Labetalol does not alter the placental and fetal blood flow or maternal prostanoids in pre-eclampsia

The effect of intravenously administered labetalol (1 mg/kg) on placental and fetal blood flow was studied in 13 pre-eclamptic women. Although the maternal blood pressure decreased, no changes occurred in the blood flows in the intervillous space, the umbilical vein or the fetal descending aorta, nor did the indices of peripheral vascular resistance in the fetal aorta change, but the placental vascular resistance did decrease. Labetalol had no effect on prostacyclin or thromboxane A2 as measured by urinary 6-keto-prostaglandin F1 alpha and serum thromboxane B2 respectively. These findings are clinically relevant since they suggest that labetalol reduces maternal blood pressure without interfering with the placental or fetal blood flow.     

Labetalol does not decrease placental perfusion in the hypertensive term-pregnant rat

The acute effect of labetalol hydrochloride, a combined nonspecific beta-adrenergic and postsynaptic alpha 1-adrenergic blocker, on maternal hemodynamics and organ perfusion was investigated in 10 hypertensive, term-pregnant, spontaneously hypertensive rats with the use of the radioactive-labeled microsphere technique. The normal fall in blood pressure during pregnancy was prevented by the reduction of litter size to two conceptuses on day 7 of gestation. Labetalol (1 to 6 mg/kg) effectively lowered mean arterial pressure 22% by decreasing cardiac output 16%; total peripheral resistance was not significantly decreased. Thus, the blood pressure lowering effect of labetalol was due primarily to its beta-adrenergic blocking effect. Regional flows to the carcass and splanchnic circulation were decreased 19% and 15%, respectively, after labetalol administration. Uterine wall and ovarian perfusion were significantly reduced, but placental perfusion was not significantly altered. Because labetalol lowers blood pressure without reducing placental perfusion, it may be a useful alternative to hydralazine for the treatment of hypertensive emergencies in pregnancy.     

Effects of dihydralazine infusion on the fetoplacental blood flow and maternal prostanoids

The hemodynamic effects of intravenously infused dihydralazine (incremental doses up to 125 micrograms per minute during 60 minutes) were studied in ten women with acute or superimposed severe preeclampsia. The intervillous and umbilical vein blood flow were measured before and during dihydralazine infusion with 133Xenon method and with a combination of real-time and Doppler ultrasonic equipment, respectively. Maternal blood pressure decreased and pulse rate increased during the infusion. Dihydralazine did not change the intervillous blood flow but it increased the blood flow in umbilical vein. No effect on the 6-ketoprostaglandin F1 alpha in maternal plasma and urine or thromboxane B2 in maternal serum was observed. The results indicate that dihydralazine affects the placental and fetal circulations differently.     

Improving placental blood flow in pre-eclampsia with prostaglandin A1.

Prostaglandin A1 is a potent hypotensive, peripheral vasodilator, a weak oxytocic, antiplatelet aggregator. It improves the renal hemodynamics. Its effect on placental circulation was evaluated (expressed as systolic/diastolic ratio and umbilical artery resistance index) in 20 women with severe pre-eclampsia and 10 normotensive pregnant women, by using the Doppler technique. Moreover, another 10 women with severe pre-eclampsia received dextrose 5% as a placebo for comparative purposes. Significant improvements in both parameters studied were observed in the women with severe pre-eclampsia. The beneficial changes differed significantly from the recorded values when using dextrose in pre-eclampsia or prostaglandin A1 in normotensive subjects. Such promising data add another important perspective to prostaglandin A1 in severe pre-eclampsia and may open up new avenues for its use in other situations with compromised placental flow.     

Mode of conception does not affect fetal or placental growth parameters or ratios in early gestation or at delivery

Purpose

Ratio of fetal weight to placenta size varies by mode of conception (fertility treatments utilized) in animals. Our objective was to assess whether fertility treatments also affect these ratios in humans.

Methods

In this retrospective study, we assessed two cohorts: (a) early gestation cohort, women with singleton pregnancies who underwent first trimester vaginal ultrasound and (b) delivered cohort, women who delivered a live-born, singleton infant with placenta disposition to pathology. Crown rump length (CRL) and estimated placental volume (EPV) were calculated from first trimester ultrasound images using a validated computation. Infant birth weight (BW), pregnancy data, placental weight (PW), and placental histopathology were collected. Fetal growth-to-placental weight ratios (CRL/EPV; BW/PW) and placentas were compared by mode of conception. Linear regression was used to adjust for confounding variables.

Results

Two thousand one hundred seventy patients were included in the early gestation cohort and 1443 in the delivered cohort. Of the early gestation cohort (a), 85.4% were spontaneous conceptions, 5.9% Non-IVF Fertility (NIFT), and 8.7% IVF. In the delivered cohort (b), 92.4% were spontaneous, 2.1% NIFT, and 80 5.5% IVF. There were no significant differences between fetal growth-to-placental weight parameters, ratios, and neonatal birth measurements based on mode of conception. Placenta accreta was significantly higher in the patients receiving fertility treatments (1.2 versus 3.6%, p?<?0.05).

