Uterine Artery Resistance Research Articles

Study of placental laterality with uterine artery Doppler in the prediction of preeclampsia

Objective To demonst rate if placental laterality combined with uterine artery Doppler can be used as a predictor for the development of preeclampsia. Background The uteroplacental blood flow may be deficient in cases with lateral placenta, and this may facilitate development of preeclampsia. Placenta is considered lateral when 75% or more of the placental mass is located at one side of the midline of uterine cavity. Uterine artery Doppler was done to all cases to find out high resistance index and abnormal protodiastolic notch in Doppler waveform. Patients and methods Ultrasonography was done for all participants at 18–22 weeks of pregnancy to determine the placenta location. Uterine artery Doppler was done for all cases at 18–24 weeks of gestation to find out the presence of protodiastolic notch and high resistance index. Results Of 73 cases with lateral placenta and high uterine artery resistance index, 56 (76.7%) cases developed preeclampsia (P = 0.026). Moreover, among 77 cases with lateral and presented protodiastolic notch, 57 (74%) cases developed preeclampsia (P = 0.050). Conclusion The risk of developing preeclampsia is significantly increased when lateral placentas are associated with uterine artery Doppler abnormality.

Ovarian and Uterine Blood Flow Indices in Patients with Unexplained Infertility Undergoing ICSI and their Relation to Clinical Pregnancy Rate

Background: Infertility is defined by the World Health Organisation (WHO) as a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and is estimated to affect as many as 48.5 million couples worldwide. Unexplained infertility (UI) constitutes an important portion of the infertility reasons (up to 30%) and is diagnosed when the causes of male or female infertility remains unknown.Aim: The aim of the study was to compare ovarian, uterine artery and subendometrial vessels resistance by measuring PI and RI of patients diagnosed as UI undergoing ICSI in the day of embryo transfer and control group diagnosed as fertile by having at least one livebirth in peri-implantation period from day 19 to day 21.Materials and Methods:The current study is a prospective case control study, which was conducted at the Assisted Reproduction Technology unit of Ain Shams University Maternity Hospital during the period from September 2017 to July 2019. The current study included two groups of patients one group is unexplained infertility attending the Assisted Reproduction Unit and the other is control fertile group each group consists of 51 women.Results: There was statistically significant difference between the unexplained infertility group and control fertile group as regard Uterine and subendometrial artery PI, RI and ovarian artery RI in which resistance indexes was significantly higher in the UI group than control group. The cut off values of PI, RI between unexplained infertility and fertile group are ≥1.88, ≥0.8 for Uterine artery, and ≥ 0.87, ≥0.53 for subendometrial arteries, and ≥ 0.59 for ovarian artery RI. Among the unexplained infertility undergoing ICSI patients the pregnancy rate is 23.5%. There was no statistically significant difference between the two groups (pregnant group and non-pregnant group) as regard the age, BMI, duration of infertility or the basal hormonal profile.Conclusion: Doppler parameters are useful tools to assess endometrial receptivity in unexplained infertility patients undergoing ICSI. This study found that Uterine, Ovarian, subendometrial arteries plasticity index (PI) and resistance index RI measured on the day of embryo transfer higher than fertile women and have value in judging endometrial receptivity and predict the final outcome of IVF/ ICSI- ET. Uterine, ovarian and subendometrial blood flow assessed by measuring PI, RI of these arteries was impaired in unexplained infertility patients compared to fertile women. Also, uterine arteries PI, ovarian and subendometrial arteries PI, RI differ in pregnancy outcome in unexplained infertility patients undergoing ICSI.

RELATIONSHIP BETWEEN TEMPORAL CHANGES OF ENDOMETRIAL BLOOD FLOW IMPEDANCE IN A NATURAL AND HORMONE REPLACEMENT CYCLE AND PREDICTION OF PREGNANCY DURING VITRIFIED-WARMED EMBRYO TRANSFER

