Glycated Albumin and Glycemia in Pregnancy and Postpartum: A Pilot Study.

OBJECTIVE: Percent glycated albumin (%GAlb) is a marker of glycemia over the past 2 to 3 weeks in nonpregnant individuals. Longitudinal changes in %GAlb extending throughout pregnancy and postpartum (PP) have not been described. We aimed to describe levels of %GAlb throughout pregnancy and PP and relationships with glycemia. STUDY DESIGN: Fifty women among those in the Study of Pregnancy Regulation of INsulin and Glucose cohort underwent 75-g oral glucose tolerance tests (OGTTs) at a mean of 13 weeks (V1) and 26 weeks (V2) of gestation and 11 weeks' PP. %GAlb was measured on frozen plasma samples. RESULTS: Total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (ß = - 0.63% 95% CI [-0.8, -0.6] p < 0.001) and remained stable between V2 and PP (ß = - 0.04% [-0.3, 0.2] p = 0.78). Body mass index (BMI) was inversely related to %GAlb in pregnancy (V1: rho = - 0.5, p = 0.0001; V2 rho = - 0.4, p = 0.006), but not PP (rho = - 0.15, p = 0.31). The longitudinal changes in %GAlb persisted after adjusting for BMI. Neither glycemia measurements nor hemoglobin A1c were associated with %GAlb at any time point, and adjustments for BMI did not reveal additional associations. CONCLUSION: %GAlb decreases between early and late gestation and remains decreased PP, despite a PP increase in total albumin above early pregnancy values. Given the lack of correlation with OGTT values or A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women. KEY POINTS: · Changes in %GAlb extending to the postpartum period have not been described.. · %GAlb decreases in pregnancy and remains decreased postpartum, despite a postpartum increase in total albumin above early pregnancy values.. · Glycemia measurements nor A1c were associated with %GAlb at any time point, therefore, %GAlb is unlikely to be useful in assessing glycemia in pregnant or postpartum women..

External Validation of a Prediction Model for External Cephalic Version Success.

External cephalic version (ECV) success correlates with numerous maternal and pregnancy factors. A prior study developed an ECV success prediction model based on body mass index, parity, placental location, and fetal presentation. We performed external validation of this model using a retrospective cohort of ECV procedures from a separate institution between July 2016 and December 2021. Four hundred thirty-four ECV procedures were performed, with a 44.4% success rate (95% CI 39.8-49.2%), which was similar to the derivation cohort (40.6%, 95% CI 37.7-43.5%, P =.16). There were significant differences in patients and practices between cohorts, including the rate of neuraxial anesthesia (83.5% derivation cohort vs 10.4% our cohort, P <.001). The area under the receiver operating characteristic curve (AUROC) was 0.70 (95% CI 0.65-0.75), which was similar to that in the derivation cohort (AUROC 0.67, 95% CI 0.63-0.70). These results suggest the published ECV prediction model's performance is generalizable outside the original study institution.

Cross-Sectional Observational Study of Typical in utero Fetal Movements Using Machine Learning.

Early variations of fetal movements are the hallmark of a healthy developing central nervous system. However, there are no automatic methods to quantify the complex 3D motion of the developing fetus in utero. The aim of this prospective study was to use machine learning (ML) on in utero MRI to perform quantitative kinematic analysis of fetal limb movement, assessing the impact of maternal, placental, and fetal factors. In this cross-sectional, observational study, we used 76 sets of fetal (24-40 gestational weeks [GW]) blood oxygenation level-dependent (BOLD) MRI scans of 52 women (18-45 years old) during typical pregnancies. Pregnant women were scanned for 5-10 min while breathing room air (21% O2) and for 5-10 min while breathing 100% FiO2 in supine and/or lateral position. BOLD acquisition time was 20 min in total with effective temporal resolution approximately 3 s. To quantify upper and lower limb kinematics, we used a 3D convolutional neural network previously trained to track fetal key points (wrists, elbows, shoulders, ankles, knees, hips) on similar BOLD time series. Tracking was visually assessed, errors were manually corrected, and the absolute movement time (AMT) for each joint was calculated. To identify variables that had a significant association with AMT, we constructed a mixed-model ANOVA with interaction terms. Fetuses showed significantly longer duration of limb movements during maternal hyperoxia. We also found a significant centrifugal increase of AMT across limbs and significantly longer AMT of upper extremities <31 GW and longer AMT of lower extremities >35 GW. In conclusion, using ML we successfully quantified complex 3D fetal limb motion in utero and across gestation, showing maternal factors (hyperoxia) and fetal factors (gestational age, joint) that impact movement. Quantification of fetal motion on MRI is a potential new biomarker of fetal health and neuromuscular development.

Change in T2* measurements of placenta and fetal organs during Braxton Hicks contractions.

Maternal-placental perfusion can be temporarily compromised by Braxton Hicks (BH) uterine contractions. Although prior studies have employed T2* changes to investigate the effect of BH contractions on placental oxygen, the effect of these contractions on the fetus has not been fully characterized. We investigated the effect of BH contractions on quantitative fetal organ T2* across gestation together with the birth information. We observed a slight but significant decrease in fetal brain and liver T2* during contractions.

High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia.

OBJECTIVE: To evaluate whether the use of inhaled nitric oxide (iNO)200 improves respiratory function. METHODS: This retrospective cohort study used data from pregnant patients hospitalized with severe bilateral coronavirus disease 2019 (COVID-19) pneumonia at four teaching hospitals between March 2020 and December 2021. Two cohorts were identified: 1) those receiving standard of care alone (SoC cohort) and 2) those receiving iNO200 for 30 minutes twice daily in addition to standard of care alone (iNO200 cohort). Inhaled nitric oxide, as a novel therapy, was offered only at one hospital. The prespecified primary outcome was days free from any oxygen supplementation at 28 days postadmission. Secondary outcomes were hospital length of stay, rate of intubation, and intensive care unit (ICU) length of stay. The multivariable-adjusted regression analyses accounted for age, body mass index, gestational age, use of steroids, remdesivir, and the study center. RESULTS: Seventy-one pregnant patients were hospitalized for severe bilateral COVID-19 pneumonia: 51 in the SoC cohort and 20 in the iNO200 cohort. Patients receiving iNO200 had more oxygen supplementation-free days (iNO200: median [interquartile range], 24 [23-26] days vs standard of care alone: 22 [14-24] days, P=.01) compared with patients in the SoC cohort. In the multivariable-adjusted analyses, iNO200 was associated with 63.2% (95% CI 36.2-95.4%; P<.001) more days free from oxygen supplementation, 59.7% (95% CI 56.0-63.2%; P<.001) shorter ICU length of stay, and 63.6% (95% CI 55.1-70.8%; P<.001) shorter hospital length of stay. No iNO200-related adverse events were reported. CONCLUSION: In pregnant patients with severe bilateral COVID-19 pneumonia, iNO200 was associated with a reduced need for oxygen supplementation and shorter hospital stay.

Maternal Morbidity in the Second Stage of Labor: Analysis to Simulate the Clinical Choice.

OBJECTIVE: The aim of the study is to analyze maternal morbidity in the second stage of labor in a manner that approximates clinical choice. STUDY DESIGN: The study design comprises secondary analysis of the Consortium for Safe Labor, which included 228,688 deliveries at 19 hospitals between 2002 and 2008. We included the 107,675 women who were undergoing a trial of labor without a prior uterine scar or history of substance abuse, who reached the second stage, with a liveborn, nonanomalous, vertex, singleton, at term of at least 2,500 g. Maternal complications included postpartum fever, hemorrhage, blood transfusion, thrombosis, intensive care unit (ICU) admission, hysterectomy, and death. For maternal complications, we simulated the clinical choice by comparing operative vaginal or cesarean deliveries to continued expectant management at every hour in the second stage. For neonatal complications, we modeled the risk of severe neonatal complication by second stage duration for spontaneous vaginal deliveries only, adjusting for maternal demographics, comorbidities, and delivery hospital. Severe neonatal complications included death, asphyxia, hypoxic-ischemic encephalopathy (HIE), seizure, sepsis with prolonged stay, need for mechanical ventilation, and 5-minute Apgar score <4. RESULTS: Maternal morbidity was higher with operative vaginal/cesarean delivery versus continued expectant management for every hour in the second stage, a difference that was statistically significant at hour 2 (18.4 vs. 14.7%; p <0.01). Overall, 951 (0.88%) deliveries were complicated by a severe neonatal complication. A second stage over 4 hours was associated with an adjusted odds of severe neonatal complication of 2.10 (95% confidence interval [CI]: 1.32-3.34) as compared with women who delivered in the first hour. CONCLUSION: There is a trade-off between maternal and neonatal morbidity in the second stage of labor. Serious neonatal complications rise throughout, however, there is no time at which maternal morbidity is improved with a cesarean or operative vaginal delivery. Strategies are needed to identify neonates at highest risk of complication for targeted intervention. KEY POINTS: · Severe neonatal complications increase with every hour in the second stage.. · Shortening the second stage is associated with higher maternal complications at every hour.. · There is a trade-off between maternal and neonatal morbidity in the second stage..

