Comparison Fetal Hemodynamic Measurements Antihypertensive Versus Control
Recruitment status was Not yet recruiting
|First Received Date ICMJE||September 24, 2008|
|Last Updated Date||September 24, 2008|
|Start Date ICMJE||August 2008|
|Estimated Primary Completion Date||August 2010 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Fetal ultrasound assessment of middle cerebral artery and umbilical artery blood flow [ Time Frame: 26 to 33 weeks gestation and 34 to 40 weeks gestational age ] [ Designated as safety issue: No ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Comparison Fetal Hemodynamic Measurements Antihypertensive Versus Control|
|Official Title ICMJE||A Comparison of Fetal Hemodynamic Measurements Between Pregnant Women Taking Anti-Hypertensive Medication and Controls|
This is a prospective case-control study to evaluate women who are pregnant and take antihypertensive medication for fetal hemodynamics (middle cerebral artery peak systolic flow and umbilical artery Doppler systolic to diastolic ratio) compared to a control group of pregnant women not taking these kinds of medications. The hypothesis is that the investigators expect to observe little to no difference in the comparison between the medication group and the control group.
Chronic hypertension is a common medical condition during pregnancy, occurring in up to 5 percent of pregnant women. There are significant maternal, fetal, and neonatal morbidity and mortality associated with this disease [1,2]. Chronic hypertension in pregnancy has been defined as elevated blood pressure detected and confirmed before the 20th week of gestation or hypertension present prior to conception. Chronic hypertension is usually classified as mild with systolic blood pressure greater than or equal to 140 mmHg or diastolic blood pressure greater than or equal to 90 mmHg. Severe hypertension is defined as systolic blood pressure greater than or equal to 180 mmHg or diastolic blood pressure greater than or equal to 110 mmHg . Adverse outcomes associated with chronic hypertension in pregnancy include preterm delivery, intrauterine growth restriction (IUGR), intrauterine fetal demise (IUFD), placental abruption, and cesarean delivery . The incidence of superimposed preeclampsia has been reported in up to 50 percent of women with severe chronic hypertension . Many of these women have medical management with anti-hypertensive medications during pregnancy. Data is lacking regarding improvement in neonatal outcome, and there is evidence that anti-hypertensive medications may interfere with uteroplacental blood flow and fetal growth [3,6]. Despite a lack of support in the literature for medication in the management of hypertension in pregnancy, current recommendations recognize a role for medication use for at least severe chronic hypertension .
The umbilical arteries arise within fetal circulation from the common iliac arteries and represent the dominant circulatory outflow of the distal aortic circulation and contribute entirely to placental circulation. Normal umbilical artery resistance to blood flow progressively decreases throughout pregnancy, reflecting the progressive increase in placental mass and the increased numbers of tertiary villous small vessels of the placenta . Doppler ultrasonography is a noninvasive technique that is used to assess the hemodynamic components of vascular impedance within the placenta. Umbilical artery Doppler flow velocimetry has been developed to evaluate fetal condition en-utero . Normally developing and growing fetuses are characterized by high velocity diastolic umbilical artery flow, while those with IUGR have decreased, absent, or reversed diastolic flow [9,10]. Abnormal umbilical artery flow has been defined as the presence of absent or reversed end diastolic flow or a flow index greater than two standard deviations above the reported mean flow index for a given gestational age [11,12]. Evaluation of umbilical artery hemodynamics is indicated as part of standard care when IUGR or significant fetal anemia due to iso-immunization is suspected [7,8].
A group of patients with pregnancies complicated by pregnancy-induced hypertension (PIH) were treated with anti-hypertensive drugs labetalol and nifedipine. These subjects had umbilical artery Doppler flow velocity and resistance index measurements at 27-32 weeks gestation and again at 33-36 weeks gestation. An increase in resistance index measurements was noted over time. The authors attributed this increase in umbilical artery resistance to progression in placental impairment due disease progression rather than the medication management of PIH . Another group of patients with pregnancies complicated by preeclampsia had significantly elevated umbilical artery systolic flow to diastolic flow (S/D) ratios compared to a control group. When treated with an antihypertensive agent alpha-methyldopa, there was a significant reduction in umbilical artery S/D ratios in the group of women with preeclampsia . An in-vitro study was undertaken with isolated segments of human umbilical cords that were evaluated for measured umbilical artery resistance. The segments were exposed to varying concentrations of common substances that affect arterial tone and are used as antihypertensive agents such as labetalol, alpha-methyldopa, nifedipine, and magnesium sulfate. All except alpha-methyldopa demonstrated a dose-dependant reduction in umbilical artery resistance due to direct umbilical artery smooth muscle relaxation .
