Placental mesenchymal disease masquerading as molar pregnancy with a favourable maternal and fetal outcome.

Placental mesenchymal dysplasia (PMD) is an exceptionally rare placental anomaly characterised by placentomegaly and grape-like vesicles resembling partial mole on ultrasonography, yet it can coexist with a viable fetus. We present the case of a primigravida who presented at 22 weeks gestation with a suspected partial mole but with a normally growing fetus. The differential diagnoses considered included placental mesenchymal disease, partial mole and twin pregnancy with molar pregnancy. With normal beta HCG levels and prenatal invasive testing reports, a probable diagnosis of PMD was made, and after thorough counselling, the decision was made to continue the pregnancy. The pregnancy progressed until 37 weeks, culminating in the uneventful delivery of a 2.4 kg healthy male infant. Histopathology confirmed PMD. Early recognition and management of PMD pose significant challenges, given its rarity. Prenatal identification of PMD during both early and late gestation could avert unnecessary termination of pregnancy.

A realistic aneurysm clipping simulation combining 3D-printed and placenta-based models-how I do it.

INTRODUCTION: Neurovascular surgery, particularly aneurysm clipping, is a critical skill for aspiring neurosurgeons. However, hands-on training opportunities are limited, especially with the growing popularity of endovascular techniques. To address this challenge, we present a novel neurovascular surgical training station that combines synthetic 3D-printed models with placental vascular structures to create a semi-realistic surgical field. METHODS: Our model consists of three components: a 3D-printed skull replica with anatomical landmarks, a malleable silicone parenchyma with a Sylvian fissure, and vascular layers (placenta). The placental vascular layer is catheterized and perfused to replicate pulsatile flow, offering a realistic aneurysm simulation. This innovative training station provides a cost-effective solution (approximately 200 USD once) without ethical constraints. Surgeons can practice essential skills such as Sylvian fissure dissection, managing anatomical constraints like bone, and achieving proximal vascular control. The model's realism allows for training in various scenarios, including clipping with different hand orientations and handling ruptures realistically. CONCLUSION: Our neurovascular surgical station bridges the gap between existing training models, offering affordability, ecological considerations, and minimal ethical concerns. It empowers neurosurgery residents to refine their skills in handling both emergencies and elective cases under close-to-real surgical conditions, with the potential for independent practice and senior supervision.

Comparing three cardiothoracic ratio measurement techniques and creating multivariable scoring system to predict Bart's hydrops fetalis at 17-22 weeks' gestation.

To assess the diagnostic performance of three cardiothoracic (CT) ratio techniques, including diameter, circumference, and area, for predicting hemoglobin (Hb) Bart's disease between 17 and 22 weeks' gestation, and to create a multivariable scoring system using multiple ultrasound markers. Before invasive testing, three CT ratio techniques and other ultrasound markers were obtained in 151 singleton pregnancies at risk of Hb Bart's disease. CT diameter ratio demonstrated the highest sensitivity among the other techniques. Significant predictors included CT diameter ratio > 0.5, middle cerebral artery-peak systolic velocity (MCA-PSV) > 1.5 multiples of the median, and placental thickness > 3 cm. MCA-PSV exhibited the highest sensitivity (97.8%) in predicting affected fetuses. A multivariable scoring achieved excellent sensitivity (100%) and specificity (84.9%) for disease prediction. CT diameter ratio exhibited slightly outperforming the other techniques. Increased MCA-PSV was the most valuable ultrasound marker. Multivariable scoring surpassed single-parameter analysis in predictive capabilities.

Velocity-selective arterial spin labeling perfusion measurements in 2nd trimester human placenta with varying BMI.

