A Comparison of Fetal Hemodynamic Measurements Between Pregnant Women Taking Anti-hypertensive Medication and Controls

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 [3]. Adverse outcomes associated with chronic hypertension in pregnancy include preterm delivery, intrauterine growth restriction (IUGR), intrauterine fetal demise (IUFD), placental abruption, and cesarean delivery [4]. The incidence of superimposed preeclampsia has been reported in up to 50 percent of women with severe chronic hypertension [5]. 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 [1].

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 [7]. 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 [8]. 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 [13]. 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 [14]. 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 [15].

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.

Specific Objectives: