Association between placental oxygen transport and fetal brain cortical development: a study in monochorionic diamniotic twins.

Normal cortical growth and the resulting folding patterns are crucial for normal brain function. Although cortical development is largely influenced by genetic factors, environmental factors in fetal life can modify the gene expression associated with brain development. As the placenta plays a vital role in shaping the fetal environment, affecting fetal growth through the exchange of oxygen and nutrients, placental oxygen transport might be one of the environmental factors that also affect early human cortical growth. In this study, we aimed to assess the placental oxygen transport during maternal hyperoxia and its impact on fetal brain development using MRI in identical twins to control for genetic and maternal factors. We enrolled 9 pregnant subjects with monochorionic diamniotic twins (30.03 ± 2.39 gestational weeks [mean ± SD]). We observed that the fetuses with slower placental oxygen delivery had reduced volumetric and surface growth of the cerebral cortex. Moreover, when the difference between placenta oxygen delivery increased between the twin pairs, sulcal folding patterns were more divergent. Thus, there is a significant relationship between placental oxygen transport and fetal brain cortical growth and folding in monochorionic twins.

Intrapartum ultrasound measurement of angle of progression at the onset of the second stage of labor for prediction of spontaneous vaginal delivery in term singleton pregnancies: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the diagnostic performance of transperineal ultrasound-measured angles of progression at the onset of the second stage of labor for the prediction of spontaneous vaginal delivery in singleton term pregnancies with cephalic presentation. DATA SOURCES: We performed a predefined systematic search in PubMed, Embase, Scopus, Web of Science, and Google Scholar from inception to February 5, 2021. STUDY ELIGIBILITY CRITERIA: Prospective cohort studies that evaluated the diagnostic performance of transperineal ultrasound-measured angles of progression (index test) at the onset of the second stage of labor (ie, when complete cervical dilation is diagnosed) for the prediction of spontaneous vaginal delivery (reference standard) were eligible for inclusion. Eligible studies were limited to those published as full-text articles in the English language and those that included only parturients with a singleton healthy fetus at term with cephalic presentation. STUDY APPRAISAL AND SYNTHESIS METHODS: Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Summary receiver operating characteristic curves, pooled sensitivities and specificities, area under the curve, and summary likelihood ratios were calculated using the Stata software. Subgroup analyses were done based on angle of progression ranges of 108° to 119°, 120° to 140°, and 141° to 153°. RESULTS: A total of 8 studies reporting on 887 pregnancies were included. Summary estimates of the sensitivity and specificity of transperineal ultrasound-measured angle of progression at the onset of the second stage of labor for predicting spontaneous vaginal delivery were 94% (95% confidence interval, 88%-97%) and 47% (95% confidence interval, 18%-78%), respectively, for an angle of progression of 108° to 119°, 81% (95% confidence interval, 70%-89%) and 73% (95% confidence interval, 57%-85%), respectively, for an angle of progression of 120° to 140°, and 66% (95% confidence interval, 56%-74%) and 82% (95% confidence interval, 66%-92%), respectively, for an angle of progression of 141° to 153°. Likelihood ratio syntheses gave overall positive likelihood ratios of 1.8 (95% confidence interval, 1-3.3), 3 (95% confidence interval, 2-4.7), and 3.7 (95% confidence interval, 1.7-8.1) and negative likelihood ratios of 0.13 (95% confidence interval, 0.07-0.22), 0.26 (95% confidence interval, 0.18-0.38), and 0.42 (95% confidence interval, 0.29-0.60) for angle of progression ranges of 108° to 119°, 120° to 140°, and 141° to 153°, respectively. CONCLUSION: Angle of progression measured by transperineal ultrasound at the onset of the second stage of labor may predict spontaneous vaginal delivery in singleton, term, cephalic presenting pregnancies and has the potential to be used along with physical examinations and other clinical factors in the management of labor and delivery.

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.

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.

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.

Timing of Antenatal Corticosteroid Administration in Monoamniotic Twins.

Objective This study was aimed to determine if different strategies of antenatal corticosteroid (ACS) administration in monoamniotic twins leads to receipt within 7 days of delivery. Study Design This is a retrospective cohort of monoamniotic twins managed at a single institution from 2007 to 2017. Patients were classified as to whether ACS were administered upon admission or at a predetermined gestational age (grouped together as "routine") or for a change in clinical status ("indicated"). We used univariate analyses to associate ACS administration strategies with our primary outcome: receipt of ACS within 7 days of delivery. We then used generalized estimating equations to examine associations between fetal monitoring patterns and delivery within 1 week. Results Twenty-four patients were included: eighteen patients in the "routine" group and six patients in the "indicated" group. There was no difference in optimal timing of ACS administration. Women experiencing delivery within the week were thrice more likely to spend on average more than 3 hours/day on the fetal monitor when compared with those who remained undelivered. Conclusion Administration of ACS on admission is not effective. Fetal heart rate tracing surveillance might be a better methodology to predict delivery and guide ACS administration.

Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy.

In humans, circulating levels of the hormone melatonin and the initiation of spontaneous labor are both higher at night than during the day. Since activation of uterine melatonin receptors can stimulate human in vitro uterine contractions and these receptors are only expressed on the uterine tissue of women in labor, we hypothesized that circulating melatonin concentrations would affect uterine contractions in vivo. We evaluated the impact of light-induced modulation of melatonin secretion on uterine contractions in women during late third trimester (~36-39 weeks) of pregnancy in two inpatient protocols. We found a significant (P < 0.05) positive linear association between circulating melatonin concentrations and the number of uterine contractions under both protocols. On average, uterine contractions increased between 1.4 and 2.1 contractions per 30 minutes for every 10 pg/mL*h increase in melatonin concentration. These findings have both basic science and clinical implications for pregnant women, since endogenous melatonin levels and melatonin receptor activity can be altered by light and/or pharmaceutical agents.

Evaluation of a Quality Improvement Intervention to Increase Vaginal Birth for Twins.

OBJECTIVE: To evaluate whether there was an association between the systematic promotion of twin vaginal delivery and an increase in the rates of twin vaginal birth. METHODS: We conducted a retrospective cohort study. We implemented a quality improvement initiative promoting twin vaginal delivery at an academic tertiary care center in 2013. The program included a needs assessment, simulation of vaginal twin delivery, online educational material, and the expansion of a dedicated twin clinic. We analyzed rates of twin vaginal birth in pregnancies at or beyond 24 weeks of gestation without a contraindication to labor, prior uterine surgery, or a demise or lethal anomaly of either twin. Using linear regression, we calculated annual adjusted rates of twin vaginal birth from 2010 to 2015 and in the 3 years before and after our intervention. We performed an interrupted time-series analysis estimating rates of change before and after the intervention to account for the influence of secular trend. RESULTS: Of 1,574 patients delivering twins, 897 (57%) were included, with 479 in the 3 years before and 418 in the 3 years after the intervention. Adjusted rates of vaginal delivery increased from 32.1% (n=153) to 44.2% (n=185) before and after the intervention (P<.01), with a decrease in elective cesarean delivery from 54.6% (n=479) to 44.3% (n=185) (P<.01). Rates of breech extraction increased after the intervention (5.7% vs 9.3%, P=.04). However, there was no difference in the rate of change in twin vaginal birth in the time period before (1.35% annual increase, P=.76) or after (5.8% annual increase, P=.40) the intervention. CONCLUSIONS: Although we observed an increased rate of twin vaginal birth in the time period after our intervention, because the rates of increase before and after the intervention were not statistically different, the increase is not attributable to our intervention and is more properly attributed to secular trend.

Angle of Progression on Ultrasound in the Second Stage of Labor and Spontaneous Vaginal Delivery.

OBJECTIVE: The objective of this study was to assess the association between the angle of progression (AoP) measured by transperineal ultrasound and mode of delivery and duration of the second stage. STUDY DESIGN: This is a prospective observational study of nulliparous women with a singleton gestation at term in which serial transperineal ultrasound examinations were obtained during the second stage of labor. Multivariable logistic regression and adjusted survival models were used for the analysis. RESULTS: A total of 137 patients were included in the analysis and median AoP for the study group was 153 degrees. The adjusted odds ratio (aOR) of requiring an operative delivery was 2.6 times higher for those patients who had an AoP < 153 degrees and the aOR of requiring a cesarean delivery was almost six times higher when compared with those patients who had an AoP ≥ 153 degrees (95% confidence interval [CI]: 1.0, 6.2; p = 0.04; aOR: 5.8, 95% CI: 1.2-28.3; p = 0.03, respectively). Those patients with an AoP < 153 degrees were at a higher hazard of staying pregnant longer (adjusted hazard ratio: 1.8, 95% CI: 1.2-2.8, p = 0.005). CONCLUSION: The AoP has the potential to predict spontaneous vaginal delivery and the duration of the second stage of labor which may be useful in counseling patients and managing their labor.

Clinical Factors Associated With Presentation Change of the Second Twin After Vaginal Delivery of the First Twin.

OBJECTIVE: To identify clinical factors associated with a change from vertex to nonvertex presentation in the second twin after vaginal birth of the first. METHODS: We assembled a retrospective cohort of women with viable vertex-vertex twin pregnancies who delivered the presenting twin vaginally. Women whose second twin changed from vertex to nonvertex after vaginal birth of the first were classified as experiencing an intrapartum change in presentation. Characteristics associated with intrapartum presentation change in a univariate analysis with a P value ≤.10 were then evaluated in a multivariate logistic regression model. RESULTS: Four-hundred fifty women met inclusion criteria, of whom 55 (12%) had intrapartum presentation change of the second twin. Women experiencing intrapartum presentation change were more likely to be multiparous (69% compared with 47%, P<.01) and to have had a change in the presentation of the second twin between the most recent antepartum ultrasonogram and the ultrasonogram done on admission to labor and delivery (11% compared with 4%, P=.04). In an adjusted analysis, multiparity and gestational age less than 34 weeks were significantly associated with presentation change (adjusted odds ratio [OR] 2.9, 95% CI 1.5-5.6 and adjusted OR 2.6, 95% CI 1.1-5.9, respectively). Women with intrapartum presentation change were more likely to undergo cesarean delivery for their second twin (44% compared with 7%, P<.01) with an adjusted OR of 10.50 (95% CI 5.20-21.20) compared with those with stable intrapartum presentation. Twenty of the 24 (83%) cesarean deliveries performed in the intrapartum presentation change group were done for issues related to malpresentation. CONCLUSION: Multiparity and gestational age less than 34 weeks are associated with intrapartum presentation change of the second twin.

In Vivo Quantification of Placental Insufficiency by BOLD MRI: A Human Study.

Fetal health is critically dependent on placental function, especially placental transport of oxygen from mother to fetus. When fetal growth is compromised, placental insufficiency must be distinguished from modest genetic growth potential. If placental insufficiency is present, the physician must trade off the risk of prolonged fetal exposure to placental insufficiency against the risks of preterm delivery. Current ultrasound methods to evaluate the placenta are indirect and insensitive. We propose to use Blood-Oxygenation-Level-Dependent (BOLD) MRI with maternal hyperoxia to quantitatively assess mismatch in placental function in seven monozygotic twin pairs naturally matched for genetic growth potential. In-utero BOLD MRI time series were acquired at 29 to 34 weeks gestational age. Maps of oxygen Time-To-Plateau (TTP) were obtained in the placentas by voxel-wise fitting of the time series. Fetal brain and liver volumes were measured based on structural MR images. After delivery, birth weights were obtained and placental pathological evaluations were performed. Mean placental TTP negatively correlated with fetal liver and brain volumes at the time of MRI as well as with birth weights. Mean placental TTP positively correlated with placental pathology. This study demonstrates the potential of BOLD MRI with maternal hyperoxia to quantify regional placental function in vivo.

Spatiotemporal alignment of in utero BOLD-MRI series.

PURPOSE: To present a method for spatiotemporal alignment of in-utero magnetic resonance imaging (MRI) time series acquired during maternal hyperoxia for enabling improved quantitative tracking of blood oxygen level-dependent (BOLD) signal changes that characterize oxygen transport through the placenta to fetal organs. MATERIALS AND METHODS: The proposed pipeline for spatiotemporal alignment of images acquired with a single-shot gradient echo echo-planar imaging includes 1) signal nonuniformity correction, 2) intravolume motion correction based on nonrigid registration, 3) correction of motion and nonrigid deformations across volumes, and 4) detection of the outlier volumes to be discarded from subsequent analysis. BOLD MRI time series collected from 10 pregnant women during 3T scans were analyzed using this pipeline. To assess pipeline performance, signal fluctuations between consecutive timepoints were examined. In addition, volume overlap and distance between manual region of interest (ROI) delineations in a subset of frames and the delineations obtained through propagation of the ROIs from the reference frame were used to quantify alignment accuracy. A previously demonstrated rigid registration approach was used for comparison. RESULTS: The proposed pipeline improved anatomical alignment of placenta and fetal organs over the state-of-the-art rigid motion correction methods. In particular, unexpected temporal signal fluctuations during the first normoxia period were significantly decreased (P < 0.01) and volume overlap and distance between region boundaries measures were significantly improved (P < 0.01). CONCLUSION: The proposed approach to align MRI time series enables more accurate quantitative studies of placental function by improving spatiotemporal alignment across placenta and fetal organs. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:403-412.

Dural Puncture Epidural Technique Improves Labor Analgesia Quality With Fewer Side Effects Compared With Epidural and Combined Spinal Epidural Techniques: A Randomized Clinical Trial.

BACKGROUND: The dural puncture epidural (DPE) technique is a modification of the combined spinal epidural (CSE) technique, where a dural perforation is created from a spinal needle but intrathecal medication administration is withheld. The DPE technique has been shown to improve caudal spread of analgesia compared with epidural (EPL) technique without the side effects observed with the CSE technique. We hypothesized that the onset of labor analgesia would follow this order: CSE > DPE > EPL techniques. METHODS: A total of 120 parturients in early labor were randomly assigned to EPL, DPE, or CSE groups. Initial dosing for EPL and DPE consisted of epidural 20 mL of 0.125% bupivacaine plus fentanyl 2 µg/mL over 5 minutes, and for CSE, intrathecal 0.25% bupivacaine 1.7 mg and fentanyl 17 µg. Upon block completion, a blinded coinvestigator assessed the outcomes. Two blinded obstetricians retrospectively interpreted uterine contractions and fetal heart rate tracings 1 hour before and after the neuraxial technique. The primary outcome was time to numeric pain rating scale (NPRS) ≤ 1 analyzed by using Kaplan-Meier curves and Cox proportional hazard model. Secondary outcomes included block quality, maternal adverse effects, uterine contraction patterns, and fetal outcomes analyzed by using the χ test with Yates continuity correction. RESULTS: There was no significant difference in the time to NPRS ≤ 1 between DPE and EPL (hazard ratio 1.4; 95% confidence interval [CI] 0.83-2.4, P = .21). DPE achieved NPRS ≤ 1 significantly slower than CSE (hazard ratio 0.36; 95% CI 0.22-0.59, P = .0001). The median times (interquartile range) to NPRS ≤ 1 were 2 (0.5-6) minutes for CSE, 11 (4-120) minutes for DPE, and 18 (10-120) minutes for EPL. Compared with EPL, DPE had significantly greater incidence of bilateral S2 blockade at 10 minutes (risk ratio [RR] 2.13; 95% CI 1.39-3.28; P < .001), 20 minutes (RR 1.60; 95% CI 1.26-2.03; P < .001), and 30 minutes (RR 1.18; 95% CI 1.01-1.30; P < .034), a lower incidence of asymmetric block after 30 minutes (RR 0.19; 95% CI 0.07-0.51; P < .001) and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; P = .011). Compared with CSE, DPE had a significantly lower incidence of pruritus (RR 0.15; 95% CI 0.06-0.38; P < .001), hypotension (RR 0.38; 95% CI 0.15-0.98; P = .032), combined uterine tachysystole and hypertonus (RR 0.22; 95% CI 0.08-0.60; P < .001), and physician top-up intervention (RR 0.45; 95% CI 0.23-0.86; p = .011). CONCLUSIONS: Analgesia onset was most rapid with CSE with no difference between DPE and EPL techniques. The DPE technique has improved block quality over the EPL technique with fewer maternal and fetal side effects than the CSE technique for parturients requesting early labor analgesia.

Chorioamniotic Separation Found on Obstetric Ultrasound and Perinatal Outcome.

Objective This study aims to evaluate pregnancy outcomes in patients with spontaneous and iatrogenic chorioamniotic separation diagnosed by ultrasound after 17 weeks. Methods This is a retrospective cohort study of women with a singleton pregnancy who were diagnosed with chorioamniotic separation (n = 106) after 17 weeks' gestation from January 2000 to January 2013. Patients with chorioamniotic separation were compared with a group of patients who had obstetric ultrasounds without a diagnosis of chorioamniotic separation. Those without chorioamniotic separation were matched (1:1) on gestational age on the date of the ultrasound ( ± 2 weeks) (n = 106). The primary outcome was preterm delivery (< 37 weeks). Secondary outcomes included intrauterine growth restriction, stillbirth, and neonatal morbidity. Results The rate of preterm delivery was significantly higher for those with chorioamniotic separation than for those without (57.5 vs. 17.1%, p < 0.0001). There were no significant differences in the rate of aneuploidy, intrauterine growth restriction, stillbirth, or neonatal demise. The rate of stillbirth was significantly higher among those with chorioamniotic separation diagnosed before 24 weeks as compared with those diagnosed after 24 weeks (9.7 vs. 0%, p = 0.03). Conclusions Chorioamniotic separation is associated with preterm delivery. If diagnosed before 24 weeks, the rate of stillbirth is significantly higher.

The Relationship Between Intertwin Membrane Separation and Pregnancy Outcome.

OBJECTIVE: To evaluate the association of intertwin membrane separation and pregnancy outcome. METHODS: This is a retrospective cohort study of women with dichorionic twins who were diagnosed with spontaneous intertwin membrane separation between 2004 and 2013 at a large tertiary care maternity hospital. Control participants were selected as the next two sets of dichorionic twins that delivered at the study institution after a case participant delivered and that did not have an intrauterine procedure. Maternal, fetal, and delivery characteristics were compared using Wilcoxon rank-sum tests. Logistic regressions were used to assess the association of membrane separation and preterm delivery. RESULTS: Among the 27 cases of spontaneous intertwin membrane separation, the median gestational age at diagnosis was 28 weeks (interquartile range 25.5-28.8) and the median gestational age at delivery was 37 weeks (interquartile range 35.3-37.0). The rate of preterm delivery, our primary outcome, was 48% for the case group and 76% for the control group (odds ratio [OR] 0.29, P=.01). The rate of spontaneous preterm delivery was also lower for the case group (19% compared with 44%; OR 0.25, P=.26) as was the rate of neonatal intensive care unit admission (37% compared with 61%; OR 0.37, P=.04). CONCLUSION: Our retrospective cohort study demonstrates that intertwin membrane separation is not associated with adverse outcomes in dichorionic twin pregnancies. Thus, it is reasonable to manage these pregnancies expectantly. LEVEL OF EVIDENCE: II.

Management of twins: vaginal or cesarean delivery?

Recent level I evidence from a single randomized-controlled trial has shown that there is no difference in fetal or neonatal outcomes (composite of fetal/neonatal death or serious neonatal morbidity) between planned cesarean delivery and planned vaginal delivery for twins between 32 and 38 6/7 weeks. As long as the presenting twin is vertex, vaginal delivery should be considered regardless of the presentation of the second twin. To avoid unnecessary cesarean deliveries and maternal morbidity, it is important to continue to train residents to perform obstetrics maneuvers necessary for vaginal delivery of twins such as vaginal breech extraction.