Uteroplacental Hemodynamics Research Articles

Maternal and fetal arrhythmia as a sign of hemodynamic deterioration: a case report

The co-existing maternal (MA) and fetal arrythmia (FA) are associated with maternal goiter disease, chorioamnionitis, or Ballantyne’s syndrome. The aim of the study - to determine the involvement of maternal arrhythmia and fetal arrhythmia in the pathogenic scenario of hemodynamic deterioration in Ballantyne’s syndrome. Clinical case. It is presented the case of sustained several weeks of MA and FA. A pregnant woman aged 36 years was admitted to the division of maternal and fetal medicine at 34 weeks of gestation. She was gravida 4 and para 3. She had complaints of rapid heartbeat, left-side chest discomfort, and lower extremities edema. The diagnosis of maternal sinus tachycardia was supported via electrocardiography. The indices of fetal, umbilical, and uteroplacental hemodynamics detected via Doppler ultrasound were appropriate. However, fetal heart rate was 209 beats/min. The transplacental attack of oral sotalol 80 mg thrice daily was prescribed. But maternal and fetal tachycardia persisted to stay. The tricuspid regurgitation was detected via Doppler ultrasound next day. The fetus was hydropic. The male baby of 2400 g, 46 cm length, 31 cm head circumference, and Apgar score 3→5 was delivered via caesarean. The newborn was discharged in 21 days. He was admitted again in one month for rehabilitation. Maternal heart rate reduced to 72 beats/min and edema regressed in three days after birth. Conclusions. MA and FA before fetal hydrops are supposed to be the early signs of mirror syndrome. This speculation needs further investigation. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Ultrasound evaluation of normal rhesus macaque fetal biometry and uteroplacental hemodynamics.

Nonhuman primates are important preclinical models for translational, reproductive, and developmental science. Clinical evaluation of human fetal development is performed using standard sonographic-derived fetal biometry, assessments of amniotic fluid, and uteroplacental hemodynamics. These noninvasive in utero measurements provide important information regarding fetal growth and pregnancy well-being. Abnormalities in fetal growth, amniotic fluid volume, or placental vascular function are associated with placental insufficiency and adverse perinatal outcomes including stillbirth. The fetal biometric parameters most commonly assessed are biparietal diameter, head circumference, abdominal circumference, and femur diaphysis length. Evaluation of amniotic fluid volume includes measuring the fluid in four quadrants of the uterus to generate an Amniotic Fluid Index. Measures of uteroplacental hemodynamics typically include doppler assessment of the umbilical artery and ductus venosus, but can also include interrogation of the uterine artery and umbilical vein. In this study, we compile prenatal ultrasound data of fetal biometry, amniotic fluid measurements, and uteroplacental hemodynamics obtained from pregnancy studies conducted at the Oregon National Primate Research Center. The data included are from control unperturbed pregnant animals who have not undergone in utero experimental manipulations. This is the first report of comprehensive sonographic measurements following standardized clinical obstetric protocols utilized in rhesus macaques. The outcome is a large, prenatal ultrasound resource to be used by laboratory animal researchers in future nonhuman primate pregnancy studies for antenatal assessment.

Hypoxic-ischemic brain damage of the fetus and newborn with hemodynamic disorders in the “mother-placenta-fetus” system

Objective: to identify the dependence of the severity of cerebral disorders in newborns and children of the first year of life on the indicators of blood flow in the utero-placental complex. Materials and methods: a total of 184 full-term newborns were examined in the period from birth to one year of life. The main group included children with cerebral ischemia of II and III severity and its consequences (group II, n=78; group III, n=42). Group I included newborns without signs of central nervous system damage, 14 of them had neurological symptoms by the end of the neonatal period (after a month, group I n =50, group II n =92). All children underwent general clinical examination, assessment of neurological status, ultrasound examination of the brain, transcranial dopplerography of cerebral vessels, electroencephalography. Maternal medical records were analyzed to identify hemodynamic parameters in the "mother-placenta-fetus" system at 12-13, 20-21, 28-32, and 36-40 weeks of gestation. Results: The features of uterine and fetal blood flow in the dynamics of gestation in mothers of the examined groups of children were determined. The associations between the values of Pi AUD, AUS, and AUM in the second and third trimesters of pregnancy in different groups were shown. The relationship between disorders of uteroplacental hemodynamics and the severity of cerebral pathology was revealed. A "method of antenatal prediction of the severity of cerebral disorders in newborns" was proposed. Conclusions: The obtained results make it possible to predict the risk of hypoxic-ischemic damage to the central nervous system in newborns antenatally using hemodynamic parameters in the mother-placenta-fetus system at 36 weeks of gestation.