Frozen-thawed embryo transfer (ET) is performed in a natural or hormone replacement therapy (HRT) cycle for endometrial preparations. However, how to determine which endometrial preparation method is suitable for the individual is unknown.This study was to examine the relationship between the temporal changes in endometrial blood flow impedance during natural and HRT cycles and clinical outcomes in vitrified-warmed ET. A single-center retrospective observational cohort study. This study was approved by the institutional review board of the Fukushima Medical University. This study included a total of 60 women, 28 with natural and 32 with HRT cycles, who underwent vitrified-warmed ET. Uterine radial artery resistance index (RA-RI) was measured during the natural and HRT cycles at the early follicular phase, days of the human chorionic gonadotropin trigger during a natural cycle or start of progesterone administration during the HRT cycle, and the day of ET. The association between the RA-RI at the different measurement point and the pregnancy were examined in the natural and HRT cycles by univariate analysis and multivariate logistic analysis. Receiver-operating characteristic analysis was used to determine the cut-off value of the RI with respect to pregnancy in natural and HRT cycles. The area under the curves (AUC) and their 95% confidence intervals (CI) were calculated. The clinical pregnancy rates of the natural and HRT cycles were 32.1% and 34.4%, respectively. In the univariate analysis, the RA-RI at the early follicular phase was significantly lower in the pregnant group than that in the non-pregnant group in the natural but not HRT cycle (P=0.04). In the multivariate logistic analysis, the RA-RI at the early follicular phase was an independent predictive factor for pregnancy in the natural but not HRT cycle (P=0.02). The odds ratio for pregnancy was 0.7 (95% CI, 0.52–0.95) when the levels of RA-RI at the early follicular phase was increased by 0.01 in the natural cycle. With the natural cycle, the area under the receiver-operating characteristic curves for the RA-RI at the early follicular phase with a threshold of 0.68 was 0.75 (95% CI, 0.57–0.93). The positive predictive and negative predictive values were 0.53 (95% CI, 0.37–0.59) and 0.92 (0.74–0.99), respectively. With the natural cycle, the RA-RI at the early follicular phase was associated with pregnancy, and this might have a potential in predicting pregnancy in vitrified-warmed ET cycles. Our findings suggest that RA-RI at the early follicular phase might be an effective and useful tool in choosing natural or HRT cycles for vitrified-warmed ET. This provides a clue to the individualization of the choice of an endometrial preparation method during the frozen-thawed ET.

Abstract P213: Placental Ischemia-Stimulated Natural Killer Cells Contribute To Hypertension, Vascular Dysfunction, And Intrauterine Growth Restriction In Pregnant Rats

The Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia mimics many characteristics of preeclampsia (PE) such as hypertension (HTN), intrauterine growth restriction (IUGR), and increased cytolytic natural killer cells (cNKs). We have previously shown that natural killer (NK) cell depletion in RUPP rats improves PE pathophysiology and that RUPP NKs have a 5-fold increase in cytotoxicity vs normal pregnant NKs. In this study, we tested the hypotheses that (1) RUPP stimulated NKs play a direct role in causing HTN and IUGR in pregnant rats and (2) normal pregnant control (Sham) NKs attenuate HTN and IUGR in RUPP rats. NKs were isolated from the placentas of Sham and RUPP rats on gestation day (GD) 19. On GD14, vehicle or 5x10 6 RUPP NKs were infused i.v. into a subset of Sham rats, and vehicle or 5x10 6 Sham NKs were infused i.v. into a subset of RUPP rats. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler Ultrasound; GD19, cNKs were quantified via flow cytometry and MAP, fetal weight, and blood were acquired. Plasma VEGF and sFlt-1 were measured via ELISA. Placental cNKs (% gated) increased from 3±1% in Sham to 19±5% in RUPP and 21±4% in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 3±1% in RUPP+Sham NK (p<0.05 vs RUPP). Circulating cNKs also followed this trend. MAP increased from 102±1 mmHg in Sham to 130±2 mmHg in RUPP and 121±2 mmHg in Sham+RUPP NK (p<0.05 vs Sham), and was blunted to 113±1 mmHg in RUPP+Sham NK (p<0.05 vs RUPP). Fetal weight decreased from 2.4±0.04 g in Sham to 2.1±0.07 g in RUPP and 2.1±0.03 g in Sham+RUPP NK (p<0.05 vs Sham), and this was normalized to 2.3±0.03 g in RUPP+Sham NK (p<0.05 vs RUPP). UARI increased from 0.56±0.05 in Sham to 0.75±0.06 in RUPP and 0.76±0.05 in Sham+RUPP NK (p<0.05 vs Sham), and decreased to 0.64±0.05 in RUPP+Sham NK (p<0.05 vs RUPP). Circulating sFlt-1 increased from 76±15 pg/mL in Sham to 1391±424 pg/mL in RUPP (p<0.05 vs Sham), 780±256 pg/mL in Sham+RUPP NK, and decreased to 67±8 pg/mL in RUPP+Sham NK (p<0.05 vs RUPP). Furthermore, circulating VEGF decreased in RUPP and Sham+RUPP NK compared to Sham (p<0.05), and increased in RUPP+Sham NK (p<0.05 vs RUPP). These data demonstrate a direct role for cNKs to mediate vascular dysfunction in PE and for normal NKs to promote positive maternal and fetal outcomes.

