Pulse wave analysis in the first trimester of pregnancy: a possible predictive test to identify women at risk of placental or maternal preeclampsia and IUGR
Creators: name: DI MARTINO, DANIELA DENIS
Publisher: name: Universit� degli Studi di Milano
Year: 2012

description: Pulse Wave Analysis in the first trimester of pregnancy: a possible predictive test to identify women at risk of placental or maternal preeclampsia and IUGR
Background: 
Preeclampsia and intrauterine growth restriction are major contributors to maternal and/or perinatal mortality and morbidity worldwide. At present preeclampsia is classified based on time domain. Just few Authors proposed classification based on different origin of the diseases: placental and maternal. The former involves inadequate placentation and consequently placental insufficiency and IUGR; the latter is thought to be caused by maternal "metabolic syndrome" characterized by low grade chronic inflammation and android obesity, but associated with normal placental function and appropriate fetal growth (AGA). 
Independently on the classification of the disease, it is well known that women with a history of preeclampsia are at increased risk of cardiovascular events later on in life. 
Recent developments in cardiological technology provided useful non-invasive tool capable to assess peripheral and central vascular resistance: applanation tonometry. By assessing the radial pulse wave it is possible to derive indices of arterial stiffness (Augmentation Index) and compliance (Pulse Way Analysis and Pulse Way Velocity). In the literature there are few studies that investigated arterial stiffness in preeclamptic women, but limited mostly by low study population. Just one report investigated applanation tonometry in the first trimester of pregnancy. None of Authors explored the role of pulse wave analysis considering the above proposed classification of preeclampsia.
Aim: to investigate maternal indices of central and peripheral vascular resistance (arterial stiffness) and indices of central pressure in aorta, in the first trimester of pregnancy, in preeclampsia of maternal and placental origin and fetal growth restriction.
Methods: applanation radial tonometry together with uterine artery Doppler have been performed between 11-13+6 wg in general population attending to our hospital for Down syndrome screening. Augmentation index corrected for heart rate (AIX75) and Aortic systolic peak have been calculated. PE was defined as placental when associated with IUGR and of maternal origin in cases with clinical manifestation of hypertension/PE but with appropriate fetal growth, independently of time of onset.
Results: 308 pregnancies were recruited: four (1%) developed PE/IUGR; four (1%) PE/AGA; seven (2,3%) GH; 16 (5,2%) IUGR, and eight (2,6%) SGA. None of the seven women with gestational hypertension had associated fetal growth restriction, so they were included in maternal preeclampsia group (PE+AGA). 
Patients with maternal PE showed a statistically higher BMI and higher rate of IVF pregnancy when compared to controls (p=0,011), while placental PE showed a higher incidence of previous pregnancy affected by preeclampsia (p=0,004). There were no statistical differences for other demographic data. 
Both maternal and placental PE group delivered at an earlier GA, but only placental PE had smaller babies and major incidence of admittance to NICU (p&lt; 0,001). There were no significant differences in heart rate and Augmentation index at 75 bpm between the two groups of PE compared with controls. Mean arterial pressure was significantly higher in both placental and maternal preeclampsia when compared to the control group, while central systolic pressure was significantly higher only in placental PE group (p&lt; 0,001).
The mean uterine artery PI was significantly higher in placental PE group (p&lt; 0,001) and maternal serum PAPP-A resulted significantly lower only in maternal PE group (p=0,024).

Conclusions: 
Although, the classification of preeclampsia based on time domain, at the moment the most used, brought to some improvements in terms of biochemical and biophysical tests prediction, at present is still not able to fulfill all diagnostic and preventive needs. Indeed, despite all scientific effort for the past three decades, at the present there does not exist universally recognized screening test of any kind capable to predict preeclampsia or IUGR and the severity of the disease. 
With this pilot study, we wanted to investigate the characteristics of preeclampsia of maternal and placental origin and pregnancies with fetal growth restriction in terms of peripheral and central vascular resistance by applanation tonometry in the first trimester of pregnancy. Due to the smallness of the cohort, we did not try to assess the prediction of the test. Nevertheless, the newness of our work stand in the understanding of the underlying physiopathology of preeclampsia.
Our data confirmed the hypothesis regarding different origin of PE: indeed, in PE of maternal origin we found the highest BMI and the highest percentage of IVF-pregnancies. Both this factors are well known to correlate to metabolic syndrome, low grade chronic inflammation and insulin resistance.
Conversely, in PE of placental origin we found the highest number of women with reoccurrence of preeclampsia that supports the immunological/genetic hypothesis that causes inadequate placentation. This hypothesis is supported also by the observation that women with preeclampsia of placental origin present significantly higher mean uterine artery PI, sign of an impaired placentation as soon as in the first trimester of pregnancy.
As it concern the hemodynamic parameters, in accordance to the literature, we found the mean arterial pressure significantly higher in both preeclampsia of placental and maternal origin when compared to the control group. Interestingly, the central pressure, both systolic and diastolic, was significantly higher only in placental PE group suggesting lower central vascular compliance in women with inadequate placentation. This could suggest a different and more severe physiopatological pathway at the basis of preeclampsia of placental origin when compared to maternal one.
Several Authors found increased values of augmentation index in women with preeclampsia (more pronounced in early and less important in late PE) at the time of onset of the disease. Conversely, we found no significant differences in Augmentation index at 75 bpm between groups, suggesting that in the first trimester the biochemical and hormonal modifications still does not reflect on peripheral vascular resistance both in preeclampsia of maternal and placental origin.
In conclusion, we found that the classification of preeclampsia based on its origin, maternal and placental, is supported by the demographic data. Our data suggest that, as soon as in first trimester, for arterial mean pressure been equal in both women that will develop PE of maternal and placental origin, and higher in respect to controls, only PE of placental origin presents higher central pressure. Nevertheless, no differences were found for wave reflection, suggesting later development of the peripheral vascular alteration.