Hypertension in Pregnancy: Pathophysiology &amp; Management Strategies

Karthikeyan, Vellore J; Lip, Gregory Y.H.

doi:10.2174/138161207781663019

Cited by 17 publications

(12 citation statements)

References 24 publications

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“…After adjustments were made for these variables, we found comparable risk profiles for labetalol-exposed pregnancies and pregnancies exposed to other β-blockers. Most β-blockers are known to cross the placenta,21 24 and effects on placental haemodynamics have been observed in both human and animal studies. A mechanism has been proposed of diminished placental blood flow due to the selective vasoconstriction of placental vessels by β-blockers without intrinsic sympathomimetic activity 24.…”

Section: Discussionmentioning

confidence: 99%

β-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study

et al. 2012

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ObjectiveTo investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort.DesignA population-based retrospective cohort study, using the Danish Fertility Database. The authors identified all pregnant women redeeming a prescription for β-blockers using the National Prescription Registry. Multivariate logistic regression models were used to assess the association between exposure and our outcomes.SettingRegister-based survey.Participants911'685 births between 1995 and 2008 obtained from the Danish Fertility Database.Outcome measuresBeing born SGA was defined as having a birth weight below the 10th percentile for the corresponding gestational week. Preterm birth was defined as birth before the 37th gestational week. Perinatal mortality was defined as either death occurring within the first 28 days of life or stillbirth. Before 2004, fetal deaths were recorded as stillbirths if they occurred after 28 weeks of gestation, but since then stillbirth is recorded for deaths after 22 gestational weeks.ResultsThe authors identified 2459 pregnancies exposed to β-blockers. β-Blocker exposure during pregnancy was found to be associated with increased risk of SGA (adjusted OR 1.97, 95% CI 1.75 to 2.23), preterm birth (adjusted OR 2.26, 95% CI 2.03 to 2.52) and perinatal mortality (adjusted OR 1.89, 95% CI 1.25 to 2.84). Analyses were adjusted for socioeconomic and maternal variables. The authors found similar risk profiles for pregnancies exposed to labetalol and for pregnancies exposed to other β-blockers.ConclusionsThe authors found that exposure to β-blockers during pregnancy was associated with being born SGA, preterm birth and perinatal mortality. Our findings show that labetalol is not safer than other β-blockers during pregnancy.

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Section: Discussionmentioning

confidence: 99%

β-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study

et al. 2012

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“…During pregnancy in humans, maternal blood volume increases 45-50%, and the vascular system must adapt to these increases in volume without dramatic changes in blood pressure. Either low or high maternal blood pressure during pregnancy can result in poor fetal outcomes in humans; however, systolic blood pressures in the SK3 T/T mice were similar to WT mice (16,29). A decreased peripheral vascular resistance in the SK3 T/T mice, as suspected from both uterine and mesenteric vessel changes, may decrease afterload of the heart, resulting in enhanced EF in these mice during pregnancy.…”

Section: E828 Sk3 Channels Induce Fetal Lossmentioning

confidence: 88%

“…Early during pregnancy, pups of SK3 T/T mothers were growth restricted, perhaps as a result of altered placental perfusion, potentially due to overoxygenation too soon after placentation. During the early stages of pregnancy, the placenta develops in a low-oxygen environment due to endovascular cytotrophoblast cells that block uterine spiral arterioles, limiting blood flow to the fetus (16). Opening these arterioles later in pregnancy rapidly increases oxygen tension and initiates rapid growth and differentiation of the placenta, a step that is essential to maintain the fetus.…”

Section: E828 Sk3 Channels Induce Fetal Lossmentioning

confidence: 99%

Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise

Rada

Pierce

Nuno

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Rada CC, Pierce SL, Nuno DW, Zimmerman K, Lamping KG, Bowdler NC, Weiss RM, England SK. Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise. Am J Physiol Endocrinol Metab 303: E825-E831, 2012. First published July 11, 2012; doi:10.1152/ajpendo.00165.2012.-The maternal cardiovascular system undergoes hemodynamic changes during pregnancy via angiogenesis and vasodilation to ensure adequate perfusion of the placenta. Improper vascularization at the maternalfetal interface can cause pregnancy complications and poor fetal outcomes. Recent evidence indicates that small conductance Ca 2ϩ -activated K ϩ channel subtype 3 (SK3) contributes to vascular remodeling during pregnancy, and we hypothesized that abnormal SK3 channel expression would alter the ability of the maternal cardiovascular system to adapt to pregnancy demands and lead to poor fetal outcomes. We investigated this hypothesis using transgenic Kcnn3 tm1Jpad /Kcnn3 tm1Jpad (SK3 T/T ) mice that overexpress the channel. Isolated pressurized uterine arteries from nonpregnant transgenic SK3 T/T mice had larger basal diameters and decreased agonist-induced constriction than those from their wild-type counterparts; however, non-receptor-mediated depolarization remained intact. In addition to vascular changes, heart rates and ejection fraction were increased, whereas end systolic volume was reduced in SK3 T/T mice compared with their wild-type littermates. Uterine sonography of the fetuses on pregnancy day 14 showed a significant decrease in fetal size in SK3 T/T compared with wild-type mice; thus, SK3 T/T mice displayed an intrauterine growth-restricted phenotype. The SK3 T/T mice showed decreased placental thicknesses and higher incidence of fetal loss, losing over half of their complement of pups by midgestation. These results establish that the SK3 channel contributes to both maternal and fetal outcomes during pregnancy and point to the importance of SK3 channel regulation in maintaining a healthy pregnancy.small conductance Ca 2ϩ -activated K ϩ channel subtype 3; pregnancy; vasculature SUCCESSFUL PREGNANCY REQUIRES rapid and diverse changes in maternal cardiovascular physiology to ensure appropriate blood flow through the placenta (20). Dynamic changes in maternal heart rate, stroke volume, venous pressure, blood volume, and systemic vascular resistance result from formation of new blood vessels at the maternal-fetal interface and dilation of existing vessels (1). These adaptive changes are essential for providing oxygen and nutrients for, as well as eliminating waste from, the fetus. In humans, hemodynamic changes start at ϳ3 wk of gestation, with maximal variations from the nonpregnant state beginning in the second trimester. These two phases of hemodynamic change correlate temporally with common time frames for miscarriage and fetal loss. In mice, changes in heart rate and mean arterial pressure can be detected in the mother as early as pregnancy days 6 -8 compared with nonpregnant states (5). In both mice a...

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“…We found a strong association between BBT exposure and being born SGA (OR 7.663, p-value 0.033). Most b-blockers are known to cross the placenta [16]. A mechanism has been proposed of diminished placental blood flow due to selective vasoconstriction of placental vessels by b-blockers [17,18].…”

Section: Discussionmentioning

confidence: 99%