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Study Question: Can three-dimensional (3D) Power Doppler (PD) ultrasound and a skeletonization algorithm be used to assess first-trimester development of the utero-placental vascular morphology?Summary Answer: The application of 3D PD ultrasonography and a skeletonization algorithm facilitates morphologic assessment of utero-placental vascular development in the first trimester and reveals less advanced vascular morphologic development in pregnancies with placenta-related complications than in pregnancies without placenta-related complications.What Is Known Already: Suboptimal development of the utero-placental vasculature is one of the main contributors to the periconceptional origin of placenta-related complications. The nature and attribution of aberrant vascular structure and branching patterns remain unclear, as validated markers monitoring first-trimester utero-placental vascular morphologic development are lacking.Study Design, Size, Duration: In this prospective observational cohort, 214 ongoing pregnancies were included before 10 weeks gestational age (GA) at a tertiary hospital between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception Cohort study.Participants/materials, Setting, Methods: By combining 3D PD ultrasonography and virtual reality, utero-placental vascular volume (uPVV) measurements were obtained at 7, 9 and 11 weeks GA. A skeletonization algorithm was applied to the uPVV measurements to generate the utero-placental vascular skeleton (uPVS), a network-like structure containing morphologic characteristics of the vasculature. Quantification of vascular morphology was performed by assigning a morphologic characteristic to each voxel in the uPVS (end-, vessel-, bifurcation- or crossing-point) and calculating total vascular network length. A Mann-Whitney U test was performed to investigate differences in morphologic development of the first-trimester utero-placental vasculature between pregnancies with and without placenta-related complications. Linear mixed models were used to estimate trajectories of the morphologic characteristics in the first trimester.Main Results and the Role Of Chance: All morphologic characteristics of the utero-placental vasculature increased significantly in the first trimester (P < 0.005). In pregnancies with placenta-related complications (n = 54), utero-placental vascular branching was significantly less advanced at 9 weeks GA (vessel points P = 0.040, bifurcation points P = 0.050, crossing points P = 0.020, total network length P = 0.023). Morphologic growth trajectories remained similar after adjustment for parity, conception mode, foetal sex and occurrence of placenta-related complications.Limitations, Reasons For Caution: The tertiary setting of this prospective observational study provides high internal, but possibly limited external, validity. Extrapolation of the study's findings should therefore be addressed with caution.Wider Implications Of the Findings: The uPVS enables assessment of morphologic development of the first-trimester utero-placental vasculature. Further investigation of this innovative methodology needs to determine its added value for the assessment of (patho-) physiological utero-placental vascular development.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). [ABSTRACT FROM AUTHOR]

Introduction: To investigate the reproducibility of first‐trimester fetal organ volume measurements using three‐dimensional (3D) ultrasound and a Virtual Reality system. Methods: Within a population‐based prospective cohort study, 3D ultrasound datasets of 25 first‐trimester fetuses were collected by three sonographers. We used the V‐scope application to perform Virtual Reality volume assessments of the fetal heart, lungs, and kidneys. All measurements were performed by two independent researchers. Results: Intraobserver analyses for volume measurements of the fetal heart, lungs, and kidneys showed intraclass correlation coefficients ≥0.86, mean differences ≤8.3%, and coefficients of variation ≤22.8%. Interobserver analyses showed sufficient agreement for right lung volume measurements, but consistent measurement differences between observers for left lung, heart, and kidney volume measurements (p‐values <0.05). Conclusion: We observed sufficient intraobserver reproducibility, but overall suboptimal interobserver reproducibility for first‐trimester fetal heart, lung, and kidney volume measurements using an innovative Virtual Reality approach. In the current stage, these measurements might be promising for the use in research settings. The reproducibility of the measurements might be further improved by novel post‐processing algorithms. [ABSTRACT FROM AUTHOR]

