Evaluation of Non-Compressive Transvaginal Cervical Elastography as a Quantitative Imaging Biomarker in Pregnancy: A Repeatability and Reliability Analysis.

OBJECTIVES: Non-compressive strain elastography has been proposed as a novel quantitative imaging biomarker for assessing the structure and function of the cervix. The current study aims to assess the repeatability, and intra- and inter-observer reliability of transvaginal non-compressive cervical strain elastography in a clinical setting. METHODS: We conducted a dual-phase single-center prospective feasibility study of singleton gestations >16-weeks gestation that required a clinically-indicated transvaginal ultrasound. Each study participant, n = 43 in phase 1 and n = 13 in phase 2, had elastography performed by two trained observers that each performed multiple image acquisitions. We performed a multivariable regression to adjust for changes in clinical characteristics between study phases and calculated the repeatability coefficients, limits of agreement, and intraclass correlations for each quantitative elastography parameter. We compared quantitative elastography parameters to cervical length measurements, acquired from the same images. RESULTS: The repeatability coefficients and percent limits of agreement were wide for all of the quantitative elastography parameters, demonstrating poor repeatability. Intraclass correlation coefficients were poor-moderate for both intra-observer (0.31-0.77) and inter-observer reliability (0.35-0.77) in both study phases, while cervical length showed excellent reliability with intraclass correlations consistently >0.90. CONCLUSIONS: Non-compressive transvaginal strain cervical elastography did not demonstrate adequate repeatability or reliability. Our results highlight the importance of rigorously assessing novel quantitative imaging biomarkers before clinical application.

Undetected Fetal Growth Restriction During the Coronavirus Disease 2019 (COVID-19) Pandemic.

This was a retrospective cohort study of patients who delivered singleton, small-for-gestational-age (SGA) neonates between April and June 2019, before the coronavirus disease 2019 (COVID-19) pandemic (pre-COVID-19), and between April and July 2020, during the pandemic (COVID-19 epoch). The primary outcome was the rate of undetected antenatal fetal growth restriction (FGR) in the two periods. A total of 268 patients met inclusion criteria. Patients who delivered small-for-gestational-age neonates during the COVID-19 epoch were significantly more likely to have undetected FGR compared with those who delivered pre-COVID-19 (70.1% vs 58.1%, P =.04). Patients who delivered SGA neonates during the COVID-19 epoch had more telehealth visits but fewer in-person prenatal visits, recorded fundal height measurements, and growth ultrasonograms. As telemedicine continues to be incorporated into prenatal care, these data may lend further support toward self-assessment of fundal height or routine third-trimester growth ultrasonograms to identify fetal growth abnormalities.

A Resolved Placenta Previa is Still Associated with Postpartum Hemorrhage.

OBJECTIVE: Our objective was to determine whether resolution of a low-lying placenta or placenta previa is associated with postpartum hemorrhage (PPH). STUDY DESIGN: This is a retrospective, matched-control cohort study of women who underwent transvaginal sonography during fetal anatomic survey between 18 and 24 weeks of gestation at the University of Pennsylvania from January 2017 to May 2019. Exposure was defined as low-lying placenta (≤1 cm from the internal cervical os) or placenta previa (covering the os) at anatomic survey that was found to be resolved by transvaginal ultrasound in the third trimester. For each exposure, we identified a control patient whose placenta was > 1 cm from internal os at anatomic survey performed on the same day. The primary outcome was PPH at delivery, defined as estimated blood loss ≥ 1,000 mL. RESULTS: A total of 450 women were included (225/group). The exposed group of resolved placental previa included 85.0% with resolved low-lying placenta and 15.0% with resolved previa. The rate of PPH was significantly higher in the exposed group versus controls (9.8% vs. 4.4%, p = 0.03). Women with resolved previa were 2.5 times more likely to experience PPH than controls (adjusted odds ratio = 2.58, 95% confidence interval: 1.17-5.69), even when controlling for parity, prior cesarean, and delivery mode. Women with resolved previa were also more likely to present to triage with bleeding (16.4% vs. 8.0%, p = 0.006), receive antenatal corticosteroids, (9.3% vs. 3.1%, p = 0.006), and receive intravenous iron postpartum (7.6% vs. 3.1%, p = 0.04). CONCLUSION: Our data demonstrate that women with a resolved low-lying placenta or placenta previa remain at significantly increased risk of bleeding-related complications in pregnancy and during delivery when compared with those who never had a previa. Clinicians should consider this association when counseling patients and performing hemorrhage risk stratification. KEY POINTS: · Women with resolved previa or low-lying placenta were 2.5 times more likely to experience PPH.. · Women with resolved previa or low-lying placenta were more likely to be induced for bleeding.. · Resolved previa or low-lying placenta is still associated with adverse hemorrhage-related outcomes..

Feasibility of Vascular Parameter Estimation for Assessing Hypertensive Pregnancy Disorders.

Hypertensive pregnancy disorders (HPDs), such as pre-eclampsia, are leading sources of both maternal and fetal morbidity in pregnancy. Noninvasive imaging, such as ultrasound (US) and magnetic resonance imaging (MRI), is an important tool for predicting and monitoring these high risk pregnancies. While imaging can measure hemodynamic parameters, such as uterine artery pulsatility and resistivity indices (PI and RI), the interpretation of such metrics for disease assessment relies on ad hoc standards, which provide limited insight to the physical mechanisms underlying the emergence of hypertensive pregnancy disorders. To provide meaningful interpretation of measured hemodynamic data in patients, advances in computational fluid dynamics can be brought to bear. In this work, we develop a patient-specific computational framework that combines Bayesian inference with a reduced-order fluid dynamics model to infer parameters, such as vascular resistance, compliance, and vessel cross-sectional area, known to be related to the development of hypertension. The proposed framework enables the prediction of hemodynamic quantities of interest, such as pressure and velocity, directly from sparse and noisy MRI measurements. We illustrate the effectiveness of this approach in two systemic arterial network geometries: an aorta with branching carotid artery and a maternal pelvic arterial network. For both cases, the model can reconstruct the provided measurements and infer parameters of interest. In the case of the maternal pelvic arteries, the model can make a distinction between the pregnancies destined to develop hypertension and those that remain normotensive, expressed through the value range of the predicted absolute pressure.

FATE: The Effect of Fetal Antenatal Testing Education on Patient Knowledge and Satisfaction.

OBJECTIVE: This study aimed to evaluate the effect of a physician-created educational infographic on the knowledge and attitudes of patients undergoing antenatal fetal surveillance. STUDY DESIGN: This single-center prospective cohort study evaluated the impact of implementing an electronic educational infographic about antenatal fetal surveillance. English-speaking women receiving antenatal surveillance between the ages of 18 to 50 years were approached for inclusion. The preimplementation group enrolled women receiving antenatal surveillance between March 8, 2021, and April 2, 2021, who received usual care. Postimplementation, from April 5 to May 6, 2021, patients at our site received the infographic about antenatal fetal surveillance at their first antenatal testing appointment. Both pre- and postimplementation groups received a 5-question multiple-choice knowledge and 12-question attitude survey between 320/7 to 336/7 weeks at baseline (prior to receipt of infographic in postimplementation group) and again between 350/7 to 366/7 weeks. Patients were included in the analysis only if they completed both surveys. Differences from initial to final survey were compared between groups. RESULTS: Of 106 patients who completed the initial survey, 74 (69.8%) participants finished both surveys (preimplementation = 39 and postimplementation = 35). There were no significant differences in demographics between the two groups, including in baseline knowledge (p = 0.58) or attitude tests (p = 0.57). There was no significant difference in knowledge on final surveys between groups (p = 0.79). However, utilization of the infographic was associated with a significant increase in attitude survey score from initial to final survey in the postimplementation group as compared with usual care (median difference: pre = 0, interquartile rang [IQR]: [-1 to +4] vs. post = +3, IQR: [+1 to +6], p = 0.016). CONCLUSION: A physician-created infographic on antepartum fetal testing was associated with overall improved patient attitude toward fetal testing, showing that small education interventions can increase patient satisfaction with care. KEY POINTS: · A physician-created, readable, and patient-oriented education resource is feasible.. · Infographic patient-education materials do not change patient knowledge about antenatal testing.. · Infographic patient-education materials can improve patient attitude toward antenatal testing..

Non-invasive monitoring of blood oxygenation in human placentas via concurrent diffuse optical spectroscopy and ultrasound imaging.

Direct assessment of blood oxygenation in the human placenta can provide information about placental function. However, the monitoring of placental oxygenation involves invasive sampling or imaging techniques that are poorly suited for bedside use. Here we show that placental oxygen haemodynamics can be non-invasively probed in real time and up to 4.2 cm below the body surface via concurrent frequency-domain diffuse optical spectroscopy and ultrasound imaging. We developed a multimodal instrument to facilitate the assessment of the properties of the anterior placenta by leveraging image-reconstruction algorithms that integrate ultrasound information about the morphology of tissue layers with optical information on haemodynamics. In a pilot investigation involving placentas with normal function (15 women) or abnormal function (9 women) from pregnancies in the third trimester, we found no significant differences in baseline haemoglobin properties, but statistically significant differences in the haemodynamic responses to maternal hyperoxia. Our findings suggest that the non-invasive monitoring of placental oxygenation may aid the early detection of placenta-related adverse pregnancy outcomes and maternal vascular malperfusion.

A Novel, Cardiac-Derived Algorithm for Uterine Activity Monitoring in a Wearable Remote Device.

Background: Uterine activity (UA) monitoring is an essential element of pregnancy management. The gold-standard intrauterine pressure catheter (IUPC) is invasive and requires ruptured membranes, while the standard-of-care, external tocodynamometry (TOCO)'s accuracy is hampered by obesity, maternal movements, and belt positioning. There is an urgent need to develop telehealth tools enabling patients to remotely access care. Here, we describe and demonstrate a novel algorithm enabling remote, non-invasive detection and monitoring of UA by analyzing the modulation of the maternal electrocardiographic and phonocardiographic signals. The algorithm was designed and implemented as part of a wireless, FDA-cleared device designed for remote pregnancy monitoring. Two separate prospective, comparative, open-label, multi-center studies were conducted to test this algorithm. Methods: In the intrapartum study, 41 laboring women were simultaneously monitored with IUPC and the remote pregnancy monitoring device. Ten patients were also monitored with TOCO. In the antepartum study, 147 pregnant women were simultaneously monitored with TOCO and the remote pregnancy monitoring device. Results: In the intrapartum study, the remote pregnancy monitoring device and TOCO had sensitivities of 89.8 and 38.5%, respectively, and false discovery rates (FDRs) of 8.6 and 1.9%, respectively. In the antepartum study, a direct comparison of the remote pregnancy monitoring device to TOCO yielded a sensitivity of 94% and FDR of 31.1%. This high FDR is likely related to the low sensitivity of TOCO. Conclusion: UA monitoring via the new algorithm embedded in the remote pregnancy monitoring device is accurate and reliable and more precise than TOCO standard of care. Together with the previously reported remote fetal heart rate monitoring capabilities, this novel method for UA detection expands the remote pregnancy monitoring device's capabilities to include surveillance, such as non-stress tests, greatly benefiting women and providers seeking telehealth solutions for pregnancy care.

Novel uterine contraction monitoring to enable remote, self-administered nonstress testing.

BACKGROUND: The serial fetal monitoring recommended for women with high-risk pregnancies places a substantial burden on the patient, often disproportionately affecting underprivileged and rural populations. A telehealth solution that can empower pregnant women to obtain recommended fetal surveillance from the comfort of their own home has the potential to promote health equity and improve outcomes. We have previously validated a novel, wireless pregnancy monitor that can remotely capture fetal and maternal heart rates. However, such a device must also detect uterine contractions if it is to be used to robustly conduct remote nonstress tests. OBJECTIVE: This study aimed to describe and validate a novel algorithm that uses biopotential and acoustic signals to noninvasively detect uterine contractions via a wireless pregnancy monitor. STUDY DESIGN: A prospective, open-label, 2-center study evaluated simultaneous detection of uterine contractions by the wireless pregnancy monitor and an intrauterine pressure catheter in women carrying singleton pregnancies at ≥32 0/7 weeks' gestation who were in the first stage of labor (ClinicalTrials.gov Identifier: NCT03889405). The study consisted of a training phase and a validation phase. Simultaneous recordings from each device were passively acquired for 30 to 60 minutes. In a subset of the monitoring sessions in the validation phase, tocodynamometry was also deployed. Three maternal-fetal medicine specialists, blinded to the data source, identified and marked contractions in all modalities. The positive agreement and false-positive rates of both the wireless monitor and tocodynamometry were calculated and compared with that of the intrauterine pressure catheter. RESULTS: A total of 118 participants were included, 40 in the training phase and 78 in the validation phase (of which 39 of 78 participants were monitored simultaneously by all 3 devices) at a mean gestational age of 38.6 weeks. In the training phase, the positive agreement for the wireless monitor was 88.4% (1440 of 1692 contractions), with a false-positive rate of 15.3% (260/1700). In the validation phase, using the refined and finalized algorithm, the positive agreement for the wireless pregnancy monitor was 84.8% (2722/3210), with a false-positive rate of 24.8% (897/3619). For the subgroup who were monitored only with the wireless monitor and intrauterine pressure catheter, the positive agreement was 89.0% (1191/1338), with a similar false-positive rate of 25.4% (406/1597). For the subgroup monitored by all 3 devices, the positive agreement for the wireless monitor was significantly better than for tocodynamometry (P<.0001), whereas the false-positive rate was significantly higher (P<.0001). Unlike tocodynamometry, whose positive agreement was significantly reduced in the group with obesity compared with the group with normal weight (P=.024), the positive agreement of the wireless monitor did not vary across the body mass index groups. CONCLUSION: This novel method to noninvasively monitor uterine activity, via a wireless pregnancy monitoring device designed for self-administration at home, was more accurate than the commonly used tocodynamometry and unaffected by body mass index. Together with the previously reported remote fetal heart rate monitoring capabilities, this added ability to detect uterine contractions has created a complete telehealth solution for remote administration of nonstress tests.

Fully Automated Placental Volume Quantification From 3D Ultrasound for Prediction of Small-for-Gestational-Age Infants.

OBJECTIVES: Early placental volume (PV) has been associated with small-for-gestational-age infants born under the 10th/5th centiles (SGA10/SGA5). Manual or semiautomated PV quantification from 3D ultrasound (3DUS) is time intensive, limiting its incorporation into clinical care. We devised a novel convolutional neural network (CNN) pipeline for fully automated placenta segmentation from 3DUS images, exploring the association between the calculated PV and SGA. METHODS: Volumes of 3DUS obtained from singleton pregnancies at 11-14 weeks' gestation were automatically segmented by our CNN pipeline trained and tested on 99/25 images, combining two 2D and one 3D models with downsampling/upsampling architecture. The PVs derived from the automated segmentations (PVCNN ) were used to train multivariable logistic-regression classifiers for SGA10/SGA5. The test performance for predicting SGA was compared to PVs obtained via the semiautomated VOCAL (GE-Healthcare) method (PVVOCAL ). RESULTS: We included 442 subjects with 37 (8.4%) and 18 (4.1%) SGA10/SGA5 infants, respectively. Our segmentation pipeline achieved a mean Dice score of 0.88 on an independent test-set. Adjusted models including PVCNN or PVVOCAL were similarly predictive of SGA10 (area under curve [AUC]: PVCNN  = 0.780, PVVOCAL  = 0.768). The addition of PVCNN to a clinical model without any PV included (AUC = 0.725) yielded statistically significant improvement in AUC (P < .05); whereas PVVOCAL did not (P = .105). Moreover, when predicting SGA5, including the PVCNN (0.897) brought statistically significant improvement over both the clinical model (0.839, P = .015) and the PVVOCAL model (0.870, P = .039). CONCLUSIONS: First trimester PV measurements derived from our CNN segmentation pipeline are significantly associated with future SGA. This fully automated tool enables the incorporation of including placental volumetric biometry into the bedside clinical evaluation as part of a multivariable prediction model for risk stratification and patient counseling.

Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI: Pilot Study.

BACKGROUND: Abnormal maternal vascular function during pregnancy stemming from systemic endothelial dysfunction (EDF) has a central role in the pathophysiology of preeclampsia (PE). PURPOSE: To utilize quantitative MRI to investigate changes in physiological measures of vascular reactivity during normal pregnancy, and to explore EDF associated with preeclampsia. STUDY TYPE: Prospective. POPULATION: Healthy pregnant (HP) (n = 14, mean GA = 26 ± 7 weeks) and nonpregnant women (NP; n = 14); newly postpartum (PP <48 hours) women with severe PE (PP-PE; n = 4) and normotensive pregnancy (PP-HP; n = 5). FIELD STRENGTH/SEQUENCE: 1.5T/3T. RF spoiled multiecho gradient-recalled echo, 1D phase-contrast MRI, time-of-flight. ASSESSMENT: The micro- and macrovascular function (vasodilatory capacity of arterioles and conduit arteries, respectively) of the femoral vascular bed was evaluated with MRI-based venous oximetry, arterial velocimetry, and luminal flow-mediated dilation quantification, during cuff-induced reactive hyperemia. Aortic arch pulse-wave velocity (aPWV) was quantified to assess arterial stiffness using an ungated 1D technique. STATISTICAL TESTS: Two-tailed unpaired t-tests were performed to address our two, primary a priori comparisons, HP vs. NP, and PP-PE vs. PP-HP. Given the pilot nature of this study, adjustments for multiple comparisons were not performed. RESULTS: In HP, microvascular function was attenuated compared to NP by a significant increase in the washout time (10 ± 2 vs. 8 ± 2 sec; P < 0.05) and reduced upslope (2.1 ± 0.5 vs. 3.2 ± 0.8%HbO2 /s; P < 0.05), time of forward flow (28 ± 5 vs. 33 ± 6 sec, P < 0.05), and hyperemic index (11 ± 3 vs. 16 ± 4 cm/s2 ; P < 0.05), but luminal flow-mediated dilatation (FMDL )was comparable between HP and NP. PP-PE exhibited significant vascular dysfunction compared to PP-HP, as evidenced by differences in upslope (2.2 ± 0.6 vs. 1.3 ± 0.2%HbO2 /s, P < 0.05), overshoot (16 ± 5 vs. 7 ± 3%HbO2 , P < 0.05), time of forward flow (28 ± 6 vs. 15 ± 7 s, P < 0.05), and aPWV (7 ± 1 vs. 8 ± 1 m/s, P < 0.05). DATA CONCLUSION: Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.

Wireless, remote solution for home fetal and maternal heart rate monitoring.

BACKGROUND: Access to prenatal care can be challenging due to physician shortages and rural geography. The multiple prenatal visits performed to collect basic fetal measurements lead to significant patient burden as well. The standard of care tools for fetal monitoring, external fetal heart rate monitoring with cardiotocography, as used today, must be applied by a medical professional in a healthcare setting. Novel tools to enable a remote and self-administered fetal monitoring solution would significantly alleviate some of the current barriers to care. OBJECTIVE: To compare maternal and fetal heart rate monitoring data obtained by 'Invu system' (a wireless, wearable, self-administered, fixed-location device containing passive electrical and acoustic sensors) to cardiotocography, toward a true remote fetal monitoring solution. MATERIALS AND METHODS: A prospective, open-label, multicenter study evaluated concurrent use of Invu and cardiotocography in pregnant women, aged 18 to 50 years, with singleton pregnancies ≥32+0 weeks' gestation (NCT03504189). Simultaneous recording sessions from Invu and cardiotocography lasted for ≥30 minutes. Data from the 8 electrical sensors and 4 acoustic sensors in the Invu belt were acquired, digitized, and sent wirelessly for analysis by an algorithm on cloud-based servers. The algorithm validates the data, preprocesses the data to remove noise, detects heartbeats independently from the two data sources (electrical and acoustic), and fuses the detected heartbeat arrays to calculate fetal heart rate (FHR) and maternal heart rate (MHR). The primary performance endpoint was Invu FHR limit of agreement within ± 10 beats per minute (bpm) of FHR measured with cardiotocography. RESULTS: A total of 147 women were included in the study analysis. The mean (SD) maternal age was 31.8 ±6.9 years, and the mean gestational age was 37.7 ±2.3 weeks. There was a highly significant correlation between FHR measurements from Invu and cardiotocography (r = 0.92; P<0.0001). The 95% limits of agreement for the difference, the range within which most differences between the two measurements will lie, were -8.84 bpm to 8.24 bpm. Invu measurements of MHR were also very similar to cardiotocography and were highly significantly correlated (r = 0.97; P<0.0001). No adverse events were reported during the study. CONCLUSION: Although captured by very different methods, the FHR and MHR outputs wirelessly obtained by the Invu system through passive methods were very similar to those obtained by the current standard of care. The limits of agreement for FHR measured by Invu were within a clinically acceptable ± 8 bpm of cardiotocography FHR. The Invu device uses passive technology to allow for safe, non-invasive and convenient monitoring of patients in the clinic and remotely. Further work should investigate how remote perinatal monitoring could best address some of the recent challenges seen with prenatal care and maternal and fetal outcomes. CLINICAL TRIAL INFORMATION: Registration date: April 20, 2018; First participant enrollment: February 28, 2018; ClinicalTrials.gov registration NCT03504189; https://clinicaltrials.gov/ct2/show/NCT03504189.

A multidisciplinary approach to improving process and outcomes in unscheduled cesarean deliveries.

BACKGROUND: Effective communication between providers of various disciplines is crucial to the quality of care provided on labor and delivery. The lack of standardized language for communicating the clinical urgency of cesarean delivery and the lack of standardized processes for responding were identified as targets for improvement by the Obstetric Patient Safety Committee at the Hospital of the University of Pennsylvania. The committee developed and implemented a protocol aimed at improving the performance of our multidisciplinary team and patient outcomes. OBJECTIVE: To evaluate whether implementation of a multidisciplinary protocol that standardizes the language and process for performing unscheduled cesarean deliveries had reduced the decision to incision interval and improved maternal and neonatal outcomes. MATERIALS AND METHODS: This was a retrospective cohort study of patients who underwent unscheduled cesarean delivery pre- and postimplementation of a protocol standardizing language, communication, provider roles, and processes. The primary outcome was cesarean decision to incision interval overall and stratified by fetal and nonfetal indications for delivery. Secondary outcomes included decision to operating room and operating room to incision intervals, operative complications, use of general anesthesia, maternal transfusion, 5-minute Apgar score <6, and umbilical cord arterial pH <7.2. Descriptive statistics were calculated. Continuous variables were tested for normality and compared using the Student t test or Mann-Whitney U test as appropriate. Categorical variables were characterized by proportions and compared by the χ2 or Fisher exact test as appropriate. RESULTS: There were 121 and 119 subjects in the pre-and postimplementation groups respectively, collected from corresponding 3-month periods. There were no significant differences in demographics, comorbidities, or indications for cesarean delivery between groups. Overall median decision to incision interval did not differ between the pre- and postimplementation groups. There was a significant decrease in median decision to incision interval (63 versus 50 minutes, P = .02) in cesarean deliveries performed for nonfetal indications. This was driven by a shorter median decision to operating room interval (32.5 versus 23 minutes, P = .01). The incidences of operative complications (35% [19/55] versus 11% [6/53], P < .01) and cord pH <7.2 (36% [20/55] versus 17% [9/53], P = .02) were also decreased in cesarean deliveries performed for nonfetal indications. The incidences of general anesthesia, maternal transfusion, and 5-minute Apgar score <6 did not differ. Outcomes did not differ between the pre- and postimplementation groups in cesarean deliveries performed for fetal indications. CONCLUSION: Implementation of a multidisciplinary process improvement protocol that standardizes language, roles, and processes for unscheduled cesarean deliveries was associated with a reduced decision to incision interval and improved maternal and neonatal outcomes in cesarean deliveries performed for nonfetal indications. Standardized process implementation on labor and delivery has the potential to improve patient outcomes.

Syncytiotrophoblast extracellular microvesicle profiles in maternal circulation for noninvasive diagnosis of preeclampsia.

Preeclampsia is the most common placental pathology in pregnant females, with increased morbidity and mortality incurred on the mother and the fetus. There is a need for improved biomarkers for diagnosis and monitoring of this condition. Placental syncytiotrophoblasts at the maternal-fetal interface release nanoparticles, including extracellular microvesicles, into the maternal blood during pregnancy. Syncytiotrophoblast extracellular microvesicles (STEVs) are being studied for their diagnostic potential and for their potential physiologic role in preeclampsia. We hypothesized that STEV profiles in maternal circulation would be altered under conditions of preeclampsia compared to normal pregnancy. Extracellular vesicles (EVs) released by BeWo cells in vitro showed high expression of syncytin-1, but no plac1 expression, demonstrating that trophoblast cell EVs express syncytin-1 on their surface. Placental alkaline phosphatase also showed high expression on BeWo EVs, but due to concern for cross reactivity to highly prevalent isoforms of intestinal and bone alkaline phosphatase, we utilized syncytin-1 as a marker for STEVs. In vivo, syncytin-1 protein expression was confirmed in maternal plasma EVs from Control and Preeclampsia subjects by Western blot, and overall, lower expression was noted in samples from patients with preeclampsia (n = 8). By nanoparticle analysis, EV profiles from Control and Preeclampsia groups showed similar total plasma EV quantities (p = 0.313) and size distribution (p = 0.415), but STEV quantitative signal, marked by syncytin-1 specific EVs, was significantly decreased in the Preeclampsia group (p = 2.8 × 10-11). Receiver operating characteristic curve demonstrated that STEV signal threshold cut-off of <0.316 was 95.2% sensitive and 95.6% specific for diagnosis of preeclampsia in this cohort (area under curve = 0.975 ± 0.020). In conclusion, we report that the syncytin-1 expressing EV profiles in maternal plasma might serve as a placental tissue specific biomarker for preeclampsia.

The Impact of Previous Obstetric History on the Risk of Spontaneous Preterm Birth in Women with a Sonographic Short Cervix.

OBJECTIVE: The natural history of women with a short cervix and a low-risk obstetric history remains poorly defined. In our study, we sought to better characterize the impact of previous obstetric history on the delivery outcomes in women diagnosed with a mid-trimester sonographic short cervix. STUDY DESIGN: We performed a retrospective cohort study of women with singleton gestations who underwent transvaginal cervical length screening between 16 and 24 weeks at two urban hospitals in Philadelphia between January 2013 and March 2018 and were found to have a short cervix (defined as ≤2 cm). Women were excluded from the cohort if there were major fetal anomalies noted or if delivery outcome information was not available. The cohort was then divided into three groups based on obstetric history: nulliparous, history of full-term birth only, or history of spontaneous preterm birth (sPTB). The primary outcome was sPTB <37 weeks, while the secondary outcome was sPTB <34 weeks. RESULTS: Our cohort included a total of 384 singleton pregnancies that were diagnosed with a sonographic short cervix: 165 women were nulliparous, 119 women had a history of full-term birth, and 100 women with a history of sPTB. We found that women with a short sonographic cervix had a sPTB rate of 39.6% with no differences found between the three groups. Only two-thirds of nulliparous women and women with a history of full-term birth received the recommended preventative treatment, compared with almost 100% of women with a history of sPTB. CONCLUSION: Women with and without a history of sPTB are at comparable risk of sPTB in the presence of a sonographically short cervix. Preventative therapies should be recommended to both nulliparous women and women with a history of full-term birth since uptake in this population are not as high.

Minimally interactive placenta segmentation from three-dimensional ultrasound images.

Purpose: Placental size in early pregnancy has been associated with important clinical outcomes, including fetal growth. However, extraction of placental size from three-dimensional ultrasound (3DUS) requires time-consuming interactive segmentation methods and is prone to user variability. We propose a semiautomated segmentation technique that requires minimal user input to robustly measure placental volume from 3DUS images. Approach: For semiautomated segmentation, a single, central 2D slice was manually annotated to initialize an automated multi-atlas label fusion (MALF) algorithm. The dataset consisted of 47 3DUS volumes obtained at 11 to 14 weeks in singleton pregnancies (28 anterior and 19 posterior). Twenty-six of these subjects were imaged twice within the same session. Dice overlap and surface distance were used to quantify the automated segmentation accuracy compared to expert manual segmentations. The mean placental volume measurements obtained by our method and VOCAL (virtual organ computer-aided analysis), a leading commercial semiautomated method, were compared to the manual reference set. The test-retest reliability was also assessed. Results: The overlap between our automated segmentation and manual (mean Dice: 0.824 ± 0.061 , median: 0.831) was within the range reported by other methods requiring extensive manual input. The average surface distance was 1.66 ± 0.96 mm . The correlation coefficient between test-retest volumes was r = 0.88 , and the intraclass correlation was ICC ( 1 ) = 0.86 . Conclusions: MALF is a promising method that can allow accurate and reliable segmentation of the placenta with minimal user interaction. Further refinement of this technique may allow for placental biometry to be incorporated into clinical pregnancy surveillance.

Adnexal Masses in Pregnancy.

With the increased use and quality of ultrasound in pregnancy, adnexal masses are being encountered with greater frequency. Fortunately, the vast majority of such masses are benign and resolve on their own. However, it is important for clinicians to be familiar with the types of adnexal masses that may be visualized in pregnancy to best counsel these women. In addition, complications such as ovarian torsion, and rarely, even malignancy can occur. In this article, we review the available literature on this subject to help guide the clinician in the diagnosis and management of adnexal masses in pregnancy.

Gestational growth trajectories derived from a dynamic fetal-placental scaling law.

Fetal trajectories characterizing growth rates in utero have relied primarily on goodness of fit rather than mechanistic properties exhibited in utero. Here, we use a validated fetal-placental allometric scaling law and a first principles differential equations model of placental volume growth to generate biologically meaningful fetal-placental growth curves. The growth curves form the foundation for understanding healthy versus at-risk fetal growth and for identifying the timing of key events in utero.

Placental Pulsatility: Quantitative Assessment of Placental Bed Vasculature by 2-Dimensional Doppler Cine Imaging.

OBJECTIVES: Vascular resistance is known to be one of the determinants of pulsatile flow. This study aimed to investigate whether quantitative 2-dimensional Doppler ultrasound can capture and evaluate the pulsatility within the placental bed vasculature. METHODS: The placental bed vasculature was imaged by directional power Doppler ultrasound. Ten-second cine clips were recorded by using standardized machine settings. A region of interest with a prominent Doppler signal in the uteroplacental interface was analyzed for the percentage of vascularity to generate a time-vascularity waveform. A vascular pulsatility index representing variation over the cardiac cycle was calculated by the ratio of the systolic-diastolic difference in vascularity to the mean vascularity. The acquisitions were repeated with 6 different pulse repetition frequencies (PRFs) and 3 wall motion filter (WMF) settings to evaluate their impact on the Doppler measurements. RESULTS: Ten sets of cine clips were analyzed for this study. The pulsatile nature of the vascularity was readily apparent in each cine clip. The measured time-vascularity waveforms showed uniform cyclic variation in vascularity over the cardiac cycle, with systolic vascularity significantly higher than diastolic vascularity at each combination of PRF and WMF (P < .05). A gradual increase in the vascular pulsatility index was observed with an increasing PRF or WMF. Normalization of systolic-to-diastolic measurement provided a stable vascular assessment across the range of PRFs. CONCLUSIONS: Doppler cine clips provide a dynamic representation of the placental bed vasculature and a novel analytic approach to quantitatively evaluating the pulsatility of this critical vascular network. Further work is warranted to explore the reproducibility and clinical potential of this approach.