Gestational Age-related Changes Research Articles

Fetal face shape analysis from prenatal 3D ultrasound images

3D ultrasound imaging of fetal faces has been predominantly confined to qualitative assessment. Many genetic conditions evade diagnosis and identification could assist with parental counselling, pregnancy management and neonatal care planning. We describe a methodology to build a shape model of the third trimester fetal face from 3D ultrasound and show how it can objectively describe morphological features and gestational-age related changes of normal fetal faces. 135 fetal face 3D ultrasound volumes (117 appropriately grown, 18 growth-restricted) of 24-34 weeks gestation were included. A 3D surface model of each face was obtained using a semi-automatic segmentation workflow. Size normalisation and rescaling was performed using a growth model giving the average size at every gestation. The model demonstrated a similar growth rate to standard head circumference reference charts. A landmark-free morphometry model was estimated to characterize shape differences using non-linear deformations of an idealized template face. Advancing gestation is associated with widening/fullness of the cheeks, contraction of the chin and deepening of the eyes. Fetal growth restriction is associated with a smaller average facial size but no morphological differences. This model may eventually be used as a reference to assist in the prenatal diagnosis of congenital anomalies with characteristic facial dysmorphisms.

Gestational age-related changes in relaxation times of neonatal brain by quantitative synthetic magnetic resonance imaging.

This study aimed to explore the correlation between T1 and T2 relaxation times of synthetic MRI (SyMRI) and gestational age (GA) in each hemisphere of preterm and term newborns at the initial 28 days of birth. Seventy preterm and full-term infants were prospectively included in this study. All subjects completed 3.0 T routine MRI and SyMRI (MAGiC) one-stop scanning within 28 days of birth (aged 34-42 W at examination). The SyMRI postprocessing software (v8.0.4) was used to measure the T1 and T2 relaxation values of each brain region. The linear regression equations of quantitative relaxation values with GA were established to compare the variation speed in each brain region. A significant linear and negative correlation was found between relaxation times and GA in the neonate cerebral cortex and subcortical gray and white matter regions (All p<.05). The relaxation time of the left centrum semiovale decreased with maximum variance with increasing GA among all white matter regions (T1: b = -51.45, β = -0.65, p < .0001; T2: b = -8.77, β = -0.71, p < .0001), whereas the right posterior limb of internal capsule showed minimal variance (T1: b = -27.94, β = -0.60, p < .0001; T2: b = -3.25, β = -0.68, p < .0001). Among all gray matter regions, the right globus pallidus and thalamus indicated the most significant decreasing degree of T1 and T2 relaxation values with GA (right globus pallidus T1: b = -33.14, β = -0.64, p < .0001; right thalamus T2: b = -3.94, β = -0.81, p < .0001), and the right and left occipital lobes indicated the least significant decreasing degree of T1 and T2 relaxation values with GA, respectively (right occipital lobes T1: b = -11.18, β = -0.26, p = .028; left occipital lobes T2: b = -1.22, β = -0.27, p = .024). SyMRI could quantitatively evaluate the linear changes of T1 and T2 relaxation values with GA in brain gray and white matter of preterm and term neonates.

Gestational age‐related changes in cervical gland length in normal singleton pregnancies from 17 to 36 weeks of gestation

To determine the gestational age-related changes in cervical gland length in relation to cervical length (CL) in normal singleton pregnancies. We studied 363 women with an uncomplicated singleton pregnancy (188 nulliparous and 175 multiparous women with one or more previous transvaginal deliveries). A total of 1138 cervical gland and CLs were measured longitudinally at 17-36 weeks of gestation using transvaginal ultrasonography along the curvature from the external os to the lower uterine segment and the internal end of the cervical gland area (CGA), respectively. Gestational age-related changes in cervical gland and CLs and their relationships were analyzed using a linear mixed model. Cervical gland and CLs decreased in different ways with advancing gestation depending on parity, and their changes were related to each other. The CGAs in nulliparous women were longer than those in multiparous women at 17-25 weeks of gestation (p < 0.05), but with no differences thereafter. CLs in multiparous women were different from those in nulliparous women at 17-23 and 35-36 weeks (p < 0.05), but there were no differences at 24-34 weeks. The cervix did not shorten compared with the CGA throughout the observational periods in nulliparous and multiparous women. Shortening of the cervix indicates changes to the lower uterine segment in normal pregnancies. The cervical gland region can be a useful marker representing the true cervix beyond 25 weeks of gestation, irrespective of parity.

Haematological Profile of Preterm Neonates:An Experience of A Specialized Tertiary Hospital in Dhaka, Bangladesh

Background: A complete blood count(CBC) elements that are abnormally high or low can influence our clinical decisions. However, the reference ranges for the various CBC elements in neonates change considerably in respect to gestational age.Objective: To observe and correlate gestational agerelated changes in the haematological profileof the preterm neonates.Methods: This cross-sectional, prospective study was conducted between July 2007 and January 2008 in collaboration between Department of Paediatrics and Department of Obstetrics &amp; Gynaecology of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) Hospital, Dhaka, Bangladesh. A total of 49 preterm newborns of different gestational age (28 males and 21 females) included in this study.They were divided into three groups based on their gestational age: group I (30 weeks; n=11), group II (31-33 weeks; n=17) and group III (34-36 weeks; n=21). Within 48 hours of delivery, 1 ml venous blood was collected from each neonate and was sent to the Department of Clinical Pathology of the same hospital. Complete blood count (CBC) was done by using Abbott’s Cell-Dyn 3200 Automated Hematology Analyzer.Results: Significant differences were observed in total count of RBC, WBC, and platelet among those three groups. However, differential count of WBC, heamoglobin level, and haematocrit value among those three groups showed no significant differences (P&gt;0.05). Gestational age showed a positive correlation with total count of RBC (r=0.216; P&lt;0.05). Gestational age had also a positive correlation with neutrophil (r=0.448; P&lt;0.001). Besides, gestational age was negatively correlated with lymphocyte (r=-0.389; P&lt;0.001) However, gestational age did not bear any correlation with total count of WBC, monocyte, and eosinophil. Finally, gestational age was found to bear a positive correlation with heamoglobin level (r=0.412; P&lt;0.001) and haematocrit value (r=0.382; P&lt;0.001).Conclusion: Our data suggest that differences exist in different haematological parameters among preterm neonates of different gestational age.International Journal of Human and Health Sciences Vol. 06 No. 03 July’22 Page: 275-279

Gestational age-related changes in the fetal functional connectome: in utero evidence for the global signal.

The human brain begins to develop in the third gestational week and rapidly grows and matures over the course of pregnancy. Compared to fetal structural neurodevelopment, less is known about emerging functional connectivity in utero. Here, we investigated gestational age (GA)-associated in vivo changes in functional brain connectivity during the second and third trimesters in a large dataset of 110 resting-state functional magnetic resonance imaging scans from a cohort of 95 healthy fetuses. Using representational similarity analysis, a multivariate analytical technique that reveals pair-wise similarity in high-order space, we showed that intersubject similarity of fetal functional connectome patterns was strongly related to between-subject GA differences (r= 0.28, P< 0.01) and that GA sensitivity of functional connectome was lateralized, especially at the frontal area. Our analysis also revealed a subnetwork of connections that were critical for predicting age (mean absolute error = 2.72weeks); functional connectome patterns of individual fetuses reliably predicted their GA (r= 0.51, P< 0.001). Lastly, we identified the primary principal brain network that tracked fetal brain maturity. The main network showed a global synchronization pattern resembling global signal in the adult brain.

3.0 Tesla normative diffusivity in 3rd trimester fetal brain.

Apparent diffusion coefficient (ADC) values in the developing fetus provide valuable information on the diagnosis and prognosis of prenatal brain pathologies. Normative ADC data has been previously established in 1.5T MR scanners but lacking in 3.0T scanners. Our objective was to measure ADC values in various brain areas in a cohort of normal singleton fetuses scanned in a 3.0T MR scanner. DWI (diffusion-weighted imaging) was performed in 47 singleton fetuses with normal or questionably abnormal results on sonography followed by normal structural MR imaging. ADC values were measured in cerebral lobes (frontal, parietal, temporal lobes), basal ganglia, and pons. Regression analysis was used to examine gestational age-related changes in regional ADC. Median gestational age was 30.1weeks (range, 26-34weeks). There was a significant effect of region on ADC values, whereby ADC values were highest in cerebral lobes (parietal > frontal > temporal lobes), compared with basal ganglia. The lowest values were found in the pons. On regression analysis, there was a decrease in ADC values in basal ganglia and pons with increasing gestational age. ADC values in frontal, parietal, and temporal lobes were stable in our cohort. Regional brain ADC values in 3.0T scanners are comparable with previously reported values in 1.5T scanners, with similar changes over gestational age. Using 3.0T scanners is increasing worldwide. For fetal imaging, establishing normal ADC values is critical as DWI enables a sensitive and quantitative technique to evaluate normal and abnormal brain development.

Physiologically Based Pharmacokinetics Model in Pregnancy: A Regulatory Perspective on Model Evaluation.

Physiologically based pharmacokinetics (PBPK) modelling is widely used in medicine development and regulatory submissions. The lack of clinical pharmacokinetic data in pregnancy is widely acknowledged; therefore, one area of current interest is in the use of PBPK modelling to describe the potential impact of anatomical and physiological changes during pregnancy on the medicine's pharmacokinetics. PBPK modelling could possibly represent a predictive tool to support the medicine benefit–risk decision and inform dose adjustment in this population and also to investigate medicine levels in the foetus to support the risk assessment to the foetus. In the context of regulatory application, there are, however, a number of considerations around model evaluation, and this should be tailored to the model purpose, in order to inform the confidence in the model for the intended application. A number of gestational age-related physiological changes are expected to alter the pharmacokinetics of medicines during pregnancy, and there are uncertainties on some parameters; therefore, well-qualified models are needed to improve assurance in the model prediction before this approach can be used to inform with confidence high-impact decisions as part of regulatory submissions.

Maternal plasma pro-atrial and C-type natriuretic peptide levels and their associations with cardiovascular and renal function in the second half of normal pregnancy: a longitudinal study

BackgroundPhysiological adaptation in pregnancy is characterized by remodeling of endocrine, cardiovascular and renal functions leading to fluid retention, volume expansion, altered cardiac loading conditions and hyperdynamic circulation. Natriuretic peptides have been used as biomarkers of cardiovascular function, but their associations with gestational age-related changes in maternal cardiac, endothelial and renal function have not been elucidated. The aim of this study was to establish longitudinal reference values for maternal plasma atrial natriuretic peptide (proANP) and C-type natriuretic peptide (CNP) and investigate their temporal association with cardiovascular and renal function in the second half of pregnancy.MethodsThis study was a prospective longitudinal study of 53 low-risk pregnancies. Women were examined every 3–5 weeks during 22–40 weeks of gestation (252 observations). Fasting maternal blood samples were obtained to measure proANP, CNP, creatinine, cystatin C, uric acid, and fibrinogen levels. Cardiac function and systemic hemodynamics were assessed noninvasively by impedance cardiography (ICG) and vascular endothelial function by flow-mediated vasodilation of brachial artery (FMD).ResultsThe plasma proANP (R2adj = 0.79; P = 0.007), CNP (R2adj = 0.54; P = 0.005) decreased between 22 and 40 weeks. The creatinine (R2adj = 0.90; P < 0.001), cystatin C (R2adj = 0.93; P = < 0.001) and uric acid (R2adj = 0.83; P < 0.001) increased significantly, whereas the estimated glomerular filtration rate (R2adj = 0.93; P < 0.001) decreased with gestational age. The FMD did not change significantly but fibrinogen (R2adj = 0.79; P < 0.001) increased with advancing gestation. The maternal systemic vascular resistance index (R2adj = 0.50; P < 0.001) increased, stroke index (R2adj = 0.62; P < 0.001) decreased, whereas the cardiac index (R2adj = 0.62; P = 0.438) and thoracic fluid content (R2adj = 0.72; P = 0.132) did not change significantly with gestation. The proANP was associated with thoracic fluid content (R2adj = 0.74; P < 0.001) and fibrinogen (R2adj = 0.78; P = 0.034) but not with other variables of systemic hemodynamics, endothelial function, or renal function. The CNP was not associated significantly with parameters of cardiovascular or renal function.ConclusionLongitudinal reference values for maternal plasma proANP and CNP were established. These natriuretic peptides decreased slightly with advancing gestation, but they did not reflect the temporal physiological changes in maternal systemic hemodynamics, vascular endothelial function and renal function during the second half of pregnancy. The proANP correlated with the thoracic fluid content reflecting volume load in pregnancy.

Simple ultrasound evaluation of fetal adrenal glands as a marker of imminent preterm birth: a preliminary report.

We present a simple 2D big ultrasound measurement of the fetal adrenal glands and their biometrical growth analysis highlighted as a potential preterm birth marker. This was a prospective observational case-control study. Sixty-four patients were included in the study (32 with the diagnosis of imminent preterm birth before 37 and 32 controls) from January 2018 to May 2020. Anteroposterior dimensions and circumferences of the whole adrenal glands and their central zones were measured by simple B-mode ultrasound imaging. For the statistical analysis, StatsDirect 3.0 and ROC curves were used. As a studied descriptor, routine standard ultrasound cervical measurements were added (cervical length, funneling, sludge, cervical dilatation, and cervical glandular area). In biometrics of gestational age-related changes, a significant analysis of the overall growth of the adrenal gland was observed (circumference p < 0.001, anteroposterior diameter p = 0.02). The growth of the central zone was observed independently of gestational age. The growth of the central zone of the fetal adrenal glands revealed significant changes between the group of patients who delivered prematurely and control groups (p < 0.01). The ideal cut-off value of the proportion of enlargement of the fetal zone as a predictor of preterm delivery before week 37 was 45.1 %, with the sensitivity of 87.5 % and specificity of 85.4 %. A simple 2D B-mode measurement of the fetal adrenal glands´ central zone growth can be applied as an additional marker in the prediction of true preterm delivery. The natural biometrical overall growth of the adrenal glands seems to be dependent on gestational age, whereas that of the central adrenal gland zone seems to be independent on gestational age (Tab. 3, Fig. 5, Ref. 26).

Study on the gestational age-related histogenesis of human fetal suprarenal glands

Background: Fetal suprarenal gland consists of three zones. They are the outer definitive zone or neocortex (DZ) that forms adult Zona Glomerulosa (ZG), the centrally located fetal zone and a third transitional zone (TZ) the future adult Zona Fasciculata (ZF) which lies just between the neocortex and fetal zone (FZ). The inner ZF that consists of large eosinophilic cells, and the outer definitive zone (DZ) consists of small, densely packed basophilic cells. As early as in 6th week of gestational Age, pheochromoblasts derived from the neural crest migrate through the fetal cortex to form the medulla at a later stage of development. The medulla unrecognizable as a distinct structure in the suprarenal gland throughout most of the gestation, except for small clusters or nests of chromaffin cells scattered throughout the body of the cortex.&#x0D; Aims and Objective: The study was designed and aimed to understand the early developmental histology of suprarenal gland.&#x0D; Materials and Methods: Study conducted at the Department of Anatomy, SV Medical College, Tirupati, Andhra Pradesh, India. The study was carried out by processing representative samples of fetal suprarenal tissues of 13 weeks, 17 weeks, 24 weeks, 25 weeks and 38 weeks gestational age. While processing, we observed the standard dissection procedure and histopathological tissue processing for the human samples.&#x0D; Results: Peripheral narrower and darker definitive zone or true cortex and an inner wider and lighter fetal zone was observed at 13, 17, 24 weeks with 10x objective. The demarcation between cortex and medulla could be seen clearly at 24 weeks. At 25 weeks capsule is very thick and vascular. A well-differentiated gland tissue with clear demarcation of cortex and medulla and a large central vein was observed. At 38 weeks degeneration of fetal zone with a thick-walled central vein was observed at lower magnification (10x objective)&#x0D; Conclusion: Observations on prenatal microscopic structure and gestational age-related changes in suprarenal glands form the basis for understanding structural changes and a foetal database for the local population.