INTRODUCTION: Proper placental development is crucial to fetal health but is challenging to functionally assess non-invasively and is thus poorly characterized in populations. Body mass index (BMI) has been linked with adverse outcomes, but the causative mechanism is uncertain. Velocity-selective arterial spin labeling (VS-ASL) MRI provides a method to non-invasively measure placental perfusion with robustness to confounding transit time delays. In this study, we report on the measurement of perfusion in the human placenta in early pregnancy using velocity-selective arterial spin labeling (VS-ASL) MRI, comparing non-obese and obese participants. METHODS: Participants (N = 97) undergoing routine prenatal care were recruited and imaged with structural and VS-ASL perfusion MRI at 15 and 21 weeks gestation. Resulting perfusion images were analyzed with respect to obesity based on BMI, gestational age, and the presence of adverse outcomes. RESULTS: At 15 weeks gestation BMI was not associated with placental perfusion or perfusion heterogeneity. However, at 21 weeks gestation BMI was associated with higher placental perfusion (p < 0.01) and a decrease in perfusion heterogeneity (p < 0.05). In alignment with past studies, perfusion values were also higher at 21 weeks compared to 15 weeks gestation. In a small cohort of participants with adverse outcomes, at 21 weeks lower perfusion was observed compared to participants with uncomplicated pregnancies. DISCUSSION: These results suggest low placental perfusion in the early second trimester may not be the culpable factor driving associations of obesity with adverse outcomes.

Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints ß = 0.017, 95% CI [0.009; 0.025], bifurcation points ß = 0.012, 95% CI [0.006; 0.018], crossing points ß = 0.017, 95% CI [0.008; 0.025], vessel points ß = 0.01, 95% CI [0.002; 0.008], and total vascular length ß = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV ß = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV ß = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV ß = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV ß -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV ß = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically. LIMITATION, REASONS FOR CAUTION: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).

Two-dimensional (2D) placental ultrasound measurements - The correlation with placental volume measured by magnetic resonance imaging (MRI).

INTRODUCTION: Information about placental size in ongoing pregnancies may aid the identification of pregnancies with increased risk of adverse outcome. Placental volume can be measured using magnetic resonance imaging (MRI). However, this method is not universally available in antenatal care. Ultrasound is the diagnostic tool of choice in pregnancy. Therefore, we studied whether simple two-dimensional (2D) ultrasound placental measurements were correlated with placental volume measured by MRI. METHODS: We examined a convenience sample of 104 ongoing pregnancies at gestational week 27, using both ultrasound and MRI. The ultrasound measurements included placental length, width and thickness. Placental volume was measured using MRI. The correlation between each 2D placental ultrasound measurement and placental volume was estimated by applying Pearson's correlation coefficient (r). RESULTS: Mean placental length was 17.2 cm (SD 2.1 cm), mean width was 14.7 cm (SD 2.1 cm), and mean thickness was 3.2 cm (SD 0.6 cm). Mean placental volume was 536 cm3 (SD 137 cm3). The 2D ultrasound measurements showed poor correlation with placental volume (placental length; r = 0.27, width; r = 0.37, and thickness r = 0.13). DISCUSSION: Simple 2D ultrasound measurements of the placenta were poorly correlated with placental volume and cannot be used as proximate measures of placental volume. Our finding may be explained by the large variation between pregnancies in intrauterine placental shape.

A longitudinal and cross-sectional study of placental circulation between normal and placental insufficiency pregnancies.

INTRODUCTION: To longitudinally and cross-sectionally study the differences in the uterine artery pulsatility index (UTPI), umbilical artery pulsatility index (UAPI) and placental vascularization indices (PVIs, derived from 3-dimensional power Doppler) between normal and placental insufficiency pregnancies throughout gestation. METHODS: UTPI, UAPI and PVI were measured 6 times at 4- to 5- week intervals from 11 to 13+6 weeks-36 weeks. Preeclampsia (PE) and fetal growth restriction (FGR) were defined as placental insufficiency. Comparisons of UTPI, UAPI and PVI between normal and insufficiency groups were performed by one-way repeated measures analysis of variance. RESULTS: A total of 125 women were included: monitored regularly from the first trimester to 36 weeks of gestation: 109 with normal pregnancies and 16 with placental insufficiency. Longitudinal study of the normal pregnancy group showed that UTPI and UAPI decreased significantly every 4 weeks, while PVIs increased significantly every 8 weeks until term. In the placental insufficiency group however, this decrease occurred slower at 8 weeks intervals and UTPI stabilized after 24 weeks. No significant difference was noted in PVIs throughout pregnancy. Cross-sectional study from different stages of gestation showed that UTPI was higher in the insufficiency group from 15 weeks onward and PVIs were lower after 32 weeks. DISCUSSION: Compared to high-risk pregnancies with normal outcome, UTPI and UAPI needed a longer time to reach a significant change in those with clinical confirmation of placental insufficiency pregnancies and no significant change was found in PVI throughout gestation. UTPI was the earliest factor in detecting adverse outcome pregnancies.

Diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol as a biomarker of placental blood circulation in patients with placenta accreta spectrum disorders: A proof-of-concept study.

OBJECTIVES: Increasing trend of PAS (placenta accreta spectrum disorders) incidence is a major health concern as PAS is associated with high maternal morbidity and mortality during cesarean section. Prenatal identification of PAS is crucial for delivery planning and patients management. This study aims to explore whether diffusion-derived vessel density (DDVD) computed from a simple diffusion MRI protocol differs in PAS from normal placenta. METHODS: We enrolled 86 patients with PAS disorders and 40 pregnant women without PAS disorders. Each patient underwent intravoxel incoherent motion (IVIM) MRI sequence with 11 b-values. Placenta diffusion-derived vessel density (DDVD-b0b50) was the signal difference between b = 0 and b = 50 s/mm2 images. DDVD(b0b50) A/N was calculated as [accreta lesion DDVD(b0b50)]/ [normal placenta DDVD(b0b50)]. The correlation between DDVD and gestational age was explored using Spearman rank correlation. Differences of DDVD(b0b50) A/N in patients with normal placentas and with PAS, and in patients with different subtypes of PAS were explored. RESULTS: DDVD was negatively correlated with gestational age (p = 0.023, r = -0.359) in patients with normal placentas. DDVD(b0b50) A/N was significantly higher in patients with PAS (median:1.16, mean: 1.261) than normal placenta (median:1.02, mean: 1.032, p < 0.001) and especially higher in patients with placenta increta (median:1.14, mean: 1.278) and percreta (median: 1.20, mean: 1.396, p < 0.001). CONCLUSION: As a higher DDVD indicates higher physiological volume of micro-vessels in PAS, this study suggests DDVD can be a potential biomarker to evaluate the placenta perfusion.

Predictive value of placental real-time shear wave elastography combined with 3-dimensional power Doppler index for preeclampsia.

This study aimed to investigate the value of placental real-time shear wave elastography combined with three-dimensional power Doppler index (3D-PDI) in the prediction of preeclampsia. We conducted a retrospective study selecting 60 pregnant women diagnosed with preeclampsia as the experimental group and 60 normal pregnant women as the control group from January 2021 to December 2022. The elastic modulus values of different regions of the placenta and placental 3D-PDI were detected and compared between the two groups. The ROC curve was used to evaluate the diagnostic value of each parameter, alone or in combination, for preeclampsia. The study findings demonstrated that the elastic modulus values of different regions of the placenta and 3D-PDI of the two groups have statistical significance. The values of SWE, VI, FI, and VFI are different in prediction of preeclampsia, and the combination of various parameters can improve the prediction value. Overall, our study provides a valuable method for the prediction of preeclampsia with the advantages of non-invasiveness, efficiency, and simplicity.

Impact of birth weight to placental weight ratio and other perinatal risk factors on left ventricular dimensions in newborns: a prospective cohort analysis.

OBJECTIVES: To investigate the association between birth weight to placental weight (BW/PW) ratio, and echocardiographic left ventricle (LV) morphology at birth, while accounting for other relevant perinatal factors. METHODS: A prospective cohort study was conducted on neonates at NewYork-Presbyterian Brooklyn Methodist Hospital from 2014 to 2018, categorized by their BW/PW percentile. Missing data were imputed with principal component analysis. Chi-squared and one-way analysis of variance were used to compare BW/PW groups and the best regression model was selected using a genetic and backward stepwise algorithm. RESULTS: We analyzed 827 neonates in three BW/PW groups: small (n=16), normal (n=488), and large (n=323). Placental thickness and smallest diameter were positively correlated with several LV parameters, including inter-ventricular septal thickness during diastole (IVSd) (p=0.002, p<0.001) and systole (IVSs) (p=0.001, p<0.001), LV posterior wall thickness at end of diastole (LVPWd) (p=0.003, p<0.001) and systole (LVPWs) (p<0.001, p<0.001), LV mass (p=0.017, p<0.001), and LV mass/volume (p=0.011, p<0.001). The BW/PW ratio correlated with an increased shortening fraction (estimate=0.29, 95 % CI 0.03-0.55, p=0.027). PW correlated with IVSs (p=0.019), while the longest placental diameter was linked to a decrease in LV internal dimension during diastole (LVIDd) (estimate=-0.07, p=0.039), LV mass (estimate=-0.11, p=0.024), and LV mass/volume (estimate=-0.55, p=0.005). CONCLUSIONS: This study found that several placental factors, including the BW/PW ratio, can independently affect LV dimension and morphology, highlighting the importance of fetal growth and placental health in the physiological adaptation of the fetal heart. More research is needed to establish causation and inform newborn prevention strategies.