Aim: To assess the possibility of embryonic posture evaluation (=feasibility, reproducibility, variation) at rest at 9 weeks' (+0–6 days) gestational age (GA) using four‐dimensional ultrasound and virtual reality (VR) techniques. Moreover, it is hypothesized that embryonic posture shows variation at the same time point in an uneventful pregnancy. Methods: In this explorative prospective cohort study, 23 pregnant women were recruited from the Rotterdam periconceptional cohort. A transvaginal four‐dimensional ultrasound examination of 30 min per pregnancy was performed between 9 and 10 weeks' GA. The acquired datasets were offline evaluated longitudinally (i.e. per frame) using VR techniques. Results: The ultrasound data of 16 (70%) out of 23 pregnancies were eligible for evaluation. At rest the analysis of the embryonic posture was feasible and showed a strong (>80%) intraobserver and interobserver reproducibility for most body parts. The majority of the body parts were in similar anatomic positions at rest. However, variations in anatomic positions (e.g. 6% rotated head, 9% laterally bent spine), within and between embryos, were seen at 9 weeks' GA. Conclusion: In this unique study, we showed for the first time that embryonic posture measurements at rest can be performed in a reliable way using state‐of‐the‐art four‐dimensional ultrasound and VR techniques. Already early in prenatal life there are differences regarding posture within and between embryos. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between periconceptional maternal dietary pattern and first-trimester embryonic growth.Methods: This was a prospective cohort study of 228 women with a singleton ongoing pregnancy, of which 135 were strictly dated spontaneous pregnancies and 93 were pregnancies achieved after in-vitro fertilization or intracytoplasmatic sperm injection (IVF/ICSI). All women underwent serial transvaginal three-dimensional ultrasound (3D-US) examinations from 6 + 0 to 13 + 0 weeks' gestation. Crown-rump length (CRL) and embryonic volume (EV) measurements were performed using a virtual reality system. Information on periconceptional maternal dietary intake was collected via food frequency questionnaires. Principal component analysis was performed to identify dietary patterns. Associations between dietary patterns and CRL and EV trajectories were investigated using linear mixed models adjusted for potential confounders.Results: A median of five (range, one to seven) 3D-US scans per pregnancy were performed. Of 1162 datasets, quality was sufficient to perform CRL measurements in 991 (85.3%) and EV measurements in 899 (77.4%). A dietary pattern comprising high intake of fish and olive oil and a very low intake of meat was identified as beneficial for embryonic growth. In strictly dated spontaneous pregnancies, strong adherence to the 'high fish and olive oil, low meat' dietary pattern was associated with a 1.9 mm (95% CI, 0.1-3.63 mm) increase in CRL (+14.6%) at 7 weeks and a 3.4 mm (95% CI, 0.2-7.81 mm) increase (+6.9%) at 11 weeks, whereas EV increased by 0.06 cm3 (95% CI, 0.01-0.13 cm3 ) (+20.4%) at 7 weeks and 1.43 cm3 (95% CI, 0.99-1.87 cm3 ) (+14.4%) at 11 weeks. No significant association was observed in the total study population or in the IVF/ICSI subgroup.Conclusion: Periconceptional maternal adherence to a high fish and olive oil, low meat dietary pattern is positively associated with embryonic growth in spontaneously conceived pregnancies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background. With the introduction of three-dimensional (3D) ultrasound it has become possible to measure volumes. The relative increase in embryonic volume (EV) is much larger than that of the crown-rump length (CRL) over the same time period. We examined whether EV is a better parameter to determine growth restriction in fetuses with structural congenital abnormalities. Study Design, Subjects, and Outcome Measures. CRL and EV were measured using a Virtual Reality (VR) system in prospectively collected 3D ultrasound volumes of 56 fetuses diagnosed with structural congenital abnormalities in the first trimester of pregnancy (gestational age 7+5 to 14+5 weeks). Measured CRL and EV were converted to z-scores and to percentages of the expected mean using previously published reference curves of euploid fetuses. The one-sample t-test was performed to test significance. Results. The EV was smaller than expected for GA in fetuses with structural congenital abnormalities (−35%  p<0.001, z-score −1.44  p<0.001), whereas CRL was not (−6.43%  p=0.118, z-score −0.43  p=0.605). Conclusions. CRL is a less reliable parameter to determine growth restriction in fetuses with structural congenital abnormalities as compared with EV. By measuring EV, growth restriction in first-trimester fetuses with structural congenital abnormalities becomes more evident and enables an earlier detection of these cases. [ABSTRACT FROM AUTHOR]