Decorin production by the human decidua: role in decidual cell maturation.

Decidualization involves the proliferation and differentiation of fibroblast-like endometrial stromal cells into epithelioid-shaped and secretory 'decidual' cells in response to steroid hormones. Human decidual cells produce insulin-like growth factor-binding protein-1 and prolactin (PRL), two well-recognized markers of decidual cell maturation and a proteoglycan decorin (DCN). We reported that DCN restrains the human trophoblast renewal, migration, invasion and endovascular differentiation needed for uterine arterial remodeling during normal pregnancy. DCN overproduction by the decidua is associated with a hypo-invasive placenta and a serious pregnancy disorder, pre-eclampsia (PE). Furthermore, elevated maternal plasma DCN levels during the second trimester is a predictive biomarker of PE. While these paracrine roles of decidua-derived DCN on trophoblast physiology and pathology have been well-defined, it remains unknown whether DCN plays any autocrine role in decidual cell development. The objectives of this study were to examine: the kinetics of DCN production during decidualization of human endometrial stromal cells; gestational age-related changes in DCN production by the first trimester decidua; and a possible autocrine role of DCN on decidual cell maturation. We found that DCN production is enhanced during decidualization of both primary and immortalized human endometrial stromal cells in vitro and during early gestation in decidual samples tested ex vivo, and that it is important for endometrial stromal cell maturation into a decidual phenotype. Decorin-depleted human endometrial stromal cells exposed to decidualizing stimuli failed to mature fully, as evidenced by fibroblastoid morphology, reduced insulin-like growth factor-binding protein-1 and PRL expression, and reduction in cellular ploidy. We identified heart and neural crest derivatives-expressed protein 2, and progesterone receptor as potential downstream mediators of DCN effects.

Placental fatty acid transport across late gestation in a baboon model of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and increased risk of lifelong disease, including neurodevelopmental impairment. Fatty acids (FA) are critical for normal brain development, although their transport across the placenta in IUGR pregnancies is poorly understood. The present study used a baboon model of IUGR (maternal nutrient restriction, MNR) to investigate placental expression of FA transport and binding proteins, and to determine gestational age-related changes in maternal and fetal plasma FA concentrations. We found MNR to be associated with increased placental expression of FA binding and transport proteins in late gestation, with fetal plasma FA concentrations that were similar to those of control animals. The present study is the first to report a profile of fetal and maternal plasma FA concentrations in a baboon model of growth restriction with data that suggest adaptation of placental transport to maintain delivery of critically needed FA. Intrauterine growth restriction (IUGR) is associated with specific changes in placental transport of amino acids, folate and ions. However, little is known about placental fatty acid (FA) transport in IUGR. We hypothesized that placental FA transport proteins (FATP) and FA binding proteins (FABP) are up-regulated and fetal plasma FA concentrations are decreased at term in a baboon model of IUGR. Pregnant baboons were fed control or maternal nutrient restricted (MNR) diet (70% of control calories) from gestation day (GD) 30 (term 184days). Plasma and placental samples were collected at GD120 (control n=8, MNR n=9), GD140 (control n=6, MNR n=7) and GD170 (control n=6, MNR n=6). Placentas were homogenized, and syncytiotrophoblast microvillous plasma membrane (MVM) and basal plasma membranes (BM) were isolated. Protein expression of FABP1, 3, 4 and 5 (homogenate) and FATP2, 4, and 6 (MVM, BM) was determined by Western blotting. FA content in maternal and umbilical vein plasma was measured by gas chromatography-mass spectrometry. Placental FABP1 and FABP5 expression was increased in MNR compared to controls at GD170, as was MVM FATP2 and FATP6 expression at GD140 and FATP2 expression at GD170. BM FATP4 and FATP6 expression was increased in MNR at GD140. Fetal plasma FA concentrations were similar in controls and MNR. These data suggest the adaptation of placental transport when aiming to maintain delivery of critically needed FAs for fetal growth and brain development.

Hypoxia with acidosis in extremely preterm born infants was not associated with an increased risk of death or impaired neurodevelopmental outcome at 6.5years.

