Femur development in fetal growth restriction as observed on prenatal magnetic resonance imaging.

OBJECTIVE: To investigate human femur development in fetal growth restriction (FGR) by analyzing femur morphometrics and distal epimetaphyseal features on prenatal magnetic resonance imaging (MRI). METHODS: This was a retrospective study of 111 fetuses (mean gestational age (GA), 27 + 2 weeks (range, 19-35 weeks)) with FGR associated with placental insufficiency without other major abnormalities and 111 GA-matched normal controls. On 1.5-Tesla echoplanar MRI, femur morphometrics, including diaphyseal length, epiphyseal length and epiphyseal width, were assessed. Using a previously reported grading system, epimetaphyseal features, including cartilaginous epiphyseal shape, metaphyseal shape and epiphyseal ossification, were analyzed qualitatively. To compare FGR cases and controls, the paired t-test was used to assess morphometrics, generalized estimating equations were used for epimetaphyseal features and time-to-event analysis was used to assess the visibility of epiphyseal ossification. RESULTS: There were significant differences in femur morphometrics between FGR cases and controls (all parameters, P < 0.001), with bone shortening observed in FGR. No significant differences were found in the distribution of epimetaphyseal features between FGR cases and controls (epiphyseal shape, P = 0.341; metaphyseal shape, P = 0.782; epiphyseal ossification, P = 0.85). Epiphyseal ossification was visible at a median of 33.6 weeks in FGR cases and at 32.1 weeks in controls (P = 0.008). CONCLUSIONS: On prenatal MRI, cases with FGR associated with placental insufficiency exhibit diaphyseal and epiphyseal shortening of the femur. However, FGR cases and normal controls share similarly graded distal epimetaphyseal features. Consequently, these features may not be appropriate MRI characteristics for the identification of FGR. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mapping Human Fetal Brain Maturation In Vivo Using Quantitative MRI.

BACKGROUND AND PURPOSE: On the basis of a single multidynamic multiecho sequence acquisition, SyMRI generates a variety of quantitative image data that can characterize tissue-specific properties. The aim of this retrospective study was to evaluate the feasibility of SyMRI for the qualitative and quantitative assessment of fetal brain maturation. MATERIALS AND METHODS: In 52 fetuses, multidynamic multiecho sequence acquisitions were available. SyMRI was used to perform multidynamic multiecho-based postprocessing. Fetal brain maturity was scored qualitatively on the basis of SyMRI-generated MR imaging data. The results were compared with conventionally acquired T1-weighted/T2-weighted contrasts as a standard of reference. Myelin-related changes in T1-/T2-relaxation time/relaxation rate, proton density, and MR imaging signal intensity of the developing fetal brain stem were measured. A Pearson correlation analysis was used to detect correlations between the following: 1) the gestational age at MR imaging and the fetal brain maturity score, and 2) the gestational age at MR imaging and the quantitative measurements. RESULTS: SyMRI provided images of sufficient quality in 12/52 (23.08%) (range, 23 + 6-34 + 0) fetal multidynamic multiecho sequence acquisitions. The fetal brain maturity score positively correlated with gestational age at MR imaging (SyMRI: r = 0.915, P < .001/standard of reference: r = 0.966, P < .001). Myelination-related changes in the T2 relaxation time/T2 relaxation rate of the medulla oblongata significantly correlated with gestational age at MR imaging (T2-relaxation time: r = -0.739, P = .006/T2-relaxation rate: r = 0.790, P = .002). CONCLUSIONS: Fetal motion limits the applicability of multidynamic multiecho-based postprocessing. However, SyMRI-generated image data of sufficient quality enable the qualitative assessment of maturity-related changes of the fetal brain. In addition, quantitative T2 relaxation time/T2 relaxation rate mapping characterizes myelin-related changes of the brain stem prenatally. This approach, if successful, opens novel possibilities for the evaluation of structural and biochemical aspects of fetal brain maturation.

Beyond Isolated and Associated: A Novel Fetal MR Imaging-Based Scoring System Helps in the Prenatal Prognostication of Callosal Agenesis.

BACKGROUND AND PURPOSE: Although "corpus callosum agenesis" is an umbrella term for multiple entities, prenatal counseling is based reductively on the presence (associated) or absence (isolated) of additional abnormalities. Our aim was to test the applicability of a fetal MR neuroimaging score in a cohort of fetuses with prenatally diagnosed isolated corpus callosum agenesis and associated corpus callosum agenesis and correlate it with neurodevelopmental outcomes. MATERIALS AND METHODS: We performed a single-center retrospective analysis of a cohort of cases of consecutive corpus callosum agenesis collected between January 2011 and July 2019. Cases were scored by 2 raters, and interater agreement was calculated. Outcome was assessed by standardized testing (Bayley Scales of Infant and Toddler Development, Kaufman Assessment Battery for Children) or a structured telephone interview and correlated with scores using 2-way ANOVA. RESULTS: We included 137 cases (74 cases of isolated corpus callosum agenesis), imaged at a mean of 27 gestational weeks. Interrater agreement was excellent (0.98). Scores were higher in associated corpus callosum agenesis (P < .0001) without a significant score difference between complete and partial corpus callosum agenesis (P = .38). Outcome was assessed in 42 children with isolated corpus callosum agenesis and 9 with associated corpus callosum agenesis (mean age, 3.1 years). MR imaging scores correctly predicted developmental outcome in 90.7% of patients with isolated corpus callosum agenesis, improving neurodevelopmental risk stratification in corpus callosum agenesis. CONCLUSIONS: The scoring system is very reproducible and can differentiate isolated corpus callosum agenesis and associated isolated corpus callosum agenesis (significantly higher scores) but not between partial and complete corpus callosum agenesis. Scores correlated with outcome in isolated corpus callosum agenesis, but there were too few associated postnatal cases of isolated corpus callosum agenesis to draw conclusions in this group.

Improved neurodevelopmental prognostication in isolated corpus callosal agenesis: fetal magnetic resonance imaging-based scoring system.

OBJECTIVES: Corpus callosal agenesis (CCA) is one of the most common brain malformations and is generally associated with a good outcome when isolated. However, up to 25% of patients are at risk of neurodevelopmental delay, which currently available clinical and imaging parameters are inadequate to predict. The objectives of this study were to apply and validate a fetal magnetic resonance imaging (MRI) anatomical scoring system in a cohort of fetuses with isolated CCA and to evaluate the correlation with postnatal neurodevelopmental outcome. METHODS: This was a retrospective cohort study of cases of prenatally diagnosed isolated CCA (as determined on ultrasound and MRI), with normal karyotype and with known postnatal neurodevelopmental outcome assessed by standardized testing. A fetal brain MRI anatomical scoring system based on seven categories (gyration, opercularization, temporal lobe symmetry, lamination, hippocampal position, basal ganglia and ventricular size) was developed and applied to the cohort; a total score of 0-11 points could be given, with a score of 0 representing normal anatomy. Images were scored independently by two neuroradiologists blinded to the outcome. For the purpose of assessing the correlation between fetal MRI score and neurodevelopmental outcome, neurodevelopmental test results were scored as follows: 0, 'below average' (poor outcome); 1, 'average'; and 2, 'above average' (good outcome). Spearman's rank coefficient was used to assess correlation, and inter-rater agreement in the assessment of fetal MRI score was calculated. RESULTS: Twenty-one children (nine females (42.9%)) fulfilled the inclusion criteria. Thirty-seven fetal MRI examinations were evaluated. Mean gestational age was 28.3 ± 4.7 weeks (range, 20-38 weeks). All fetuses were delivered after 35 weeks' gestation with no perinatal complications. Fetal MRI scores ranged from 0 to 6 points, with a median of 3 points. Inter-rater agreement in fetal MRI score assessment was excellent (intraclass correlation coefficient, 0.959 (95% CI, 0.921-0.979)). Neurodevelopmental evaluation was performed on average at 2.6 ± 1.46 years (range, 0.5-5.8 years). There was a significant negative correlation between fetal MRI score and neurodevelopmental outcome score in the three areas tested: cognitive (ρ = -0.559, P < 0.0001); motor (ρ = -0.414, P = 0.012) and language (ρ = -0.565, P < 0.0001) skills. Using fetal MRI score cut-offs of ≤ 3 (good outcome) and ≥ 4 points (high risk for poor outcome), the correct prognosis could be determined in 20/21 (95.2% (95% CI, 77.3-99.2%)) cases. CONCLUSION: By assessing structural features of the fetal brain on MRI, it may be possible to better stratify prenatally the risk of poor neurodevelopmental outcome in CCA patients. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Quantitative fetal magnetic resonance imaging assessment of cystic posterior fossa malformations.