DOPPLER ASSESSMENT OF UTERO-PLACENTAL HEMODYNAMICS IN PREGNANT WOMEN WITH A HISTORY OF CORONAVIRUS DISEASE (COVID-19)

The latest viral disease, which continues to spread today, is caused by a new coronavirus and poses a serious threat to public health around the world. To date, the effects of COVID-19 on pregnant women and infants have not been fully studied and remain a key area of interest. The study aimed to assess utero-placental circulation using Doppler ultrasound for pregnant women with a case history of coronavirus disease (COVID-19). A Doppler screening of utero-placental hemodynamics was performed for 156 pregnant women at 18-22 weeks. Of those, 75 pregnant women with a case history of coronavirus disease COVID-19 were in the first trimester of pregnancy. An abnormal blood flow was observed within the experimental group in 14 cases (18.6%). The analysis of spectrograms revealed the unevenness of the diastolic component with the formation of a dicrotic notch in the early diastolic phase in 5 cases (6.6%). In comparison with the control group, pregnant women with COVID-19 were twice as likely to have impaired blood flow in the uterine arteries. Uterine artery doppler measurement is really important for predicting adverse pregnancy outcomes and perinatal losses. Doppler indices of utero-placental blood flow have clinical value for pregnant women who have recovered from COVID-19.

Early neonatal period of newborns from mothers with sexually transmitted infections in the case history

The objective: to analyze the perinatal consequences of childbirth and the early neonatal period of the newborns from mothers with sexually transmitted infections in the case history. Materials and methods. In order to meet the objective, we examined 80 pregnant women on the basis of the Kyiv City Center of Reproductive and Perinatal Medicine (the clinical base of the Department of Obstetrics, Gynecology and Reproductology of Shupyk National Healthcare University of Ukraine) for the period of 2020–2021. There were two groups: group I – 50 pregnant women with STIs in the case history and group II – a control group – 30 practically healthy pregnant women with a successful reproductive history and uncomplicated course of the present pregnancy. Clinical and statistical analysis of perinatal consequences of childbirth and early neonatal period in newborns from these women was conducted. Results. The analysis of perinatal consequences of childbirth from women with sexually transmitted infections in the case history showed a high frequency of intranatal asphyxia of varying severity – 19 children (38.0%), severe – 2 children (4.0%). The early neonatal period disease incidence of infants born from the women in this group is 38 (38.0%; p<0.05) cases against 13.3% in the control group. The frequency of detection of fetal growth retardation syndrome in women patients of group I significantly increased compared to women from the control group - up to 10.0% (p<0.05 by criterion χ2). The fetal growth retardation syndrome occurred in women of group I, due to the placenta dysfunction, which was caused by the primary deterioration of uteroplacental hemodynamics and microthrombosis in the placenta. At the same time, early FGR (up to 32 weeks) was detected in women of group I – 80.0% of cases. It can be assumed that the development of FGR syndrome coincides with the manifestation of the underlying sexually transmitted disease during gestation. Manifestations of intrauterine infection were observed in newborns from women from group I in 18.0% of cases, which was statistically significant compared to the control (p<0.05 by criterion χ2). Among this category of newborns, inflammatory processes of the skin (44.4%), urinary tract infections (33.3%), and pneumonia (22.2%) were most of ten observed. Conclusions. The study confirms and suggests that the presence sexually transmitted infection in the case history adversely affects perinatal outcomes. This had a negative effect on the newborn with the realization in the form of asphyxia, decreased weight growth, CNS damage, conjugative jaundice, intrauterine infection and its implementation in the early neonatal period. Ensuring quality care for this category of newborns requires special attention of neonatologists to predict neonatal complications of intrauterine infection.

Maternal lysine, methionine and choline supplementation in twin-bearing Merino ewes during mid-to-late gestation does not alter pregnancy outcomes or progeny growth and survival

High twin lamb mortality in Merino sheep is a major cost for the Australian wool and sheep meat industry. Most lambs die within three days of birth due to low birthweight and/or complications arising during parturition. Maternal arginine supplementation can potentially increase birthweight by improving utero-placental haemodynamics; but availability and cost of rumen-protected arginine are barriers. Therefore, we sought to increase circulating concentrations of arginine, lamb birthweight and survival by supplementing twin-bearing Merino ewes with lysine, methionine and choline from day 80 of gestation (dG 80) to parturition. Each day, ewes were individually fed a supplement (barley, pea, pollard and molasses) with addition of either 14 g lysine, 7 g methionine and 7 g choline (amino acid; AA; n = 48); or no amino acids (control; CTL; n = 48). Supplementation did not alter circulating amino acid profiles in ewes at dG 120. Parturition difficulty of ewes and meconium staining of lambs did not differ between AA and CTL groups. Rectal temperatures during the first 24 h of life and serum IgG concentrations (indicative of colostrum intake) at 24 h after birth were similar in lambs born to AA and CTL ewes. AA supplementation did not alter lamb weights from birth to weaning (~three months of age), or lamb survival to weaning (CTL: 75%; AA: 84.8%, P > 0.05). The lack of response to maternal supplementation with this combination of rumen-protected lysine, methionine and choline suggests that alternate strategies are needed to increase maternal arginine abundance and twin lamb survival.