Predictive value of ultrasonic artificial intelligence in placental characteristics of early pregnancy for gestational diabetes mellitus.

Background: To explore the predictive value of placental features in early pregnancy for gestational diabetes mellitus (GDM) using deep and radiomics-based machine learning (ML) applied to ultrasound imaging (USI), and to develop a nomogram in conjunction with clinical features. Methods: This retrospective multicenter study included 415 pregnant women at 11-13 weeks of gestation from two institutions: the discovery group from center 1 (n=305, control group n=166, GDM group n=139), and the independent validation cohort (n=110, control group n=57, GDM group n=53) from center 2. The 2D USI underwent pre-processed involving normalization and resampling. Subsequently, the study performed screening of radiomics features with Person correlation and mutual information methods. An RBF-SVM model based on radiomics features was constructed using the five-fold cross-validation method. Resnet-50 as the backbone network was employed to learn the region of interest and constructed a deep convolutional neural network (DLCNN) from scratch learning. Clinical variables were screened using one-way logistic regression, with P<0.05 being the threshold for statistical significance, and included in the construction of the clinical model. Nomogram was built based on ML model, DLCNN and clinical models. The performance of nomogram was assessed by calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Results: The AUCs for the ML model in the discovery cohort and independent validation cohort were 0.91 (0.88-0.94) and 0.86 (0.79-0.93), respectively. And 0.65 (0.59-0.71), 0.69 (0.59-0.79) for the DLCNN, 0.66 (0.59-0.72), 0.66 (0.55-0.76) for the clinical model, respectively. The nomogram exhibited the highest performance with AUCs of 0.93 (0.90-0.95) and 0.88 (0.81-0.94) The receiver operating characteristic curve (ROC) proved the superiority of the nomogram of clinical utility, and calibration curve showed the goodness of fit of the model. The DCA curve indicated that the nomogram outperformed other models in terms of net patient benefit. Conclusions: The study emphasized the intrinsic relationship between early pregnancy placental USI and the development of GDM. The use of nomogram holds potential for clinical applications in predicting the development of GDM.

Longitudinal intravital imaging of mouse placenta.

Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.

Value of early pregnancy ultrasound combined with ultrasound score in the evaluation of placenta accreta in scar uterus: A retrospective cohort study.

The objective of this study is to investigate the value of early pregnancy ultrasound combined with ultrasound score (USS) for the evaluation of placenta accreta (PA) in scar uteri. Thirty cases of PA in scar uteri diagnosed by ultrasound at our hospital between June 2021 and June 2022 were selected retrospectively (observation group). In addition, 30 patients had placenta attached to the anterior wall of the uterus and covered the internal orifice of the cervix; however, no PA was selected in the same period (control group). The results of surgical pathology and ultrasound examination in the first trimester of pregnancy (11-14 weeks of pregnancy, fetal top hip length 4.5-8.4 cm) were analyzed. Ultrasonic image characteristics of the 2 groups were scored using an ultrasonic scoring scale. The ultrasonic signs and ultrasonic scores of the 2 groups were analyzed. The diagnostic value of ultrasound and USS for PA in the scarred uterus alone and in combination was analyzed based on the gold standard of surgical and pathological results. The rich blood flow signal at the junction of the uterine serosa and bladder, the rate of blood flow in the cavity of the placental parenchyma, the thinning rate of the myometrium after placenta, and the abnormal rate of the low echo area after placenta in the observation group were significantly higher than those in the control group (P < .05). The USS of the observation group was significantly higher than that of the control group (P < .05). The sensitivity (93.33%) and accuracy (95.00%) of the combined examinations were significantly higher than those of ultrasound (70.00% and 83.33%, respectively) (P < .05). The sensitivity and accuracy of combined examination were slightly higher than those of USS examination (83.33% and 90.00%), but the difference was not statistically significant (P > .05). There was no significant difference between the specificity of combined examination (93.33%) and ultrasound (96.67%) and USS (96.67%) (P > .05). Early pregnancy ultrasound and USS evaluation have high application value in the diagnosis and evaluation of early scar uterine PA. The combination of the 2 methods can further improve the sensitivity and accuracy of diagnosis.

Effects of permanent placental injury due to severe acute respiratory syndrome coronavirus 2 infection during pregnancy on the feto-placental circulation: a cross-sectional study.

OBJECTIVE: The aim of this study was to evaluate the effects of permanent placental injury due to a severe acute respiratory syndrome coronavirus 2 infection during pregnancy on feto-placental circulation. METHODS: In this cross-sectional study, 83 pregnant women with planned deliveries were divided into two groups according to their severe acute respiratory syndrome coronavirus 2 infection statuses during pregnancy. Their demographic parameters, obstetric histories, and prenatal risks were evaluated. A prenatal fetal Doppler ultrasound examination was performed for all participants, and umbilical artery and middle cerebral artery Doppler parameters were obtained. Postpartum placentas were examined for pathological findings under appropriate conditions. All placentas were evaluated according to the Amsterdam consensus criteria. Mann-Whitney U test, Student's t-test, and chi-square test were used for comparisons. RESULTS: Demographic parameters were statistically similar, except that they were borderline significant for gestational weeks at delivery (p=0.044). In the pathological examination of the placenta, regardless of the trimester of exposure to viral infection, perivillous fibrin deposition and villus dystrophic calcification were more common in group 2 (p=0.016 and p=0.048, respectively) than in group 1. In the prenatal Doppler examination between the groups, no statistically significant difference was found for all of the umbilical artery pulsatile index, middle cerebral artery pulsatile index, and cerebro-placental ratio values. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy causes an increase in perivillous fibrin deposition and villus dystrophic calcification in the placenta. Placental injury caused by the severe acute respiratory syndrome coronavirus 2 virus does not affect fetal Doppler parameters.

Clinical significance of three-dimensional power Doppler combined with two-dimensional Doppler ultrasonography for evaluating fetal growth restriction.

OBJECTIVES: To assess the predictive accuracy of three-dimensional (3D) power Doppler combined with two-dimensional (2D) Doppler ultrasonography in detecting fetal growth restriction (FGR). METHODS: The study was conducted on singleton pregnancies presenting for growth ultrasound examinations between 20 and 40 weeks of gestation. 63 patients with FGR were enrolled and matched 1:1.8 for gestational age with normal fetuses. Both groups were further divided into subgroups, with 32 weeks as the threshold-early-onset and late-onset FGR groups, and corresponding control groups. Conventional 2D Doppler parameters and standardized 3D power Doppler measurements of the placenta, including vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were obtained for each patient. RESULTS: (1) The average gestational weeks of delivery and birth weight of newborns in early-onset and late-onset FGR case groups were lower than those in control groups, while the incidence of placenta previa and adverse pregnancy outcomes were higher than those in control groups. (2) The biparietal diameter, head circumference, abdominal circumference, femur length, estimated fetal weight, middle cerebral artery systolic/diastolic velocity ratio (S/D), pulsatility index (PI), resistance index (RI), and placental blood perfusion indices of vascular index (VI), flow index (FI), vascular flow index (VFI), and cerebro-placental ratio (CPR) of the early-onset and late-onset FGR case groups were all lower than those of the control group. Moreover, the S/D, PI, and RI of the umbilical and uterine arteries were higher than those of the corresponding control group. (3) For early-onset FGR, the area under the curve (AUC) of the umbilical artery PI was the largest (0.861), exhibiting the highest predictive value. When combined with the placental blood perfusion index, the AUC was 0.789. For late-onset FGR, the AUC of the CPR was 0.861. After integrating the placental blood perfusion index, the AUC increased to 0.877. The positive likelihood ratio (PLR) of combined 2D Doppler indexes (21.938) and negative likelihood ratio (NLR) of VFI (0.565) were the highest in the early-onset FGR group. The PLR of combined 3D Doppler indexes (8.536) and NLR of VFI (0.557) were the highest in the late-onset FGR group. CONCLUSIONS: The combination of 3D Doppler indices with 2D Doppler ultrasonography demonstrated superior predictive value in diagnosing late-onset FGR compared to other conventional indicators. The 3D Dower index, VFI, has a good true-negative predictive value for both early- and late-onset FGR.

