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.

Are Neonatal Birth Weights Reduced in Low-Risk Patients Diagnosed with COVID-19 during Pregnancy?

OBJECTIVE: Studies have shown that the 2019 novel coronavirus disease (COVID-19) may be associated with an increased risk of adverse pregnancy outcomes including preeclampsia, preterm birth, and stillbirth. However, the relationship between COVID-19 and abnormal fetal growth (i.e., low neonatal birth weight) has not been elucidated. Because other viruses affect fetal growth, obstetrical providers began to recommend ultrasound studies during the third trimester to assess fetal growth in patients with COVID-19 during pregnancy. The aim of this study was to determine if neonatal birth weight was different between low-risk patients diagnosed with COVID-19 during pregnancy and low-risk patients without COVID-19 in pregnancy, to ascertain if third trimester growth ultrasound is warranted in this patient population. STUDY DESIGN: We performed a retrospective cohort study of low-risk pregnant patients (who had no other indications for sonographic fetal surveillance during the third trimester) with and without COVID-19 during pregnancy. Patient demographics, gestational dating, neonatal birth weights, and corresponding Alexander growth curve birth weight percentiles were collected. The primary outcome was small-for-gestational age (SGA) neonates, defined as birth weight < 10th percentile for gestational age at delivery (SGA10). RESULTS: Our cohort (N = 513) included 248 COVID-19-exposed patients and 265 patients who did not have COVID-19 during pregnancy. Gestational age at delivery and average neonatal birth weights were similar in COVID-19-exposed (38 weeks 5 days, 3,266 g) and unexposed patients (38 weeks 4 days, 3,224 g; p = 0.434, 0.358). Rates of SGA10 neonates were similar in the COVID-19-exposed (22/248, 8.9%) and -unexposed (23/265, 8.7%, p = 0.939) groups. Timing and severity of COVID-19 during pregnancy also were not associated with rates of SGA neonates. CONCLUSION: In a cohort of low-risk patients, rates of SGA neonates were similar in patients with and without COVID-19 during pregnancy. These findings suggest that ultrasound surveillance to detect fetal growth restriction in low-risk patients with COVID-19 during pregnancy is not warranted. KEY POINTS: · COVID-19 may be associated with fetal growth restriction.. · There are normal infant weights in patients with COVID-19 in pregnancy.. · Growth ultrasound is not needed in patients with COVID-19..

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.

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.

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.

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..

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..

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.

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.

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.

Assessment of uterine artery geometry and hemodynamics in human pregnancy with 4d flow mri and its correlation with doppler ultrasound.

BACKGROUND: Uterine artery (UtA) hemodynamics might be used to predict risk of hypertensive pregnancy disorders, including preeclampsia and intrauterine growth restriction. PURPOSE OR HYPOTHESIS: To determine the feasibility of 4D flow MRI in pregnant subjects by characterizing UtA anatomy, computing UtA flow, and comparing UtA velocity, and pulsatility and resistivity indices (PI, RI) with transabdominal Doppler ultrasound (US). STUDY TYPE: Prospective cross-sectional study from June 6, 2016, to May 2, 2018. POPULATION OR SUBJECTS OR PHANTOM OR SPECIMEN OR ANIMAL MODEL: Forty-one singleton pregnant subjects (age [range] = 27.0 ± 5.9 [18-41] years) in their second or third trimester. We additionally scanned three subjects who had prepregnancy diabetes or chronic hypertension. FIELD STRENGTH/SEQUENCE: The subjects underwent UtA and placenta MRI using noncontrast angiography and 4D flow at 1.5T. ASSESSMENT: UtA anatomy was described based on 4D flow-derived noncontrast angiography, while UtA flow properties were characterized by net flow, systolic/mean/diastolic velocity, PI and RI through examination of 4D flow data. PI and RI are standard hemodynamic parameters routinely reported on Doppler US. STATISTICAL TESTS: Spearman's rank correlation, Wilcoxon signed rank tests, and Bland-Altman plots were used to preliminarily investigate the relationships between flow parameters, gestational age, and Doppler US. or RESULTS: 4D flow MRI and UtA flow quantification was feasible in all subjects. There was considerable heterogeneity in UtA geometry in each subject between left and right UtAs and between subjects. Mean 4D flow-based parameters were: mean bilateral flow rate = 605.6 ± 220.5 mL/min, PI = 0.72 ± 0.2, and RI = 0.47 ± 0.1. Bilateral flow did not change with gestational age. We found that MRI differed from US in terms of lower PI (mean difference -0.1) and RI (mean difference < -0.1) with Wilcoxon signed rank test P = 0.05 and P = 0.13, respectively. DATA CONCLUSION: 4D flow MRI is a feasible approach for describing UtA anatomy and flow in pregnant subjects. LEVEL OF EVIDENCE: Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:59-68.