OBJECTIVE: Normal cognitive development usually requires a structurally intact and complete cerebellar vermis. The aim of this study was to evaluate whether quantification by fetal magnetic resonance imaging (MRI) of vermis- and brainstem-specific imaging markers improves the definition of cystic posterior fossa malformations (cPFM). METHODS: Fetuses diagnosed with cPFM that had an available midsagittal plane on T2-weighted MRI were identified retrospectively and compared with gestational-age (GA) matched brain-normal controls. Fetuses with cPFM were assigned to three groups, according to standard criteria (vermian size and brainstem-vermis (BV) angle): normal vermian area and BV angle < 25° (Group 1); reduced vermian area and/or BV angle of 25-45° (Group 2); and reduced vermian area and BV angle > 45° (Group 3; Dandy-Walker malformation (DWM) group). The number of differentiable vermian lobules and the areas of the vermis, mesencephalon, pons and medulla oblongata were quantified, correlated with and controlled for GA, and compared between the study groups. RESULTS: In total, 142 cases of cPFM were included, with a mean GA of 25.20 ± 5.11 weeks. Cases comprised Blake's pouch cyst (n = 46), arachnoid cyst (n = 12), inferior vermian hypoplasia (n = 5), megacisterna magna (n = 35) and classic DWM (n = 44). In the control group, 148 fetuses were included, with a mean GA of 25.26 ± 4.12 weeks. All quantified areas and the number of differentiable vermian lobules had a significant positive correlation with GA. The number of vermian lobules and the areas of all quantified regions, except for that of the medulla oblongata, differed significantly between the study groups (P ≤ 0.015 for all). The control group had the highest number of differentiable vermian lobules and the DWM group had the lowest (P < 0.01). CONCLUSIONS: Prenatal MRI assessment of vermian lobules is a useful addition to standard neuroradiological and neurosonographic techniques. The quantification of vermian lobules using fetal MRI allows further differentiation of cPFM into subgroups and thereby improves the classification of hindbrain malformations. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal assessment of cerebellar vermian lobulation: fetal MRI with 3-Tesla postmortem validation.

OBJECTIVES: To optimize the imaging assessment of fetal hindbrain malformations, this observational magnetic resonance imaging (MRI) study aimed to assess whether fetal vermian lobulation can be quantified accurately and whether the relative growth of vermian lobules is uniform. METHODS: This retrospective study included singleton fetuses which underwent T2-weighted MRI in vivo with a 1.5-Tesla (T) scanner or within 24 h postmortem with a 3-T scanner between January 2007 and November 2016 at the Medical University of Vienna. We included only those showing normal structural brain development on ultrasound and MRI and which had image quality appropriate for quantitative analysis, i.e. good image quality and a precise midsagittal slice. Fetal brains were segmented and, for all discernible vermian lobules, we determined the mean relative area contribution (MRAC, the proportion of the lobule relative to the total vermian area, in terms of number of voxels). Inter- and intrarater measurement variability of a representative selection (21 cases) was determined by intraclass correlation coefficient (ICC) for voxel-based differences. A linear regression model was used to assess the correlation between the relative size of each vermian lobule (i.e. MRAC) and gestational age. RESULTS: A total of 78 fetuses scanned in vivo aged 18-32 gestational weeks and seven fetuses scanned postmortem aged 16-30 weeks had a precise midsagittal slice and image quality sufficient for quantitative analysis. After 22 weeks of gestation, seven of the nine known vermian lobules could be discriminated reliably. The MRAC showed a mean ± SD difference of only 2.89 ± 3.01% between in-vivo and postmortem measurements. The ICC of voxel-based interrater differences was mean ± SD, 0.91 ± 0.05 and the intrarater ICC was 0.95 ± 0.03. Growth of cerebellar lobules was non-uniform: the MRAC of culmen and DFT (declive + folium + tuber) increased with gestational age, whereas that of lingula, centralis, pyramis and nodulus decreased. The growth of the uvula showed no significant correlation with gestational age. CONCLUSIONS: Fetal vermian lobulation can be assessed accurately and reliably after 22 weeks on precise midsagittal sequences with 1.5-T T2-weighted MRI. Fetal vermian lobules show non-uniform growth, with expansion of DFT and culmen at the expense of the other vermian lobules. Evaluation and elucidation of vermian lobulation in normal fetuses should enable better characterization of fetuses with hindbrain malformations. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal microarray analysis as second-tier diagnostic test: single-center prospective study.

