Pharmacodynamics of clonidine therapy in pregnancy: a heterogeneous maternal response impacts fetal growth.
BACKGROUND
Clonidine, a centrally acting antihypertensive agent, has been used successfully in pregnancy. We sought to describe the pharmacodynamic effects of clonidine in pregnancy and the associated impact on fetal growth.


METHODS
A retrospective cohort study was performed. Maternal hemodynamics were measured before and after treatment. Responses to clonidine were categorized by the predominant hemodynamic effect: decreased vascular resistance, decreased cardiac output (CO), or mixed. Multinomial logistic regression was used to evaluate predictors of hemodynamic response to clonidine and association between response group and birth weight.


RESULTS
Sixty-six pregnant women were studied. Treatment was associated with a reduction of mean arterial pressure (MAP) (-9.2 mm Hg, P < 0.001), a reduction in total peripheral resistance (TPR) (-194 dyne·cm·sec⁻⁵, P < 0.001), and an increase in CO (+0.5 l/min, P < 0.001). The hemodynamic response was characterized by decreased resistance in 34 women; decreased CO in 22; and mixed effect in 10. No maternal demographic characteristics were associated with a reduction in CO. Mean birth weight percentile was lower in the group that experienced a reduction in CO compared to the group with a reduction in vascular resistance (26.1 vs. 43.6, P = 0.02). The rate of birth weight <10th percentile was also higher in the group experiencing decreased CO (41 vs. 8.8%, P = 0.008).


CONCLUSIONS
The hemodynamic effect of clonidine in pregnancy is heterogeneous. The category of effect, reduction in vascular resistance vs. reduction in CO, significantly impacts fetal growth. A reduction in heart rate (HR) after therapy identifies pregnancies at risk for reduced fetal growth.
Rothberger
Sophia
S
Department of Obstetrics and Gynecology, University of Washington, Seattle, USA.
Carr
Darcy
D
Brateng
Debra
D
Hebert
Mary
M
Easterling
Thomas R
TR
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001724:Birth Weight / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005317:Fetal Growth Retardation / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy*; D007231:Infant, Newborn; D011247:Pregnancy; D011256:Pregnancy Outcome; D012189:Retrospective Studies; D012307:Risk Factors; D014655:Vascular Resistance / Q000187:drug effects; D055815:Young Adult
D000959:Antihypertensive Agents; D003000:Clonidine