Goal-Directed Therapy in Pregnant Women at High Risk of Developing Preeclampsia

• Systemic vascular resistance [ Time Frame: 20-22, 24-26, 28, 30-32 and 36 weeks gestational age ] [ Designated as safety issue: Yes ]
  Systemic vascular resistance is measured at the above time points, and more frequently at the discretion of the attending obstetrician.
  
  

• Maximum change in maternal blood pressure [ Time Frame: 20-22, 24-26, 28, 30-32 and 36 weeks gestational age ] [ Designated as safety issue: Yes ]
  Blood pressure is taken on the NICOM at the above time points, and more frequently at obstetric appointments in between.
  
  
• Gestational age at delivery [ Time Frame: 25-41 weeks gestational age ] [ Designated as safety issue: No ]
  
• Fetal weight at delivery [ Time Frame: 25-41 weeks gestational age ] [ Designated as safety issue: No ]
  
• Gestational age at time of first hospitalization [ Time Frame: 25-41 weeks gestational age ] [ Designated as safety issue: No ]
  
• Gestational age at peak maternal blood pressure [ Time Frame: 20-41 weeks ] [ Designated as safety issue: No ]
  
• Gestational age at which steroids are administered [ Time Frame: 25-41 weeks gestational age ] [ Designated as safety issue: No ]
  
• Serum s-Flt and PlGF levels [ Time Frame: 12-41 weeks gestational age ] [ Designated as safety issue: No ]
  

Invasive hemodynamic techniques have long identified significant increases in heart rate (HR), blood volume, left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and cardiac output (CO) during the first and second trimesters of pregnancy. In normal pregnancy, CO increases from as early as 5 weeks gestation, with a 30-40% increase by the end of the first trimester of pregnancy. Cardiac output continues to rise throughout the second trimester until it reaches a level approximately 50% greater than that of non-pregnant women. Cardiac output slightly decreases during the third trimester. Despite these changes, maternal blood pressure (BP) still falls due to a large reduction in systemic vascular resistance (SVR) from systemic vasodilatation and the formation of a low-resistance utero-placental circulation. Systemic vascular resistance falls during early gestation, reaching its nadir (35% decline) at 20 weeks gestation, and rises during late pregnancy.

Transthoracic bioreactance is a newer technique of non-invasive continuous cardiac output monitoring. It is based on an analysis of relative phase shifts of oscillating currents that occur when this current traverses the thoracic cavity, as opposed to the traditional bioimpedance-based system, which rely only on measured changes in signal amplitude. Unlike bioimpedance, bioreactance-based non-invasive CO measurement does not use the static impedance and does not depend on the distance between the electrodes for the calculations of SV and CO, which significantly reduces the uncertainty in the result. Moreover, its readings were shown to correlate well with results derived from pulmonary artery catheter derived measurement of cardiac output. In addition, it has also been shown that the non-invasive cardiac output measurement (NICOM®) system has acceptable accuracy, precision and responsiveness for CO monitoring in patients experiencing a wide range of circulatory situations and has recently been used in the obstetric population.

The purpose of this study is to use non-invasive cardiac output monitoring to capture the earliest inappropriate rise in SVR during the pre clinical phase of disease, in patients at high risk of developing preeclampsia, as predicted by the placenta profile. In case an increase in SVR is identified, the purpose of this study is to implement a goal-directed therapy in an attempt to decrease the severity, and postpone the onset of clinical disease.

The hypothesis of this study is that the increases in SVR detected during the pre-clinical phase of preeclampsia can be treated with a goal directed therapy without fetal compromise and that this intervention may improve maternal and fetal/neonatal outcome.