The role of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in patients with pregnancy-induced hypertension.

OBJECTIVES: To examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH). STUDY DESIGN: This prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated. MAIN OUTCOME MEASURE: The role of CPUR in predicting CAPO in preeclampsia and gestational hypertension. RESULTS: The CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001). CONCLUSION: CPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH.

Comparative study of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea. / ä¸åŒå‰‚é‡éº¦ç²’ç¸å¯¹å¯’æ¹¿å‡æ»žåž‹åŽŸå‘æ€§ç—›ç»æ‚£è€ å­å®«åŠ¨è„‰è¡€æµå½±å“çš„æ¯”è¾ƒç ”ç©¶.

OBJECTIVES: To observe the differences in the effects of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea (PD). METHODS: A total of 60 patients with PD were randomly divided into 3 groups with 20 cases in each group. Acupoints Sanyinjiao (SP6), Diji (SP8) and Xuehai (SP10) were selected in all the 3 groups, and different dosages of grain-sized moxibustion were used (3 moxa cones, 6 moxa cones, 9 moxa cones) respectively. Treatment started 7 days before menstruation for 3 times, lasting for a total of 3 menstrual cycles. The values of uterine artery blood flow parameters including pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded before and after treatment. The visual analog scale (VAS) score and cox menstrual symptom scale (CMSS) score (including severity ［CMSS-S］ and time of duration ［CMSS-T］) were evaluated before treatment, at the end of each menstrual cycle, and one menstrual cycle after treatment. RESULTS: The values of uterine artery blood flow parameters (PI, RI, S/D) after treatment in the 9 moxa cones group were lower than those before treatment, as well as lower than those in the 3 and 6 moxa cones groups after treatment (P<0.05). The VAS scores of the 3 moxa cones group were lower than those before treatment in the first and second cycle (P<0.05). The VAS scores of the 6 and 9 moxa cones groups were lower than those before treatment at each observation point (P<0.05), and were lower than those of the 3 moxa cones group in the third cycle of treatment and follow-up period (P<0.05). And the VAS score of the 9 moxa cones group was lower than that of the 6 moxa cones group during the follow-up period (P<0.05). Compared with the scores before treatment, the CMSS-T scores at each observation point after treatment were lower in the 9 moxa cones group (P<0.05)；the CMSS-T scores in the second and third cycle after treatment, and follow-up period were lower in the 6 moxa cones group (P<0.05), with the CMSS-S scores in the second and third cycle after treatment, and follow-up period lower in the 6 and 9 moxa cones groups (P<0.05). The CMSS-T and CMSS-S scores of the 6 and 9 moxa cones groups were lower than those of the 3 moxa cones group in the third cycle and follow-up period (P<0.05). The CMSS-T and CMSS-S scores of the 9 moxa cones group were lower than those of the 6 moxa cones group during the follow-up period (P<0.05). CONCLUSIONS: Grain-Sized moxibustion has dose-effect relationship in the treatment of PD. Compared with 3 and 6 moxa cones groups, 9 moxa cones group has advantages in improving uterine artery blood flow parameters and alleviating dysmenorrhea symptoms in PD patients.

Maternal vascular indices at 36 weeks' gestation in pregnancy with small or growth-restricted fetus.

OBJECTIVE: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10th percentile. FGR was diagnosed if, in addition to birth weight < 10th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95th percentile or fetal middle cerebral artery PI was < 5th percentile. RESULTS: Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower. CONCLUSIONS: SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Adverse perinatal outcomes are strongly associated with degree of abnormality in uterine artery Doppler pulsatility index.

