Blood Flow In Normal Pregnancy Research Articles

Longitudinal assessment of spiral and uterine arteries in normal pregnancy using novel ultrasound tool.

To use superb microvascular imaging (SMI) to evaluate longitudinally spiral artery (SA) and uterine artery (UtA) vascular adaptation in normal human pregnancy, and to develop reference ranges for use at various gestational ages throughout pregnancy. The data for this study were obtained from the National Institutes of Health (NIH)-funded Human Placenta Project. Women aged 18-35 years, with a body mass index < 30 kg/m2 , without comorbidities, with a singleton gestation conceived spontaneously, and gestational age at or less than 13 + 6 weeks were eligible for inclusion. The current analysis was restricted to uncomplicated pregnancies carried to term. Exclusion criteria included maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation or delivery < 37 weeks. Women who fulfilled the inclusion criteria formed the reference population of the Human Placenta Project study. Each participant underwent eight ultrasound examinations during pregnancy. The pulsatility index (PI) of both the left and right UtA were obtained twice for each artery and the presence or absence of a notch was noted. Using SMI technology, the total number of SA imaged was recorded in a sagittal placental section at the level of cord insertion. The PI and peak systolic velocity (PSV) were also measured in a total of six SA, including two in the central portion of the placenta, two peripherally towards the uterine fundal portion, and two peripherally towards the lower uterine segment. A total of 90 women fulfilled the study criteria. Maternal UtA-PI decreased throughout the first half of pregnancy from a mean ± SD of 1.39 ± 0.50 at 12-13 weeks' gestation to 0.88 ± 0.24 at 20-21 weeks' gestation. The mean number of SA visualized in a sagittal plane of the placenta increased from 8.83 ± 2.37 in the first trimester to 16.99 ± 3.31 in the late-third trimester. The mean SA-PI was 0.57 ± 0.12 in the first trimester and decreased progressively during the second trimester, reaching a nadir of 0.40 ± 0.10 at 24-25 weeks, and remaining constant until the end of pregnancy. SA-PSV was highest in early pregnancy with a mean of 57.16 ± 14.84 cm/s at 12-13 weeks' gestation, declined to a mean of 49.38 ± 17.88 cm/s at 20-21 weeks' gestation and continued to trend downward for the remainder of pregnancy, reaching a nadir of 34.50 ± 15.08 cm/s at 36-37 weeks' gestation. A statistically significant correlation was noted between SA-PI and UtA-PI (r = 0.5633; P < 0.001). Multilevel regression models with natural cubic splines were used to create reference ranges of SA-PSV and SA-PI for given gestational ages. From early gestation, we have demonstrated the ability to image and quantify SA blood flow in normal pregnancy, and have developed reference ranges for use at various gestational ages throughout pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Correlation of Ultrasound Umbilical Venous Blood Flow in Normal Pregnancy with Gestational Age and Foetal Weight

Background: Umbilical venous (UV) blood flow is a direct and physiological measurement of vascular placental function.&#x0D; Objectives: To correlate UV blood flow with gestational age (GA) and foetal weight (FW) in a cohort of normal pregnant Nigerian women.&#x0D; Materials and Methods: 2,247 women with normal singleton pregnancy between 20 – 40 weeks were included in this study, which was conducted between May 2020 – October 2022, in Bayelsa State, South-South Nigeria. The women had ultrasound assessment of UV blood flow and foetal biometric parameters and weight. Data was analysed using SPSS version 25, associations between categorical variables and between categorical and continuous variables were assessed using chi square and t-test, respectively, with p-value &lt;0.05 considered statistically significant. Correlation analysis was done, and presented in tables and charts.&#x0D; Results: There was a strong linear correlation between UV blood flow volume and GA (correlation coefficient, ɼ= 0.95; p=0.001), FW (ɼ=0.81; p=0.001), foetal biparietal diameter (BPD) (ɼ=0.88; P=0.001) and abdominal circumference (AC) (ɼ=0.75; P=0.001). Conversely, UV blood flow volume/FW showed a strong inverse relationship with FW (ɼ=- 0.73; p = 0.001), and a weak inverse relationship with GA (ɼ=- 0.36; p = 0.001).&#x0D; Conclusion: UV blood flow increases with advancing gestation and FW. The increase in UV blood flow in later gestation is however surpassed by the increase in FW, resulting in a reduction in UV blood flow volume per unit FW in the third trimester. The linear increase in UV blood flow volume with foetal BPD and AC suggests that these three parameters could be used in combination to estimate both GA and FW.

Hemodynamic consequences of incomplete uterine spiral artery transformation in human pregnancy, with implications for placental dysfunction and preeclampsia.