Association between peripartum hysterectomy and venous thromboembolism.

BACKGROUND: The risk of venous thromboembolism after delivery is modified by mode of delivery, with the risk of venous thromboembolism being higher after cesarean delivery than vaginal delivery. The risk of venous thromboembolism after peripartum hysterectomy is largely unknown. OBJECTIVE: This study aimed to compare the incidence and risk of venous thromboembolism among women who had and did not have a peripartum hysterectomy. Furthermore, we sought to compare the risk of venous thromboembolism after hysterectomy with other patient, pregnancy, and delivery risk factors known to be associated with venous thromboembolism. STUDY DESIGN: This was a cross-sectional study of women with delivery encounters identified in the Nationwide Readmissions Database from October 2015 to December 2017. Delivery encounters and all variables of interest were identified using the International Classification of Diseases, Tenth Revision diagnosis and procedure codes. The incidence of venous thromboembolism during delivery and rehospitalizations within 6 weeks after discharge was compared among women who had and did not have a peripartum hysterectomy. Multivariable logistic regressions were used to estimate associations between venous thromboembolism and hysterectomy, adjusted for the following characteristics: maternal age, payer at time of delivery, obesity, hypertension, diabetes mellitus, tobacco use, multifetal gestation, peripartum infection, and peripartum hemorrhage. Similarly, venous thromboembolism risk was compared by mode of delivery, including hysterectomy. Diagnoses that may have been indications for peripartum hysterectomy were identified among patients who underwent a hysterectomy and compared between those who did and did not have venous thromboembolism. Analyses used survey weights to obtain population estimates. RESULTS: Of the 4,419,037 women with deliveries, 5098 (11.5 per 10,000 deliveries) underwent a hysterectomy. Moreover, 110 patients (215.8 per 10,000 deliveries) were diagnosed with venous thromboembolism after hysterectomy. The risk of venous thromboembolism was significantly higher in women who underwent a hysterectomy than in women who did not have a hysterectomy (unadjusted odds ratio, 25.1 [95% confidence interval, 20.0-31.5]; adjusted odds ratio, 11.2 [95% confidence interval, 8.7-14.5]; P<.001). Comparing the risk of venous thromboembolism by mode of delivery, the unadjusted and adjusted incidences of venous thromboembolism were 6.9 (95% confidence interval, 6.5-7.3) and 7.4 (95% confidence interval, 6.9-7.8) per 10,000 deliveries among women after vaginal delivery without peripartum hysterectomy, 12.5 (95% confidence interval, 11.8-13.1) and 11.3 (95% confidence interval, 10.7-12.0) per 10,000 deliveries after cesarean delivery without hysterectomy; and 217.2 (95% confidence interval, 169.1-265.2) and 96.9 (95% confidence interval 76.9-126.5) per 10,000 deliveries after hysterectomy, regardless of mode of delivery. Of the 110 diagnoses of venous thromboembolism with peripartum hysterectomy, 89 (81%) occurred during delivery admission. Of the remaining 21 cases, 50% occurred within the first 10 days after discharge from delivery, and 75% occurred within 25 days after discharge. CONCLUSION: These findings have demonstrated that peripartum hysterectomy is associated with a markedly increased risk of venous thromboembolism in the postpartum period, even when controlling for other known risk factors for postpartum thromboembolic events. Here, the incidence of venous thromboembolism after peripartum hysterectomy (2.2%) met some guideline-based risk thresholds for routine thromboprophylaxis, potentially for at least 2 weeks after delivery. Further investigation into the role of routine venous thromboembolism prophylaxis during and after delivery is needed.