Abstract MP20: Prepartum 1,3-butanediol Treatment Improves Placental Perfusion In The Preeclamptic Dahl Salt-sensitive Rat

Chronic hypertension increases the risk of developing superimposed preeclampsia (PE). Previous reports showed that 1,3-Butanediol (BD) lowers blood pressure (BP) in male Dahl salt-sensitive (S) rats and female congenic S.SHR(11) rats which exhibit increased kidney injury over Dahl S rats. The goal of this study was to test if attenuating hypertension before pregnancy through the placentation period via BD prevents the onset of PE. Female Dahl S rats (a spontaneous model of superimposed PE, 11-16 weeks old) were divided into two groups: BD treated (20% via drinking water) and control (ad libitum water). Animals received BD for 7 weeks, baseline BP measurements (telemetry) were taken, and both groups were then mated. On gestation day (GD) 12, treatment was stopped because pilot studies showed that treatment reduced water intake during late pregnancy. Both groups were maintained on low-salt rodent chow (Teklad 7034, 0.3% NaCl; n=8/group). At GD18 (late pregnancy), uterine artery resistance index (UARI) was measured via Doppler ultrasound, 24h urine was collected on GD19, and tissues were harvested on GD20. Mean arterial pressure was lower in the treated group at baseline (141.9 ± 4.1 vs. 165.7 ± 4.5 mmHg, p= 0.008), early (135.9 ± 3.4 vs. 168.9 ± 4.6 mmHg, p= 0.0003), mid (142.0 ± 5.2 vs. 170.8 ± 4.61, p= 0.0048) but not late pregnancy (144.9 ± 5.9 vs. 161.9 ± 4.5 mmHg, p= 0.165). Late pregnancy maternal body weight was similar between groups (299.3 ± 5.6 vs. 311.3 ±7.0 g, p=0.201). Treated dams had a lower UARI (0.71 ± 0.02 vs. 0.81 ± 0.02, p=0.008) and less fetal resorptions (1.12 ± 0.29 vs. 2.25 ± 0.41, p= 0.043). No harm to the fetus was noted as no differences in pup weight (2.20 ±0.05 vs. 2.20 ± 0.09, p= 0.994) and pup length (30.19 ±0.24 vs. 29.45 ± 0.28 cm, p=0.072) were observed. Placentas from treated dams had decreased VEGF levels via ELISA (276.2 ± 33.4 vs. 498.9 ± 16.8 pg/mL, p= 0.001), suggesting reduced placental ischemia. In this study, we observed slightly improved placental perfusion and lower fetal demise following prepartum BD treatment; however, the antihypertensive effects of BD were not sustained through late pregnancy when supplementation was stopped at mid-pregnancy.

Abstract MP21: Suppression Of Reactive Oxygen Species Protects The Dahl Salt-sensitive Rat From Developing Maternal Syndrome

The Dahl Salt-Sensitive (SS) rat maintained on a low salt diet exhibits a differential response to pregnancy; approximately half develop maternal syndrome (hypertension and proteinuria) while the other half are protected. The exact mechanisms of maternal syndrome are unclear, but it is proposed that reactive oxygen species (ROS) are involved. Previous studies from our laboratory demonstrated the importance of NADPH oxidase (NOX) 2-derived ROS produced by immune cells in the development of salt-sensitive hypertension and renal disease. Given the role of NOX2-derived ROS in the Dahl SS rat, we tested the hypothesis that genetic deletion of the p67phox subunit of NOX2 (SS Ncf2-/- ) will result in the protection from developing maternal syndrome. To test this hypothesis, 8 week old female Dahl SS and SS Ncf2-/- were instrumented with radio-telemeters for continuous measurement of mean arterial pressure (MAP). After a recovery period, baseline MAP was measured as well as an overnight urine collection for markers of renal damage before females were mated with males of the same strain and age. Virgin litter-mate controls were run in parallel. As expected, MAP and protein excretion levels were comparable at baseline between virgin and mated SS Ncf2-/- rats. These parameters remained comparable at the late pregnancy time point (108±3 vs 112±1mmHg, 9±3 vs 16±5mg/day, p >0.05). In contrast to the SS preeclamptic pregnancy, the SS Ncf2-/- mated rats are protected from the development of maternal syndrome (141±8 vs 112±1mmHg, p <0.001; and 98±16 vs 16±5mg/day, p <0.001; in the SS vs SS Ncf2-/- , respectively). This protection is accompanied with a significant reduction in uterine artery resistance index which is a marker of impaired blood flow, in the SS Ncf2-/- (0.85±0.03 vs 0.59±0.02, p <0.01). Despite these phenotypic differences, the number of infiltrating immune cells into kidneys or placentas do not differ between these two groups. These results suggest that NOX2-derived ROS contribute to the pathogenesis of maternal syndrome in the Dahl SS rat, and further investigations are necessary to clarify the source of the ROS within key organs such as the kidney and placenta.