Study Question: Is periconceptional maternal one-carbon (I-C) metabolism associated with embryonic morphological development in non-malformed ongoing pregnancies?Summary Answer: Serum vitamin B12, red blood cell (RBC) folate and plasma total homocysteine (tHcy) are associated with embryonic development according to the Carnegie stages.What Is Known Already: Derangements in maternal I-C metabolism affect reproductive and pregnancy outcomes, as well as future health of the offspring.Study Design, Size, Duration: Between 2010 and 2014, women with singleton ongoing pregnancies were enrolled in a prospective periconceptional cohort study.Participants/materials, Setting, Methods: A total of 234 pregnancies, including 138 spontaneous or IUI pregnancies with strict pregnancy dating and 96 pregnancies derived from IVF, ICSI or cryopreserved embryo transfer (IVF/ICSI pregnancies), underwent longitudinal transvaginal three-dimensional ultrasound (3D US) scans from 6+0 up to 10+2 weeks of gestation. Carnegie stages were defined using internal and external morphologic criteria in a virtual reality system. Maternal venous blood samples were collected at enrollment for serum vitamin B12, RBC folate and plasma tHcy assessment. Associations between biomarker concentrations and longitudinal Carnegie stages were investigated using linear mixed models.Main Results and the Role Of Chance: We performed a median of three 3D US scans per pregnancy (range 1-5) resulting in 600 good quality data sets for the Carnegie stage annotation (80.5%). Vitamin B12 was positively associated with embryonic development in the total study population (β = 0.001 (95% CI: 0.000; 0.002), P < 0.05) and in the subgroup of strictly dated spontaneous pregnancies (β = 0.002 (95% CI: 0.001; 0.003), P < 0.05). Low vitamin B12 concentrations (-2SD, 73.4 pmol/l) were associated with delayed embryonic development by 1.4 days (95% CI: 1.3-1.4) compared with high concentrations (+2SD, 563.1 pmol/l). RBC folate was positively associated with Carnegie stages only in IVF/ICSI pregnancies (β = 0.001 (95% CI: 0.0005; 0.0015), P < 0.05). In this group, low RBC folate concentrations (-2SD, 875.4 nmol/l) were associated with a 1.8-day delay (95% CI: 1.7-1.8) in development compared with high concentrations (+2SD, 2119.9 nmol/l). tHcy was negatively associated with embryonic development in the total study population (β = -0.08 (95% CI: -0.14; -0.02), P < 0.01), as well as in the IVF/ICSI subgroup (β = -0.08 (95% CI: -0.15; -0.01), P < 0.05). High tHcy concentrations (+2SD, 10.4 µmol/l) were associated with a delay of 1.6 days (95% CI: 1.5-1.7) in embryonic development compared with low concentrations (-2SD, 3.0 µmol/l).Limitations, Reasons For Caution: The study was performed in a tertiary care center, resulting in high rates of folic acid supplement use and comorbidity that may reduce the external validity of our findings.Wider Implications Of the Findings: In periconceptional care, maternal I-C biomarkers should be taken into account as predictors of embryonic morphological development. Combining embryonic size measurements with morphological assessment could better define normal embryonic development.Study Funding/competing Interest(s): The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. RPMST is CSO of the startup company Slimmere Zorg and CEO of eHealth Care Solutions. The authors declare no conflicts of interest.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Study Question: Can growth trajectories of the human embryonic head be created using 3D ultrasound (3D-US) and virtual reality (VR) technology, and be associated with second trimester fetal head size and periconceptional maternal conditions? Summary Answer: Serial first trimester head circumference (HC) and head volume (HV) measurements were used to create reliable growth trajectories of the embryonic head, which were significantly associated with fetal head size and periconceptional maternal smoking, age and ITALIC! in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) treatment. What Is Known Already: Fetal growth is influenced by periconceptional maternal conditions. Study Design, Size, Duration: We selected 149 singleton pregnancies with a live born non-malformed fetus from the Rotterdam periconception cohort. Participants/materials, Setting, Methods: Bi-parietal diameter and occipital frontal diameter to calculate HC, HV and crown-rump length (CRL) were measured weekly between 9 + 0 and 12 + 6 weeks gestational age (GA) using 3D-US and VR. Fetal HC was obtained from second trimester structural anomaly scans. Growth trajectories of the embryonic head were created with general additive models and linear mixed models were used to