Quantitative T1 and T2 mapping by magnetic resonance fingerprinting (MRF) of the placenta before and after maternal hyperoxia.

INTRODUCTION: MR relaxometry has been used to assess placental exchange function, but methods to date are not sufficiently fast to be robust to placental motion. Magnetic resonance fingerprinting (MRF) permits rapid, voxel-wise, intrinsically co-registered T1 and T2 mapping. After characterizing measurement error, we scanned pregnant women during air and oxygen breathing to demonstrate MRF's ability to detect placental oxygenation changes. METHODS: The accuracy of FISP-based, sliding-window reconstructed MRF was tested on phantoms. MRF scans in 9-s breath holds were acquired at 3T in 31 pregnant women during air and oxygen breathing. A mixed effects model was used to test for changes in placenta relaxation times between physiological states, to assess the dependency on gestational age (GA), and the impact of placental motion. RESULTS: MRF estimates of known phantom relaxation times resulted in mean absolute errors for T1 of 92 ms (4.8%), but T2 was less accurate at 16 ms (13.6%). During normoxia, placental T1 = 1825 ± 141 ms (avg ± standard deviation) and T2 = 60 ± 16 ms (gestational age range 24.3-36.7, median 32.6 weeks). In the statistical model, placental T2 rose and T1 remained contant after hyperoxia, and no GA dependency was observed for T1 or T2. DISCUSSION: Well-characterized, motion-robust MRF was used to acquire T1 and T2 maps of the placenta. Changes with hyperoxia are consistent with a net increase in oxygen saturation. Toward the goal of whole-placenta quantitative oxygenation imaging over time, we aim to implement 3D MRF with integrated motion correction to improve T2 accuracy.

Establishing Better Evidence on Remote Monitoring for Postpartum Hypertension: A Silver Lining of the Coronavirus Pandemic.

The transformation of our health care system in response to coronavirus disease 2019 (COVID-19) provides a unique opportunity to examine the use of telehealth for postpartum care. The postpartum period can pose significant risks and challenges, particularly for women with hypertensive disorders of pregnancy. Remote blood pressure monitoring has proven feasible and acceptable among women and providers but has not been widely implemented or researched. Early studies have identified improved outcomes with use of telehealth, including increased compliance with care and decreased disparity in hypertension follow-up. Preliminary data make a compelling case for remote monitoring as a promising treatment strategy to manage postpartum hypertension. Remote monitoring technology should be incorporated as a standard component for the comprehensive management of postpartum hypertension during COVID-19. As a consequence of the pandemic, we now have an opportunity to research the impact of postpartum remote blood pressure monitoring on maternal outcome and disparities within these outcomes.

Placental MRI: Development of an MRI compatible ex vivo system for whole placenta dual perfusion.

PURPOSE: Placental dysfunction plays a key role in diseases that affect the fetus in utero and after birth. Aiming to develop a platform for validating in vivo placental MRI and investigations into placental physiology, we designed and built a prototype MRI-compatible perfusion chamber with an integrated MRI receive coil for high SNR ex vivo placental imaging. PRINCIPAL RESULTS: After optimizing placenta vascular clearing and perfusion protocols, we performed contrast enhanced MR angiography and MR relaxometry on eight carefully selected placentas while they were perfused via the umbilical arteries (UAs). Additionally, two of these placentas underwent maternal perfusion via the intervillous space (IVS). Despite striving for homogenous perfusion across the whole placenta, imaging results were highly heterogeneous for both UA and IVS perfused placentas. By histology, we observed blood congestion in the villi in regions that showed low UA perfusion during MRI. In two placentas prominent chorionic arteries followed by adjacent veins underwent contrast enhancement in the absence of villous capillary blush. The single placenta from a pregnancy affected by IUGR had the most homogeneous villous capillary perfusion. MAJOR CONCLUSIONS: A dual perfusion system for ex vivo placentas compatible with MRI permitted assessment of UA and IVS placental perfusion. We observed spatial UA perfusion heterogeneity and evidence for arteriovenous shunting in placentas from normal pregnancies and deliveries, but relative villous capillary perfusion homogeneity in a single IUGR placenta. Future work will focus on system optimization, followed by physiological manipulation and validation of in vivo placental MRI.

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Placental MRI: Effect of maternal position and uterine contractions on placental BOLD MRI measurements.