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.

In vivo whole-blood T2 versus HbO2 calibration by modulating blood oxygenation level in the femoral vein through intermittent cuff occlusion.

PURPOSE: To investigate the feasibility of estimating calibration constants (K and T2o ) in vivo for converting whole-blood T2 to blood hemoglobin oxygen saturation (HbO2 ) according to the Luz-Meiboom model, 1/T2=1/T2o+K(1-HbO2)2, where K and T2o are relaxivity and transverse relaxation time of fully saturated blood, respectively. METHODS: A range of HbO2 values was achieved in the superficial femoral vein with intermittent cuff occlusion in seven healthy adults (four males) to establish a calibration curve between blood T2 and HbO2 at 1.5T. HbO2 was derived via MR susceptometry, a technique previously validated, and the transverse relaxation time was quantified with an optimized T2 -prepared balanced steady-state free precession pulse sequence. To evaluate the accuracy of the in vivo calibration method, T2 and HbO2 were quantified in the superior sagittal sinus in six additional subjects and compared with susceptometry. RESULTS: Two sets of gender-specific calibration constants were derived, one for each gender corresponding to hematocrits of 0.47 ± 0.02 for males and 0.38 ± 0.01 for females, yielding K/T2o = 41 Hz/260 ms and 26 Hz/280 ms, respectively. The in vivo calibration returned physiologically plausible superior sagittal sinus SvO2 values (65 ± 5% HbO2 ), and there was no significant difference between the results from the two methods (average difference -0.3% HbO2 ). CONCLUSION: The results show feasibility of performing in vivo calibration for converting whole-blood T2 to HbO2 . The proposed approach bypasses the involved and cumbersome processes associated with in vitro calibration. Magn Reson Med 79:2290-2296, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

T2 -prepared balanced steady-state free precession (bSSFP) for quantifying whole-blood oxygen saturation at 1.5T.

PURPOSE: To establish a calibration equation to convert human blood T2 to the full range of oxygen saturation levels (HbO2 ) and physiologic hematocrit (Hct) values using a T2 -prepared balanced steady-state free precession sequence (T2 -SSFP) at 1.5T. METHODS: Blood drawn from 10 healthy donors (29.1 ± 3.9 years old) was prepared into samples of varying HbO2 and Hct (n = 79), and imaged using T2 -SSFP sequence at 37°C and interrefocusing interval τ180 = 12 ms. The relationship between blood T2 , HbO2 , and Hct was established based on the model R2=R2,plasma+Hct (R2,RBC-R2,plasma)+k·Hct·(1-Hct)·(1-HbO2)2. Measured R2 and HbO2 levels were fit by the model yielding values of R2,plasma, R2,RBC, and k. T2 -SSFP and the established calibration equation were applied to extract HbO2 at the superior sagittal sinus (SSS) in vivo and were compared with susceptometry-based oximetry. RESULTS: Constants derived from the fit were: k = 74.2 [s-1 ], R2,plasma = 1.5 [s-1 ], R2,RBC = 11.6 [s-1 ], the R2 of the fit was 0.95. Average HbO2 at the SSS in seven healthy volunteers was 65% ± 7% and 66% ± 7% via T2 - and susceptometry-based oximetry, respectively. Bland-Altman analysis indicated agreement between the two oximetric methods with no significant bias. CONCLUSION: The calibration constants presented here should ensure improved accuracy for whole-blood oximetry based on T2 -SSFP at 1.5T. Magn Reson Med 79:1893-1900, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Cell-free DNA fetal fraction and preterm birth.