OBJECTIVE: To investigate the association between varying degrees of abnormality in the Doppler uterine artery pulsatility index (UtA-PI) and adverse perinatal outcome. METHODS: This was a prospective study of women with a singleton, non-anomalous pregnancy in whom UtA-PI was measured universally in midpregnancy and who gave birth in Oxford University Hospitals, Oxford, UK, between 2016 and 2023. Relative risk ratios (RRR) for the primary outcomes of extended perinatal mortality and live birth with a severe small-for-gestational-age (SGA) neonate were calculated using multinomial logistic regression, for early preterm birth (before 34 + 0 weeks' gestation) and late preterm/term birth (at or after 34 + 0 weeks). Risks were also investigated for iatrogenic preterm birth and a composite adverse outcome before 34 + 0 weeks. RESULTS: Overall, 33 364 pregnancies were included in the analysis. Compared to those with a normal UtA-PI, the risk of extended perinatal mortality with delivery before 34 + 0 weeks was higher in women with UtA-PI ≥ 90th percentile (RRR, 4.7 (95% CI, 2.7-8.0); P < 0.001), but this was not demonstrated in births at or after 34 + 0 weeks. The risk of live birth with severe SGA was associated strongly with abnormal UtA-PI for early births (RRR, 26.0 (95% CI, 11.6-58.2); P < 0.001) and later births (RRR, 2.3 (95% CI, 1.8-2.9); P < 0.001). Women with raised UtA-PI were more likely to have an early iatrogenic birth (RRR, 7.8 (95% CI, 5.5-11.2); P < 0.001). For each outcome before 34 + 0 weeks and the composite outcome, the risk increased significantly in association with the degree of abnormality in the UtA-PI (from < 90th, 90-94th, 95-98th to ≥ 99th percentile) (Ptrend < 0.001). When using the 90th percentile as opposed to the 95th, there was a significant improvement in the overall predictive accuracy (as determined by the area under the receiver-operating-characteristics curve) for the composite adverse outcome (χ2 = 6.64, P = 0.01) and iatrogenic preterm birth (χ2 = 4.10, P = 0.04). CONCLUSIONS: Elevated UtA-PI is a key predictor of iatrogenic preterm birth, severe SGA and perinatal loss up to 34 + 0 weeks' gestation. The 90th percentile for UtA-PI should be used, and management should be tailored according to the degree of abnormality, as pregnancies with very raised UtA-PI measurement constitute a group at extreme risk of adverse outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A new Doppler index, cerebro-placental-uterine ratio, and fetal cardiac parameters in early onset preeclampsia.

OBJECTIVE: Our aim was to investigate the significance of cerebro-placento-uterine ratio CPUR, a new Doppler index, and fetal cardiac parameters (Mod MPI, EFT) in early-onset preeclampsia (EOPE) and to examine whether these parameters are related to perinatal outcome. STUDY DESIGN: Forty participants diagnosed with EOPE (preeclampsia cases diagnosed before 34 weeks of gestation) and 40 healthy pregnant women were included in this study. Demographic data were recorded. Doppler parameters such as middle cerebral artery (MCA), umbilical artery (UA), and uterine artery (Ut-A), and left modified myocardial performance index (Mod-MPI) and epicardial fat thickness (EFT) were measured. Cerebroplacental ratio (CPR) was determined by dividing MCA pulsatility index (PI) by UA PI. CPUR was calculated as the ratio of CPR to mean UtA-PI (CPUR = CPR/UtA-PI). All parameters were compared between the EOPE and control groups. Correlation tests were used to examine the relationship between Doppler parameters and perinatal outcome. p values less than 0.05 were considered statistically significant. RESULTS: The pulsatility index of the middle cerebellar artery, CPUR and CPR values were statistically lower in the EOPE group than in the control group (p = 0.002; p = <0.001; p = <0.001; respectively). No statistical differences were found between groups for isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), ejection time (ET), left mod-MPI, EFT (p = 0.117; p = 0.093; p = 0.398; p = 0.882; p = 0.202, respectively). Umbilical artery Doppler pulsatility index (PI), mean uterine artery Doppler pulsatility index (PI), were higher in the EOPE group than in the control group (p = 0.006; and p = <0.001, respectively). The CPUR value for predicting EOPE was ≤1.3652 with 74. 4% sensitivity and 94.9% specificity. Positive correlations were found between CPUR, CPR, and some neonatal parameters. CONCLUSION: CPUR, a new index combining fetal and uterine Doppler indices, may add contribution to predict adverse perinatal outcome and EOPE.

Persistence of abnormal uterine artery flow postpartum: Case-control study.

Cohort study of singleton pregnancies with risk factors for placental insufficiency, managed at St. Michael's Hospital in Toronto, Canada. Patients undergone UA Doppler assessment at 18-22 weeks' gestation and 6 weeks postpartum. 15 pregnancies complicated by preeclampsia or intrauterine growth restriction (IUGR) (cases) were compared to 17 unaffected pregnancies (controls). Cases with preeclampsia and/or IUGR had higher UA PI at 18-22 weeks than controls. By 6 weeks' postpartum, the corresponding mean values were 2.60 and 2.14 (p = 0.20). This preliminary study suggests a potential different trajectory for physiologic recovery of UA flow after a pregnancy affected by placental insufficiency.

Value of Ultrasonic Image Features in Diagnosis of Perinatal Outcomes of Severe Preeclampsia on account of Deep Learning Algorithm.

This study is aimed at discussing the value of ultrasonic image features in diagnosis of perinatal outcomes of severe preeclampsia on account of deep learning algorithm. 140 pregnant women singleton with severe preeclampsia were selected as the observation group. At the same time, 140 normal singleton pregnant women were selected as the control group. The hemodynamic indexes were detected by color Doppler ultrasound. The CNN algorithm was used to classify ultrasound images of two groups of pregnant women. The differential scanning calorimetry (DSC), mean pixel accuracy (MPA), and mean intersection of union (MIOU) values of CNN algorithm were 0.9410, 0.9228, and 0.8968, respectively. Accuracy, precision, recall, and F1-score were 93.44%, 95.13%, 95.09%, and 94.87%, respectively. The differences were statistically significant (P < 0.05). Compared with the normal control group, the umbilical artery (UA), uterine artery-systolic/diastolic (UTA-S/D), uterine artery (UTA), and digital video (DV) of pregnant women in the observation group were remarkably increased; the minimum alveolar effective concentration (MCA) of the observation group was obviously lower than the MCA of the control group, and the differences between groups were statistically valid (P < 0.05). Logistic regression analysis showed that UA-S/D, UA-resistance index (UA-RI), UTA-S/D, UTA-pulsatility index (UTA-PI), DV-peak velocity index for veins (DV-PVIV), and MCA-S/D were independent risk factors for the outcome of perinatal children with severe preeclampsia. In the perinatal management of severe epilepsy, the combination of the above blood flow indexes to select the appropriate delivery time had positive significance to improve the pregnancy outcome and reduce the perinatal mortality.

Maternal Nanomaterial Inhalation Exposure: Critical Gestational Period in the Uterine Microcirculation is Angiotensin II Dependent.

Maternal inhalation exposure to engineered nanomaterials (ENM) has been associated with microvascular dysfunction and adverse cardiovascular responses. Pregnancy requires coordinated vascular adaptation and growth that are imperative for survival. Key events in pregnancy hallmark distinct periods of gestation such as implantation, spiral artery remodeling, placentation, and trophoblast invasion. Angiotensin II (Ang II) is a critical vasoactive mediator responsible for adaptations and is implicated in the pathology of preeclampsia. If perturbations occur during gestation, such as those caused by ENM inhalation exposure, then maternal-fetal health consequences may occur. Our study aimed to identify the period of gestation in which maternal microvascular functional and fetal health are most vulnerable. Additionally, we wanted to determine if Ang II sensitivity and receptor density is altered due to exposure. Dams were exposed to ENM aerosols (nano-titanium dioxide) during three gestational windows: early (EE, gestational day (GD) 2-6), mid (ME, GD 8-12) or late (LE, GD 15-19). Within the EE group dry pup mass decreased by 16.3% and uterine radial artery wall to lumen ratio (WLR) increased by 25.9%. Uterine radial artery response to Ang II sensitivity increased by 40.5% in the EE group. Ang II receptor density was altered in the EE and LE group with decreased levels of AT2R. We conclude that early gestational maternal inhalation exposures resulted in altered vascular anatomy and physiology. Exposure during this time-period results in altered vascular reactivity and changes to uterine radial artery WLR, leading to decreased perfusion to the fetus and resulting in lower pup mass.