Abstract P218: Tumor Necrosis Factor Alpha Improves Placental Perfusion And Attenuates Intrauterine Growth Restriction In A Rodent Model Of Preeclampsia

Preeclampsia ( PE ) is not only detrimental to the mother and her fetus during pregnancy, but it is also associated with increased cardiovascular ( CV ) risk in the mother and her intrauterine growth restricted ( IUGR ) offspring in later life. Currently there are no known treatment options for PE beyond early delivery. Thus, there is a critical need to identify therapeutic treatments for PE. The inflammatory cytokine TNF-α is increased in women with PE. In the clinically relevant Reduced Uterine Perfusion Pressure ( RUPP ) model of PE in the rat, TNF-α is also increased and importantly, etanercept abolishes maternal hypertension. Etanercept is a soluble receptor that binds TNF-alpha to inhibit the inflammatory response. Although not yet prescribed for PE, etanercept is non-contraindicated during pregnancy. Therefore, this study tested the hypothesis that maternal administration of etanercept will mitigate IUGR in the RUPP model of PE and that improvement in fetal growth occurs in association with improved uteroplacental perfusion, placental morphology, and placental nutrient transporter protein expression. Sham or RUPP was performed at gestational day 14 ( G14 ). Dams were administered vehicle or the TNF-α inhibitor (etanercept, 0.4 mg/kg, s.c.) at G18. At G20 uterine artery resistance index ( UARI ) was significantly increased in vehicle RUPP (0.69±0.02 mm/s) vs. vehicle Sham (0.60±0.02mm/s)( p <0.05), indicative of reduced uteroplacental perfusion, but UARI was no longer increased in treated RUPP (0.65±0.03 mm/s)( p <0.05). At G20, fetal weight was significantly reduced in vehicle RUPP (3.52g±0.10) vs. vehicle Sham (3.82 g±0.09)( p <0.05). Yet, fetal weight was significantly increased in treated RUPP (3.82g±0.12) vs. vehicle RUPP ( p <0.05). Fetal brain weight did not differ in Sham or RUPP, regardless of maternal treatment. However, fetal liver weight was significantly increased in treated RUPP (0.29g ±0.02) vs. vehicle RUPP (0.24g±0.01)( p <0.05) suggesting attenuation of asymmetric growth restriction. These findings indicate that maternal administration of a TNF-α inhibitor during PE improves fetal growth in association with improved uteroplacental blood flow. Future studies are warranted to investigate the long-term benefit in IUGR offspring.

Contrast-Enhanced Ultrasound in Cystic Endometrial Hyperplasia-Pyometra Complex in the Bitch: A Preliminary Study.

Simple SummaryIn canine cystic endometrial hyperplasia–pyometra (CEH) syndrome, toxic factors and endometrial inflammatory reactions are responsible of increased blood flow and lower vascular resistance in uterine arteries. Color Doppler ultrasound is regarded as an adjunctive tool for quantitative assessment of endometrial vascularization during uterine disorders. The aim of this study was to assess, through contrast-enhanced ultrasound (CEUS) exam, the vascularization in endometrial microvessels in CEH-pyometra in order to evaluate the possibility of application in this syndrome. In twelve female dogs with clinical symptoms related to pyometra, echographic, Color Doppler and CEUS exams were performed. Histopathological examination revealed severe CEH and pyometra, immunohistochemical stain with CD 34 confirmed the presence of angiogenesis. CEUS exam revealed a widespread, intense and rapidly developing homogeneous enhancement of the hyperplastic endometrium with absence of signal only in cystic areas. All parameters of the quantitative analysis were not significantly influenced by region of interest dimension and position. CEUS may improve not invasive evaluations in the CEH-pyometra syndrome and virtually in CEH-mucometra.In cystic endometrial hyperplasia (CEH)–pyometra syndrome, toxic factors and endometrial remodeling culminate in changes characterized by exudative and degenerative inflammatory reaction. Recent studies on hemodynamic found an increased blood flow and lower vascular resistance in uterine arteries, suggesting color Doppler ultrasound as an adjunctive tool for quantitative assessment of endometrial vascularization during pyometra. The aim of this study was to assess, through contrast-enhanced ultrasound (CEUS) exam, the vascularization in endometrial microvessels in CEH-pyometra in order to evaluate the possibility of application in this syndrome. In twelve female dogs with clinical symptoms related to pyometra, B-mode, color Doppler and CEUS exams were performed. In CEH-pyometra uteri, histopathological examination revealed severe CEH and pyometra, immunohistochemical stain with CD 34 confirmed the presence of angiogenesis. CEUS exams revealed a widespread, intense and rapidly developing homogeneous enhancement of the hyperplastic endometrium, with absence of signal only in cystic areas. All parameters of the quantitative analysis were not significantly influenced by region of interest dimension and position. CEUS has the potential to improve clinical not invasive evaluations in the CEH-pyometra syndrome and virtually in CEH-mucometra.