BACKGROUND: Cell-free deoxyribonucleic acid (DNA) is increasingly being used to screen for fetal aneuploidy. The majority of fetal cell-free DNA in the maternal blood results from release from the syncytiotrophoblast as a result of cellular apoptosis and necrosis. Elevated levels of fetal cell-free DNA may be indicative of underlying placental dysfunction, which has been associated with preterm birth. Preliminary studies have demonstrated that fetal cell-free DNA is increased in pregnancies complicated by spontaneous preterm birth. There are limited data on the association between fetal cell-free DNA levels and fetal fraction and preterm birth in asymptomatic women in the first and second trimesters. Preliminary studies have failed to find an association between first-trimester cell-free DNA levels and preterm birth, whereas there is conflicting evidence as to whether elevated second-trimester cell-free DNA is associated with a subsequent spontaneous preterm birth clinical event. OBJECTIVE: The objective of the study was to evaluate the association between first- and second-trimester cell-free DNA fetal fraction and preterm birth. STUDY DESIGN: This was a retrospective cohort study of women with singleton pregnancies at increased risk for aneuploidy who had cell-free DNA testing at 10-20 weeks' gestation between October 2011 and May 2014. The cohort was subdivided by gestational age at the time of cell-free DNA testing (10-14 weeks or 14.1-20 weeks). The primary outcome was preterm birth less than 37 weeks' gestation, and the secondary outcomes were preterm birth at less than 34 weeks' gestation and spontaneous preterm birth at less than 37 and 34 weeks' gestation. RESULTS: Among 1349 pregnancies meeting inclusion criteria 119 (8.8 %) had a preterm birth prior to 37 weeks with 49 cases (3.6 %) delivering prior to 34 weeks. Whereas there was no significant association between fetal fraction and the preterm birth outcomes for those who underwent cell-free DNA testing at 10-14 weeks' gestation, there were significant associations among those screened at 14.1-20.0 weeks' gestation. Fetal fraction greater than or equal to the 95th percentile at 14.1-20.0 weeks' gestation was associated with an increased risk for preterm birth less than 37 and 34 weeks' gestation (adjusted odds ratio, 4.59; 95% confidence interval, 1.39-15.2; adjusted odds ratio, 22.0; 95% confidence interval, 5.02-96.9). CONCLUSION: Elevated fetal fraction levels at 14.1-20.0 weeks' gestation were significantly associated with an increased incidence of preterm birth. Our findings warrant future exploration including validation in a larger, general population and investigation of the potential mechanisms that may be responsible for the initiation of preterm labor associated with increased fetal cell-free DNA.

Second-Trimester 3-Dimensional Placental Sonography as a Predictor of Small-for-Gestational-Age Birth Weight.

OBJECTIVES: We previously reported the association between first-trimester 3-dimensional (3D) placental measurements and small-for-gestational-age (SGA) neonates. In this study, we sought to determine whether second-trimester measurements further contribute to the antenatal detection of SGA and preeclampsia. METHODS: We prospectively collected 3D sonographic volume sets and uterine artery pulsatility indices of singleton pregnancies at 18 to 24 weeks. Placental volume, placental quotient (placental volume/gestational age), mean placental diameter and chorionic diameter, placental morphologic index (mean placental diameter/placental quotient), placental chorionic index (mean chorionic diameter/placental quotient), and placental growth (volume per week) were assessed and evaluated as predictors of SGA and preeclampsia as a composite and alone. RESULTS: Of 373 pregnancies, the composite outcome occurred in 67 (18.0%): 36 (9.7%) manifested SGA alone; 27 (7.2%) developed preeclampsia alone, and 4 (1.1%) developed both. The placental volume, placental quotient, mean placental diameter, mean chorionic diameter, and volume per week were significantly smaller, whereas the placental morphologic index and chorionic index were significantly larger in pregnancies with the composite outcome (P < .01). Further analyses revealed that the significant associations with placental parameters were limited to the SGA outcome. Each placental measure remained significantly associated with SGA after adjusting for confounders. The mean uterine artery pulsatility index was not associated with either outcome. Placental parameters were moderately predictive of SGA, with adjusted areas under the curve ranging from 0.72 to 0.76. Sensitivity for detection of SGA ranged from 32.5% to 45.0%, with positive predictive values ranging from 17.3% to 22.7%. CONCLUSIONS: Second-trimester 3D placental measurements can identify pregnancies at risk of SGA. However, there appears to be no significant improvement compared to those obtained in the first trimester.