OBJECTIVE: To evaluate the usefulness of chromosome microarrays as a second-tier test in prenatal genetic testing. METHODS: We prospectively analyzed 75 high-risk pregnancies undergoing invasive prenatal genetic testing in which the karyotype either was normal or had findings other than a common non-mosaic autosomal aneuploidy. RESULTS: Chromosomal microarray analysis (CMA) was performed successfully in all cases. Pathological copy-number variations (CNVs) explaining the phenotypes were found in 11 cases (14.7%). Four cases were detected with an unbalanced translocation. In three of these cases, subsequent genetic analysis demonstrated that a parent was an unknown carrier of a balanced translocation. Among the 67 cases with normal karyo-types, submicroscopic rearrangements with pathological significance were detected in five (7.5%) and CNVs of unclear significance were detected in one (1.5%). CMA was able to discriminate correctly between true mosaicism and confined or pseudomosaicism in all six mosaic cases. CONCLUSION: CMA is a valuable second-tier test in high-risk pregnancies for which identification or further delineation of genetic aberrations is important. Its higher resolution results in a higher detection rate of aberrant cases, with a clear clinical benefit for estimation of risk of recurrence.

Penile biometry on prenatal magnetic resonance imaging.

OBJECTIVE: In view of the implementation of magnetic resonance imaging (MRI) as an adjunct to ultrasonography in prenatal diagnosis, this study sought to demonstrate normal penile growth on prenatal MRI. METHODS: This was a retrospective study of MRI of 194 male fetuses (18-34 weeks' gestation) with normal anatomy or minor abnormalities. On sagittal T2-weighted MRI sequences, we measured penile length from the glans tip to the scrotal edge (outer length) and from the glans tip to the symphyseal border (total length). Descriptive statistics, as well as correlation and regression analysis, were used to evaluate penile length in relation to gestation. T-tests were calculated to compare mean outer/total length on MRI with published ultrasound data. RESULTS: Mean length values, including 95% CIs and percentiles, were defined. Penile length as a function of gestational age was expressed by the following regression equations: outer mean length = - 5.514 + 0.622 × gestational age in weeks; total mean length = - 8.865 + 1.312× gestational age in weeks. The correlation coefficients, r = 0.532 and r = 0.751, respectively, were statistically significant (P < 0.001). Comparison of outer penile length on MRI with published ultrasound penile length data showed no significant differences, while total penile length on MRI was significantly greater than ultrasound penile length (P < 0.001). CONCLUSION: Our MRI results provide a reference range of fetal penile length, which, in addition to ultrasonography, may be helpful in the identification of genital anomalies. Outer penile length on MRI is equivalent to penile length measured on ultrasound, whereas total length is significantly greater.

Abnormalities of the upper extremities on fetal magnetic resonance imaging.