The purpose of this study is to obtain information regarding umbilical and middle cerebral artery hemodynamics during pregnancies complicated by chronic hypertension managed with anti-hypertensive medication and compare the measured values obtained to pregnancies not complicated by chronic hypertension. We postulate that the use of anti-hypertensive agents during pregnancy do not significantly affect umbilical artery Doppler flow and middle cerebral artery peak systolic velocity measurements.
This study will employ a prospective case-control design. A group of women with a history of chronic hypertension managed with anti-hypertensive medication will be identified as potential subjects for the study cohort. Each potential subject will have an assessment of her hypertension history, management, and associated vascular complications. A detailed review of her complete medical, surgical, gynecologic, and obstetrical history will be obtained as dictated by standard care. Appropriate management for each potential subject's medical and obstetrical condition will be provided according to accepted practice. Potential subjects for this cohort will be obstetrical patients cared for at the Regional Perinatal Center, Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, SUNY Upstate Medical University.
A second group of women with no history of chronic hypertension will be identified as potential subjects for the control cohort. Each potential subject will have a detailed review of her complete medical, surgical, gynecologic, and obstetrical history will be obtained as dictated by standard care. Appropriate management for each potential subject's medical and obstetrical condition will be provided according to accepted practice. Potential subjects for this cohort will be obstetrical patients cared for at the Regional Perinatal Center, Division of Maternal Fetal Medicine, Department of Obstetrics & Gynecology, SUNY Upstate Medical University.
The subjects enrolled in both cohorts are seen at the Regional Perinatal Center for management of high-risk pregnancies. As part of intensified obstetrical care, ultrasound evaluation of interval fetal growth with an assessment of estimated fetal weight, average gestational size, and amniotic fluid index is standard around 28 weeks gestation and again at about 35 weeks gestation. Umbilical artery Doppler studies are usually reserved for fetuses with a diagnosis of suspected intrauterine growth restriction. Fetal middle cerebral artery peak flow velocity studies are usually reserved for suspected severe fetal anemia and have been used on an investigational basis for suspected intrauterine growth restriction. We anticipate most subjects will not have a pregnancy complicated by IUGR, therefore performing Doppler studies for umbilical artery S/D ratio and middle cerebral arterial peak velocity will not be standard care. Data will be collected in a database in a single computer on site at the Regional Perinatal Center. This computer is password protected and reserved for use by care providers at the Perinatal Center that will be investigators for this study. The database will record specific patient identifiers including subject name and chart number. These specific identifiers will be removed at the completion of data collection prior to data analysis.
Statistical Methods, Data Analysis, Interpretation:
There are few studies published regarding the use of anti-hypertensive agents during pregnancy and the effect of these agents on umbilical artery hemodynamics. These few studies usually involved 20 to 30 subjects. At this point, there is not enough information to estimate how many subjects would be required to measure a statistically significant difference potentially attributable to the use of these agents. For this preliminary study, we will obtain 30 subjects for the study cohort and 30 subjects for the control cohort. It is anticipated that it will take approximately one year to complete this study.
Once data collection is complete as described above, a comparison of means will be undertaken for umbilical artery Doppler studies between the two cohorts at the first and then again for the second gestational age measurements.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Time Perspective: Prospective
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
Women with established singleton pregnancy at least 18 years of age, with diagnosis of chronic hypertension or with no diagnosis of hypertension
|Intervention ICMJE||Procedure: ultrasound evaluation in pregnancy
Subjects enrolled will have a series of ultrasound evaluations to assess parameters in the study. Ultrasound is a non-invasive technique for creating images that does not use radiation and is routine in obstetrical practice
Other Name: Sonogram
|Study Group/Cohort (s)||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Not yet recruiting|
|Estimated Enrollment ICMJE||60|
|Estimated Completion Date||August 2010|
|Estimated Primary Completion Date||August 2010 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Potential subjects for the control cohort:
|Ages||18 Years to 50 Years|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00759278|
|Other Study ID Numbers ICMJE||IRBPHS 5215|
|Has Data Monitoring Committee||No|
|Responsible Party||John J. Folk, M.D., SUNY Upstate Medical University|
|Study Sponsor ICMJE||State University of New York - Upstate Medical University|
|Collaborators ICMJE||Not Provided|
|Information Provided By||State University of New York - Upstate Medical University|
|Verification Date||September 2008|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP