Third-trimester Fetuses Research Articles

Precise Localization of the Posterior Clinoid Process in the Fetal Skull Base.

To determine the precise position of the posterior clinoid process (PCP) in fetuses. Skull bases of 32 fetuses (11 males/21 females) aged 17 to 32 weeks in utero were included in the study. The distances of PCP to certain reference points were measured. The distances of PCP to the foramen ovale, foramen rotundum, superior orbital fissure, anterior clinoid process, foramen magnum, and crista galli were measured as 7.70±1.86mm, 6.99±1.65mm, 6.07±1.85mm, 3.85±1.10mm, 15.34±3.38mm, and 14.49±2.65mm, respectively. All parameters were similar for both sides (P>0.05). Apart from the distance of PCP to the foramen magnum, the remaining parameters were similar for both genders. This parameter was greater in males than females (P=0.001). All parameters were greater in the third-trimester fetuses than the second-trimester fetuses. All parameters increased with advancing gestational weeks (P<0.001). Linear functions were calculated for the distances of PCP to the crista galli (y = 1.311 + 0.551 × age), to the foramen magnum (y = 0.086 + 0.638 × age), to the anterior clinoid process (y = -0.303 + 0.174 × age), to the superior orbital fissure (y = - 2.013 + 0.338 × age), to the foramen rotundum (y = 1.803 + 0.217 × age), and to the foramen ovale (y = 0.760 + 0.290 × age). The measured distances increased with growth. The linear functions displaying the growth dynamics of PCP-related parameters may be used to estimate the distances.

Crista Galli Morphology in Fetuses.

To determine alterations in the crista galli (CG) size in fetuses with advancing weeks. Skull bases of 32 fetuses (11 males/21 females) aged 17 to 32 weeks in utero were included in the study. The width (width of CG), height (height of CG), and length (length of CG) of CG were measured, and also olfactory fossa depth (OFD) was measured to determine the relation of CG with OFD. Width of CG, height of CG, length of CG, and OFD were measured as 1.77 ± 0.59mm, 5.10 ± 1.70mm, 12.32 ± 2.25mm, and 1.56 ± 0.56mm, respectively. No significant difference was observed between the measurements in terms of sex and side (P> 0.05). Apart from OFD, the parameters were greater in the third-trimester fetuses than in the second-trimester fetuses (P< 0.001). Olfactory fossa depth was similar in both trimester fetuses (P= 0.798). Olfactory fossa depth did not alter with advancing gestational weeks (P= 0.077), but the others increased (P< 0.01). Only one configuration regarding Keros types was observed. Type 1 was detected in all fetuses (100%). A linear function was calculated as y=1.442+0.455×age for the length of CG, y=-2.566+0.321×age for the height of CG, y=0.641+0.039×age for OFD, and y=-1.088+0.119×age for the width of CG. Crista galli size increased with advancing fetal weeks. The authors detected Keros type 1 in all fetuses. The authors' linear functions representing the growth pattern of CG and OFD in fetuses may be useful in estimating their dimensions.

Developmental three-dimensional examination of the pelvic cavity of Hamdani crossbred sheep fetuses (Ovis aries) in the last two periods of gestation.

Türkiye is a country in the world ranking in terms of sheep breeding. Hamdani crossbred sheep breed is one of the sheep breeds that can adapt to the difficult conditions in our country. In addition, the sentence may be corrected as 'Especially in the southeastern part of the Türkiye, crossbreeding is preferred by breeders to increase the yield characteristics of sheep'. In our study, it was aimed to perform a pelvimetric analysis of Hamdani crossbred sheep fetuses in the second and third trimesters by three-dimensional modelling method. For this purpose, a total of 40 second-trimester (10 females, 10 males) and third-trimester (10 females, 10 males) fetuses were used. The pelvises of the fetuses were imaged with CT and 3D models were created. Sixteen pelvimetric measurements were performed from the models. The results obtained were evaluated statistically. The study found statistically significant differences between male and female fetuses in terms of vertical diameter (VD) and foramen obturatum width (FOW) measurement parameters in the second trimester. In the third trimester, there were statistically significant differences between genders in acetabulum (AC) (p < 0.01), medial ischial tuberosities (MIT), and ischiatic arch (IA) (p < 0.05) parameters. As a result of the correlation analysis, it was determined that the pelvis length (PL) measurement parameter was positively correlated with different parameters in varying degrees in both periods, while the IA parameter did not show significant correlations with the other parameter in the last two periods of pregnancy. In conclusion, the data obtained will be useful in pelvimetric evaluations of human and animal fetuses, anatomy education, zooarchaeology and taxonomy studies.