Conclusions

Mode of conception does not appear to influence fetal growth-to-placental weight ratios throughout gestation. In addition, findings in animal models may not always translate into human studies of infertility treatment outcomes.

     

Prostacyclin does not influence placental blood pool in vivo

In 20 healthy pregnant women placental blood pool was estimated by means of placental scintigrams before, during and after infusion of either prostacyclin (PGI2) or placebo for 10 min to study the effect of PGI2 on the local regulation of uterine blood flow. There was no difference in the mean number of counts between the PGI2- and the placebo-treated group. Therefore no effect of PGI2 on uteroplacental blood pool could be detected in healthy gravidae.     

Uteroplacental blood flow index in intrauterine growth retardation of fetal or maternal origin

Summary. Uteroplacental blood flow index was determined in 30 women with intrauterine growth retardation (IUGR group) and in 26 women without fetal growth retardation (control group) during the last trimester of pregnancy. After 1 mCi (37 MBq) of indium-113m chloride had been injected intravenously the radiation was registered by a computer-linked scintillation camera positioned above the placenta during 10 s-intervals for 240 s. From the isotope accumulation curve a Uteroplacental blood flow index could be calculated for each patient. The median blood flow index in the IUGR group was less than half of that in the control group. In the IUGR group the index was as low in the six women who gave birth to infants with congenital malformations as in the other 24 women in whom fetal growth retardation was due to maternal factors.     

Relationship of maternal placental blood flow to the placental clearance of maternal plasma dehydroisoandrosterone sulfate through placental estradiol formation

We have suggested that the placental clearance of maternal plasma dehydroisoandrosterone sulfate (DS) through estradiol (E2) formation (PC-DSE2) is reflective of uteroplacental blood flow (F). Clewell and Meschia13 suggested that PC-DSE2 is related to F as follows: Cobs = F(1-e-C/F), where Cobs = PC-DSE2 and C = total placental clearance of maternal plasma DS. This equation contains two unknown quantities, F and C. To solve the equation, Clewell and Meschia assumed that C was constant. Using 19.7 ml/min for C, they allowed PC-DSE2 to vary widely and computed F. Upon finding that F was unrealistically low for some values of PC-DSE2, they concluded that reductions in PC-DSE2 do not reflect alterations in uteroplacental blood flow. In the analysis of the relationship of F to PC-DSE2, it is important to know the value of C. Since the direct measurement of C is not possible at this time, we have evaluated C by measuring the difference between the metabolic clearance rate of DS (MCR-DS) prior to and immediately following delivery. Any change in MCR-DS before and after delivery should be a reflection of the amount of maternal plasma DS cleared by the placenta through all metabolic routes including PC-DSE2, providing nonplacental clearances of maternal plasma DS before and immediately after delivery are the same. We measured MCR-DS and PC-DSE2 in 15 pregnant women within 5 days before delivery and repeated the MCR-DS measurement in these women beginning 90 minutes after delivery. Among these 15 women, C ranged from a low of 4.7 ml/min in a woman with severe pre-eclampsia to a high of 28.5 ml/min in a woman with twins. In addition to the finding that C varied widely, it was also ascertained that PC-DSE2 was positively correlated with C (r = 0.908; p less than 0.001). The finding that low or high values for PC-DSE2, observed in complicated pregnancies, were associated with similar changes in C is suggestive that a change in PC-DSE2 is reflective of a change in uteroplacental blood flow.     

Doppler measurements of maternal and fetal blood flow

Data accumulated over the last decade suggest that Doppler flow velocity waveforms can be used to study both maternal and fetal circulation. Information obtained with this technique appears useful as a screen for both maternal and fetal risk, as an aid to understanding perinatal anatomy and physiology, and as an adjunct to standard means of fetal surveillance.     

Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood

Objective: The study was aimed to compare trace elements concentrations in women with and without severe pre-eclampsia (PE). Methods: A prospective case-control study was conducted comparing 43 parturients with severe PE (who received magnesium sulfate [MgSO4]) and 80 healthy parturients and their newborns, matched for gestational age and mode of delivery. Inductively coupled plasma mass spectrometry (ICPMS) was used for the determination of zinc (Zn), copper (Cu), selenium (Se) and magnesium (Mg) levels in maternal as well as arterial and venous umbilical cord serum. Results: Zn levels (µg/L) were significantly higher in fetal arterial and venous blood of the PE group (947.3?±?42.5 vs. 543.1?±?226, 911.1?±?220.2 vs. 422.4?±?145, p?<?0.001; respectively). Se levels (µg/L) were significantly lower in maternal and fetal arterial and venous cord blood of the PE group (98.6?±?24.2, 110.7?±?19.4, 82?±?17.8 vs. 111.6?±?17.6, 82.1?±?17.4 vs. 107.1?±?25.7, p?<?0.001; respectively). Cu levels (µg/L) were significantly lower in fetal arterial and venous cord blood (581.6?±?367.4 vs. 949?±?788.8, p?=?0.022, 608.3?±?418.1 vs. 866.9?±?812.6, p?=?0.001 respectively) but higher in maternal blood (2264.6?±?751.7 vs. 1048?±?851.1, p?<?0.001). These differences remained significant while controlling for the mode of delivery. Mg levels were significantly higher in the PE group as compared with the control group. Conclusions: Severe PE is associated with abnormal concentrations of Zn, Cu and Se. Therefore, trace elements may have a crucial role in the pathogenesis of severe PE.     