Development and validation of model for prediction of placental dysfunction-related stillbirth from maternal factors, fetal weight and uterine artery Doppler at mid-gestation.

OBJECTIVE: To examine the performance of a model combining maternal risk factors, uterine artery pulsatility index (UtA-PI) and estimated fetal weight (EFW) at 19-24 weeks' gestation, for predicting all antepartum stillbirths and those due to impaired placentation, in a training dataset used for development of the model and in a validation dataset. METHODS: The data for this study were derived from prospective screening for adverse obstetric outcome in women with singleton pregnancy attending for routine pregnancy care at 19 + 0 to 24 + 6 weeks' gestation. The study population was divided into a training dataset used to develop prediction models for placental dysfunction-related antepartum stillbirth and a validation dataset to which the models were then applied. Multivariable logistic regression analysis was used to develop a model based on a combination of maternal risk factors, EFW Z-score and UtA-PI multiples of the normal median. We examined the predictive performance of the model by, first, the ability of the model to discriminate between the stillbirth and live-birth groups, using the area under the receiver-operating-characteristics curve (AUC) and the detection rate (DR) at a fixed false-positive rate (FPR) of 10%, and, second, calibration by measurements of calibration slope and intercept. RESULTS: The study population of 131 514 pregnancies included 131 037 live births and 477 (0.36%) stillbirths. There are four main findings of this study. First, 92.5% (441/477) of stillbirths were antepartum and 7.5% (36/477) were intrapartum, and 59.2% (261/441) of antepartum stillbirths were observed in association with placental dysfunction and 40.8% (180/441) were unexplained or due to other causes. Second, placental dysfunction accounted for 80.1% (161/201) of antepartum stillbirths at < 32 weeks' gestation, 54.2% (52/96) at 32 + 0 to 36 + 6 weeks and 33.3% (48/144) at ≥ 37 weeks. Third, the risk of placental dysfunction-related antepartum stillbirth increased with increasing maternal weight and decreasing maternal height, was 3-fold higher in black than in white women, was 5.5-fold higher in parous women with previous stillbirth than in those with previous live birth, and was increased in smokers, in women with chronic hypertension and in parous women with a previous pregnancy complicated by pre-eclampsia and/or birth of a small-for-gestational-age baby. Fourth, in screening for placental dysfunction-related antepartum stillbirth by a combination of maternal risk factors, EFW and UtA-PI in the validation dataset, the DR at a 10% FPR was 62.3% (95% CI, 57.2-67.4%) and the AUC was 0.838 (95% CI, 0.799-0.878); these results were consistent with those in the dataset used for developing the algorithm and demonstrate high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 1.029 and the intercept was -0.009, demonstrating good agreement between the predicted risk and observed incidence of placental dysfunction-related antepartum stillbirth. The performance of screening was better for placental dysfunction-related antepartum stillbirth at < 37 weeks' gestation compared to at term (DR at a 10% FPR, 69.8% vs 29.2%). CONCLUSIONS: Screening at mid-gestation by a combination of maternal risk factors, EFW and UtA-PI can predict a high proportion of placental dysfunction-related stillbirths and, in particular, those that occur preterm. Such screening provides poor prediction of unexplained stillbirth or stillbirth due to other causes. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Failure of physiological transformation and spiral artery atherosis: their roles in preeclampsia.