How automated techniques ease functional assessment of the fetal heart: Applicability of two-dimensional speckle-tracking echocardiography for comprehensive analysis of global and segmental cardiac deformation using fetalHQ®.

Prenatal echocardiographic assessment of fetal cardiac function has become increasingly important. Fetal two-dimensional speckle-tracking echocardiography (2D-STE) allows the determination of global and segmental functional cardiac parameters. Prenatal diagnostics is relying increasingly on artificial intelligence, whose algorithms transform the way clinicians use ultrasound in their daily workflow. The purpose of this study was to demonstrate the feasibility of whether less experienced operators can handle and might benefit from an automated tool of 2D-STE in the clinical routine. A total of 136 unselected, normal, singleton, second- and third-trimester fetuses with normofrequent heart rates were examined by targeted ultrasound. 2D-STE was performed separately by beginner and expert semiautomatically using a GE Voluson E10 (FetalHQ®, GE Healthcare, Chicago, IL). Several fetal cardiac parameters were calculated (end-diastolic diameter [ED], sphericity index [SI], global longitudinal strain [EndoGLS], fractional shortening [FS]) and assigned to gestational age (GA). Bland-Altman plots were used to test agreement between both operators. The mean maternal age was 33 years, and the mean maternal body mass index prior to pregnancy was 24.78kg/m2. The GA ranged from 16.4 to 32.0weeks (average 22.9weeks). Averaged endoGLS value of the beginner was -18.57%±6.59 percentage points (pp) for the right and -19.58%±5.63 pp for the left ventricle, that of the expert -14.33%±4.88 pp and -16.37%±5.42 pp. With increasing GA, right ventricular endoGLS decreased slightly while the left ventricular was almost constant. The statistical analysis for endoGLS showed a Bland-Altman-Bias of -4.24 pp±8.06 pp for the right and -3.21 pp±7.11 pp for the left ventricle. The Bland-Altman-Bias of the ED in both ventricles in all analyzed segments ranged from -.49mm±1.54mm to -.10mm±1.28mm, that for FS from -.33 pp±11.82 pp to 3.91 pp±15.56 pp and that for SI from -.38±.68 to -.15±.45. Between both operators, our data indicated that 2D-STE analysis showed excellent agreement for cardiac morphometry parameters (ED and SI), and good agreement for cardiac function parameters (EndoGLS and FS). Due to its complexity, the application of fetal 2D-STE remains the domain of scientific-academic perinatal ultrasound and should be placed preferably in the hands of skilled operators. At present, from our perspective, an implementation into clinical practice "on-the-fly" cannot be recommended.

Assessment of Human Fetuses Undergoing Acute Pain: Validation of the Fetal-7 Scale

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often through surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved 2 steps: 1) 4 fetuses with the indication of surgery were evaluated in 3 conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; 2) assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and 2 fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach’s alpha (α) of .99. Intrarater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient was .95, and inter-rater reliability was .99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third-trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of postoperative pain in fetuses and its effects after birth. PerspectiveRecordings with 3-dimensional ultrasound of human fetuses undergoing preoperative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

Microscopic Structure of the Sigmoido-Jugular Junction in the Third-Trimester Fetus

Microscopic Structure of the Sigmoido-Jugular Junction in the Third-Trimester Fetus

How Automated Techniques Ease Functional Assessment of the Fetal Heart: Applicability of MPI+™ for Direct Quantification of the Modified Myocardial Performance Index.

(1) Objectives: In utero functional cardiac assessments using echocardiography have become increasingly important. The myocardial performance index (MPI, Tei index) is currently used to evaluate fetal cardiac anatomy, hemodynamics and function. An ultrasound examination is highly examiner-dependent, and training is of enormous significance in terms of proper application and subsequent interpretation. Future experts will progressively be guided by applications of artificial intelligence, on whose algorithms prenatal diagnostics will rely on increasingly. The objective of this study was to demonstrate the feasibility of whether less experienced operators might benefit from an automated tool of MPI quantification in the clinical routine. (2) Methods: In this study, a total of 85 unselected, normal, singleton, second- and third-trimester fetuses with normofrequent heart rates were examined by a targeted ultrasound. The modified right ventricular MPI (RV-Mod-MPI) was measured, both by a beginner and an expert. A calculation was performed semiautomatically using a Samsung Hera W10 ultrasound system (MPI+™, Samsung Healthcare, Gangwon-do, South Korea) by taking separate recordings of the right ventricle's in- and outflow using a conventional pulsed-wave Doppler. The measured RV-Mod-MPI values were assigned to gestational age. The data were compared between the beginner and the expert using a Bland-Altman plot to test the agreement between both operators, and the intraclass correlation was calculated. (3) Results: The mean maternal age was 32 years (19 to 42 years), and the mean maternal pre-pregnancy body mass index was 24.85 kg/m2 (ranging from 17.11 to 44.08 kg/m2). The mean gestational age was 24.44 weeks (ranging from 19.29 to 36.43 weeks). The averaged RV-Mod-MPI value of the beginner was 0.513 ± 0.09, and that of the expert was 0.501 ± 0.08. Between the beginner and the expert, the measured RV-Mod-MPI values indicated a similar distribution. The statistical analysis showed a Bland-Altman bias of 0.01136 (95% limits of agreement from -0.1674 to 0.1902). The intraclass correlation coefficient was 0.624 (95% confidence interval from 0.423 to 0.755). (4) Conclusions: For experts as well as for beginners, the RV-Mod-MPI is an excellent diagnostic tool for the assessment of fetal cardiac function. It is a time-saving procedure, offers an intuitive user interface and is easy to learn. There is no additional effort required to measure the RV-Mod-MPI. In times of reduced resources, such assisted systems of fast value acquisition represent clear added value. The establishment of the automated measurement of the RV-Mod-MPI in clinical routine should be the next level in cardiac function assessment.

Sonographic estimation of gestational age using transverse cerebellar diameter among late trimester pregnancies in Kano, Northwest Nigeria

Background/Context: Accurate estimation of fetal gestational age (GA) is of paramount importance in the management of all pregnancies, especially for the planning of mode of the delivery and management of high-risk pregnancies. Obstetric ultrasonography is a simple, available, affordable, and noninvasive modality for estimating fetal GA due to its high safety profile. The fetal cerebellum is easily visualized and reliably identified on ultrasound in the posterior cranial fossa after 14 weeks of gestation. Aim: The aim of this study was to evaluate the utility of transverse cerebellar diameter (TCD) in determining GA in second- and third-trimester pregnancies and compare its accuracy with other established sonographically derived fetal biometric parameters. Materials and Methods: A total of 424 pregnant women in their second and third trimesters who were sure of their last menstrual period (LMP) were recruited into the study over a period of 6 months (May to November 2019) at the Radiology Department of AKTH-Kano, Nigeria. The corresponding fetal TCD and other established fetal biometric indices (biparietal diameter [BPD], head circumference [HC], abdominal circumference [AC], and femur length [FL]) were sonographically obtained and correlated. Pearson’s bivariate coefficient was used to establish the correlation between the traditional biometric indices with TCD and GA derived by LMP. Multivariate linear regression analysis was used to assess the accuracy of the studied indices in predicting GA. Results: The range for TCD in second- and third-trimester fetuses was 15.9–57.5 mm. The TCD parameter was more accurate (±1.753 days) than BPD (±2.298 days), HC (±2.337 days), and AC (±4.342 days) and marginally less accurate than FL (±1.165 days) in predicting GA among study subjects (P &lt; 0.001). Conclusion: TCD is a reliable and accurate parameter for GA estimation in late second- and third-trimester pregnancies when compared with established fetal biometric parameters among pregnant women in Kano, Nigeria.

