Am. J. Respir. Crit. Care Med., Volume 164, Number 4, August 2001, 546-553

Alterations of Placental Vascular Function in Asthmatic Pregnancies

VICKI L. CLIFTON, WARWICK B. GILES, ROGER SMITH, ANDREW T. BISITS, PHILIP A. J. HEMPENSTALL, CAROLYN G. KESSELL, and PETER G. GIBSON

Mothers and Babies Research Centre and Respiratory Medicine, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia

Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p < 0.05). However, at 30 wk gestation there were no significant differences in umbilical artery flow velocity between control and asthmatic women (ANOVA, p > 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F₂ were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.

Keywords: pregnancy; asthma; placenta; vascular

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