Second-Trimester Sonographic Thymus Measurements Are Not Associated With Preterm Birth and Other Adverse Obstetric Outcomes.

OBJECTIVES: Previous studies have demonstrated an association between adverse obstetric outcomes, such as preterm birth, and in utero inflammation. The fetal thymus, which can be visualized in the anterior mediastinum on obstetric sonography, may involute in response to such inflammation and thus may identify pregnancies at increased risk for these outcomes. We therefore sought to determine whether second-trimester fetal thymus measurements are associated with preterm birth. METHODS: Transabdominal fetal thymus measurements were prospectively obtained in singleton pregnancies at gestational ages of 18 weeks to 23 weeks 6 days during a 5-month period. The transverse and anterorposterior thymus diameters and the thymic-thoracic ratio were measured. Delivery outcomes were collected from our clinical database. The primary outcome was preterm birth, which we defined as delivery between 24 weeks and 36 weeks 6 days. Small for gestational age (SGA) and pregnancy-related hypertension, which are adverse obstetric outcomes that may also be associated with in utero inflammation, were included as secondary outcomes. RESULTS: We included 520 patients with thymus measurements and obstetric outcome data. The prevalence of preterm birth was 12.3% (n = 64). None of the thymus measurements were associated with preterm birth. Similarly, there was no association between thymus measurements and SGA or pregnancy-related hypertension. CONCLUSIONS: Sonographic assessment of the second-trimester fetal thymus did not identify patients at increased risk for preterm birth, SGA, and pregnancy-related hypertension. Routine thymus measurements during the second-trimester anatomic scan are not clinically useful for prediction of preterm birth and other adverse outcomes.

Utility of a Single 3-Vessel View in the Evaluation of the Ventricular Outflow Tracts.

OBJECTIVES: Prenatal diagnosis of congenital heart disease can improve neonatal outcomes. The purpose of this study was to evaluate the utility of an isolated 3-vessel view image in evaluating the ventricular outflow tracts. METHODS: Three-vessel view images were prospectively collected from consecutive patients referred to a regional fetal heart center for fetal echocardiography between gestational ages of 18 weeks and 23 weeks 6 days. Cardiac malformations were categorized as anomalies of the outflow tracts, the 4-chamber view, or combined lesions. A single representative still-frame 3-vessel view image was reviewed by 2 independent and blinded observers who were asked to label each image as "normal" or "abnormal." Test characteristics of the isolated 3-vessel view were calculated. RESULTS: During the study period, 122 consecutive patients (139 fetuses) underwent fetal echocardiography. Eight fetuses with fetal chest anomalies and 12 fetuses with oblique images were excluded. Thirty-four of 119 fetuses (28.6%) had abnormal echocardiograms, including 11 outflow tract anomalies and 16 combined anomalies. Using the 3-vessel view alone, both reviewers achieved 91% sensitivity for the detection of isolated outflow tract anomalies and mean sensitivity of 88% for combined anomalies. All cases of tetralogy of Fallot and transposition of the great arteries were identified in the 3-vessel view. CONCLUSIONS: A single 3-vessel view image can serve as a representative view of the outflow tracts and can show ventricular outflow tract anomalies with high sensitivity. Given that the conventional outflow tract views can be difficult to obtain, the 3-vessel view may serve as an effective first-line view when evaluating the ventricular outflow tracts for congenital heart disease.

miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that aberrant expression of miR-210 may contribute to trophoblast function and that miR-210 is a novel predictive serum biomarker for preeclampsia that can help in identifying at-risk women for monitoring and treatment.