Anatomical and diffusion-weighted imaging of brain abnormalities in third-trimester fetuses with cytomegalovirus infection.

In this study of cytomegalovirus (CMV)-infected fetuses with first-trimester seroconversion, we aimed to evaluate the detection of brain abnormalities using magnetic resonance imaging (MRI) and neurosonography (NSG) in the third trimester, and compare the grading systems of the two modalities. We also evaluated the feasibility of routine use of diffusion-weighted imaging (DWI) fetal MRI and compared the regional apparent diffusion coefficient (ADC) values between CMV-infected fetuses and presumed normal, non-infected fetuses in the third trimester. This was a retrospective review of MRI and NSG scans in fetuses with confirmed first-trimester CMV infection performed between September 2015 and August 2019. Brain abnormalities were recorded and graded using fetal MRI and NSG grading systems to compare the two modalities. To investigate feasibility of DWI, a four-point rating scale (poor, suboptimal, good, excellent) was applied to assess the quality of the images. Quantitative assessment was performed by placing a freehand drawn region of interest in the white matter of the frontal, parietal, temporal and occipital lobes and the basal ganglia, pons and cerebellum to calculate ADC values. Regional ADC measurements were obtained similarly in a control group of fetuses with negative maternal CMV serology in the first trimester, normal brain findings on fetal MRI and normal genetic testing. Fifty-three MRI examinations of 46 fetuses with confirmed first-trimester CMV infection were included. NSG detected 24 of 27 temporal cysts seen on MRI scans, with a sensitivity of 78% and an accuracy of 83%. NSG did not detect abnormal gyration visible on two (4%) MRI scans. Periventricular calcifications were detected on two MRI scans compared with 10 NSG scans. While lenticulostriate vasculopathy was detected on 11 (21%) NSG scans, no fetus demonstrated this finding on MRI. MRI grading correlated significantly with NSG grading of brain abnormalities (P < 0.0001). Eight (15%) of the DWI scans in the CMV cohort were excluded from further analysis because of insufficient quality. The ADC values of CMV-infected fetuses were significantly increased in the frontal (both sides, P < 0.0001), temporal (both sides, P < 0.0001), parietal (left side, P = 0.0378 and right side, P = 0.0014) and occipital (left side, P = 0.0002 and right side, P < 0.0001) lobes and decreased in the pons (P = 0.0085) when compared with non-infected fetuses. The ADC values in the basal ganglia and the cerebellum were not significantly different in CMV-infected fetuses compared with normal controls (all P > 0.05). Temporal and frontal ADC values were higher in CMV-infected fetuses with more severe brain abnormalities compared to fetuses with mild abnormalities. Ultrasound and MRI are complementary during the third trimester in the assessment of brain abnormalities in CMV-infected fetuses, with a significant correlation between the grading systems of the two modalities. On DWI in the third trimester, the ADC values in several brain regions are abnormal in CMV-infected fetuses compared with normal controls. Furthermore, they seem to correlate in the temporal area and, to a lesser extent, frontal area with the severity of brain abnormalities associated with CMV infection. Larger prospective studies are needed for further investigation of the microscopic nature of diffusion abnormalities and correlation of different imaging findings with postnatal outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Umbilical artery pulsatility index and half-peak systolic velocity in second- and third-trimester fetuses with trisomy 18 and 13.