Physiological transformation with remodeling of the uteroplacental spiral arteries is key to a successful placentation and normal placental function. It is an intricate process that involves, but is not restricted to, complex interactions between maternal decidual immune cells and invasive trophoblasts in the uterine wall. In normal pregnancy, the smooth muscle cells of the arterial tunica media of uteroplacental spiral arteries are replaced by invading trophoblasts and fibrinoid, and the arterial diameter increases 5- to 10-fold. Poor remodeling of the uteroplacental spiral arteries is linked to early-onset preeclampsia and several other major obstetrical syndromes, including fetal growth restriction, placental abruption, and spontaneous preterm premature rupture of membranes. Extravillous endoglandular and endovenous trophoblast invasions have recently been put forth as potential contributors to these syndromes as well. The well-acknowledged disturbed extravillous invasion of maternal spiral arteries in preeclampsia is summarized, as are briefly novel concepts of disturbed extravillous endoglandular and endovenous trophoblast invasions. Acute atherosis is a foam cell lesion of the uteroplacental spiral arteries associated with poor remodeling. It shares some morphologic features with early stages of atherosclerosis, but several molecular differences between these lesions have also recently been revealed. Acute atherosis is most prevalent at the maternal-fetal interface, at the tip of the spiral arteries. The localization of acute atherosis downstream of poorly remodeled arteries suggests that alterations in blood flow may trigger inflammation and foam cell development. Acute atherosis within the decidua basalis is not, however, confined to unremodeled areas of spiral arteries or to hypertensive disorders of pregnancy and may even be present in some clinically uneventful pregnancies. Given that foam cells of atherosclerotic lesions are known to arise from smooth muscle cells or macrophages activated by multiple types of inflammatory stimulation, we have proposed that multiple forms of decidual vascular inflammation may cause acute atherosis, with or without poor remodeling and/or preeclampsia. Furthermore, we propose that acute atherosis may develop at different gestational ages, depending on the type and degree of the inflammatory insult. This review summarizes the current knowledge of spiral artery remodeling defects and acute atherosis in preeclampsia. Some controversies will be presented, including endovascular and interstitial trophoblast invasion depths, the concept of 2-stage trophoblast invasion, and whether the replacement of maternal spiral artery endothelium by fetal endovascular trophoblasts is permanent. We will discuss the role of acute atherosis in the pathophysiology of preeclampsia and short- and long-term health correlates. Finally, we suggest future opportunities for research on this intriguing uteroplacental interface between the mother and fetus.

STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Uterine artery Doppler for the prediction of outcome in pregnancies complicated by hypertensive disorders of pregnancy.

OBJECTIVES: To evaluate, in pregnancies complicated by hypertensive disorders of pregnancy (HDP), the predictive role of uterine artery (UtA) Doppler for pregnancy outcome compared to the definition of preeclampsia (PE) established by ISSHP recommendations. STUDY DESIGN: Retrospective cohort study including singleton pregnancies diagnosed with HDP, who underwent UtA Doppler assessment at admission in 2011-2017. The study population was classified considering the presence or absence of PE and according to the presence or absence of abnormal UtA Doppler (mean pulsatility index > 95th percentile). MAIN OUTCOME MEASURES: Pregnancy outcome, maternal and fetal complications, evaluated as composite outcomes (CO), and duration of pregnancy (from admission to delivery). RESULTS: A total of 311 mother-infant couples was included.The diagnostic ability of the two classifications was analysed comparing the relative likelihood ratio in the Biggerstaff graph. ISSHP definition turned out to be more efficient in detecting maternal adverse CO in comparison to UtA Doppler, relative positive likelihood ratio 1.50 (1.35-1.66) and 1.31 (1.07-1.60). UtA Doppler classification resulted more efficient in predicting adverse neonatal CO than PE definition, relative positive likelihood ratio 2.21 (1.77-2.75) and 1.61 (1.37-1.90). UtA Doppler was significantly associated with delivery at earlier gestational ages both for patients affected by PE and for women affected by HDP without superimposed PE (respectively p = 0.009 and p = 0.037). CONCLUSIONS: UtA Doppler at HDP diagnosis is a useful bedside marker of fetal/neonatal complications, and is associated with pregnancy duration.