Normal human pregnancy requires a dramatic increase in uteroplacental blood flow, which is achieved by a transformation in the geometry of uterine spiral arteries, a key element in this blood supply system. The transformation is mediated by trophoblast invasion directed at converting a portion of the spiral artery into an open funnel, thereby greatly reducing resistance to flow. The converted portion lies within the depth of the decidua and part of the myometrium. Insufficient depth of trophoblast invasion in early pregnancy predisposes to inadequate perfusion of the developing placenta and fetus and may lead to preeclampsia, fetal growth restriction, and preterm delivery, sometimes referred to as the "Great Obstetrical Syndromes." We examine the hemodynamic consequences of spiral artery transformation in human pregnancy and the relationship between the degree of transformation and the corresponding change in flow rate and resistance to flow. We identify two key variables in determining the hemodynamic change: the longitudinal converted fraction of the spiral artery and the relative downstream diameter of the open funnel. Our results indicate that there is a critical threshold in the value of the converted fraction required to achieve the marked increase in uteroplacental blood flow in normal pregnancy. This finding validates common clinical observations that the depth of trophoblast invasion reflects the "adequacy" of the increase in uteroplacental blood supply required in normal human pregnancy. Our results provide a quantitative measure of that adequacy and may serve as a future diagnostic marker for high-risk pregnancy.NEW & NOTEWORTHY Human pregnancy requires dramatic increase in uteroplacental blood supply achieved by geometric transformation of uterine spiral arteries and facilitated by trophoblast invasion of these arteries to greatly reduce resistance to flow. Incomplete transformation has been associated with failed pregnancies, preeclampsia, and other pathologies, but a quantitative measure of "incompleteness" has been unavailable so far. We use a mathematical model to obtain a numerical threshold for this measure which may serve as a future diagnostic marker.

A longitudinal study of maternal endothelial function, inflammatory response and uterine artery blood flow during the second half of pregnancy

The objective of this study was to investigate serial changes in maternal endothelial function, inflammatory response and uterine artery blood flow in normal pregnancy, and to explore their inter-relation. In this prospective longitudinal observational study, 53 women with uncomplicated pregnancies were examined at 4-weekly intervals (248 observations) during 22-40 weeks of gestation. Uterine artery blood flow was measured using Doppler ultrasonography. Maternal endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Circulating endothelial progenitor cells (EPC), defined as CD34(+) CD133(+) VEGFR2(+) cells, were quantified by flow cytometry. Biomarkers of inflammation, such as leptin and high sensitivity C-reactive protein (hsCRP), were measured in plasma samples. Multilevel modeling was used to investigate gestational-age-associated serial changes. The EPC increased from 6.5 to 12.3 per million mononuclear cells (p < 0.01) and FMD decreased from 16.3 to 13.4% (p = 0.20). Leptin increased from 18 to 22 ng/mL (p < 0.01), and hsCRP did not change significantly (p = 0.61). There was no significant association between FMD and EPC (p = 0.66). FMD was significantly associated with hsCRP (p = 0.002) and leptin (p = 0.003), but the EPC were not. Neither FMD nor EPC were significantly associated with uterine artery blood flow. Changes in FMD were significantly associated with inflammatory biomarkers, suggesting that the reduced nitric oxide-dependent vasodilatation in late gestation is related to maternal inflammatory response. As EPC and FMD did not correlate, mechanisms other than mobilization of EPC to repair endothelial damage must be responsible for the gestational-age-associated increase in EPC.

Endothelial Nitric Oxide Synthase Deficiency Reduces Uterine Blood Flow, Spiral Artery Elongation, and Placental Oxygenation in Pregnant Mice

Preeclampsia is associated with impaired uteroplacental adaptations during pregnancy and abnormalities in the endothelial NO synthase (eNOS)-NO pathway, but whether eNOS deficiency plays a causal role is unknown. Thus, the objective of the current study was to determine the role of eNOS in the mother and/or conceptus in uteroplacental changes during pregnancy using eNOS knockout mice. We quantified uterine artery blood flow using microultrasound, visualized the uteroplacental vasculature using vascular corrosion casts, and used pimonidazole and hypoxia-inducible factor 1α immunohistochemistry as markers of hypoxia in the placentas of eNOS knockout mice versus the background strain, C57Bl/6J (wild type). We found that increases in uteroplacental blood flow, uterine artery diameter, and spiral artery length were reduced, and markers of placental hypoxia in the junctional zone were elevated in late gestation in eNOS knockout mice. Both maternal and conceptus genotypes contributed to changes in uterine artery diameter and flow. Despite placental hypoxia, placental soluble fms-like tyrosine kinase 1 and tumor necrosis factor-α mRNA, and in maternal plasma, soluble fms-like tyrosine kinase 1 were not elevated in eNOS knockout mice. Thus, our results show that both eNOS in the mother and the conceptus contribute to uteroplacental vascular changes and increased uterine arterial blood flow in normal pregnancy.