Maternal folate, one-carbon metabolism and pregnancy outcomes.

Single nucleotide polymorphisms and pre‐ and peri‐conception folic acid (FA) supplementation and dietary data were used to identify one‐carbon metabolic factors associated with pregnancy outcomes in 3196 nulliparous women. In 325 participants, we also measured circulating folate, vitamin B12 and homocysteine. Pregnancy outcomes included preeclampsia (PE), gestational hypertension (GHT), small for gestational age (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM). Study findings show that maternal genotype MTHFR A1298C(CC) was associated with increased risk for PE, whereas TCN2 C766G(GG) had a reduced risk for sPTB. Paternal MTHFR A1298C(CC) and MTHFD1 G1958A(AA) genotypes were associated with reduced risk for sPTB, whereas MTHFR C677T(CT) genotype had an increased risk for GHT. FA supplementation was associated with higher serum folate and vitamin B12 concentrations, reduced uterine artery resistance index and increased birth weight. Women who supplemented with <800 μg daily FA at 15‐week gestation had a higher incidence of PE (10.3%) compared with women who did not supplement (6.1%) or who supplemented with ≥800 μg (5.4%) (P < .0001). Higher serum folate levels were found in women who later developed GDM compared with women with uncomplicated pregnancies (Mean ± SD: 37.6 ± 8 nmol L−1 vs. 31.9 ± 11.2, P = .007). Fast food consumption was associated with increased risk for developing GDM, whereas low consumption of green leafy vegetables and fruit were independent risk factors for SGA and GDM and sPTB and SGA, respectively. In conclusion, maternal and paternal genotypes, together with maternal circulating folate and homocysteine concentrations, and pre‐ and early‐pregnancy dietary factors, are independent risk factors for pregnancy complications.

Predictive Value of both Serum Placental protein 13 Level and Uterine Artery Doppler for Prediction of Pre-Eclampsia

Background: Preeclampsia [PE] is one of the commonest medical emergencies. It had high morbidity for the mother and her infant. Early diagnosis could reduce such morbidity. Aim of the work: To evaluate the role of maternal serum placental protein [PP13] levels and uterine artery Doppler in early prediction and prognosis of preeclampsia.Patients and Methods: The study included 60 pregnant women in their first and early second trimester with high risk for preeclampsia. Patients were divided into three groups: control, mild and sever preeclampsia. All were subjected to proper history taking, clinical and obstetrical examination, laboratory investigations and ultrasound examination.Results: Cesarean delivery was significantly increased in preeclampsia compared to controls [55% of mild and 20% of severe disease compared to 15% of controls]. Both uterine artery resistance index [RI] and pulsatility index [PI] were significantly increased in PE when compared to control and in severe when compared to mild PE groups. Finally, PP13 was significantly decreased in patients with severe PE [171.7±35.9] when compared to mild PE [213.1±41.8] or control group [254.8±51.1]. In addition, there was significant decrease in cases with mild PE when compared to control group. Finally, there was inverse [negative], moderate and statistically significant correlation between PP-13 from one side and each of systolic BP, diastolic BP, uterine artery RI and PI. In addition, both RI and PI were proportionally correlated with PI and RI.Conclusion: The present study showed that PP13 combined with PI or RI can predict PE with a good sensitivity and specificity.

Associations of maternal age at the start of pregnancy with placental function throughout pregnancy: The Generation R Study

ObjectiveTo examine the associations of maternal age at the start of pregnancy across the full range with second and third trimester uterine and umbilical artery flow indices, and placental weight. Study designIn a population-based prospective cohort study among 8271 pregnant women, we measured second and third trimester uterine artery resistance and umbilical artery pulsatility indices and the presence of third trimester uterine artery notching using Doppler ultrasound. ResultsCompared to women aged 25−29.9 years, higher maternal age was associated with a higher third trimester uterine artery resistance index (difference for women 30−34.9 years was 0.10 SD (95% Confidence Interval (CI) 0.02 to 0.17), and for women aged ≥40 years 0.33 SD (95% CI 0.08 to 0.57), overall linear trend 0.02 SD (95% CI 0.01 to 0.03) per year). Compared to women aged 25−29.9 years, women younger than 20 years had an increased risk of third trimester uterine artery notching (Odds Ratio (OR) 1.97 (95% CI 1.30–3.00)). A linear trend was present with a decrease in risk of third trimester uterine artery notching per year increase in maternal age (OR 0.96 (95% CI 0.94 to 0.98)). Maternal age was not consistently associated with umbilical artery pulsatility indices or placental weight. ConclusionsYoung maternal age is associated with higher risk of third trimester uterine artery notching, whereas advanced maternal age is associated with a higher third trimester uterine artery resistance index, which may predispose to an increased risk of pregnancy complications.