OBJECTIVE: In view of the increasing use of fetal magnetic resonance imaging (MRI) as an adjunct to prenatal ultrasonography, we sought to demonstrate the visualization of upper extremity abnormalities and associated defects on MRI, with regard to fetal outcomes and compared with ultrasound imaging. METHODS: This retrospective study included 29 fetuses with upper extremity abnormalities visualized with fetal MRI following suspicious ultrasound findings and confirmed by postnatal assessment or autopsy. On a 1.5-Tesla unit, dedicated sequences were applied to image the extremities. Central nervous system (CNS) and extra-CNS anomalies were assessed to define extremity abnormalities as isolated or as complex, with associated defects. Fetal outcome was identified from medical records. MRI and ultrasound findings, when available, were compared. RESULTS: Isolated upper extremity abnormalities were found in three (10.3%) fetuses. In 26 (89.7%) fetuses complex abnormalities, including postural extremity disorders (21/26) and structural extremity abnormalities (15/26), were demonstrated. Associated defects involved: face (15/26); musculoskeletal system (14/26); thorax and cardio/pulmonary system (12/26); lower extremities (12/26); brain and skull (10/26); and abdomen (8/26). Of the 29 cases, 18 (62.1%) pregnancies were delivered and 11 (37.9%) were terminated. MRI and US findings were compared in 27/29 cases: the diagnosis was concordant in 14 (51.9%) of these cases, and additional findings were made on MRI in 13/27 (48.1%) cases. CONCLUSIONS: Visualization of upper extremity abnormalities on fetal MRI enables differentiation between isolated defects and complex ones, which may be related to poor fetal prognosis. MRI generally confirms the ultrasound diagnosis, and may provide additional findings in certain cases.

Monitoring and treatment of anti-D in pregnancy.

Prophylactic anti-D is a very safe and effective therapy for the suppression of anti-D immunization and thus prevention of haemolytic disease of the foetus and newborn. However, migration from countries with low health standards and substantial cuts in public health expenses have increased the incidence of anti-D immunization in many "developed" countries. Therefore, this forum focuses on prenatal monitoring standards and treatment strategies in pregnancies with anti-D alloimmunization. The following questions were addressed, and a response was obtained from 12 centres, mainly from Europe.

Prenatal diagnosis of a supernumerary aberrant chromosome 9.

For counselling of parents, as well as to basically understand how chromosome aneuploidies affect embryonic or fetal development, it is of great importance to analyse and collect genotypes of fetuses with clinical anomalies. This report describes the first prenatal diagnosis of a supernumerary chromosome 9 with deletion of the chromosome region 9q34. Ultrasound examination in the 13th week of gestation detected increased nuchal translucency of 6.9 mm, fetal ascites and a pronounced facial anomaly. Hysteroscopic examination before curettage made it possible to describe this facial anomaly as a double-sided, median defect of the superior lip with protrusion of parts of intersegments. This report provides evidence that the absence of trisomy 9 in 9q34 does not prevent abnormal facial development.

[The intrauterine rupture of the fetal bladder as a complication of low urinary tract obstruction]. / Die intrauterine Blasenruptur als Komplikation infravesikaler Harnentleerungsstörungen beim Feten.

Lower urinary tract obstruction in fetuses causes megacystis, megaureter and hydronephrosis. The spontaneous rupture of the fetal bladder represents a rare complication in cases of total bladder outlet obstruction. We report about two different cases, present pre- and postnatal therapeutic regimes and discuss the possibility of spontaneous healing of a ruptured fetal bladder before delivery.

[Complication rates of invasive intrauterine procedures in a centre for prenatal diagnosis and therapy]. / Zur Komplikationsrate bei invasiven, intrauterinen Eingriffen an einer pränataldiagnostischen Schwerpunktabteilung.