It is not clear whether perinatal acidosis can predict poor outcomes in extremely preterm infants and we investigated associations between intrapartum hypoxia and mortality and neurodevelopmental outcomes. We used nationwide data on 705 infants from the Extremely Preterm Infants in Sweden Study, delivered at 22-26weeks of gestation during 2004-2007. Comprehensive neurodevelopmental assessments were performed on survivors at 2.5 (n=456) and 6.5 (n=441) years of corrected age. Gestational age-related changes in umbilical cord arterial pH were compared with reference values for term newborn infants, and base excess was also calculated. Associations between low blood gas values (<10th percentile) and mortality and neurodevelopmental outcome were estimated. Cord blood determination was more common in surviving infants (P<.001), with pH determined in 322/705 (46%) and base excess in 311/705 (44%). Extremely preterm infants had higher pH values than term infants (P<.0001), with no change from 22 to 26weeks of gestation (P=.61, r2 =.001). Multiple logistic regression showed no association between low blood gas values and risk of death or neurodevelopmental impairment at 6.5years (P≥.17). Hypoxia with acidosis at birth was not associated with an increased risk of death or impaired neurodevelopmental in extremely preterm born children at 6.5years.

Bimodal distribution of fasting, one and two hour post load plasma glucose in Asian Indian pregnant women without pre-gestational diabetes: Gestational age related changes

•After exclusion of pre-gestational diabetes, Asian Indian pregnant women have bimodal distribution of plasma glucose.•Bimodality is observed for fasting, 1 and 2 h post glucose load plasma glucose distribution.•Cut off values for gestational diabetes diagnosis could not identified for any glucose parameter.•In women with high gestational diabetes risk factors, the bimodality is evident before 24 weeks of gestation.•By third trimester, the bimodality is significant for all glucose parameters.

Gestational age-related changes in shear wave speed of the uterine cervix in normal pregnancy at 12-35 weeks' gestation.

Background This study aimed to analyze age-related changes in shear wave speed (SWS) of the normal uterine cervix. Methods We studied 362 women with a normal singleton pregnancy at 12-35 weeks' gestation. The SWS of the cervix was measured using transvaginal ultrasonography at the internal os region of the anterior cervix (IOA), posterior cervix (IOP) and cervical canal (IOC), and at the external os region of the anterior cervix (EOA), posterior cervix (EOP) and cervical canal (EOC). The following parameters were analyzed: (1) time trend of SWS of the individual sampling points, (2) comparison of SWS in the internal cervical region and SWS in the external cervical region, and (3) comparison of SWS between the internal and external cervical regions. Statistical analyses were performed using mixed-effects models. Results The SWS of IOP decreased in bilinear regression, with a critical change in the rate at 22 weeks, whereas the SWS of the remaining points decreased linearly. The estimated values of SWS of IOP at 84, 154 and 251 days were higher than those of IOA and IOC (P<0.001). The estimated values of SWS of IOP at 84 and 154 days were higher than those of EOP (P<0.001). Significant differences between IOP and EOP were shown until 244 days (P<0.05). The estimated value of SWS of IOC at 84 days was higher than that of EOC (P<0.001). Significant differences between IOC and EOC were shown until 210 days (P<0.05). Conclusion The SWS of the uterine cervix in pregnancy decreases with advancing gestation. The SWS of IOP had the highest value among the sampling points with unique characteristics.

Microvascular perfusion of the placenta, developing fetal liver, and lungs assessed with intravoxel incoherent motion imaging.