P10.06: Three‐dimensional power Doppler ultrasound for the assessment of the fetal brain vascularization and blood flow in normal pregnancy

P10.06: Three‐dimensional power Doppler ultrasound for the assessment of the fetal brain vascularization and blood flow in normal pregnancy

Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical artery resistance in vitro

BackgroundThe non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs), and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP), and a PAR-1 antagonist on human umbilical artery tone in vitro.MethodsHuman umbilical artery samples were obtained from 17 women at term. Arterial rings were suspended under physiologic conditions for isometric recording. The in vitro effects of thrombin (0.5 units/mL to 3 units/mL), PAR1-AP TFLLR-NH2 [10(-9) to 10(-6) M], and PAR-1 antagonist (N-trans cinnamoyl- p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Orn-NH2) [10(-9) M to 10(-5) M] on umbilical artery tone were measured.ResultsBoth thrombin and TFLLR-NH2 exerted a potent cumulative vasodilatory effect on human umbilical artery resistance (P < 0.001). The mean net maximal inhibition (MMI) for thrombin was 53.05% (n = 6; SEM = 1.43) at tissue bath concentration of 3 units/mL. The MMI with TFLLR-NH2 was 61.50 % (n = 6; SEM = 1.43) at bath concentration of 10(-6) M. In comparison to vehicle control, the PAR-1 antagonist did not show a significant relaxant or contractile effect (P > 0.05).ConclusionThese findings highlight a potential role for thrombin and PAR-1 receptors in vascular regulation of feto-placental blood flow in normal pregnancy, and in association with the vascular lesions associated with IUGR and pre-eclampsia.

Neurokinin B causes concentration-dependent relaxation of isolated human placental resistance vessels

Placental neurokinin B (NKB) was recently identified as the causative agent in preeclampsia, a condition characterized by increased maternal and feto-placental vascular resistance. We hypothesized that NKB should constrict placental resistance vessels. Placentas were obtained from normotensive pregnancies. Immediately after delivery, stem villous arteries (300 μm diameter, 1.2 mm long) were dissected from macroscopically normal tissue in cold HEPES–physiological salt solution (PSS), mounted on a wire myograph system, and bathed in HEPES–PSS at 37 °C. After determination of the passive-tension internal circumference characteristics, the arteries were set to 90% of the internal circumference they would have under a normal physiological transmural pressure. Cumulative concentration–response curves were constructed for NKB (1×10 −12 to 1×10 −5 mol/l). Since there was no constrictive response to NKB, cumulative constrictive concentration–response curves were constructed to the thromboxane A 2 mimetic U46619 (1×10 −9 to 1×10 −5 mol/l). The vessels were then pre-constricted to 80% of maximal response and exposed to cumulative concentrations of NKB (1×10 −12 to 1×10 −6 mol/l). NKB caused a concentration-dependent relaxation (Maximal response NKB, 51±5%, n=5; time control, 12±6%, n=4; P<0.05). Removal of the endothelium did not alter the vasodilatory response to NKB. We conclude that, contrary to our hypothesis, NKB causes an endothelium-independent relaxation of the placental resistance vessels. We propose that NKB plays a role in the maintenance of high placental blood flow in normal pregnancy.

A longitudinal study of resting peripheral blood flow in normal pregnancy and pregnancies complicated by chronic hypertension and pre-eclampsia.

To investigate the hypothesis that reduced resting tissue blood flow precedes the clinical onset of pre-eclampsia in women at risk of the disease. We used venous occlusion plethysmography to compare resting calf muscle blood flow in 18 normal pregnant controls, 18 pregnant women with chronic hypertension, and 23 pregnant women at increased risk of developing pre-eclampsia. Calf blood flow was measured at 16, 20, 24, 28, 32 and 36 weeks of gestation. Blood flow increased with gestation in normal pregnancy (P = 0.004) and chronic hypertension (P = 0.006), but not in the 'at risk' women who did not develop pre-eclampsia (P = 0.36). In contrast, blood flow decreased significantly in eight out of the 23 women 'at risk', who developed pre-eclampsia (P < 0.00001, ANOVA). The decrease in flow preceded the clinical diagnosis of the pre-eclampsia by several weeks. Moreover, a significant inverse correlation was observed between resting blood flow and plasma uric acid concentrations (r = -0.86, P = 0.03) in the women that developed pre-eclampsia. We have shown that reduced resting blood flow precedes the clinical onset of pre-eclampsia independently of hypertension per se. These findings support the notion that impaired tissue blood flow may be involved at an early stage in the pathophysiology of the disease.