Diagnostic accuracy of uterine artery and spiral artery Doppler for evaluation of endometrial pathology in postmenopausal bleeding.

INTRODUCTION: Traditional diagnostic workup for Endometrial carcinoma in women with post-menopausal bleeding (PMB) involves endometrial biopsy. Addition of colour and power Doppler ultrasound to transvaginal ultrasonography (TVS) might help in differentiating subset of women who are at high risk of carcinoma. The aim of this study was to determine the diagnostic value of Pulsatility Index (PI) and Resistance Index (RI) of uterine and spiral artery in PMB and to determine the diagnostic value of power Doppler flow mapping in them. MATERIAL AND METHODS: A prospective study was done amongst 50 women with PMB. All women were subjected to TVS including uterine artery and spiral artery Doppler velocimetry, power Doppler flow mapping of spiral artery, hysteroscopy and endometrial biopsy. RESULTS: Uterine artery PI and RI values were overlapping between benign and malignant endometrial pathologies. Whereas spiral artery PI ≤ 0.33 and RI ≤ 0.5 helps in differentiating malignant frombenign pathology. Power Doppler multiple vessel pattern is also found to have a better diagnostic ability in picking endometrial cancer. CONCLUSION: Addition of spiral artery velocimetry and power Doppler flow mapping to those with thickened endometrium, aids in differentiating endometrial malignancy from benign pathology. This might be helpful in counselling the women for endometrial biopsy, as histopathological analysis is the gold standard diagnostic modality.

Contingent screening in stratification of pregnancy care based on risk of pre-eclampsia at 19-24 weeks' gestation.

OBJECTIVE: To explore the possibility of carrying out routine screening for pre-eclampsia (PE) with delivery at < 28, < 32, < 36 weeks' gestation by maternal factors, uterine artery pulsatility index (UtA-PI) and mean arterial pressure (MAP) in all pregnancies and reserving measurements of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) for only a subgroup of the population. METHODS: This was a prospective observational study in two UK maternity hospitals involving women with singleton pregnancy attending for routine assessment at 19-24 weeks' gestation. The improvement in performance of screening for PE, at fixed risk cut-offs, by the addition of serum PlGF and sFlt-1 to screening by maternal factors, UtA-PI and MAP, was estimated. We examined a policy of contingent screening in which biochemical testing was reserved for only a subgroup of the population. The main outcome measures were the additional contribution of PlGF and sFlt-1 to the performance of screening for PE and the proportion of the population requiring measurement of PlGF and sFlt-1 for maximum performance of screening. RESULTS: The study population included 37 886 singleton pregnancies. At each risk cut-off, the highest detection rates for delivery with PE and the lowest screen-positive rates were achieved in screening with maternal factors, UtA-PI, MAP, PlGF and sFlt-1. The maximum performance by such screening was also achieved by contingent screening in which PlGF and sFlt-1 were measured in only about 40% of the population. CONCLUSION: The performance of screening for PE by a combination of maternal factors, UtA-PI and MAP is improved by measurement of PlGF and sFlt-1 in about 40% of the population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

What is the role of glycemic control in the development of preeclampsia among women with type 1 diabetes?