To analyze umbilical artery (UA) Doppler velocimetry and its possible role in placenta-mediated fetal growth restriction (FGR) in second- and third-trimester fetuses with trisomy 18 and 13. UA pulsatility index (PI) and half-peak systolic velocity deceleration time (hPSV-DT) were measured in fetuses with trisomy 18 and 13. Correlation with gestational age, birthweight, and perinatal outcome was analyzed. A total of 80 measurements were taken from 33 fetuses with trisomy 18 and 19 with trisomy 13. Overall, there was a high prevalence of abnormal UA Doppler velocimetry. In fetuses with trisomy 18, 54% (27/50) of the UA PI values and 58% (29/50) of the UA hPSV-DT values were abnormal. In fetuses with trisomy 13, 80% (24/30) of the UA PI values and 87% (26/30) of the UA hPSV-DT values were abnormal. The prevalence of abnormal UA Doppler velocimetry increased with gestational age in both types of aneuploidy. However, this trend was only significant for trisomy 13 (p<0.05). All fetuses with trisomy 18 and 86% of fetuses with trisomy 13 were classified at birth as FGR. There were no perinatal survivors in this series. A high prevalence of abnormal UA Doppler velocimetry was found in second- and third-trimester fetuses with trisomy 18 and 13, which further increased with gestational age. These results may well correlate with alterations described previously in the placenta, suggesting placental insufficiency has an important role in the development of FGR in these autosomal aneuploid fetuses.

Which is the best ultrasound parameter for the prediction of adverse perinatal outcome within 1 day of delivery?

Objective To compare the accuracies of several sonographic parameters for the prediction of adverse perinatal outcome (APO) prior to delivery. Methods This was a prospective study of fetuses attending the day hospital unit of a tertiary referral hospital that were scanned at 34-41 weeks and gave birth within 24 h of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring urgent cesarean section, neonatal umbilical cord pH < 7.10, 5’ Apgar score <7 and postpartum admission to neonatal or pediatric intensive care units. The accuracies of the middle cerebral, vertebral and umbilical arteries pulsatility index multiples of the median (MoM), the cerebroplacental and vertebroplacental ratios MoM and the EFW in centiles for the prediction of APO was evaluated by means of ROC curves and logistic regression analysis. Results A total of 2140 fetuses were prospectively scanned, however only 182 entered into spontaneous or induced labor and were delivered within 24 h of examination. In this group, MCA PI MoM was the best predictor of APO (AUC = 0.76, 95% CI 0.66–0.85, p < .0001) followed by the CPR MoM (AUC = 0.73, 95% CI 0.63–0.84, p < .0001) and the VPR MoM (AUC = 0.71, 95% CI 0.61–0.81, p < .001). Logistic regression analysis indicated that MCA PI MoM was the only independent determinant for the prediction of APO. Conclusion In a high-risk population of third-trimester fetuses delivering within 24 h of examination, the outcome may be moderately anticipated just with the information provided by the cerebral flow.

Fetal weight estimation by automated three-dimensional limb volume model in late third trimester compared to two-dimensional model: a cross-sectional prospective observational study

BackgroundAccurate estimation of fetal weight is important for prenatal care and for detection of fetal growth abnormalities. Prediction of fetal weight entails the indirect measurement of fetal biometry by ultrasound that is then introduced into formulae to calculate the estimated fetal weight. The aim of our study was to evaluate the accuracy of fetal weight estimation of Chinese fetuses in the third trimester using an automated three-dimensional (3D) fractional limb volume model, and to compare this model with the traditional two-dimensional (2D) model.MethodsProspective 2D and 3D ultrasonography were performed among women with singleton pregnancies 7 days before delivery to obtain 2D data, including fetal biparietal diameter, abdominal circumference and femur length, as well as 3D data, including the fractional arm volume (AVol) and fractional thigh volume (TVol). The fetal weight was estimated using the 2D model and the 3D fractional limb volume model respectively. Percentage error was defined as (estimated fetal weight - actual birth weight) divided by actual birth weight and multiplied by 100. Systematic errors (accuracy) were evaluated as the mean percentage error (MPE). Random errors (precision) were calculated as ±1 SD of percentage error. The intraclass correlation coefficient (ICC) was used to analyze the inter-observer reliability of the 3D ultrasound measurements of fractional limb volume.ResultsUltrasound examination was performed on 56 fetuses at 39.6 ± 1.4 weeks’ gestation. The average birth weight of the newborns was 3393 ± 530 g. The average fetal weight estimated by the 2D model was 3478 ± 467 g, and the MPE was 3.2 ± 8.9. The average fetal weights estimated by AVol and TVol of the 3D model were 3268 ± 467 g and 3250 ± 485 g, respectively, and the MPEs were − 3.3 ± 6.6 and − 3.9 ± 6.1, respectively. For the 3D TVol model, the proportion of fetuses with estimated error ≤ 5% was significantly higher than that of the 2D model (55.4% vs. 33.9%, p < 0.05). For fetuses with a birth weight < 3500 g, the accuracy of the AVol and TVol models were better than the 2D model (− 0.8 vs. 7.0 and − 2.8 vs. 7.0, both p < 0.05). Moreover, for these fetuses, the proportions of estimated error ≤ 5% of the AVol and TVol models were 58.1 and 64.5%, respectively, significantly higher than that of the 2D model (19.4%) (both p < 0.05). The inter-observer reliability of measuring fetal AVol and TVol were high, with the ICCs of 0.921 and 0.963, respectively.ConclusionIn this cohort, the automated 3D fractional limb volume model improves the accuracy of weight estimation in most third-trimester fetuses. Prediction accuracy of the 3D model for neonatal BW, particularly < 3500 g was higher than that of the traditional 2D model.

Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection

BackgroundMechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC).ResultsIn experiment 1, paraffin embedded fetal tissues collected 21 days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses.ConclusionsThere is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.

How to define late fetal growth restriction.

A fraction of third-trimester small fetuses does not achieve their endowed growth potential mainly due to placental insufficiency, usually not evident in terms of impaired umbilical artery Doppler, but severe enough to increase the risk of perinatal adverse outcomes and long-term complications. The identification of those fetuses at higher-risk helps to optimize their follow-up and to decrease the risk of intrauterine demise. Several parameters can help in the identification of those fetuses at higher risk, defined as fetal growth restricted (FGR) fetuses. Severe smallness and the cerebroplacental ratio are the most consistent parameters; regarding uterine artery Doppler, although some evidence in favour has been published, there is currently no consensus about its use. Thirty-two weeks of gestation is the accepted cut-off to define late FGR. The differentiation with early FGR is necessary as these two entities have different clinical maternal manifestations, and different associated short-term and long-term neonatal outcomes. The use of angiogenic factors is promising but more research is needed on this field.

Three-Dimensional Volumetric Magnetic Resonance Imaging Detects Early Alterations of the Brain Growth in Fetuses With Congenital Heart Disease.

Several published studies have shown alterations of brain development in third-trimester fetuses with congenital heart disease (CHD). However, little is known about the timing and pattern of altered brain development in fetuses with CHD. To investigate the changes in the volume of intracranial structures in fetuses with CHD by three-dimensional (3D) volumetric magnetic resonance imaging (MRI) in the earlier stages of pregnancy (median gestational age [GA], 26 weeks). Retrospective. Forty women carrying a fetus with CHD (including 20 fetuses with GA <26 weeks) and 120 pregnant women carrying a healthy fetus (including 50 fetuses with GA <26 weeks). Two-dimensional single-shot turbo spin echo sequence at 1.5-T. Three-dimensional volumetric parameters from slice-to-volume registered images, including cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum, brainstem, and extra-cerebrospinal fluid (e-CSF) were quantified by manual segmentation from one primary and two secondary observers. Volumes were presented graphically with quadratic curve fitting. Scatterplots were produced mapping volumes against GA in normal and CHD fetuses. For GA <26 weeks, Z scores were calculated and Student's t-tests were conducted to compare volumes between the normal and CHD fetuses. In fetuses with CHD GMV, SBV, cerebellum, and brainstem were significantly reduced (all P < 0.05) in early stages of pregnancy (GA <26 weeks), with differences becoming progressively greater with increasing GA. Compared with normal fetuses, e-CSF, e-CSF to ICV ratio, and VV were higher in fetuses with CHD (all P < 0.05). However, ICV volume and the GMV to SBV ratio were not significantly reduced in the CHD group (P=0.94 and P=0.13, respectively) during the middle gestation (GA <26 weeks). There appear to be alterations of brain development trajectory in CHD fetuses that can be detected by 3D volumetric MRI in the earlier stages of pregnancy. 4 TECHNICAL EFFICACY: Stage 3.

Tractography of the Cerebellar Peduncles in Second- and Third-Trimester Fetuses.