Mild maternal undernutrition in the first half of ovine pregnancy influences placental morphology but not fetal Doppler flow velocity waveforms and fetal heart size

AIMS: We wanted to investigate whether experimental dietary manipulations during early pregnancy influence placental growth and subsequently the cardiovascular system as assessed non-invasively by ultrasonography in the sheep fetus. METHODS: 21 ewes bearing singletons of uniform age were randomly assigned for the first half of pregnancy to one of the following study groups: fed 100% of their nutritional requirements (i.e. controls), global reduction in total intake by 30% (i.e. 70% global) and reduction in protein intake by 30% (i.e. 70% protein). RESULTS: Placentas from the 70% protein group had significantly more small placentomes, but significantly fewer large placentomes compared to the 70% global group. However, there were no significant differences between the three dietary groups for either the aortic or the umbilical Doppler velocimetry parameters and the fetal heart rate or heart size. CONCLUSIONS: The present study shows that early mild maternal undernutrition produces subtle changes in cotelydonary weight. However, Doppler and echocardiographic parameters were not affected by these changes.     

Intravenous glucose infusion in labor does not affect maternal and fetal acid-base balance

OBJECTIVE: This prospective randomized trial compares the effects of a 5% glucose solution or no infusion during labor on glucose levels, pH, pO2, pCO2, and base excess (BE) of normal pregnant women in early labor and at delivery, and on fetal cord blood. METHODS: Forty-three women were randomized to glucose infusion and 38 were controls. RESULTS: Starting glucose levels were independent from the fasting state. When no glucose supplementation was given, the labor itself was associated with a reduction of mean pH (from 7.42 to 7.36, P = 0.00001), mean pCO2 (from 25.7 to 24.4 mm Hg, P = 0.04), and mean BE (from -6.3 to -9.8 mEq/L, P = 0.00001), and an increase of capillary glucose (from a mean of 83 to 105 mg/dL, P = 0.00001). Infusions of glucose did not significantly alter maternal acid-base balance at delivery. pH, PO2, pCO2, and BE were similar in arterial and venous cord blood of both groups. No variables correlated with cord blood glucose levels or with glucose vein-artery difference. CONCLUSIONS: We conclude that a 5% glucose infusion does not significantly reduce maternal acidemia associated with vaginal delivery and therefore its use cannot be recommended, since maternal glucose is largely available during labor. Intrapartum glucose infusions do not alter the acid-base balance, when the fetus is well oxygenated.     

Comparison between measurements of maternal placental blood flow with dynamic placental scintigraphy and radioactive microspheres

Two methods for measurements of maternal placental blood flow were compared, dynamic placental scintigraphy using 113mIndium and the radioactive microsphere distribution technique which was the reference method. These methods were both used before and after the blood flow was altered by a noradrenaline infusion in pregnant monkeys (Macaca fascicularis). The change of the blood flow values obtained by the two methods were compared. A statistically significant correlation between the two methods was found (r = 0.90, p less than 0.01). It is concluded that dynamic placental scintigraphy can be used as a technique for clinical measurements of relative changes of the maternal placental blood flow.     

The current status of maternal and fetal blood flow velocimetry

Significant progress has been achieved in regard to normative data for uteroplacental and fetal blood flow velocity and the factors which may affect these observations. Associations have been demonstrated between abnormal indices of maternal and fetal blood flow velocity and pregnancy-induced hypertension, fetal growth retardation, fetal blood gas measures, and intrapartum clinical fetal distress. However, in general, the predictive power is modest and no evidence has yet been provided to indicate that these measures can be used as a screening test in the general obstetric population. Continuing research is highly desirable. At the present time, the use of Doppler assessment of blood flow in pregnancy should be limited to the investigational setting.     

Acute effects of maternal smoking on fetal blood flow

Thirty healthy pregnant women were studied to assess the immediate cardiovascular responses of the fetus to the smoking of one cigarette. The fetal blood flow was measured in the aorta and in the umbilical vein by combining real-time ultrasonography and the pulsed Doppler technique. Following maternal smoking, a significant increase was found in the maternal heart rate and also in the blood pressure. In the fetus, a significant transient increase in the aortic and the umbilical blood flow was measured, as characterized by the increase in the fetal heart rate, the mean and maximum blood velocity, and the vessel diameter. Thus, maternal smoking induced acute circulatory changes in the fetus similar to those found in adults. Furthermore, the study demonstrated the feasibility of the method to evaluate non-invasively the immediate effect of a given stress stimulus on the cardiovascular system of the human fetus.