )* Generalised vasoconstriction
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KEY vessel
for prediction of pre-eclampsia
UTERINE ARTERY
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Uterine artery Doppler
Quality assurance :
* Angle of insonation : always < 45 degrees* Sampling gate size : 2 mm* Main uterine artery ( not branches )* 1 cm above the crossing site * No compression of uterine artery by transducer
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Predictive Values with/without notches for all complicationsHarrington K et al UOG 1996
Sensiti-vity (%)
Specifi-city (%)
PPV (%)
NPV (%)
Any notchAny complications *Severe complications **
5154
7674
3213
8896
Bilateral NotchesAny ComplicationSevere complications
3176
9193
4347
8698
No notch/Mean RI > 90th
Any complicationSevere complications
2439
9291
4019
8595
* Any complication: PPIH, SGA <10th, placental abruption, stillbirth/NND** Severe complications: PPIH prior to 37 wks, SGA < 3rd, plac.abruption, still birth
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DOWN’S SYNDROME PRE-ECLAMPSIA
Prevalence 1:600 Prevalence Severe (Del. < 34 wks): 1:200Very severe ( Del. <32 wks): 1:300
Triple Test UTA Doppler
Sensitivity (15 w): 60% Severe Very severeSensitivity (14 w) 40% 60 % (23 w) 77% 93%
False Positive Rate = 5%Martin 2001, Papageorghiou 2001
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The future :
First trimester screening for PE
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Early biomarkers to predict PE
* Angiogenic proteins : VEGF, PIGF* Anti-angiogenic proteins : SFLT 1, s-Endoglyn * PAPP-A* PP 13* Inhibin A , Activin A
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Sensitivity for Predicting early onset PE with different FPR using BCH markers and UTAPI
Markers FPR 1 % FPR 2% FPR 5% FPR 10%
Early onset PEPP13PIGFMAPUTAPI
34313740
44414751
58556267
69677479
MAP & UTAPI 59 70 83 91
PAPP-A, MAP & UTAPI
64 74 86 93
PP13, PAPP-A, MAP & UTAPI
71 80 88 94
PIGF, PAPP-A, MAP & UTAPI
74 83 92 97
8366 women; 165 PE (20%); 37 early onset PE (0.4%).K. Nicolaides Data ( Cuckle, UOG 2011)
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Prevention of Pre-eclampsia
UTA Doppler as non-invasive tool for monitoring of therapeutical effect in PE
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Agents that have been tried :
HeparinLow-dose Aspirin Nitric oxide SteroidsFish oilAntioxidants(vit. E)MagnesiumCalcium
Yellow = some benefit Red = potentially dangerous
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Low dose Aspirin therapy
Bujold et al : J Obstet Gynecol Can 2009; 31(9):818-826Metaanalysis of 9 randomised studies on basis of abnormalUTA Doppler Low-dose-Aspirin started :
< or 16 weeks : Relative risk (RR) 0.48; 95%CI (0.33-0.68)
17-19 weeks : Relative risk (RR) 0.55; 95%CI (0.17-1.76)
> 20 weeks : Relative risk (RR) 0.82; 95% CI ( 0.62-1.09 )
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UTA Doppler in non-invasive assessment of therapeutical effect of
nitric oxide donors in severe PE
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Impaired Endothelial Nitric oxide Release in PE
ACH
Impaired vascular relaxation
Sodium Nitroprusside (NO donor)
Vascular relaxation Restored
McCarthy et al, AJOG 1993
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NITRIC OXIDE & PLATELETS
NO
Inhibits Aggregation
Inhibits Adhesion
Inhibits Activation
Promotes Disaggregation
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Trapani A et al: Transdermal nitroglycerin (GTN) patch in patients with severe PE : effect on UTAPI,UMAPI and MCAPI values.UOG 2011; 38:389-394* Prospective study, 30 pregnant women (24-31 wks of gestation)* Severe PE , abnormal UMAPI and UTAPI values* Transdermal GTN patch (average dose 0.4mg/h) for 3 days
Results :* Significant reduction of UTAPI values(25.3+/-4.9%; p<0.001 )* Significant reduction of UMAPI values(23.1+/-6.9%; p<0.001)* No significant changes in MCAPI values* The mean arterial blood pressure decreased from 119.5+/-4.5mmHg to 114.8+/- 4.4 mmHg( p< 0.05)
Double-blind, randomized, placebo-controlled study will be soon published
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Conclusions :
* PE is one of the leading causes of maternal and perinatal morbidity and mortality.
UTAD is a promising technique for predicting PE , however has low sensitivity and predictive validity.
More attention need to be focused on combined screening for PE , including maternal risk factors, UTAD, and biochemical markers , to improve the predictive validity of the test.
* Uterine artery Doppler fulfils almost all the criteria required for efficient prenatal screening test.
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* Low dose aspirin appears to be effective in preventing severe PE when administered before 16 weeks gestation.
* Nitric Oxide donors appear to be safe and effective in treating severe PE and may be valuable in long term prophylaxis.
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THANK YOU
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Randomised placebo controlled trial of vitamin C and E for prevention of PE in high-risk women
St.Thomas Hospital, London, 20062395 patients : 1196 allocated to vitamins C and E1205 allocated to placebo
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Results :
* No reduction of PE frequency (15% vs.16%)* More SGA neonates (<2500g) were born to women randomised to receive vitamins C and E (28% vs 24%)* No difference in the rate of SGA < 5th centile* The number of stillbirths >24 weeks gestation was higher in women receiving vitamins C and E RR 2.70; 95%CI(1.02-7.14 )
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“ The likelihood of developing pre-eclampsia is increased in women who are :
*nulliparous*aged 30 years or over*those with a prior or a family history of PET*those with a BMI of 35 or above*and those with pre-existing vascular disease”
Antenatal care : routine care for the healthy pregnant woman, NICE guideline 6 , 2006
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The best screening tests have to be :
* accessible * safe* relatively inexpensive* acceptable to patients* reproducible results* easy to perform with training and experience
McLeod L : CMAJ 2008; 178 : 727-732