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.

Population screening for gestational hypertensive disorders using maternal, fetal and placental characteristics: A population-based prospective cohort study.

ObjectiveTo determine screening performance of maternal, fetal and placental characteristics for selecting pregnancies at risk of gestational hypertension and preeclampsia in a low‐risk multi‐ethnic population.MethodIn a prospective population‐based cohort among 7124 pregnant women, we collected maternal characteristics including body mass index, ethnicity, parity, smoking and blood pressure in early‐pregnancy. Fetal characteristics included second and third trimester estimated fetal weight and sex determined by ultrasound. Placental characteristics included first and second trimester placental growth factor concentrations and second and third trimester uterine artery resistance indices.ResultsMaternal characteristics provided the best screening result for gestational hypertension (area‐under‐the‐curve [AUC] 0.79 [95% Confidence interval {CI} 0.76‐0.81]) with 40% sensitivity at 90% specificity. For preeclampsia, the maternal characteristics model led to a screening performance of AUC 0.74 (95% CI 0.70‐0.78) with 33% sensitivity at 90% specificity. Addition of second and third trimester placental ultrasound characteristics only improved screening performance for preeclampsia (AUC 0.78 [95% CI 0.75‐0.82], with 48% sensitivity at 90% specificity).ConclusionRoutinely measured maternal characteristics, known at the start of pregnancy, can be used in screening for pregnancies at risk of gestational hypertension or preeclampsia within a low‐risk multi‐ethnic population. Addition of combined second and third trimester placental ultrasound characteristics only improved screening for preeclampsia.

Maternal thyroid function with placental hemodynamics and their effect on fetal and maternal outcomes

Objectives To evaluate the relationship between maternal mild fluctuation in thyroid hormones not amounting to hypothyroidism or hyperthyroidism and altered fetoplacental hemodynamic changes allowing early detection of adverse maternal and perinatal outcomes. Background Suboptimal placental function is associated with preeclampsia and intrauterine growth restriction. Studies suggested that thyroid hormones play a role in placental development through the effects on trophoblastic invasion. Patients and methods A prospective cohort study, included 123 healthy pregnant women recruited from the antenatal care in Obstetrics and Gynecology Department, at Menoufia University Hospital and Damas Central Hospital, from October 2018 till August 2019. Free thyroxine (FT4) concentrations and thyroid-stimulating hormone were measured in early pregnancy (at 9 and 18 weeks). Placental function was measured by Doppler ultrasound measuring umbilical artery pulsatility index and uterine artery resistance index (between 18–23 and 28–32 gestational weeks). Results The data of 123 patients were analyzed. Increased FT4 concentration in early pregnancy was associated with higher vascular resistance in the second and third trimesters in both umbilical artery pulsatility index and uterine artery resistance index. These effects on placental function may demonstrate the association of FT4 with pregnancy outcomes, such as preeclampsia and birth weight. Conclusion The data shows that increased) FT4 concentration in early pregnancy is associated with placental vascular function during the second and third trimesters. Other pregnancy-associated complications are preeclampsia and low birth weight.

Soluble Guanylate Cyclase in a Rodent Model of Preeclampsia: Is Benefit in the Mother Associated with Benefit in the Offspring?