In utero intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI) provides a novel method for examining microvascular perfusion fraction and diffusion in the developing human fetus. To characterize gestational changes in the microvascular perfusion fraction of the placenta, fetal liver, and lungs using IVIM-MRI. Retrospective, cross-sectional study. Fifty-five datasets from 33 singleton pregnancies were acquired (17-36 gestational weeks). In utero diffusion-weighted echo-planar imaging at 1.5T and 3.0T with b-factors ranging from 0 to 900 s/mm2 in 16 steps. Using the IVIM principle, microvascular perfusion fraction (f), pseudodiffusion (D*), and diffusion coefficients (d) were estimated for the placenta, liver, and lungs with a biexponential model. A free-form nonlinear deformation algorithm was used to correct for the frame-by-frame motion of the fetal organs and the placenta. The IVIM parameters were then compared to a Doppler ultrasound-based assessment of the umbilical artery resistance index. Pearson product-moment correlation coefficient (PMCC) to reveal outlier corrected correlations between Doppler and IVIM parameters. Gestational age-related changes were assessed using linear regression analysis (LR). Placental f (0.29 ± 0.08) indicates high blood volume in the microvascular compartment, moderately increased during gestation (LR, R = 0.338), and correlated negatively with the umbilical artery resistance index (PMCC, R = -0.457). The f of the liver decreased sharply during gestation (LR, R = -0.436). Lung maturation was characterized by increasing perfusion fraction (LR, R = 0.547), and we found no gestational changes in d and D* values (LR, R = -0.013 and R = 0.051, respectively). The Doppler measurements of the umbilical artery and middle cerebral artery did not correlate with the IVIM parameters of the lungs and liver. Gestational age-associated changes of the placental, liver, and lung IVIM parameters likely reflect changes in placental and fetal circulation, and characterize the trajectory of microstructural and functional maturation of the fetal vasculature. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017.

OP10.03: Gestational age‐related changes in uterine cervical elasticity in normal pregnancy at 12–35 weeks' gestation evaluated using shear wave elastography

To analyse the gestational age-related changes in elasticity of the normal uterine cervix at 12-35 weeks' gestation using shear wave elastography. The subjects consisted of 417 cases of normal singleton pregnancy at 12-35 weeks' gestation, cared for in our hospital from July 2016 to January 2017. The shear wave speed (SWS) of the cervix was measured using transvaginal ultrasonography (Aplio 500, Toshiba). On the sagittal section, sampling points were placed on the anterior (A), posterior (P), and cervical canal (C) regions of the internal and external os (IO/EO). After dividing the observational period into 6 groups at 4-week interval, the following parameters were analysed: 1) the changes in SWS at each point with advancing gestation; 2) comparison of SWSs at both the IO and EO for A, P and C. Statistical analyses were made using piecewise linear regression analysis, the Mann-Whitney U-test, the Kruskal-Wallis and the Wilcoxon test as post-hoc test. Significance was set at P<0.05. The SWSs of posterior at the IO decreased in piecewise linear regression, with a critical point at 20 weeks, whereas the SWSs of the remaining points decreased linearly. At the IO, the SWSs of P were higher than those of A and C at all age-groups. The SWSs of P and A at the IO were higher than those at the EO at all age-groups. The SWSs of C at the IO were higher than those at the EO before 20-23 weeks, respectively, however, the SWSs were not different between the points thereafter. The SWSs of A at the IO were higher than those at the EO before 28-31 weeks, respectively, however, the SWSs were not different between the points thereafter. The posterior cervix at the internal os, the hardest point of the cervix at all age-groups, softened with advancing gestation, while the endocervix was harder than the ectocervix before 35 weeks, showing a physiological cervical maturation with advancing gestation.

A novel approach to assessing fetal tissue stiffness using virtual touch tissue quantification.

Virtual touch tissue quantification (VTTQ) has been widely used in adults, but its application in fetuses has not been reported. The purposes of this study were to describe the normal shear wave velocity (SWV) values of fetal brain, lung, and liver by VTTQ and to examine the clinical usefulness of this procedure in THE evaluation of gestational age-related SWV changes in the fetal brain, lung and liver. One hundred fetuses were enrolled in this study and were evaluated at 18 weeks (second trimester) and 35 weeks (third trimester) during pregnancy. The SWV was measured at the cerebral parenchyma, thalamus, cerebellum, choroid plexus, left lung, right lung, right and left lobe of the liver in each participant. The SWV at the cerebral parenchyma were all significantly greater in the third trimesters than in the second trimesters (3.29+/-1.05 vs. 2.22+/-0.97 m/s, p<0.001), while the velocities at thalamus, cerebellum, choroid plexus, left lung, right lung, right lobe of the liver and left lobe of the liver did not differ between the second and the third trimesters (p>0.05). Moreover, the SWV at the cerebral parenchyma correlated significantly with gestational age (r=0.47, p<0.001). VTTQ can provide numerical measurements of fetal brain, lung and liver stiffness and can effectively and objectively indicate gestational age-related changes in cerebral parenchyma stiffness by measuring SWV values.

