Tela-choroidea-to-anterior-cerebral-artery distance (TACAD): novel marker on color Doppler to identify fetuses with complete or partial agenesis of corpus callosum.

OBJECTIVES: To assess objectively the course of the anterior cerebral artery (ACA) by measuring its distance to the tela choroidea in the midsagittal view, and to compare this distance in normal fetuses with that in those with agenesis of the corpus callosum (ACC), a condition known to be associated with an abnormal course of the ACA. METHODS: The tela-choroidea-to-anterior-cerebral-artery distance (TACAD) was measured in the midsagittal view of the brain on color Doppler, between the anterior border of the tela choroidea and the ACA at the level of the callosal genu. Reference ranges in relation to gestational age were established in a prospective, cross-sectional study of 253 normal healthy fetuses between 19 and 36 weeks of gestation. The study group included fetuses with complete ACC (n = 28) or partial ACC (n = 18). RESULTS: TACAD of normal fetuses showed an increase during the second half of pregnancy, with a mean value of 10.1 mm and 14.2 mm at 22 and 30 weeks of gestation, respectively. All (28/28) fetuses with complete ACC and 83% (15/18) of those with partial ACC had significantly shorter TACAD, with mean values of 3.9 mm and 6.6 mm, respectively. CONCLUSIONS: TACAD is a measurement that is simple to obtain during fetal color Doppler neurosonography, which enables quantification of the course of the ACA and pericallosal artery. TACAD is shorter in fetuses with complete or partial ACC than in normal fetuses and provides an objective, quantifiable value, rather than merely descriptive information. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal screening and diagnosis of pulmonary artery anomalies.

Congenital pulmonary artery anomalies are rare. Their antenatal diagnosis requires good knowledge of fetal cardiac anatomy because their clinical presentation varies depending on the type and severity of the underlying lesion. Screening of these vascular anomalies can be straightforward in some cases because of significant associated consequences that are detected easily on ultrasound, while other anomalies have considerably less obvious features. There may be an associated genetic syndrome. The aim of this review was to define anomalies of the main pulmonary artery and its branches and to propose, through the identification of suspicious findings during routine antenatal heart examination, an optimal screening method for the pulmonary artery pathway. We propose that pulmonary artery anomalies can be classified antenatally into four types of disorder. Herein we describe 14 cases subgrouped accordingly as: anomalies of the pulmonary valvular region, with stenosis or atresia of the valve (n = 4); conotruncal abnormalities (n = 4); anomalies associated with abnormal origin or course of the pulmonary artery (n = 4); and anomalies associated with abnormal growth of the pulmonary artery and its branches (n = 2). We highlight the need to differentiate the three-vessel view from the three-vessel-and-trachea view when assessing a fetus with a congenital pulmonary artery anomaly. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Low torcular Herophili position and large brainstem-tentorium angle in fetuses with open spinal dysraphism at 11-13 weeks' gestation.

OBJECTIVE: To evaluate whether in fetuses with open spina bifida (OSB) the tentorium can be seen to be displaced downwards and vertically oriented by the time of the 11-13-week scan and whether this is reflected in an alteration of the brainstem-tentorium (BST) angle. METHODS: The study population was recruited between 2015 and 2020 from three fetal medicine referral centers and comprised a control group and a study group of pregnancies with OSB. The control group was recruited prospectively and included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome. The study group was selected retrospectively and included all cases with OSB between 2015 and 2020. All cases underwent detailed ultrasound assessment at 11 + 0 to 13 + 6 weeks' gestation. The position of the torcular Herophili (TH) was identified in the midsagittal view of the fetal brain with the use of color Doppler and was considered as a proxy for the insertion of the tentorium on the fetal skull. The BST angle was calculated in the same view and was compared between the two groups. RESULTS: Sixty normal fetuses were included in the control group and 22 fetuses with OSB in the study group. In both groups, the BST angle was found to be independent of gestational age or crown-rump length (P = 0.8815, R2 = 0.0003861 in the controls, and P = 0.2665, R2 = 0.00978 in the OSB group). The mean BST angle was 48.7 ± 7.8° in controls and 88.1 ± 1.18°, i.e. close to 90°, in fetuses with OSB. Comparison of BST-angle measurements between the control group and cases with OSB showed a statistically significant difference (P = 0.0153). In all fetuses with OSB, the downward displacement of the TH and tentorium was clearly visible at the 11-13-week scan. CONCLUSIONS: In fetuses with OSB, the BST angle is significantly larger than in normal controls, with the tentorium being almost perpendicular to the brainstem. This sign confirms the inferior displacement of the tentorium cerebelli with respect to its normal insertion on the occipital clivus as early as the first trimester of pregnancy and is useful in the diagnosis of Chiari-II malformation at this early stage. In fetuses with OSB, the low position of the tentorium and TH is clearly visible, even subjectively, at the 11-13-week scan. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Two different prenatal imaging cerebral patterns of tubulinopathy.

To illustrate the prenatal cerebral imaging features associated with tubulinopathy, we report on five affected fetuses from unrelated families, with a de-novo heterozygous variant in a tubulin gene (TUBA1A, TUBB2B or TUBB3). We identified two distinct prenatal imaging patterns related to tubulinopathy: a severe form, characterized by enlarged germinal matrices, microlissencephaly and a kinked brainstem; and a mild form which has not been reported previously in the prenatal literature. The latter form is associated with non-specific features, including an asymmetric brainstem, corpus callosal dysgenesis, a lack of Sylvian fissure operculization and distortion of the anterior part of the interhemispheric fissure with subsequent impacted medial borders of the frontal lobes, the combination of which, in the absence of additional extracerebral anomalies, is highly suggestive of tubulinopathy. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Performance of a targeted cell-free DNA prenatal test for 22q11.2 deletion in a large clinical cohort.

OBJECTIVE: 22q11.2 deletion is more common than trisomies 18 and 13 combined, yet no routine approach to prenatal screening for this microdeletion has been established. This study evaluated the clinical sensitivity and specificity of a targeted cell-free DNA (cfDNA) test to screen for fetal 22q11.2 deletion in a large cohort, using blinded analysis of prospectively enrolled pregnancies and stored clinical samples. METHODS: In order to ensure that the analysis included a meaningful number of cases with fetal 22q11.2 deletion, maternal plasma samples were obtained by prospective, multicenter enrolment of pregnancies with a fetal cardiac abnormality and from stored clinical samples from a research sample bank. Fetal genetic status, as evaluated by microarray analysis, karyotyping with fluorescence in-situ hybridization or a comparable test, was available for all cases. Samples were processed as described previously for the Harmony prenatal test, with the addition of DANSR (Digital Analysis of Selected Regions) assays targeting the 3.0-Mb region of 22q11.2 associated with 22q11.2 deletion syndrome. Operators were blinded to fetal genetic status. Sensitivity and specificity of the cfDNA test for 22q11.2 deletion were calculated based on concordance between the cfDNA result and fetal genotype. RESULTS: The final study group consisted of 735 clinical samples, including 358 from prospectively enrolled pregnancies and 377 stored clinical samples. Of 46 maternal plasma samples from pregnancies with a 22q11.2 deletion, ranging in size from 1.25 to 3.25 Mb, 32 had a cfDNA result indicating a high probability of 22q11.2 deletion (sensitivity, 69.6% (95% CI, 55.2-80.9%)). All 689 maternal plasma samples without a 22q11.2 deletion were classified correctly by the cfDNA test as having no evidence of a 22q11.2 deletion (specificity, 100% (95% CI, 99.5-100%)). CONCLUSIONS: The results of this large-scale prospective clinical evaluation of the sensitivity and specificity of a targeted cfDNA test for fetal 22q11.2 deletion demonstrate that this test can detect the common and smaller, nested 22q11.2 deletions with a low (0-0.5%) false-positive rate. Although the positive predictive value (PPV) observed in this study population was 100%, the expected PPV in the general pregnant population is estimated to be 12.2% at 99.5% specificity and 41.1% at 99.9% specificity. The use of this cfDNA test to screen for 22q11.2 deletion could enhance identification of pregnancies at risk for 22q11.2 deletion syndrome without significantly increasing the likelihood of maternal anxiety and unnecessary invasive procedures related to a false-positive result. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ratio of fetal choroid plexus to head size: simple sonographic marker of open spina bifida at 11-13 weeks' gestation.

OBJECTIVES: To measure the ratio of choroid plexus (CP) size to head size in normal fetuses and to compare it to that in fetuses with open spina bifida (OSB) and quantify the subjective sign of a 'dry brain'. METHODS: This was a retrospective study of ultrasound images, obtained during first-trimester screening between 11 and 13 weeks of gestation, from 34 fetuses with OSB and 160 normal fetuses. From the hospital databases, we retrieved images of the fetal head in the transventricular axial plane. We measured the areas of both CPs and the head and calculated the ratio between them. We also measured the longest diameter of each CP and calculated their mean (CP length), and measured the occipitofrontal diameter (OFD) and calculated the ratio of CP length to OFD. Measurements from the OSB fetuses were plotted on crown-rump length (CRL) reference ranges constructed using data from the normal fetuses, and Z-scores were calculated. RESULTS: In the normal fetuses, the CP area increased, while the ratios of CP area to head area and CP length to OFD decreased, with increasing CRL. In 30 of the 34 (88%) fetuses with OSB, both ratios were increased significantly and the CPs filled the entirety of the head, giving the impression of a dry brain. In these cases, the borders of the lateral ventricles could not be identified. CONCLUSIONS: At 11-13 weeks, the majority of fetuses with OSB have reduced fluid in the lateral ventricles such that the CPs fill the head. The dry brain sign is easily visualized during routine first-trimester ultrasound examination while measuring the biparietal diameter, and can be quantified by comparing the size of the CPs to the head size. Until prospective data confirm the usefulness of this sign in screening for OSB, it should be considered as a hint to prompt the examiner to assess thoroughly the posterior fossa and spine. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Cavum septi pellucidi (CSP) ratio: a marker for partial agenesis of the fetal corpus callosum.

OBJECTIVE: While complete agenesis of the corpus callosum is often suspected on fetal ultrasound due to absence of the cavum septi pellucidi (CSP), suspicion of partial agenesis of the corpus callosum (pACC) is a challenge since the CSP is almost always present. The aim of this study was to measure the length and width of the CSP and calculate the length-to-width ratio (CSP ratio), and compare these between fetuses with pACC and normal fetuses. METHODS: In this retrospective case-control study, the length and width of the CSP were measured in the axial plane of the fetal head, and the CSP length-to-width ratio calculated, in 323 normal fetuses and in 20 fetuses with pACC between 20 and 34 weeks' gestation. From the normal population we constructed reference ranges in relation to biparietal diameter (BPD). For all fetuses we calculated Z-scores for the CSP ratio. RESULTS: In the normal population, the length and width of the CSP increased with increasing BPD, while the CSP ratio decreased. The CSP was short (< 5th centile) in 85% (17/20) of fetuses with pACC and wide (> 95th centile) in 65% (13/20). The CSP ratio was small (< 5th centile) in 95% (19/20) of pACC fetuses, with 16/20 (80%) having a ratio below an empirical cut-off of 1.5. Analysis of Z-scores showed that fetuses with pACC had a significantly smaller CSP ratio (P < 0.0001) compared with the normal population. CONCLUSIONS: Fetuses with a normal-sized corpus callosum have a rectangular-shaped CSP, with a CSP ratio > 1.5 in the second half of gestation. Most fetuses with pACC have an abnormally shaped, wide and short CSP, with a decreased CSP ratio. This simple ratio has the potential to identify fetuses at high risk for pACC. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Intrathymic and other anomalous courses of the left brachiocephalic vein in the fetus.