Something old, something new: digital quantification of uterine vascular remodelling and trophoblast plugging in historical collections provides new insight into adaptation of the utero-placental circulation.

What is the physiological extent of vascular remodelling in and trophoblast plugging of the uterine circulation across the first half of pregnancy? All levels of the uterine vascular tree (arcuate, radial and spiral arteries (SAs)) dilate ∼2.6- to 4.3-fold between 6 and 20 weeks of gestation, with significant aggregates of trophoblasts persisting in the decidual and myometrial parts of SAs beyond the first trimester. In early pregnancy, endovascular trophoblasts form 'plugs' in the SAs, transiently inhibiting blood flow to the placenta, whilst concurrently the uterine vasculature undergoes significant adaption to facilitate increased blood delivery to the placenta later in gestation. These processes are impaired in pregnancy disorders, but quantitative understanding of the anatomical changes even in normal pregnancy is poor. Serial sections of normal placentae in situ (n = 22) of 6.1-20.5 weeks of gestation from the Boyd collection and Dixon collection (University of Cambridge, UK) were digitalized using a slide scanner or Axio Imager.A1 microscope. Spiral (n = 45), radial (n = 40) and arcuate (n = 39) arteries were manually segmented. Using custom-written scripts for Matlab® software, artery dimensions (Feret diameters; major axes; luminal/wall area) and endovascular trophoblast plug/aggregate (n = 24) porosities were calculated. Diameters of junctional zone SAs within the myometrium (n = 35) were acquired separately using a micrometre and light microscope. Decidual thickness and trophoblast plug depth was measured using ImageJ. By all measures, radial and arcuate artery dimensions progressively increased from 6.1 to 20.5 weeks (P < 0.01). The greatest increase in SA calibre occurred after 12 weeks of gestation. Trophoblast aggregates were found to persist within decidual and myometrial parts of SA lumens beyond the first trimester, and up to 18.5 weeks of gestation, although those present in the second trimester did not appear to prevent the passage of red blood cells to the intervillous space. Trophoblasts forming these aggregates became more compact (decreased in porosity) over gestation, whilst channel size between cells increased (P = 0.01). Decidual thickness decreased linearly over gestation (P = 0.0003), meaning plugs occupied an increasing proportion of the decidua (P = 0.02). N/A. Although serial sections were assessed, two-dimensional images cannot completely reflect the three-dimensional properties and connectivity of vessels and plugs/aggregates. Immersion-fixation of the specimens means that vessel size may be under-estimated. Uterine vascular remodelling and trophoblast plug dispersion is a progressive phenomenon that is not completed by the end of the first trimester. Our quantitative findings support the concept that radial arteries present a major site of resistance until mid-gestation. Their dimensional increase at 10-12 weeks of gestation may explain the rapid increase in blood flow to the placenta observed by others at ∼13 weeks. Measured properties of trophoblast plugs suggest that they will impact on the resistance, shear stress and nature of blood flow within the utero-placental vasculature until mid-gestation. The presence of channels within plugs will likely lead to high velocity flow streams and thus increase shear stress experienced by the trophoblasts forming the aggregates. Quantitative understanding of utero-placental vascular adaptation gained here will improve in silico modelling of utero-placental haemodynamics and provide new insights into pregnancy disorders, such as fetal growth restriction. This work was supported by a Royal Society Te Aparangi Marsden Grant [18-UOA-135]. A.R.C. is supported by a Rutherford Discovery Fellowship [14-UOA-019]. The authors have no conflict of interest to declare.

Pravastatin plus L-arginine prevents adverse pregnancy outcomes in women with uteroplacental vascular dysfunction

BackgroundUteroplacental vascular dysfunction, characterized by diminished uterine artery (UtA) blood flow in the second trimester is a clinically useful predictor of the further development of preeclampsia, fetal growth restriction and stillbirth. Efforts to develop effective treatments to protect pregnancies with abnormal UtA Dopplers would be of significant clinical benefit for mothers and their fetuses. ObjectiveThe aim of this pilot non randomized control study was to use pravastatin +L-arginine to improve uteroplacental haemodynamics and prevent adverse maternal and neonatal outcomes in women with abnormal Dopplers and high risk for developing adverse pregnancy outcomes. Study designThis study was performed between 2015 and 2018. All women received primary care at OB/GYN Polyclinic Jurisic and Narodni Front University Hospital, University of Belgrade Medical School, Serbia. Approval for investigational drug use was obtained and all women gave informed consent.10 pregnant women with a poor obstetric history that developed uteroplacental dysfunction (UtA pulsatility index (PI) above the 95th percentile and notching) at 20.5 weeks IQR [17.7–22] gave consent to be treated daily with pravastatin (40 mg) and L-arginine (1.5 g) to improve placental blood flow and pregnancy outcomes. 5 women remained untreated after diagnosis at 21 weeks [20−22] (control group). Due to presence of risk factors for pregnancy complications, close maternal and fetal monitoring was undertaken in all patients. Doppler examinations were performed to monitor changes in placental vascular resistance and fetal well-being and growth. ResultsPRAV+L-arginine improved uteroplacental haemodynamics, increased fetal growth and prevented early onset preeclampsia leading to delivery close to term (delivery date: median 38 weeks, IQR[36.5–39]) and appropriate weight for gestational age compared to controls, in which placental blood flow did not improve and 2 women developed severe early onset preeclampsia. Neonates from the control group were born preterm (25 weeks IQR[23.5–25]), growth restricted and spent several months at NICU. Two neonates died due to prematurity-associated complications. PRAV+L-arginine treatment prolonged pregnancies for 4.1 months, compared to 26 days in the untreated group, preventing neonatal complications associated with prematurity. The infants are now 1–3 years old and show normal growth and development. ConclusionThis study describes the successful management with pravastatin+L-arginine of 10 pregnant patients with uteroplacental vascular dysfunction and high risk of adverse maternal and fetal outcomes. A larger study is being organized to confirm these observations.

THE CONDITION OF UTEROPLACENTAL HEMODYNAMICS IN PREGNANT WOMEN AS A RESULT OF THE ASSISTED REPRODUCTIVE TECHNOLOGIES APPLICATION

The aim of research. To study in the dynamics of the First trimester of pregnancy the features of hemodynamics in pregnant women after ART .Materials and methods. 299 pregnant women were comprehensively examined: the main group included 249 women whose pregnancy occurred as a result of the ART application. The control group consisted of 50 pregnant women with spontaneous pregnancy and its physiological course, which were registered in antenatal clinic at 6-8 weeks. The I group included 94 women with tubal-peritoneal factor of infertility, the II group was formed by 87 women with endocrine factor of infertility, and the III group included 68 women whose infertility is caused by the male factor.Common clinical and laboratory tests were performed on pregnant women of the examined groups, which included a General analysis of blood, urine, and Doppler measurements of uterine arteries indicators.The results of the research and their discussion. Determination of utero-placental hemodynamics in women of the main group after the ART application indicates the need for their dynamic monitoring during the I trimester of pregnancy.As a result of the analysis of the obtained data, it was found that the highest intensity of hemodynamics in the uterine artery basin at 11-12 weeks of gestation was registered in the group of patients with the physiological course of pregnancy. Thus, the systolic-diastolic ratio in the right and left uterine arteries in these patients was 1,9 (1,8-2,7) and 2,1 (1,9-2,6), respectively.In contrast to the subjects with uncomplicated course (group IV), in pregnant women after the ART application analyzed indicators were significantly higher (1,6 – 1,9 times, p<0,0001). The systolic-diastolic ratio in the right uterine artery in group III was 3,0 (2,4-3,5), and in group I – 3,3 (3,1- 3,4). Similar data were obtained during the curves of blood flow rates analyses the in the left uterine artery – 2,9 (2,1-3,5) and 3,0 (2,7-3,6), respectively.The highest peripheral resistance, both in the right (3,6 (3,4-3,7)) and in the left (3,5 (3,2-3,8)) uterine arteries, was registered naturally in group II pregnant women.Own research has shown that the vast majority of 36 (72,0%) patients with uncomplicated course and favorable gestational outcome at 11-12 weeks of pregnancy did not register blood flow in the interval space. Less than one-third of the patients - 14 (28,0%) color Doppler mapping revealed continuous venous-like blood flow. Arterioid-like pulsating type of flow does not reveal any one pregnant in this group.In contrast, the vast majority - 50 (73,5%) of group I pregnant women registered two types of blood flow in the intervertebral space: pulsating arterioid and continuous venous flow. Only 18 (26,5%) patients of this group the blood flow in intervention space was not determined.Conclusions. The results of the research allow us to attribute Doppler to highly informative research methods, which makes it possible to predict pregnancy complications in pregnant women as a result of art quite effectively. Pregnant women with no hemodynamic abnormalities in the utero-placental pool in combination with normal ultrasound data, including assessment of the fetal condition, constitute a group with a truly low risk of an adverse outcome

Effects of early aspirin therapy on utero-placental hemodynamics in patients at risk of preeclampsia

Objectives To evaluate the effects of early aspirin therapy on the mean pulsatility index of both uterine arteries (utA PI) at 1st and 2nd trimester in women at risk of preeclampsia (PE). Methods Uterine artery (utA) blood flow characteristics were obtained in 315 women, 73 women at risk for PE and early aspirin treatment (group 1), 124 without specific risk factors and no aspirin treatment (group 2) and 118 women with manifest PE (group 3). Mean utA PI of group 1 and group 2 were compared within and between the groups at the 1st and 2nd trimester time points. Furthermore, values at 2nd trimester were compared with those of group 3. Observed to expected mean utA PI ratio (O/E ratio) were calculated for comparison between the groups. Results Mean utA PI of group 1 was significantly higher in the 1st trimester compared to group 2 (1.74 vs. 1.47, p = .0117). In the 2nd trimester mean PI decreased significantly in both groups from 1.74 to 1.16 in group 1 and from 1.47 to 0.90 in group 2 (p < .0001). Nevertheless, the difference between the groups was significantly higher in the 2nd trimester than in the 1st trimester (0.29 vs. 0.27, p < .001). Correction for gestational age by analyzing mean utA O/E ratios showed a comparable pattern with a significantly decrease in both groups (1.40 to 1.10 in group 1 and 1.18 to 0.78 in group 2, p < .0001), but a significant higher decrease in the 2nd trimester in group 2 (0.31 vs.0.22, p < 0001). The prevalence of PE was 15.1% (11/73) in group 1 (4 early/7 late onset PE) and 4.7% (6/124) in group 2 (1 early/5 late onset). Mean utA PI and O/E ratio obtained in the 2nd trimester were higher in all PE cases with no significant difference between early and late onset PE (1.49/1.57 and 1.25/1.36 in group 1 and 0.80/0.97 and 0.77/0.99 in group 2). However, mean utA PI and O/E ratio decreased in all cases without PE in both groups, whereas mean utA PI was 1,37 and O/E-ratio was 1,29 in patients with manifest PE at admission, with significantly higher values in early onset than in late onset PE (1.45/1.31 vs. 1.07/1.02, p < .0001). Conclusions Our results show that early aspirin treatment leads to a decrease of elevated mean utA PI between 1st and 2nd trimester in patients at elevated risk for PE which is inferior to the decrease observed in women at standard risk for PE. While aspirin improves trophoblast invasion during early second trimester, vascular resistance remains well above average levels. Limited vascular remodeling capacity in the utero-placental perfusion area seems to be the explanation why aspirin does not abrogate PE in all women and has little effect on birth weight. Another explanation might be that a dose of 100 mg aspirin was used as compared to the 150 mg which is recommended today. Our findings underscore the need to study the effects of intervention already during the early stages of trophoblast invasion in the first trimester.

Associations of Maternal Early-Pregnancy Glucose Concentrations With Placental Hemodynamics, Blood Pressure, and Gestational Hypertensive Disorders.

Gestational diabetes mellitus is associated with increased risks of gestational hypertension and preeclampsia. We hypothesized that high maternal glucose concentrations in early pregnancy are associated with adverse placental adaptations and subsequently altered uteroplacental hemodynamics during pregnancy, predisposing to an increased risk of gestational hypertensive disorders. In a population-based prospective cohort study from early pregnancy onwards, among 6,078 pregnant women, maternal early-pregnancy non-fasting glucose concentrations were measured. Mid and late pregnancy uterine and umbilical artery resistance indices were assessed by Doppler ultrasound. Maternal blood pressure was measured in early, mid, and late pregnancy and the occurrence of gestational hypertensive disorders was assessed using hospital registries. Maternal early-pregnancy glucose concentrations were not associated with mid or late pregnancy placental hemodynamic markers. A 1 mmol/l increase in maternal early-pregnancy glucose concentrations was associated with 0.71 mm Hg (95% confidence interval 0.22-1.22) and 0.48 mm Hg (95% confidence interval 0.10-0.86) higher systolic and diastolic blood pressure in early pregnancy, respectively, but not with blood pressure in later pregnancy. Also, maternal glucose concentrations were not associated with the risks of gestational hypertension or preeclampsia. Maternal early-pregnancy non-fasting glucose concentrations within the normal range are associated with blood pressure in early pregnancy, but do not seem to affect placental hemodynamics and the risks of gestational hypertensive disorders.

Influence of Estrogens on Uterine Vascular Adaptation in Normal and Preeclamptic Pregnancies.

During pregnancy, the maternal cardiovascular system undergoes significant changes, including increased heart rate, cardiac output, plasma volume, and uteroplacental blood flow (UPBF) that are required for a successful pregnancy outcome. The increased UPBF is secondary to profound circumferential growth that extends from the downstream small spiral arteries to the upstream conduit main uterine artery. Although some of the mechanisms underlying uterine vascular remodeling are, in part, known, the factors that drive the remodeling are less clear. That higher circulating levels of estrogens are positively correlated with gestational uterine vascular remodeling suggests their involvement in this process. Estrogens binding to the estrogen receptors expressed in cytotrophoblast cells and in the uterine artery wall stimulate an outward hypertrophic remodeling of uterine vasculature. In preeclampsia, generally lower concentrations of estrogens limit the proper uterine remodeling, thereby reducing UPBF increases and restricting the growth of the fetus. This review aims to report estrogenic regulation of the maternal uterine circulatory adaptation in physiological and pathological pregnancy that favors vasodilation, and to consider the underlying molecular mechanisms by which estrogens regulate uteroplacental hemodynamics.

P205 Maternal left ventricular global longitudinal strain correlates with parameters of fetal intrauterine growth and uteroplacental hemodynamics

Abstract Impairment of physiological mechanisms responsible for maternal cardiovascular adaptation during pregnancy may be associated to intrauterine growth restriction (IUGR). Purpose To compare maternal cardiac parameters between pregnancies with IUGR and with fetal growth appropriate for gestational age (AGA). Methods Twenty-one IUGR (median age 31 years) were compared with 18 AGA matched for age, body size and gestational age (p &amp;gt; 0.35 for all). LV volumes and ejection fraction (LVEF) were measured by 3D echocardiography, and LV mass (LVM) and outflow velocity time integral (VTI) by conventional echocardiography. LV longitudinal strain (GLS) was assessed by speckle-tracking. Results Compared to AGA, IUGR mothers had similar LV volumes and LVEF, but larger LV mass (76 vs 63 g/m2, p = 0.006), LV mass/volume (1.14 vs 1.0 g/ml, p = 0.036) and lower VTI (19.9 vs 21.5 cm, p = 0.046) and GLS (-20 vs -22%, p = 0.032). Maternal LV GLS correlated with fetal growth and utero-placental hemodynamics (Table). At ROC curve analysis, maternal GLS had a good ability to discriminate IUGR from AGA (Figure). Conclusions IUGR had larger LV mass/volume and lower GLS than AGA. GLS was more sensitive than LVEF to detect LV function changes in IUGR. This is the first study reporting that worse maternal LV GLS correlates with fetal growth restriction and suboptimal utero-placental hemodynamics. Rho Spearman p APGAR score 0.36 0.03 Birthweight percentile 0.38 0.02 Biparietal diameter 0.47 0.003 Cranial circumference 0.31 0.07 Abdominal circumference 0.30 0.07 Umbilical vein velocity 0.64 0.003 Uterine artery mean pulsatility index -0.36 0.028 LV length 0.36 0.034 LV mid diameter 0.32 0.05 LV end-systolic volume 0.34 0.046 MAPSE 0.45 0.006 TAPSE 0.41 0.004 Mitral E wave 0.50 0.002 Mitral A wave 0.38 0.02 Correlation of maternal GLS (considered as positive) and fetal parameters. Abstract P205 Figure. GLS ability to discriminate IUGR vs AGA

PSII-7 Uterine artery hemodynamics and placentome quantification during maternal nutrient restriction in beef cattle

Abstract Proper fetal nutrition via adequate uteroplacental blood flow is critical for maximizing fetal development and reducing mortality. However, our understanding of adaptations during maternal nutrient restriction is incomplete. The purpose of this study was to determine the effect of nutrient restriction during mid to late gestation on utero-placental hemodynamics and placentome morphometrics in gestating beef cattle. Animals (n = 10) were randomly assigned one of 2 treatments: Control (CON; 100% NRC Requirements) vs Restricted Feed (NR; 60% of NRC Requirements) from 140 to 240 days of gestation. Hemodynamic parameters were collected by Doppler ultrasonography 1 week prior to slaughter from the ipsilateral and contralateral uterine arteries, after which, total uterine artery blood flow was calculated. Six animals (n = 3 per treatment) were slaughtered on day 240 of gestation (Group 1) and the remaining 4 animals were slaughtered on 265 ± 15 days (Group 2). Placentome tissues were harvested for weight and number determination. Placentome number decreased (P = 0.01) in nutrient restricted (49 ± 6) versus control (83 ± 6) fed dams. There was an interaction between treatment and group in which ipsilateral diameter increased (P &amp;lt; 0.05) in group 2 NR animals versus group 2 CON animals while there was no difference between NR and CON in group 1. There was no difference (P = 0.30) in total uterine artery blood flow in fetal weight, which averaged 212 ± 37 mL/min*kg in nutrient restricted versus 153 ± 34 mL/min*kg in control fed dams. In summary, these data indicate limited alterations in uterine artery blood flow and fetal weight in nutrient restricted dams during the last half of gestation. The decrease in placentome number with no difference in placentome weight could indicate larger placentomes in nutrient restricted dams were able to compensate for the reduction in total number.

Trophoblast-induced spiral artery remodelling and uteroplacental haemodynamics in pregnant rats with increased blood pressure induced by heme oxygenase inhibition