OBJECTIVE: To investigate the role of glycemic control in development of preeclampsia (PE) in women with type 1 diabetes mellitus (T1DM). METHODS: An observational case-control study comparing 244 women with type 1 diabetes and 488 controls was conducted. Among women with T1DM HbA1c, average daily glucose values, fasting, preprandial, 1-hour and 2-hour postprandial glucose levels, and daily 3 meals postprandial glucose areas were evaluated. Uterine artery pulsatility indices (PI) at 16, 20, 24 weeks' gestation were obtained. Data analysis included rates of PE in both groups, and association between glycemic control, uterine artery PI and development of PE among women with T1DM. RESULTS: PE developed in 13.1% of diabetic women and in 3.5% of women in the control group (odds ratio 4.2; 95% CI 2.2-8.1). In multivariate logistic regression analysis, HbA1c in the 1st trimester, mean daily glucose level in the 1st and 2nd trimester, daily 3 meal postprandial glucose area in the 1st and 2nd trimester, and the uterine arteries PI at 24 weeks' gestation were found to be associated with development of PE. The uterine arteries PI showed a significant positive correlation with the 3 meal postprandial glucose area at 16, 20, 24 weeks. CONCLUSION: In women with T1DM, poor glycemic control early in pregnancy is associated with an increased risk of subsequent PE. An association between poor placentation, as indicated by the increased PI of uterine arteries, and a maternal metabolic factor, that is the 3 meal post-prandial glucose area, has been shown, supporting the increased rate of PE among women with T1DM.

Play and Learn for Surgeons: A Serious Game to Educate Medical Residents in Uterine Artery Ligation Surgery.

Objective: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality. Surgical interventions, such as uterine artery ligation and utero-ovarian arteries ligation (UAL and UOAL), are considered as effective methods to control PPH. Owing to PPH's severe outcomes, various educational tools have been developed to train surgical residents. A potential educational medium for this purpose could be serious digital games. In this pilot study, we assessed the usability and effectiveness of a serious game to promote the surgical skills of UAL/UOAL among obstetrics and gynecology (OB/GYN) residents. Methods: We designed and developed the Play and Learn for Surgeons (PLS) game to train OB/GYN residents. We assessed and compared the usability challenges of PLS before and after revising the game. To assess the effectiveness of PLS, residents were allocated randomly in control and intervention groups. Surgical skills of the residents were assessed pre- and post-test using the Objective Structured Assessment of Technical Skills checklist. Setting: This pilot study took place at the OB/GYN wards of Omolbanin Hospital (Mashhad University of Medical Sciences) and Imam Ali Hospital (Zahedan University of Medical Sciences) in Iran. Participants: Thirteen subject matter experts (nine OB/GYN experts and four senior clinical assistants) participated in the user interface design and usability assessment of PLS. Total of 46 OB/GYN residents participated in the educational effectiveness analysis of PLS. All participants were female with mean ages of 40.6, 29.9 and 28.0 years for OB/GYN experts, assistants, and residents, accordingly. Results: All participants completed the study. PLS significantly improved the skills of residents for UAL (P-value = 0.018) and UOAL (P-value <0.001) procedures. Conclusion: Serious games can be an effective and affordable approach in training OB/GYN residents for UAL and UOAL procedures. Approval number: (# IR.MUMS.fm.REC.1396.345) Trial registration number: (# IRCT2017092436366N1).

Interferon γ neutralization reduces blood pressure, uterine artery resistance index, and placental oxidative stress in placental ischemic rats.

Preeclampsia (PE) is characterized by maternal hypertension, intrauterine growth restriction, and increased cytolytic natural killer cells (cNKs), which secrete interferon γ (IFNγ). However, the precise role of IFNγ in contributing to PE pathophysiology remains unclear. Using the reduced uterine perfusion pressure (RUPP) rat model of placental ischemia, we tested the hypothesis that neutralization of IFNγ in RUPPs will decrease placental reactive oxygen species (ROS) and improve vascular function resulting in decreased MAP and improved fetal growth. On gestation day (GD) 14, the RUPP procedure was performed and on GDs 15 and 18, a subset of normal pregnant rats (NP) and RUPP rats were injected with 10 µg/kg of an anti-rat IFNγ monoclonal antibody. On GD 18, uterine artery resistance index (UARI) was measured via Doppler ultrasound and on GD 19, mean arterial pressure (MAP) was measured, animals were euthanized, and blood and tissues were collected for analysis. Increased MAP was observed in RUPP rats compared with NP and was reduced in RUPP + anti-IFNγ. Placental ROS was also increased in RUPP rats compared with NP rats and was normalized in RUPP + anti-IFNγ. Fetal and placental weights were reduced in RUPP rats, but were not improved following anti-IFNγ treatment. However, UARI was elevated in RUPP compared with NP rats and was reduced in RUPP + anti-IFNγ. In conclusion, we observed that IFNγ neutralization reduced MAP, UARI, and placental ROS in RUPP recipients. These data suggest that IFNγ is a potential mechanism by which cNKs contribute to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes in PE.