Placenta-derived exosomes continuously increase in maternal circulation over the first trimester of pregnancy.

BackgroundHuman placenta releases specific nanovesicles (i.e. exosomes) into the maternal circulation during pregnancy, however, the presence of placenta-derived exosomes in maternal blood during early pregnancy remains to be established. The aim of this study was to characterise gestational age related changes in the concentration of placenta-derived exosomes during the first trimester of pregnancy (i.e. from 6 to 12 weeks) in plasma from women with normal pregnancies.MethodsA time-series experimental design was used to establish pregnancy-associated changes in maternal plasma exosome concentrations during the first trimester. A series of plasma were collected from normal healthy women (10 patients) at 6, 7, 8, 9, 10, 11 and 12 weeks of gestation (n = 70). We measured the stability of these vesicles by quantifying and observing their protein and miRNA contents after the freeze/thawing processes. Exosomes were isolated by differential and buoyant density centrifugation using a sucrose continuous gradient and characterised by their size distribution and morphology using the nanoparticles tracking analysis (NTA; Nanosight™) and electron microscopy (EM), respectively. The total number of exosomes and placenta-derived exosomes were determined by quantifying the immunoreactive exosomal marker, CD63 and a placenta-specific marker (Placental Alkaline Phosphatase PLAP).ResultsThese nanoparticles are extraordinarily stable. There is no significant decline in their yield with the freeze/thawing processes or change in their EM morphology. NTA identified the presence of 50–150 nm spherical vesicles in maternal plasma as early as 6 weeks of pregnancy. The number of exosomes in maternal circulation increased significantly (ANOVA, p = 0.002) with the progression of pregnancy (from 6 to 12 weeks). The concentration of placenta-derived exosomes in maternal plasma (i.e. PLAP+) increased progressively with gestational age, from 6 weeks 70.6 ± 5.7 pg/ml to 12 weeks 117.5 ± 13.4 pg/ml. Regression analysis showed that weeks is a factor that explains for >70% of the observed variation in plasma exosomal PLAP concentration while the total exosome number only explains 20%.ConclusionsDuring normal healthy pregnancy, the number of exosomes present in the maternal plasma increased significantly with gestational age across the first trimester of pregnancy. This study is a baseline that provides an ideal starting point for developing early detection method for women who subsequently develop pregnancy complications, clinically detected during the second trimester. Early detection of women at risk of pregnancy complications would provide an opportunity to develop and evaluate appropriate intervention strategies to limit acute adverse sequel.

Regional apparent diffusion coefficient values in 3rd trimester fetal brain.

Apparent diffusion coefficient (ADC) values in the developing fetus can be used in the diagnosis and prognosis of prenatal brain pathologies. To this end, we measured regional ADC in a relatively large cohort of normal fetal brains in utero. Diffusion-weighted imaging (DWI) was performed in 48 non-sedated 3rd trimester fetuses with normal structural MR imaging results. ADC was measured in white matter (frontal, parietal, temporal, and occipital lobes), basal ganglia, thalamus, pons, and cerebellum. Regional ADC values were compared by one-way ANOVA with gestational age as covariate. Regression analysis was used to examine gestational age-related changes in regional ADC. Four other cases of CMV infection were also examined. Median gestational age was 32 weeks (range, 26-33 weeks). There was a highly significant effect of region on ADC, whereby ADC values were highest in white matter, with significantly lower values in basal ganglia and cerebellum and the lowest values in thalamus and pons. ADC did not significantly change with gestational age in any of the regions tested. In the four cases with fetal CMV infection, ADC value was associated with a global decrease. ADC values in normal fetal brain are relatively stable during the third trimester, show consistent regional variation, and can make an important contribution to the early diagnosis and possibly prognosis of fetal brain pathologies.