estimate associations with maternal periconceptional conditions as a function of GA and CRL, respectively. Main Results: A total of 303 3D-US images of 149 pregnancies were eligible for embryonic head measurements (intra-class correlation coefficients >0.99). Associations were found between embryonic HC and fetal HC ( ITALIC! ρ = 0.617, ITALIC! P < 0.001) and between embryonic HV and fetal HC ( ITALIC! ρ = 0.660, ITALIC! P < 0.001) in ITALIC! Z-scores. Maternal periconceptional smoking was associated with decreased, and maternal age and IVF/ICSI treatment with increased growth trajectories of the embryonic head measured by HC and HV (All ITALIC! P < 0.05). Limitations, Reasons For Caution: The consequences of the small effect sizes for neurodevelopmental outcome need further investigation. As the study population consists largely of tertiary hospital patients, external validity should be studied in the general population. Wider Implications Of the Findings: Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. Study Funding/competing Interests: This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. [ABSTRACT FROM AUTHOR]

Objective To investigate accuracy and reliability of four different ultrasound-related volume-measuring methods. Design Observational study. Setting Both in vitro and in vivo. Population or Sample Ten phantoms for in vitro measurements and 28 pregnancies with gestational ages ranging from 6 to 11 weeks for in vivo measurements were included. Methods Three-dimensional (3D) ultrasound images of phantoms (with known variable contents) and yolk sacs were used to calculate volumes using four different methods: Virtual Organ Computed-Aided AnaLysis (VOCAL), inversion mode, Sono Automatic Volume Calculation (SonoAVC) and V-Scope. V-Scope is a newly developed 3D volume visualisation application using a Barco I-Space virtual reality system. Intra- and interobserver agreement was established by calculating intraclass correlation coefficients (ICC). Main outcome measure Evaluation of accuracy and reliability by comparing the different techniques with true volumes ( in vitro) and with each other ( in vitro and in vivo). Results In the in vitro study, volume measurements by VOCAL, inversion mode and V-Scope proved to be accurate. SonoAVC measurements resulted in a substantial systematic underestimation. Correlation coefficients of measured versus true volumes were excellent in all four techniques. For all techniques, an intra- and interobserver agreement of at least 0.91 was found. Yolk sac measurements by the different techniques proved to be highly correlated (ICCs > 0.91). Conclusions We demonstrated that VOCAL, inversion mode and V-Scope can all be used to measure volumes of hypoechoic structures. The newly introduced V-Scope application proved to be accurate and reliable. [ABSTRACT FROM AUTHOR]

The article explores the reliability of three-dimensional (3D) ultrasound measurements in early pregnancy using a virtual reality system, the Barco I-Space. Results suggest that early pregnancy measurements in the I-Space are reliable. New areas of embryonic and fetal biometry can be examined using this method, which is tentatively called virtual embryoscopy.

Objective: To study the association between periconceptional paternal folate status and embryonic growth trajectories in early pregnancy.Design: Prospective periconceptional cohort study.Setting: Single tertiary hospital.Patient(s): A total of 511 singleton pregnancies, with 303 conceived spontaneously and 208 after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.Intervention(s): None.Main Outcome Measure(s): Crown-rump length (CRL) and embryonic volume (EV) at 7, 9, and 11 weeks of gestation measured offline using three-dimensional ultrasound data and a virtual reality system.Result(s): Using the third quartile of paternal red blood cell (RBC) folate levels as reference values, we found statistically significantly negative associations between RBC folate and longitudinal CRL measurements in the second quartile (beta: -0.14 √mm [95% confidence interval (CI), -0.28 to -0.006]) and fourth quartile (beta: -0.19 √mm [95% CI, -0.33 to -0.04]) in spontaneously conceived pregnancies. Comparable results were found for longitudinal EV measurements in the fourth quartile (beta: -0.12 ∛cm3 [95% CI, -0.20 to -0.05]). No statistically significant associations were observed between RBC folate levels and embryonic growth trajectories in IVF-ICSI pregnancies.Conclusion(s): These data demonstrate for the first time that low and high periconceptional paternal RBC folate levels are associated with reduced embryonic growth trajectories in spontaneously conceived pregnancies. These data underline the importance of paternal folate status during the periconception period. [ABSTRACT FROM AUTHOR]