The initiating event in preeclampsia (PE) involves improper placental remodeling, placental ischemia, maternal hypertension and asymmetric intrauterine growth restriction (IUGR). IUGR offspring have increased risk for chronic disease such as hypertension and cardiovascular disease. Currently, the only treatment option for PE is delivery of the baby and placenta. Therefore, identifying maternal therapies for treatment for PE that do not inflict harm on the developing fetus are crucial. Nitric oxide (NO) is reduced in PE resulting in reduced blood flow and increased maternal blood pressure. Soluble guanylate cyclase (sGC) inducers, a component of the NO pathway, reduce maternal blood pressure and improve reduced fetal weight in a rodent model of PE induced by reduced uterine perfusion pressure (RUPP). However, the long‐term benefit or harm in the offspring is unknown. Thus, this study tested the hypothesis that maternal treatment with a sGC inducer will improve uterine blood flow and placental nutrient transport resulting in improvement in asymmetric growth restriction in the RUPP model of PE. Sham or RUPP was performed at day 14 of gestation followed by administration of vehicle or a sGC inducer (riociguat, 10mg/kg/day, s.c.) until gestation day 20 (G20) or birth. At G20 uterine artery resistance index (UARI) was significantly increased, indicative of poor placental perfusion, in vehicle‐treated RUPP (0.64±0.01 mm/s) vs. vehicle‐treated Sham (0.57±0.01 mm/s) (p&lt;0.05), but was also increased in sGC‐treated Sham (0.64±0.01 mm/s) vs. vehicle‐treated Sham (p&lt;0.05). Placental nutrient transporter heart fatty acid binding protein (hFABP) protein expression was also significantly increased in vehicle‐treated RUPP (821.5±55.6 A.U.) vs. vehicle‐treated Sham (588.8±30.4 A.U.) (p&lt;0.05). Yet, placental hFABP protein expression was also significantly increased in sGC‐treated Sham (814.7±77.4 A.U.)(p&lt;0.05); up‐regulation that may be a compensatory mechanism to maintain normal brain development. Although an increase in gestational length in women with risk of PE‐associated preterm delivery is beneficial, gestational length at birth was significantly lengthened in full‐term sGC‐treated RUPP, an increase of 24 hours vs. vehicle‐treated Sham. Asymmetric growth at birth was not abolished and treatment in the RUPP was associated with a significant decrease in survival at birth (26.3%±6.5 survival rate versus 62.3%±10.0 survival rate, sGC‐treated RUPP vs. vehicle‐treated Sham; p&lt;0.05). Pup weight at birth was not asymmetric but was reduced in sGC‐treated Sham (5.3±0.2 grams) vs. vehicle‐treated Sham (5.9±0.2 grams) (p&lt;0.05). Thus, these findings indicate that maternal interventions using sGC inducers during PE may not provide benefit to the developing fetus despite improvement in maternal blood pressure implicating caution in the translation of this agent to the clinical setting. Future studies will investigate the long‐term effect of this maternal therapeutic on cardiovascular risk in the offspring born to Sham and RUPP dams.Support or Funding InformationHL143459, P20GM121334, P20GM104357, HL51971, T32HL105324

RETRACTED: Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: A randomized controlled trial from Shanghai, China

ObjectivesTo evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia. Study designThis prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy. Main outcome measures: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered. ResultsLow-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058–1.867; P = 0.019). ConclusionLow-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy.

Sodium Thiosulfate in the Pregnant Dahl Salt-Sensitive Rat, a Model of Preeclampsia.

Aberrant production of hydrogen sulfide (H2S) has been linked to preeclampsia. We hypothesized that sodium thiosulfate (STS), a H2S donor, reduces hypertension and proteinuria, and diminishes fetal growth restriction in the Dahl salt-sensitive (S) rat, a spontaneous model of superimposed preeclampsia. In addition to a control group (n = 13), two groups received STS via drinking water at a dose of 2 g (n = 9) or 3 g per kg body weight per day (n = 8) from gestational day (GD) 10 to 20. Uterine artery resistance index was measured (GD18), urinary protein excretion rate was determined (GD19), and blood pressure and fetal outcomes were evaluated (GD20). At 2 g, STS had no effect on preeclamptic symptoms or fetal outcome. At 3 g, STS reduced maternal hypertension (121.8 ± 3.0 vs. 136.3 ± 2.9), but increased proteinuria (89 ± 15 vs. 56 ± 5 mg/24 h), and relative kidney weight (0.86 ± 0.04 vs. 0.73 ± 0.02%). Fetal/placental weight ratio was reduced (3.83 ± 0.07 vs. 4.31 ± 0.08) without affecting litter size. No differences in uterine artery flow or renal histological damage were noted across treatment groups. While these data suggest a promising antihypertensive effect that could imply prolongation of preeclamptic pregnancies, the unfavorable effects on proteinuria, kidney weight, and fetal/placental weight ratio implies that clinical implementation of STS is contra-indicated until safety for mother and child can be verified.

Evidence for uteroplacental malperfusion in fetuses with major congenital heart defects.