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia

Resting peripheral blood flow in normal pregnancy and in pre-eclampsia

Multiple organ dysfunction followed by end organ failure occurs in pre-eclampsia. While one would intuitively reason that one of the factors contributing to the end organ failure is poor nutritional blood flow, this has yet to be demonstrated. The aim of the present study was to determine whether changes in resting nutritional blood flow occur in pre-eclampsia. We used strain-gauge plethysmography to study calf blood flow in 19 women with pre-eclampsia, 13 normal pregnant women and 17 non-pregnant controls. We reasoned that, since the calf comprises mostly skeletal muscle, without anastomotic channels, blood flowing through this region would primarily reflect nutritive flow. Calf blood flow was significantly reduced in women with pre-eclampsia (1.95+/-0.9 ml.min(-1).100 ml(-1)) compared with normal pregnant (3.9+/-1.4 ml.min(-1).100 ml(-1)) and non-pregnant (3.8+/-1.0 ml.min(-1).100 ml(-1)) women (P=0.0004 and P=0.0005 respectively; ANOVA). Blood flow in pre-eclampsia was also correlated significantly with platelet count as an index of disease severity. In addition, there was a significant negative correlation between blood flow and systolic blood pressure (r=-0.69, P=0.004) in the women with pre-eclampsia. These findings support the hypothesis that nutritional blood flow is reduced in pre-eclampsia. We suggest that measurement of resting calf blood flow could give a non-invasive index of deterioration of nutritive blood flow to vital organs in pre-eclampsia.

Abstracts of literature

Abstracts of literature

The effect of lumbar epidural anesthesia on maternal middle cerebral artery blood flow in normal pregnancy: A prospective, randomized, double-blind comparison study

Objective: Lumbar epidural anesthesia is associated with a transient elevation in intracranial pressure in both animals and humans and decreased cerebral blood flow in animals. We sought to determine the effect of medium-onset and slow-onset local anesthetic lumbar epidural anesthesia on maternal cerebral blood flow in normal human pregnancy. Study Design: In an Institutional Review Board–approved, double-blind study, 24 healthy, normotensive, nonlaboring, term gravida women undergoing elective cesarean section were prospectively placed into random groups to receive either 2% lidocaine with 8.4% sodium bicarbonate (1:10) or 0.5% bupivacaine lumbar epidural anesthesia. After prehydration with 20 mL/kg crystalloid and 15-degree left-wedged supine positioning with 15-degree head tilt, transcranial Doppler ultrasound (Nicolet Pioneer EME) and simultaneous electrocardiogram, automatic blood pressure (Dinamap), and end-tidal CO 2 (SAR-Trans) monitoring were performed. Pulse, blood pressure, respiratory rate, end-tidal CO 2 , middle cerebral artery blood flow velocity, and pulsatility index were measured at (1) baseline (once supine positioning was assumed); (2) immediately after administration of 20 mL local anesthetic; and (3) every 5 minutes for 25 minutes. Timing of the attainment of a T4 dermatome anesthetic level was noted. Comparisons were made by t test, rank sum tests, χ 2 , and repeated measures analysis of variance. P < .05 was considered significant. Results: Maternal heart rate, blood pressure, respiratory rate, and end-tidal CO 2 were not significantly different within or between groups. No significant difference was found in baseline middle cerebral artery blood flow velocity or pulsatility index values between groups. Neither middle cerebral artery blood flow velocity nor pulsatility index changed significantly within or between groups up to 25 minutes after institution of epidural anesthesia. Conclusions: Maternal middle cerebral artery blood flow velocity, as measured by transcranial Doppler ultrasonography, is maintained in normotensive, nonlaboring term gravida women receiving either lidocaine or bupivacaine lumbar epidural anesthesia, which supports intact cerebrovascular autoregulation in normal pregnancy. (Am J Obstet Gynecol 1998;179:1237-40.)

A longitudinal study of maternal bloodflow in normal pregnancy and the puerperium: analysis of Doppler waveforms using Laplace transform techniques.