IntroductionThe aim of the present study was to determine the contribution of the heme oxygenase (HO) system to the adaptation of the uteroplacental circulation to pregnancy in the rat, and its relationship with the maintenance of blood pressure during late gestation. MethodsThe HO inhibitor, stannous mesoporphyrin (SnMP), or vehicle were administered intraperitoneally to virgin and midpregnant rats. Mean arterial pressure (MAP) was measured before and after the treatment, in the conscious rats. Uterine and radial arteries blood flow velocities were obtained from pregnant rats at days 14 and 19 of gestation using high frequency ultrasonography. Trophoblast invasion and spiral arteries remodelling were analyzed in the mesometrial triangle of pregnant rats by immunohistochemistry. ResultsHO activity inhibition during late gestation induced a significantly increase in the MAP of pregnant rats (114 ± 1 mmHg vs 100 ± 2 mmHg, p < 0.05) but it did not affect this parameter in virgin rats (121 ± 2 mmHg vs 124 ± 3 mmHg). MAP elevation was associated with marked (p < 0.05) decreases in the systolic and diastolic flow velocities in uterine and radial arteries, as compared with pregnant control rats. Furthermore, spiral arteries of pregnant rats treated with SnMP showed lower (p < 0.001) proportion of lumen circumference covered by trophoblast (21 ± 3%) and a higher (p < 0.05) proportion of vascular smooth muscle (33 ± 5%) than control pregnant rats (59 ± 5% and 16 ± 5%, respectively) DiscussionThese data indicate that HO system play an important role in the adaptation of the uteroplacental circulation to pregnancy and in the blood pressure regulation during late gestation.

Изменения маточно-плацентарной гемодинамики при кесаревом сечении и пути ее оптимизации

The objective: to examine the effects of spinal anesthesia (SA) in the mother and Central hemodynamics parameters blood in utero-placenta vascular circuit when childbirth women operation of caesarean section (CS), practicing techniques to optimize utero-placental hemodynamics. Materials and methods. In order to practice the technique of optimizing hemodynamics of the mother and uteroplacental vascular circuit during the MCA surgery, the CS performed a series of Doppler ultrasound studies in 34 women who underwent the MCA to anesthetize the planned operation, prior to the onset of uterine contractile activity. Blood flow parameters in the uterine arteries and umbilical arteries were evaluated. The measurements were performed using the apparatusPhilips HD 11XE. Results. It has been established that the SA in women with anesthetic, there is a problem quickly advancing and more expressed arterial hypotension, compared with patients’ gynecological operations. Justified and refined technique of optimization of hemodynamics of mother and utero-placental vascular path while carrying out operations by introducing the SA for CS mini-doses of oxytocin (0,1–0,5 units) at the beginning of the spinal anesthesia, which helped to improve the degree of anesthesia safety benefits to the mother and fetus. Conclusion. Use in pregnant women under the influence of spinal anesthesia, carried out with the aim of anesthesia of cesarean section, intravenous administration of oxytocin in a mini-dose (0.1–0.5 units) prevents the development of early and severe arterial hypotension by reducing the potential capacity of the uterine vascular bed and it does not have a negative impact on the state of the fetus. Key words: caesarean section, spinal anesthesia, hemodynamics.

The effect of maternal antidepressants on third trimester uteroplacental hemodynamics and the neonatal abstinence syndrome: a retrospective cohort study.

The objective of this study is to determine whether maternal antidepressant use during pregnancy influences uteroplacental hemodynamics, thereby affecting fetal growth and gestational age at delivery. The secondary aim was to determine the incidence of neonatal abstinence syndrome (NAS) among infants exposed to antidepressant medications. The charts of women who received obstetrical care and had a history of depression from January 2014 to December 2016 at Mount Sinai Hospital in Toronto, Canada, were reviewed. Exclusion criteria were substance abuse; narcotic or lithium use at the time of delivery.In total, 205 women met the inclusion criteria (92 took antidepressants; 113 women did not). There were no significant differences in umbilical artery pulsatility index (PI), gestational age at delivery, or birth weight when comparing women based on antidepressant use. A small proportion (18%) of neonates had mild withdrawal symptoms; one baby had a score (≥ 8) consistent with severe NAS. In women with a history of depression, there was no difference in uteroplacental hemodynamics as measured by third trimester Doppler ultrasonography when comparing women who took antidepressant medication versus those who did not. The large majority of babies who were exposed to antidepressants in utero did not show withdrawal symptoms. These results lend support for the relative safety of antidepressants during pregnancy.

Maternal high-fat diet reversal improves placental hemodynamics in a nonhuman primate model of diet-induced obesity.

BackgroundIn a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high fat, ‘Western-style’ diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development. Thus, the objective of the current study was to determine whether simple preconception diet reversal would improve placental function.MethodsFemale Japanese macaques were divided in to three groups: diet reversal animals (n=5) were switched from a chronic WSD (36% fat) to a low fat, control diet (14% fat) prior to conception and throughout pregnancy. The control (n=6) and WSD (n=6) cohorts were maintained on their respective diets throughout pregnancy. Maternal body weight and composition were regularly assessed and advanced non-invasive imaging was performed at mid-gestation (gestational day 90, G90 or 0.5 of gestation, where full term is G175), and G129, one day prior to C-section delivery at G130 (0.75 of gestation). Imaging studies comprised Doppler ultrasound (US), Contrast-Enhanced US (CEUS) and Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to assess uteroplacental hemodynamics and maternal-side placental perfusion.ResultsDietary intervention resulted in significant maternal weight loss prior to pregnancy, and improved lean to fat mass ratio. By advanced imaging we demonstrated that a chronic WSD led to decreased blood flow velocity in the intervillous space, delayed blood flow transfer through the maternal spiral arteries and reduced total placental blood flow compared to control fed animals. Dietary reversal ameliorated these concerning derangements, restoring these hemodynamic parameters to control levels.ConclusionPreconception dietary modification has beneficial effects on the maternal metabolic phenotype, and results in improved placental hemodynamics.