First-trimester 3D power Doppler imaging markers of utero-placental vascular development are associated with placental weight and diameter at birth: The Rotterdam Periconception Cohort.

INTRODUCTION: Early utero-placental vascular development impacts placental development and function throughout pregnancy. We investigated whether impaired first-trimester utero-placental vascular development is associated with pathologic features of the postpartum placenta. METHODS: In this prospective observational study of 65 ongoing pregnancies, we obtained three-dimensional power Doppler ultrasounds of the placenta at 7, 9 and 11 weeks of gestation. We applied VOCAL software to measure placental volume (PV), virtual reality based segmentation to measure utero-placental vascular volume (uPVV) and applied a skeletonization algorithm to generate the utero-placental vascular skeleton (uPVS). Vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-, crossing- or vessel point). Following delivery, placentas were measured and histologically examined according to the Amsterdam criteria to assess maternal vascular malperfusion (MVM). We used linear mixed models to estimate trajectories of PV, uPVV and uPVS development. Multivariable linear regression analysis with adjustments for confounders was used to evaluate associations between PV, uPVV and uPVS development and features of the postpartum placenta. RESULTS: We observed no associations between first-trimester PV development and measurements of the postpartum placenta. Increased first-trimester utero-placental vascular development, reflected by uPVV (ß = 0.25 [0.01; 0.48]), uPVS end points (ß = 0.25 [0.01; 0.48]), bifurcation points (ß = 0.22 [0.05; 0.37]), crossing points (ß = 0.29 [0.07; 0.52]) and vessel points (ß = 0.09 [0.02; 0.17]) was positively associated with the postpartum placental diameter. uPVV was positively associated with postpartum placental weight. No associations were found with MVM. DISCUSSION: Development of the first-trimester utero-placental vasculature is associated with postpartum placental size, whereas placental tissue development contributes to a lesser extent.

Evaluation of utero-placental vascularization using contrast-enhanced ultrasound: Early first trimester maternal perfusion of the intervillous space is confirmed.

INTRODUCTION: The objective was to confirm and semiquantify the maternal perfusion of the intervillous space between 8 and 13 + 6 gestational weeks (GW). METHODS: We conducted a prospective, multicenter, and nonrandomized open study. Women undergoing voluntary termination of pregnancy at three different gestational ages (Group 8 GW: 8 to 8 + 6 GW, Group 11GW: 11 to 11 + 6 GW and Group 13GW: 13 to 13 + 6 GW) were included, with 14 subjects per group. Women presenting with a personal risk of preeclampsia and/or intrauterine growth restriction were excluded. Contrast-enhanced ultrasound (CEUS) was performed with an intravenous bolus administration of 2.4 mL of microbubbles. The region of interest (ROI) was the entire placenta. The perfusion curves and kinetic parameters, including wash-in perfusion index, peak enhancement and mean transit time, were calculated. RESULTS: Of the 42 women initially included, interpretable perfusion curves could be obtained for 33. Regardless of the gestational age, contrast was observed in the entire placenta. No significant difference in perfusion parameters was observed between groups. There was an association between signal intensity and both maternal heart frequency and placental location. Signal intensity was decreased when the heart frequency increased (p < 0.05) and when the placenta was in a nonanterior position (p > 0.005). DISCUSSION: We confirmed the presence of maternal perfusion of the intervillous space as early as 8 GW. No significant increase in perfusion parameters was observed between 8 and 13 + 6 GW. Our observations, in accordance with the previous experiment published by Roberts et al.1, strongly challenge the classic trophoblastic plug theory.