Little is known about microstructural development of cerebellar white matter in vivo. This study aimed to investigate developmental changes of the cerebellar peduncles in second- and third-trimester healthy fetuses using motion-corrected DTI and tractography. 3T data of 81 healthy fetuses were reviewed. Structural imaging consisted of multiplanar T2-single-shot sequences; DTI consisted of a series of 12-direction diffusion. A robust motion-tracked section-to-volume registration algorithm reconstructed images. ROI-based deterministic tractography was performed using anatomic landmarks described in postnatal tractography. Asymmetry was evaluated qualitatively with a perceived difference of >25% between sides. Linear regression evaluated gestational age as a predictor of tract volume, ADC, and fractional anisotropy. Twenty-four cases were excluded due to low-quality reconstructions. Fifty-eight fetuses with a median gestational age of 30.6 weeks (interquartile range, 7 weeks) were analyzed. The superior cerebellar peduncle was identified in 39 subjects (69%), and it was symmetric in 15 (38%). The middle cerebellar peduncle was identified in all subjects and appeared symmetric; in 13 subjects (22%), two distinct subcomponents were identified. The inferior cerebellar peduncle was not found in any subject. There was a significant increase in volume for the superior cerebellar peduncle and middle cerebellar peduncle (both, P < .05), an increase in fractional anisotropy (both, P < .001), and a decrease in ADC (both, P < .001) with gestational age. The middle cerebellar peduncle had higher volume (P < .001) and fractional anisotropy (P = .002) and lower ADC (P < .001) than the superior cerebellar peduncle after controlling for gestational age. A robust motion-tracked section-to-volume registration algorithm enabled deterministic tractography of the superior cerebellar peduncle and middle cerebellar peduncle in vivo and allowed characterization of developmental changes.

Memory Traces Formed in Utero-Newborns' Autonomic and Neuronal Responses to Prenatal Stimuli and the Maternal Voice.

In our pilot study, we exposed third-trimester fetuses, from week 34 of gestation onwards, twice daily to a maternal spoken nursery rhyme. Two and five weeks after birth, 34 newborns, who were either familiarized with rhyme stimulation in utero or stimulation naïve, were (re-)exposed to the familiar, as well as to a novel and unfamiliar, rhyme, both spoken with the maternal and an unfamiliar female voice. For the stimulation-naïve group, both rhymes were unfamiliar. During stimulus presentation, heart rate activity and high-density electroencephalography were collected and newborns’ responses during familiar and unfamiliar stimulation were analyzed. All newborns demonstrated stronger speech–brain coupling at 1 Hz during the presentation of the maternal voice vs. the unfamiliar female voice. Rhyme familiarity originating from prenatal exposure had no effect on speech–brain coupling in experimentally stimulated newborns. Furthermore, only stimulation-naïve newborns demonstrated an increase in heart rate during the presentation of the unfamiliar female voice. The results indicate prenatal familiarization to auditory speech and point to the specific significance of the maternal voice already in two- to five-week-old newborns.

Feasibility of Semiautomatic Fetal Intelligent Navigation Echocardiography for Different Fetal Spine Positions: A Matter of "Time"?

We investigated the feasibility of a semiautomatic approach for assessments of the fetal heart (fetal intelligent navigation echocardiography [FINE]) in cases of optimal and unfavorable fetal spine positions. In this study, a total of 1693 spatiotemporal image correlation volumes of first-, second-, and third-trimester fetuses were evaluated by experts using the FINE approach. The data were analyzed regarding proper reconstruction of the diagnostic cardiac planes depending on the fetal spine position. A total of 1531 volumes were included. The volumes were divided into 4 groups depending on the fetal spine position: 5-7 o'clock, 4 + 8 o'clock, 3 + 9 o'clock, and 2 + 10 o'clock. In total, 93.2% of the diagnostic planes were displayed properly. Between 5 and 7 o'clock, 94.9% of the diagnostic planes were displayed properly. The correct depiction rates in the other groups were 92.4% (4 + 8 o'clock; n = 538; P = 0.0027), 88.3% (3 + 9 o'clock; n = 156; P < .0001), and 87.3% (2 + 10 o'clock; n = 41; P = .0139). In total, the highest dropout rates were found in the sagittal planes: ductal arch, 13.9%; aortic arch, 10.5%; and venae cavae, 12.0%. Based on our results, the FINE technique is an effective method, but its feasibility depends on the fetal position. The use of this semiautomatic work flow-based approach supports evaluation of the fetal heart in a standardized manner. Semiautomatic evaluation of the fetal heart might be useful in facilitating the detection of fetal cardiac anomalies.