Trophoblast plugs: impact on utero-placental haemodynamics and spiral artery remodelling.

How does trophoblast plugging impact utero-placental haemodynamics? Physiological trophoblast plug structures are dense enough to restrict flow of oxygenated blood to the intervillous space (IVS) in the first trimester, and result in a shear stress environment upstream of the plugs that promotes spiral artery remodelling. Trophoblast plugging of the uterine spiral arteries is thought to be the dominant factor restricting the flow of oxygenated maternal blood to the placenta in the first trimester of pregnancy. However, the extent of plugging, the timing of plug break up, and the impact of plug structure on pregnancy outcomes is debated. A computational model of the uterine radial and spiral arteries, incorporating arteriovenous anastomoses was developed. The model was parameterized with our own histological data and previous literature descriptions of the dimensions of the spiral arteries, and the structural properties (porosity) of trophoblast plugs. Structural data were acquired from the literature, and supplemented by images of the spiral arteries acquired by standard thin-section 2D immunohistochemistry, and whole mount immunohistochemistry imaged in 3D by micro-CT. Computational models were solved using Matlab software, via custom written scripts. We confirm that physiological lengths (>0.1 mm) and porosities (0.2-0.6) of trophoblast plugs are sufficient to restrict the flow of oxygenated maternal blood flow to the placental surface. Trophoblast plugs also have important haemodynamic consequences upstream in the spiral arteries by generating shear stress conditions of <2 dyne/cm2 that promote trophoblast-induced spiral artery remodelling. Structural changes in plugs as they dislodge are likely to result in rapid increases in blood flow to the IVS, and it is likely at this stage of gestation that the major source of resistance in the utero-placental circulation transitions from the spiral arteries to the radial arteries, which then act as a the 'rate-limiting' step to IVS flow. Structural descriptions of the spiral arteries, radial arteries and trophoblast plugs largely rely on 2D histological sections, or historical measurements. Increased focus on quantitatively assessing the 3D structure of the uterine arteries using more modern imaging technologies in the future will strengthen model predictions. Our work suggests that trophoblast plugs play a previously under-appreciated role in regulating spiral artery remodelling in the first trimester of human pregnancy. This creates the possibility that inadequate trophoblast plugging in the first trimester may contribute to the inadequate artery remodelling observed in pregnancy pathologies such as pre-eclampsia. The incorporation of arteriovenous anastomoses in our model highlights the important influence that shunted blood can play in utero-placental haemodynamics, and together with the emerging role of radial arteries in regulating blood flow to the placenta, the influence of arteriovenous anastomoses on radial artery haemodynamics in normal and pathological pregnancies warrants further investigation. This research was supported by a Royal Society of New Zealand Marsden Fund award (13-UOA-032). A.R.C. is supported by a Royal Society of New Zealand Rutherford Discovery Fellowship (14-UOA-019). R.S. was supported by a Gravida (National Centre for Growth and Development) postgraduate scholarship. The authors have no conflicts of interest. N/A.

Understanding abnormal uterine artery Doppler waveforms: A novel computational model to explore potential causes within the utero-placental vasculature

IntroductionUterine artery (UtA) Doppler indices are one of the most commonly employed screening tests for pre-eclampsia worldwide. Abnormal indices appear to result from increased uterine vascular resistance, but anatomical complexity and lack of appropriate animal models mean that little is known about the relative contribution of each of the components of the uterine vasculature to the overall UtA Doppler waveform. Previous computational models suggested that trophoblast-mediated spiral artery remodeling has a dominant effect on the UtA Doppler waveform. However, these models did not incorporate the myometrial arterio-venous anastomoses, which have significant potential to affect utero-placental haemodynamics. MethodsWe present a more anatomically complete computational model, explicitly incorporating a structural description of each component of the uterine vasculature, and crucially including myometrial arterio-venous anastomoses as parallel pathways for blood-flow away from the placental bed. Wave transmission theory was applied to the network to predict UtA waveforms. ResultsOur model shows that high UtA resistance indices, combined with notching, reflect an abnormal remodeling of the entire uterine vasculature. Incomplete spiral artery remodeling alone is unlikely to cause abnormal UtA Doppler waveforms as increased resistance in these arteries can be ‘buffered’ by upstream anastomoses. Critically, our results indicate that the radial arteries, may have a more important effect on utero-placental flow dynamics, and the UtA Doppler waveform than previously thought. ConclusionsThis model suggests that to appropriately interpret UtA Doppler waveforms they must be considered to be reflecting changes in the entire system, rather than just the spiral arteries.