Placental Pathology Contributes to Impaired Volumetric Brain Development in Neonates With Congenital Heart Disease.

BACKGROUND: Neonates with congenital heart disease are at risk for impaired brain development in utero, predisposing children to postnatal brain injury and adverse long-term neurodevelopmental outcomes. Given the vital role of the placenta in fetal growth, we assessed the incidence of placental pathology in fetal congenital heart disease and explored its association with total and regional brain volumes, gyrification, and brain injury after birth. METHODS AND RESULTS: Placentas from 96 term singleton pregnancies with severe fetal congenital heart disease were prospectively analyzed for macroscopic and microscopic pathology. We applied a placental pathology severity score to relate placental abnormalities to neurological outcome. Postnatal, presurgical magnetic resonance imaging was used to analyze brain volumes, gyrification, and brain injuries. Placental analyses revealed the following abnormalities: maternal vascular malperfusion lesions in 46%, nucleated red blood cells in 37%, chronic inflammatory lesions in 35%, delayed maturation in 30%, and placental weight below the 10th percentile in 28%. Severity of placental pathology was negatively correlated with cortical gray matter, deep gray matter, brainstem, cerebellar, and total brain volumes (r=-0.25 to -0.31, all P<0.05). When correcting for postmenstrual age at magnetic resonance imaging in linear regression, this association remained significant for cortical gray matter, cerebellar, and total brain volume (adjusted R2=0.25-0.47, all P<0.05). CONCLUSIONS: Placental pathology occurs frequently in neonates with severe congenital heart disease and may contribute to impaired brain development, indicated by the association between placental pathology severity and reductions in postnatal cortical, cerebellar, and total brain volumes.

Is salivary uric acid, a putative biomarker of pre-eclampsia, of maternal, placental, or fetal origin?

OBJECTIVES: Increased salivary uric acid (sUA) represents a potential biomarker predictive of pre-eclampsia (PE), but its origin is unclear. The study explores whether sUA levels reflect maternal or feto-placental physiological stress and whether sUA levels in these cases correlate with amniotic fluid (fetal origin), maternal blood (maternal origin), or cord blood (fetal vs placental origin). STUDY DESIGN: Pregnant women (n = 39) undergoing amniotomy or caesarean section after 34 gestational weeks were designated into three groups of either maternal, feto-placental, or no signs of physiological stress: women (n = 15) in the established first phase of active labour and without any signs of fetal growth restriction (FGR) or PE were assigned to the maternal stress group, women (n = 6) with an ultrasound-based diagnosis of FGR, with or without PE, were assigned to the feto-placental stress group, and women (n = 18) not yet in active labour and without any signs of FGR or PE, were assigned to the control group. Uric acid levels in corresponding samples of amniotic fluid, saliva, maternal blood, and cord blood were compared between groups and between body compartments within each group. RESULTS: The feto-placental stress group showed increased UA levels in saliva (median, interquartile range [IQR]: 0.47 [0.38] mmol/L, P = 0.023) and maternal blood (0.42 [0.13] mmol/L, P = 0.032), but no differences in amniotic fluid or cord blood compared with the other groups. Within the control and maternal stress group, sUA levels were lower compared with maternal blood (0.20 [0.08] vs 0.25 [0.08] mmol/L, Pcontrol = 0.018; 0.20 [0.06] vs 0.26 [0.08] mmol/L, Pmaternal = 0.001) and highest in amniotic fluid (control group (0.49 [0.18] mmol/L): Pmaternal,blood = 0.001, Pumbilical,artery = <0.001, Pumbilical,vein = <0.001, Psaliva = <0.001) (maternal stress group (0.56 [0.23] mmol/L): Pmaternal,blood = 0.021, Pumbilical,artery = 0.006, Pumbilical,vein = 0.004, Psaliva = 0.003). Levels did not differ between compartments in the feto-placental stress group. CONCLUSIONS: Salivary and maternal blood UA levels were increased in the feto-placental stress group with salivary levels increasing more than blood levels compared with the maternal stress and control groups, whilst UA in amniotic fluid were not different between the groups, suggesting a placental origin and potential use of sUA as a biomarker of placental dysfunction, including FGR and severe PE.