Goal-Directed Therapy in Pregnant Women at High Risk of Developing Preeclampsia
Condition: Pre-Eclampsia; Pregnancy; Hypertension
MeSH terms: Pre-Eclampsia; Eclampsia; Hypertension
Study type: Interventional

Summary: 
      Preeclampsia is associated with significant maternal and fetal morbidity and mortality. Early
      identification and subsequent management of patients at risk of developing preeclampsia
      presents an ongoing challenge in prenatal care. Some at risk pregnancies may be identified
      from:

        -  serum screening abnormalities in the first or second trimester

        -  placental shape and texture at the 18-20 anatomical ultrasound

        -  uterine artery blood flow.

      Early identification and effective treatment of patients would permit the safe completion of
      the pregnancy for the mother and infant. Recent advances in non-invasive cardiovascular
      monitoring have enabled the study of maternal hemodynamics in normal and at-risk pregnancies.
      This study hopes to identify the earliest significant changes in maternal hemodynamics which
      may allow targeted therapeutic interventions in patients at high risk of developing
      preeclampsia.

      The hypothesis of this study is that systemic vascular resistance rises during the
      pre-clinical phase of preeclampsia and this can be captured using non invasive bioreactance
      technology. Treatment of the abnormally high vascular tone may decrease the severity and
      postpone the onset of clinical disease.
    

Detailed description: 
      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.
    

Intervention name(s): Nifedipine
Intervention type(s): Drug
Intervention description(s): 30-60 mg, twice daily
Other intervention name(s): Adalat XL
Intervention MeSH terms: Nifedipine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non invasive cardiac output monitor; NICOM; Hypertension; Pregnancy; Pre-Eclampsia