AIM: A retrospective analysis of all complications occurring after invasive prenatal procedures was performed in order to have exact data for patient information and quality control in our department. METHOD: During a period of two years 2256 invasive ultrasound-guided procedures were performed. With the help of a computer data base, the follow-up of 2066 patients was possible. We retrospectively investigated all cases of severe complications resulting in intrauterine foetal death or abortion within 14 days after the invasive procedure. RESULTS: Depending on the method of invasive testing there were different rates of severe complications in single pregnancies, which varied from 0.44 % up to 0.99 % (Amniocentesis [AC]): 0.74 %, late placental biopsy: 0.44 %, chorionic villi sampling: 0.99 %, cordocentesis: 0.75 %. The complication rate after AC was 1.49 % in younger, inexperienced colleagues compared to 0.58 % in specialists for prenatal medicine. The complication rate in twin pregnancies (AC) was 1.99 %. CONCLUSION: Before invasive prenatal procedures can be performed, detailed information has to be given to the patients. The exact rate of complications should be included in this information. More complicated invasive procedures should be centralized in a tertiary centre for prenatal medicine because wider experience of the investigators leads to a decreased rate of severe complications.

[Prenatal diagnosis of full, non mosaic trisomy 22 in the third trimester]. / Zur pränatalen Ultraschall-Diagnostik des Vollbildes der Trisomie 22 im III. Trimenon.

A 31-year-old Caucasian women was referred to our department after IUGR was suspected by her gynaecologist at 29 weeks' amenorrhea in her second pregnancy. Multiple anomalies were detected by prenatal ultrasound in the 29th week of gestation. Chordocentesis was performed and revealed a Trisomy 22 in all fetal blood cells. The pregnancy was terminated. Post-mortem investigations excluded chromosomal mosaicism. Prenatal ultrasound findings and post-mortem features are presented.

Prenatal diagnosis of a de novo supernumerary marker derived from chromosome 16.

Marker chromosomes are supernumerary chromosomes of unknown origin and are seldom found in prenatal diagnosis. Application of fluorescent in situ hybridization (FISH) allows the identification of the chromosomal origin of markers. Estimation of the risk of an abnormal phenotype outcome can be enabled by collecting data on phenotypes associated with markers of the same chromosomal origin. So far only very few cases of prenatal diagnosis of de novo supernumerary markers derived from chromosome 16 have been reported. Here the prenatal diagnosis of a de novo supernumerary marker chromosome 16 is described and the relevant literature discussed.

Ultrasound imaging of Bartholin's cysts.

In a prospective, randomized study, Bartholin's cysts were depicted in 36 patients by means of ultrasound imaging. Patients were requested to return for a follow-up US examination after surgery. We were able to show that Bartholin's cysts can easily be expressed with ultrasonographic techniques. In clinical practice, this approach may not only help to improve diagnostics, but may also make therapy measurable and, for the first time, objectifiable.

Prenatal diagnosis of fetal urinary ascites.

We report on a rare in utero appearance of the rupture of the fetal bladder caused by low urinary tract obstruction with subsequent urinary ascites. The findings on prenatal sonography, postnatal X-ray examinations and postnatal surgical treatment are described and the literature is reviewed.

The value of echogenic foci ('golfballs') in the fetal heart as a marker of chromosomal abnormalities.

OBJECTIVE: The aim of our study was to determine the significance of antenatally detected hyperechogenic foci in the fetal heart. DESIGN: Prospective study. SUBJECTS AND METHODS: During a 21-month period, 6995 women underwent a sonographic screening investigation. A detailed structural survey was performed on each fetus according to our sonography protocol, including a four-chamber view and an evaluation of the great vessels, as permitted by gestational age. We prospectively identified each fetus with an echogenic intracardiac focus. RESULTS: A total of 150 fetuses with this sonographic finding were identified. The incidence rate was 2.15%. In 114 patients (76%), prenatal karyotyping was performed. The aneuploidy rate was 4.4%. CONCLUSIONS: The echogenic intracardiac focus can be easily diagnosed in most cases. This should prompt an extensive search for other 'soft' markers. The presence of an echogenic intracardiac focus as a single soft marker should raise the question of prenatal karyotyping. It might help in the decision-making regarding invasive prenatal testing in cases with an otherwise low risk for chromosomal abnormality. In cases with other markers for chromosomal abnormality (advanced maternal age, sonographic signs, positive serum marker screening), the presence of an echogenic intracardiac focus should be an additional incentive for a chromosomal examination.