AimsFetuses affected by congenital heart defects (CHD) are considered to be at increased risk of fetal growth restriction and intrauterine demise. Whether these risks are a direct consequence of fetal CHD or a result of associated uteroplacental dysfunction is not evident from the data of recent studies. The aim of this study was to investigate the prevalence of uteroplacental dysfunction reflected by abnormal uterine artery Doppler indices and reduced fetal growth in CHD pregnancies.MethodsThis is a retrospective case-control study including singleton pregnancies referred for detailed fetal cardiac assessment subsequently diagnosed with or without CHD. Mid-trimester uterine artery Doppler assessment at 20–24 weeks as well as third trimester fetal biometry and arterial Doppler pulsatility indices (PI) were performed. All fetal biometry were converted into centiles and Doppler values to multiples of median (MoM) to adjust for physiological changes with gestation.ResultsThe study included 811 pregnancies including 153 cases where the fetus was diagnosed with CHD. Mid-pregnancy uterine artery PI was significantly higher in women with fetal CHD compared to controls (0.90MoM vs 0.83MoM; p = 0.006). In the third trimester, median centiles for fetal head circumference (45.4 vs 57.07; p<0.001), abdominal circumference (51.17 vs 55.71; p = 0.014), estimated fetal weight (33.6 vs 56.7; p<0.001) and cerebroplacental ratio (CPR: 0.84MoM vs 0.95MoM; p<0.001) were significantly lower in fetuses with CHD compared to controls. The percentage of small for gestational age births <10th centile (24.0% vs 10.7%; <0.001) and low CPR <0.6MoM (11.7% vs 2.5%; p<0.001) were significantly higher in the fetal CHD cohort.ConclusionsMid-pregnancy uterine artery resistance is increased and subsequent fetal biometry reduced in pregnancies with CHD fetuses. These findings suggest that fetal CHD are associated with uteroplacental dysfunction, secondary to impaired maternal uteroplacental perfusion resulting in relative fetal hypoxaemia and reduced fetal growth.

The Effects of Prenatal Exposure to Marijuana on Early Childhood Development: A Systematic Literature Review

To assess the effect of prenatal marijuana exposure (PME) on the newborn, infant and early childhood development through review of current literature. A systematic literature review was conducted in the electronic database from 1996 to 2017 for the effects of PME and their fetal and early childhood outcomes. 7% of pregnant women self-reported using marijuana in the last year, while 16% of them reported near-daily use. Marijuana use has been reported to: a) interfere with normal placentation leading to miscarriage, preeclampsia and preterm labor through imbalance in Cannabinoid receptor type 1 (CBR1) stimulation; b) could lead to reduction of fetal growth and head circumference due to increased plasticity and resistance of uterine artery; c) be associated with impaired memory function, decreased verbal scores, increased aggression and hyperactivity, impaired abstract and visual reasoning; and d) could alter sleep patterns. Finally, there is no consensus regarding the effects of marijuana through breastfeeding exposure and no postpartum withdrawal effects in the newborn were reported. Research on the effects of PME on offspring has been limited by several confounding factors including self-reporting bias, concomitant use of other illicit drugs and psychosocial factors. Overall, PME may lead to negative consequences on the developing offspring. Public health messages to health care providers and pregnant women regarding the harmfulness of PME should become a high priority. Further research is needed to reinforce the existing data and examine additional potential negative effects on the developing child.

Predictive Factors of Response to Selective Progesterone Receptor Modulator (Ulipristal Acetate) in the Pharmacological Treatment of Uterine Fibroids.

Background: Selective progesterone receptor modulator ulipristal acetate (UPA) is a drug used in management of symptomatic myomas. It was observed that the response to UPA treatment in uterine myomas varied amongst patients. An attempt was thus made at establishing predictive factors conducive to better reaction to treatment with UPA. The aim of this study was to assess the efficacy of UPA treatment in women with myomas, depending on pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Materials and methods: The study included patients with one to four myomas. The UPA treatment was a preparation stage for surgical treatment in all patients. The study group was divided into the subgroups according to pretreatment myomas’ volume, number of myomas, age of patients, estrogenic status of women, and pretreatment blood flow in uterine arteries. Results: A better effect of reduction in size of myomas after UPA treatment was noted when pretreatment myomas’ volume was lower than 30 cm3. A significant reduction in fibroids’ size was observed after UPA therapy independently of the number of myomas and age of patients. A good response after the UPA therapy was observed when pretreatment estradiol concentration was below 50 pg/mL and when uterine artery resistance index (RI) was above 0.8. Conclusions: Our research demonstrates that treatment with ulipristal acetate is an efficient method in preoperative preparation of patients with uterine fibroids. The most important factor of positive response to UPA therapy is myoma volume. The number of myomas and patient’s age do not interfere with effects of UPA therapy. Pretreatment estradiol concentration is significant, yet secondary for the effects of therapy. The UPA therapy has no impact on blood flow in the uterine arteries and no adverse influence on estradiol concentrations.