Third-trimester in utero fetal brain diffusion tensor imaging fiber tractography: a prospective longitudinal characterization of normal white matter tract development.

White matter is responsible for inter-neuronal connections throughout the brain that are a driving force in cognitive development. Diffusion tensor imaging (DTI) fiber tractography has been used to evaluate white matter development in the fetal brain; however, longitudinal studies of DTI fiber tractography to assess white matter development in the third trimester are lacking. To characterize in utero longitudinal changes in the fetal brain DTI fiber tracts of normal third-trimester fetuses. For this single-center prospective longitudinal observational pilot study, we recruited 28 pregnant females with normal third-trimester pregnancies who had routine prenatal ultrasound. MRI of the in utero fetal brain was performed with a Siemens 1.5-tesla (T) Espree scanner at 31weeks, 33weeks and 36weeks of gestation, with 14 DTI tractography parameters quantified in 7 brain regions using DTI-studio version 2.4 (Johns Hopkins University, Baltimore, MD; n=98 measurements). We used multilevel mixed models to examine the relationship between longitudinal changes in DTI measurements and between 98 DTI measurements at 31weeks and 4 routine fetal brain anatomical biometrics (n=392 assessments). We observed statistically significant decreases in radial diffusivity and apparent diffusion coefficient in 13 of 14 brain regions from 31weeks to 36weeks of gestation (P<0.001 for all regions except the genu of the corpus callosum). Significant decreases in radial diffusivity from weeks 33 to 36 and weeks 31 to 36 were seen in the corticospinal tracts, centrum semiovale, posterior limb of the internal capsule, and crus cerebri (P<0.001 for all). When considering all possible combinations of DTI fiber tract measurements and the routine morphological fetal brain biometrics, only 6% (24/392) had a significant association (P<0.05), indicating relative independence of the DTI fiber tract measurements from anatomical biometrics. In utero longitudinal changes in fetal brain DTI fiber tractography are quantifiable in normal third-trimester fetuses and are largely independent of morphological brain changes.

Is Fetal Intelligent Navigation Echocardiography Helpful in Screening for d-Transposition of the Great Arteries?

To evaluate the performance of fetal intelligent navigation echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volumes in generating 3 specific abnormal cardiac views (left ventricular outflow tract, right ventricular outflow tract, and 3-vessel and trachea) used to screen for d-transposition of the great arteries (d-TGA). In this prospective study, 1 or more STIC volumes were obtained from the 4-chamber view in 34 second- and third-trimester fetuses with d-TGA. Each appropriate STIC volume was evaluated by STICLoop (Samsung Medison, Seoul, Korea) before applying the FINE method. One optimal volume per fetus was selected by observers. The visualization rates of the 3 specific abnormal cardiac views of d-TGA and their diagnostic elements were calculated, and the reliability between 2 observers was verified by the intraclass correlation coefficient. Fetal intelligent navigation echocardiography applied to STIC volume data sets of fetuses with d-TGA successfully generated the 3 specific abnormal cardiac views in the following manner for 2 observers: 75.0% (n = 21) for the left ventricular outflow tract, 89.2% (n = 25) for the right ventricular outflow tract, and 85.7% (n = 24) for the 3-vessel and trachea view. Twenty-four (85.7%) of the STIC volume data sets showed 2 or 3 of the abnormal cardiac views. The interobserver intraclass correlation coefficients between the 2 observers ranged from 0.842 to 1.000 (95% confidence interval), indicating almost perfect reliability for the 2 observers. In cases of d-TGA, the FINE method has a high success rate in generating 3 specific abnormal cardiac views and therefore can be performed to screen for this congenital defect.