To describe changes in the maternal cerebral circulation and the external iliac arteries throughout pregnancy and the puerperium using the Laplace transform analysis of Doppler waveforms. A prospective longitudinal study. Department of Obstetrics and Gynaecology, Nottingham University Hospital. A cohort of 17 healthy women studied every four weeks from early pregnancy until term and up to three months postpartum. Pre-conception data were available for 10 subjects. Doppler signals were recorded from the internal carotid, middle cerebral and external iliac arteries. The waveforms were analysed using two different techniques: standard indices (systolic:diastolic ratio, pulsatility and resistance indices) and Laplace transform analysis, an alternative method of waveform shape analysis which may provide additional haemodynamic information. Vessel wall tone decreased at an early stage in pregnancy in the cerebral circulation and in the external iliac artery, but this rose again following delivery. The Laplace transform analysis techniques suggest dramatic eight-fold increases in downstream resistance within the external iliac artery in the second half of pregnancy. An increase in downstream resistance to flow also occurred in the internal carotid artery whereas more stable conditions were noted in the middle cerebral artery. Having a preliminary idea of the normal ranges for the Laplace transform analysis variables during pregnancy in a variety of maternal vessels, haemodynamic changes in pregnancies complicated by conditions, such as pre-eclampsia, can now be studied.

Understanding utero-placental blood flow in normal and hypertensive pregnancy through a mathematical model.

Normal development of utero-placental circulation is crucial not only for the survival and growth of the fetus in utero, but also for maternal well-being. Any disturbance or abnormality may reflect underlying pathology. Geometric conversion of a pre-pregnant spiral vessel into a divergent low-resistance vessel is believed to be responsible for the increased utero-placental blood flow in normal pregnancy. Known biomedical investigative techniques have failed to explain many such underlying haemodynamic changes taking place in the utero-placental system. Therefore, proper understanding of the system using a mathematical model has been found to be useful. The physiological fluid dynamic study is the first in this branch of physiology. Abnormal pressure gradient, axial velocity, volume flow and shear rate are obtained for various slowly changing geometries such as, tapering, divergence, local constrictions and sinusoidal tube for low Womersley parameters. The model can explain many enhanced patho-physiological changes, such as persistence or the appearance of local constriction in the utero-placental vessels. Such pathological changes are considered to be responsible for very high utero-placental resistance, leading to blood flow insufficiency in pre-eclampsia or intra-uterine growth retardations. It is believed that these changes may be caused by low shear rate on the pre-existing deranged or abnormal endothelium. Furthermore, this derangement is caused by an abnormal proliferation of either spiral vessels or the invading non-villous trophoblasts. Doppler flow study can explain and validate some of the theoretically derived flow velocity results. The study opens up a new area of research into utero-placental physiological fluid dynamics.

Skin Blood Flow in Normal Pregnancy Measured by Venous Occlusion Plethysmography of the Hand

Total hand blood flow was measured by venous occlusion plethysmography in 14 healthy primigravid women. Consecutive measurements were made from the 15th week of pregnancy until term and after delivery. During pregnancy the mean hand blood flow, measured under standard resting conditions with the subjects supine, increased progressively from 7.7 in early pregnancy to 28.9 ml/100 ml/min at term. Simultaneously the peripheral vascular resistance decreased from 19.3 to 3.3 PRU100. When examined at 6--16 weeks after delivery hand blood flow and peripheral resistance were not yet returned to normal.

Peripheral blood flow in normal pregnancy.

During pregnancy the mean blood flow through the hands, measured under standard conditions with the subjects supine, rose progressively from 2·7 ml./100 ml.min. to 18·1 ml. at term. The flow subsided during the puerperium, but by the sixth week it was still, at 9·1 ml., significantly elevated above the level of early pregnancy. The blood flow through the feet showed similar, though less striking, changes. The flows were somewhat higher in twin-pregnancies than in singleones. The blood flow through the forearm and calf of the leg remained little changed throughout.

Myometrial blood flow in pregnancy measured with xenon-133.

Fetal wellbeing is believed to be related to among other factors the maternal blood supply to the placenta. Previous efforts to measure the myometrial blood flow with sodium have not been wholly successful. Clinical research was done to measure the flow in 3rd-trimester pregnant women with Xenon an inert radioactive gas. The Xenon was deposited directly into the myometrium transabdominally. As with sodium preliminary results showed a marked scatter. The pattern however indicates a definite reduction in the blood flow in abnormal pregnancies. These included patients with preeclampsia placental insufficiency fetal death hypertension and subsequent fetal deaths during labor. The mean myometrial blood flow in normal pregnancies was between 12 and 13 ml/100 g/min with a range from 2-32 ml. The mean blood flow in abnormal pregnancies was 10 ml/100 g/min with a range from 2-26 ml. Possible reasons for the scatter of measurements are discussed. Radiation doses to the fetus and gonads through this method is only 5% of that received when the measurement was performed with sodium.