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Forward flow from cardiac action. Maternal haemodynamics at 11-13 weeks of gestation and the risk of pre-eclampsia. Asma Khalil Ranjit Akolekar Argyro Syngelaki Mohamed ElKhouli Kypros Nicolaides. Blood vessel. Reflected flow from peripheral resistance.
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Forward flow from cardiac action Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Asma Khalil Ranjit Akolekar Argyro Syngelaki Mohamed ElKhouli Kypros Nicolaides Blood vessel Reflected flow from peripheral resistance University College Hospital, King’s College Hospital, London
NHS 1.0 0.8 National Institute for Clinical Excellence 0.6 Mortality rate/100,000 maternities Routine antenatal care in the UK 0.4 0.2 At first contact a woman’s risk for preeclampsia should be evaluated so that a plan for her schedule of antenatal appointments can be formulated. 0 1997-99 2000-02 2003-05 1991-93 1994-96 CEMACH 2005 Early screening for preeclampsia PE: risks in later life 3,488,160 women 198,252 with PE 1961-2006 4 RR 3 2 1 0 Cancer Death Hypertension Ischemic heart Thromboembolism Bellamy 2007
Maternal history: a priori risk + Biophysical markers + Biochemical markers Early screening for PE } Adjusted risk
3.0 1.3 2.5 1.2 2.0 1.1 Uterine artery PI MoM 1.5 Mean arterial pressure (MoM) 1.0 1.0 0.9 0.5 0.8 0.0 Normal Early PE Late PE 0.7 Normal Early PE Late PE Early screening for PE History
PlGF (MoM) PAPP-A (MoM) 3.0 3.0 2.5 2.5 2.0 2.0 1.5 1.5 1.0 1.0 0.5 0.5 0.0 0.0 Normal Early PE Late PE Normal Early PE Late PE Early screening for PE Impaired trophoblastic invasion of the maternal spiral arteries Placental hypoxia Release of inflammatory cytokines Platelet and endothelial cell activation and damage Clinical symptoms of preeclampsia
Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Objectives To examine the value of maternal hemodynamics at 11-13 wks in the early prediction of preeclampsia Methods • Screening for PE at 11-13 wks (n=5,042) • Comparison of history / maternal characteristics and augmentation index (AIx), pulse wave velocity (PWV) and central systolic blood pressure (sBPAo) • Preeclampsia 146 (3.1%) • Gestational hypertension 114 (2.4%) • Unaffected controls 4,436
AIx: Relation to Heart Rate 2.2 2.1 4.0 2.0 Log 10 augmentation index 1.9 3.0 1.8 Log 10 augmentation index 2.0 1.7 1.0 1.6 1.6 1.7 1.8 1.9 2.0 2.1 2.2 0.0 Heart rate (beats per minute) 0.8 0.9 1.0 1.0 1.1 1.2 1.3 1.4 Maternal mean arterial pressure (mmHg)
Augmentation index Normal pregnancy at 11-13 wks n=4,436 10.0 10.0 8.0 8.0 6.0 6.0 Log 10augmentation index Log 10 Augmentation index 4.0 4.0 2.0 2.0 0.0 0.0 45 50 55 60 65 70 75 80 85 15 20 25 30 35 40 45 50 Fetal crown rump length (mm) Maternal age (yrs)
5.0 10.0 10.0 8.0 8.0 4.8 6.0 6.0 Log 10 augmentation index Log 10 augmentation index Log 10 augmentation index (95% CI) 4.6 4.0 4.0 4.4 2.0 2.0 0.0 0.0 4.2 40 60 80 100 120 140 150 160 170 180 190 White Black Asian Maternal weight (Kg) Maternal height (cm) Augmentation index Normal pregnancy at 11-13 wks n=4,436
.83 1.3 1.3 1.3 1.2 1.2 1.2 .82 1.1 1.1 1.1 .81 1.0 1.0 1.0 Log10 Pulse wave velocity 0.9 0.9 0.9 .80 0.8 0.8 0.8 .79 0.7 0.7 0.7 0.6 0.6 0.6 .78 15 20 25 30 35 40 45 50 40 60 80 100 140 120 150 160 170 180 190 Smoker Age Weight Height Pulse wave velocity Normal pregnancy at 11-13 wks n=4,436
1.5 1.4 1.3 1.2 1.1 Augmentation index-75 (MoM) 1.0 0.9 0.8 0.7 0.6 0.5 Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Results P<0.0001 P<0.0001 1.5 1.5 P<0.0001 1.4 1.4 1.3 1.3 1.2 1.2 1.1 1.1 Pulse wave velocity (MoM) Central systolic blood pressure (MoM) 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 Normal PE GH Normal PE GH Normal PE GH
2.25 3.0 2.00 2.00 2.5 1.75 1.75 2.0 1.50 1.50 Uterine artery PI (MoM) Pulse wave velocity (MoM) PAPP-A (MoM) 1.25 1.5 1.25 1.00 1.0 1.00 0.75 0.5 0.75 0.50 0.25 0.0 0.50 24 28 32 36 40 42 24 24 28 28 32 32 36 36 40 40 42 42 Gestation at delivery (wks) Gestation at delivery (wks) Gestation at delivery (wks) Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Results • NO significant association of AIx-75, PWV and sBPAo with gestation at delivery • Significant association between uterine artery PI and PAPP-A with gestation at delivery
Detection rate at FPR 10% 100 % 80 Combined 60 61.6% History sBPAo 46.6% 40 PWV Aix-75 33.6% 20 22.6% 21.9% 0 Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Conclusions • 1/3rd of women who develop PE have increased arterial stiffness and SBPAo which are evident from the first-trimester. • In these cases the mechanism of association with PE is NOT mediated by impaired placental perfusion and function. • Similar performance in predicting late-PE Thank you
1.5 1.5 1.6 P<0.0001 P=0.037 1.4 1.2 1.2 P<0.0001 1.2 Mean arterial pressure (MoM) Return time (MoM) Heart rate (MoM) 1.0 1.0 1.0 0.8 0.7 0.7 0.6 0.5 0.5 0.4 Normal PE Normal PE Normal PE Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Screening for PE at 11-13 wks: Normal n=4,436 ; PE n=146
Maternal haemodynamicsat 11-13 weeks of gestation and the risk of pre-eclampsia Screening for PE at 11-13 wks: Normal n=4,436 ; PE n=146