INTRODUCTION: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia. METHODS: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O2), followed by 5 min of 100% FiO2. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R2* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions. RESULTS: In mothers without contractions, increases in global placental R2* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R2* decreases during the contraction. CONCLUSION: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R2* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals.

Cardiac Surgery During Pregnancy.

The need for cardiac surgery during pregnancy is rare. Only 1% to 4% of pregnancies are complicated by maternal cardiac disease and most of these can be managed with medical therapy and lifestyle changes. On occasion, whether due to natural progression of the underlying cardiac disease or precipitated by the cardiovascular changes of pregnancy, cardiac surgical therapy must be considered. Cardiac surgery is inherently dangerous for both, the mother and fetus with mortality rates near 10% and 30%, respectively. For some conditions, percutaneous cardiac intervention offers effective therapy with far less risk to the mother and her fetus. For others, cardiac surgery, including procedures that mandate the use of cardiopulmonary bypass, must be entertained to save the life of the mother. Given the extreme risks to the fetus, if the patient is in the third trimester, strong consideration should be given to delivery before surgery involving cardiopulmonary bypass. At earlier gestational ages when this is not feasible, modifications to the perfusion protocol including higher flow rates, normothermic perfusion, pulsatile flow, and the use of intraoperative external fetal heart rate monitoring should be considered.

Preliminary evaluation of dynamic glucose enhanced MRI of the human placenta during glucose tolerance test.

BACKGROUND: To investigate dynamic glucose enhanced (DGE) chemical exchange saturation transfer (CEST) MRI as a means to non-invasively image glucose transport in the human placenta. METHODS: Continuous wave (CW) CEST MRI was performed at 3.0 Tesla. The glucose contrast enhancement (GCE) was calculated based on the magnetization transfer asymmetry (MTRasym), and the DGE was calculated with the positive side of Z-spectra in reference to the first time point. The glucose CEST (GlucoCEST) was optimized using a glucose solution phantom. Glucose solution perfused ex vivo placenta tissue was used to demonstrate GlucoCEST MRI effect. The vascular density of ex vivo placental tissue was evaluated with yellow dye after MRI scans. Finally, we preliminarily demonstrated GlucoCEST MRI in five pregnant subjects who received a glucose tolerance test. For human studies, the dynamic R2* change was captured with T2*-weighted echo planar imaging (EPI). RESULTS: The GCE effect peaks at a saturation B1 field of about 2 µT, and the GlucoCEST effect increases linearly with the glucose concentration between 4-20 mM. In ex vivo tissue, the GlucoCEST MRI was sensitive to the glucose perfusate and the placenta vascular density. Although the in vivo GCE baseline was sensitive to field inhomogeneity and motion artifacts, the temporal evolution of the GlucoCEST effect showed a consistent and positive response after oral glucose tolerance drink. CONCLUSIONS: Despite the challenges of placental motion and field inhomogeneity, our study demonstrated the feasibility of DGE placenta MRI at 3.0 Tesla.

Placental MRI: Developing Accurate Quantitative Measures of Oxygenation.

The Human Placenta Project has focused attention on the need for noninvasive magnetic resonance imaging (MRI)-based techniques to diagnose and monitor placental function throughout pregnancy. The hope is that the management of placenta-related pathologies would be improved if physicians had more direct, real-time measures of placental health to guide clinical decision making. As oxygen alters signal intensity on MRI and oxygen transport is a key function of the placenta, many of the MRI methods under development are focused on quantifying oxygen transport or oxygen content of the placenta. For example, measurements from blood oxygen level-dependent imaging of the placenta during maternal hyperoxia correspond to outcomes in twin pregnancies, suggesting that some aspects of placental oxygen transport can be monitored by MRI. Additional methods are being developed to accurately quantify baseline placental oxygenation by MRI relaxometry. However, direct validation of placental MRI methods is challenging and therefore animal studies and ex vivo studies of human placentas are needed. Here we provide an overview of the current state of the art of oxygen transport and quantification with MRI. We suggest that as these techniques are being developed, increased focus be placed on ensuring they are robust and reliable across individuals and standardized to enable predictive diagnostic models to be generated from the data. The field is still several years away from establishing the clinical benefit of monitoring placental function in real time with MRI, but the promise of individual personalized diagnosis and monitoring of placental disease in real time continues to motivate this effort.