Tumor Necrosis Factor-alpha Blockade Improves Uterine Artery Resistance, Maternal Blood Pressure, and Fetal Growth in Placental Ischemic Rats.

We recently reported that adoptive transfer of cytolytic Natural Killer cells (cNKs) from the Reduced Uterine Perfusion Pressure (RUPP) rat induces a preeclampsia (PE)-like phenotype in pregnant rats, accompanied by increased TNF-α. The purpose of this study was to investigate a role for increased TNF-α to induce oxidative stress (ROS), decrease nitric oxide (NO) bioavailability, and induce vascular dysfunction as mechanisms of hypertension (HTN) and intrauterine growth restriction (IUGR) in RUPPs. Pregnant Sprague Dawley rats underwent the RUPP or a Sham procedure on gestation day (GD) 14. On GDs 15 and 18, a subset of Sham and RUPP rats received i.p.injections of vehicle or 0.4 mg/kg of Etanercept (ETA), a soluble TNF-α receptor (n = 10/group). On GD18, Uterine Artery Resistance Index (UARI) was measured, and on GD19, mean arterial pressure (MAP), fetal and placental weights were measured, and blood and tissues were processed for analysis. TNF-α blockade normalized the elevated MAP observed RUPP. Additionally, both fetal and placental weights were decreased in RUPP compared to Sham, and were normalized in RUPP + ETA. Placental ROS was also increased in RUPP rats compared to Sham, and remained elevated in RUPP + ETA. Compared to Sham, UARI was elevated in RUPPs while plasma total nitrate was reduced, and these were normalized in ETA treated RUPPs. In conclusion, TNF-α blockade in RUPPs reduced MAP and UARI, improved fetal growth, and increased NO bioavailability. These data suggest that TNF-α regulation of NO bioavailability is a potential mechanism that contributes to PE pathophysiology and may represent a therapeutic target to improve maternal outcomes and fetal growth.

Is endothelial function impaired among women with placenta-mediated fetal growth restriction? Evidence from a prospective cohort study using peripheral artery tonometry.

INTRODUCTION: Women with pregnancies complicated by IUGR are at increased risk for future cardiovascular disease. Nevertheless, it is unknown whether endothelial function of women with pregnancies complicated by IUGR is already impaired during pregnancy. Hence, we evaluated maternal endothelial function in pregnancies complicated by IUGR due to placental dysfunction. METHODS: Prospective cohort study assessing systemic endothelial function of women with singleton pregnancies and estimated fetal weight (EFW) below 10th percentile and abnormal umbilical artery flow (n = 15). Control group included women with singleton pregnancies and normal EFW (n = 22). Endothelial function was assessed using EndoPAT™ device which evaluates the change in peripheral vascular tone in reaction to temporal ischemia, a process called reactive hyperemia. The ratio of the readings before and after ischemia is used to assess endothelial function and called reactive hyperemia index (RHI). Low RHI values indicate endothelial dysfunction. RESULTS: The median gestational age at endoPAT examination was comparable between the IUGR and control groups (32; IQR 31,33; p = 0.18). The median RHI was significantly lower in the IUGR group compared to the control group (1.3 vs 1.5, p = 0.02). Median gestational age at delivery and mean neonatal birth weight were lower in the IUGR group compared to the control group (36.7 (35.6,37.2) vs 37.7 (35.3, 39.3), p = 0.04 and 1647 ± 414 g vs 2785 ± 587 g, p < 0.001). DISCUSSION-: Pregnant women with IUGR due to placental dysfunction are characterized by impaired systemic endothelial function.