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Background: Nifedipine is a widely used drug in pregnancies complicated by maternal hypertensive disorders that can be associated with placental insufficiency and fetal hypoxemia. The evidence regarding fetal myocardial responses to nifedipine in hypoxemia is limited.Objective: We hypothesized that nifedipine would not impair fetal sheep cardiac function under hypoxemic environment. In particular, we investigated the effects of nifedipine on fetal ventricular functional parameters and cardiac output.Study Design: A total of 21 chronically instrumented fetal sheep at 122 to 134 gestational days (term, 145 days) were included in this study. Fetal cardiac function was evaluated by measuring global longitudinal strain, indices describing ventricular systolic and diastolic function, and cardiac outputs using two-dimensional speckle tracking and tissue and spectral pulsed-wave Doppler echocardiography. Fetal carotid artery blood pressure and blood gas values were invasively monitored. After baseline data collection, fetal hypoxemia was induced by maternal hyperoxygenation. After hypoxemia phase data collection, 9 fetuses received nifedipine infusion, and 12 fetuses received saline infusion. Data were collected 30 and 120 minutes after the infusion was started. After 120 minutes of data collection, maternal and fetal oxygenation were normalized, and normoxemia phase data were collected, while infusion was continued.Results: Hypoxemia decreased fetal carotid artery mean arterial pressure from 40 (8) mm Hg to 35 (8) mm Hg (P<.007), and left ventricular global longitudinal strain showed less deformation than at baseline (P=.001). Under hypoxemia, nifedipine caused a reduction in right ventricular global longitudinal strain (P<.05), a decrease in right ventricular isovolumic relaxation velocity and its deceleration (P<.01) indicating diastolic dysfunction, and a drop in right ventricular cardiac output (P<.05). Nifedipine did not alter fetal left ventricular functional parameters or cardiac output. When normoxemia was restored, fetal right ventricular functional parameters and cardiac output returned to baseline level.Conclusion: In hypoxemic fetus, nifedipine impaired right ventricular function and reduced its cardiac output. The detrimental effects of nifedipine on fetal right ventricular function were abolished, when normoxemia was restored. Our findings suggest that in a hypoxemic environment nifedipine triggers detrimental effects on fetal right ventricular function. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that a decrease in fetal oxygenation without acidemia in a near-term fetal sheep leads to cardiovascular hemodynamic changes that are detectable by Doppler ultrasonography. Study design: Twelve ewes and fetuses were instrumented at 112 to 127 days of gestation. After a 5-day recovery period, experiments were performed with general anesthesia. Uterine and placental volume blood flows and fetal arterial and venous blood pressures were measured. Fetal cardiovascular hemodynamics was assessed by Doppler ultrasonography. All the measurements were performed at baseline, during fetal hypo-oxygenation, and at recovery phase. Results: A drop in fetal Po2 was related to increased (P < .05) weight-indexed right ventricular and combined cardiac outputs and proximal branch pulmonary artery pulsatility index values. The increase in proximal branch pulmonary artery pulsatility index values correlated (R = .59; P < .05) with the decrease in fetal oxygen saturation. In the aortic isthmus, the time-velocity integral ratio between antegrade and retrograde blood flow components decreased (P < .05) when fetal Po2 dropped. Conclusion: During decreased fetal oxygenation Doppler ultrasonography demonstrated increased fetal cardiac output and pulmonary arterial vascular impedance and a relative increase in the retrograde blood flow component in the aortic isthmus. [ABSTRACT FROM AUTHOR]

The purpose of this study was to construct new reference ranges for serial measurements of commonly used umbilical artery Doppler indices (pulsatility index, resistance index, and systolic:diastolic ratio). Study design: This was a prospective longitudinal study of the umbilical artery Doppler indices that were obtained serially at the free-loop of umbilical cord at 4-week intervals at 19 to 42 weeks of gestation in 130 low-risk singleton pregnancies. A total of 513 observations were used to construct the reference ranges with the use of multilevel modeling. Results: Longitudinally established percentiles of Doppler indices from the present study show a continuous reduction throughout the second half of pregnancy without any plateau or increase near term, as reported previously. There was a significant negative association between Doppler indices and placental weight and neonatal birth weight, but not with gender. The intraobserver coefficients of variation for the umbilical artery pulsatility index, resistance index, and systolic:diastolic ratio were 10.5%, 6.8%, and 13.0%, respectively. Conclusion: New reference ranges for umbilical artery Doppler indices that are based on longitudinal observations appear to be slightly different from cross-sectional studies and are more appropriate for serial evaluation of fetal hemodynamics. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to investigate the expression and subcellular localization of laeverin, a placenta-specific membrane-bound aminopeptidase, in preeclamptic placentas and its role in trophoblast cell migration and invasion. Study Design Expression of laeverin was investigated in 6 normal and 6 preeclamptic placentas with the use of immunofluorescence, sodium dodecylsulfate-polyacrylamide gel electrophoresis with Western blot analysis and immunoelectron microscopy. The role of laeverin in trophoblast migration and invasion was studied with the use of the xCelligence system and Boyden chambers with Matrigel in HTR-8/SVneo cells. The effect of laeverin gene-silencing on selected genes that are involved in cell transformation and tumorigenesis was evaluated by polymerase chain reaction array. The Student t test, Mann-Whitney U test, χ 2 test, or F-test was used to compare groups as appropriate. Results Laeverin was expressed in the cell membrane of villous trophoblasts in third-trimester healthy placentas; in preeclamptic placentas, it was expressed ectopically in the cytoplasm, especially in microvesicles. Immunoelectron microscopy showed laeverin leakage into the fetal capillaries and abundant expression in microvesicles in preeclamptic placentas. Migration and invasion of HTR-8/SVneo cells were reduced by 11.5% ( P = .023) and 56.7% ( P = .001), respectively, by laeverin gene–silencing. Analysis of downstream pathways affected by laeverin-silencing demonstrated significant down-regulation of integrin A2 (39-fold), integrin B3 (5-fold), and matrix metalloprotease 1 (36-fold). Conclusion Expression of laeverin protein is altered in preeclamptic placentas. Its ectopic expression in the cytoplasm and microvesicles, rather than the cell membrane and leakage into the fetal capillaries, may have a role in the pathophysiologic condition of preeclampsia. Laeverin gene appears to be involved in trophoblast cell migration and invasion through interaction with integrins and matrix metalloprotease 1. [ABSTRACT FROM AUTHOR]

Objective: Mouse embryonic exposure to alcohol, lithium, and homocysteine results in intrauterine growth restriction (IUGR) and cardiac defects. Our present study focused on the placental effects. We analyzed the hypothesis that expression of nonmuscle myosin (NMM)-II isoforms involved in cell motility, mechanosensing, and extracellular matrix assembly are altered by the 3 factors in human trophoblast (HTR8/SVneo) cells in vitro and in the mouse placenta in vivo. Study Design: After exposure during gastrulation to alcohol, homocysteine, or lithium, ultrasonography defined embryos exhibiting abnormal placental blood flow. Results: NMM-IIA/NMM-IIB are differentially expressed in trophoblasts and in mouse placental vascular endothelial cells under pathological conditions. Misexpression of NMM-IIA/NMM-IIB in the affected placentas continued stably to midgestation but can be prevented by folate and myoinositol supplementation. Conclusion: It is concluded that folate and myoinositol initiated early in mouse pregnancy can restore NMM-II expression, permit normal placentation/embryogenesis, and prevent IUGR induced by alcohol, lithium, and homocysteine. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the recurrence risk of hypertensive disorders in subsequent pregnancies and to explore the associations among hypertensive disorders of pregnancy and maternal cardiovascular risk factor profile and the development of cardiovascular diseases later in life. Study Design: We used population-based, cross-sectional data from the fourth survey of the Tromsø Study. Results: Preeclampsia in the first pregnancy increased the risk of recurrence in later pregnancies (relative risk, 6.6; 95% confidence interval, 5.5–7.9) compared with a normotensive first pregnancy. Women with a history of preeclampsia or nonproteinuric hypertension had an unfavorable cardiovascular risk profile. Hypertension was prevalent in 25% and 28% of the women, respectively. The carotid artery intima-media thickness and total carotid plaque area were significantly larger in women with previous preeclampsia. Conclusion: A strong association between hypertensive disorders of pregnancy and an increased risk of atherosclerosis and cardiovascular diseases was demonstrated by the assessment of risk factors that can be potentially modified. [ABSTRACT FROM AUTHOR]