OBJECTIVE: The left brachiocephalic vein (LBCV), or innominate vein, connects the left jugular vein to the right superior vena cava. Its course is posterior to the thymus and directly anterior and superior to the aortic arch. Pediatric and adult cardiology studies have reported on the subaortic or retrotracheal courses of the LBCV and the presence of double LBCV. We observed recently in the fetus that the LBCV may have a course through the thymus (intrathymic) or be absent in the presence of a left superior vena cava. The aim of this study was to report the prevalence of isolated intrathymic and absent LBCV in normal fetuses undergoing second-trimester ultrasound screening, as well as the prevalence of other courses in association with cardiac anomalies. METHODS: In the prospective part of this study, consecutive second-trimester ultrasound examinations were evaluated to assess the presence and course of the fetal LBCV. In the retrospective case-control part of this study, the databases of two fetal medicine centers were reviewed for cardiac anomalies and the pattern and prevalence of anomalous courses of the LBCV were reported. RESULTS: One thousand four hundred and eighteen consecutive fetuses were examined prospectively. An intrathymic course of the LBCV with a typical bent shape was found in 1.76% (1 : 57) of cases and the absence of a LBCV in association with a persistent left superior vena cava (LSVC) was found in 0.28% (1 : 350). All fetuses with an isolated intrathymic course or absence of the LBCV had a normal outcome. Over a period of 4.5 years, a total of 1544 fetuses with cardiac malformations were reviewed at two centers. Among these, an anomalous course of the LBCV was noted in eight (0.5%) cases: six subaortic, one retrotracheal and one double LBCV. CONCLUSION: An intrathymic LBCV is a common condition and appears to be a normal variant in the fetus. The prevalence of a LSVC in our screening population was similar to that reported in previous studies. Anomalous courses of the LBCV are seen occasionally in cases with cardiac malformation. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound of the Fetal Veins Part 3: The Fetal Intracerebral Venous System.

The study of the intracerebral venous system in the fetus can only be achieved by means of high-resolution ultrasound equipment with sensitive color Doppler. In the past two decades, there has been a growing interest in the ultrasound examination of the fetal brain with few studies reporting on the brain vasculature during various stages of gestation. In comparison to other fetal venous systems, reports on the assessment of the fetal cerebral venous system are still scarce. This article presents a review on the fetal intracranial venous system with detailed discussions on the anatomy of the superficial and deep cerebral veins. Color Doppler of the main fetal cerebral veins to include the superior sagittal sinus, the straight sinus, the vein of Galen, the internal cerebral veins, the transverse sinuses and others is also discussed. Furthermore, this article highlights abnormal clinical conditions such as aneurysm of the vein of Galen, thrombosis of the dural sinus and variation in the course of some veins such as the straight sinus and falcine sinus. The role of pulsed Doppler examination in normal and growth-restricted fetuses is also discussed.

Quality Requirements for the early Fetal Ultrasound Assessment at 11-13+6 Weeks of Gestation (DEGUM Levels II and III).

The early fetal ultrasound assessment at 11 - 13(+6) weeks of gestation remains the cornerstone of care despite the progress in diagnosing fetal chromosomal defects using cell-free fetal DNA (cffDNA) from the maternal circulation. The measurement of nuchal translucency (NT) allows the risk calculation for the fetal trisomies 21, 18 and 13 but also gives information on those fetal chromosomal defects which are at present unable to be detected using cffDNA. Nuchal translucency is the only auditable parameter at 11 - 13(+6) weeks and gives thus information on the quality of the first trimester anomaly scan. In addition it gives indirect information on the risks for fetal defects and for cardiac anomalies. Also the chances for a healthy live baby can be estimated. As experience with first trimester anomaly scanning increases, and the resolution of the ultrasound equipment has increased substantially, more and more details of the fetal anatomy become accessible at the first trimester scan. Therefore fetal anatomical defects and complex anomalies have become amenable to examination in the first trimester. This guideline describes compulsory and optional parameters for investigation at the first trimester scan and outlines a structured method of examining a first trimester fetus at 11 - 13(+6) weeks of gestation.

Maxillary gap at 11-13 weeks' gestation: marker of cleft lip and palate.

OBJECTIVE: To describe a new sign of cleft lip and palate (CLP), the maxillary gap, which is visible in the mid-sagittal plane of the fetal face used routinely for measurement of nuchal translucency thickness. METHODS: This was a retrospective study of stored images of the mid-sagittal view of the fetal face at 11-13 weeks' gestation in 86 cases of CLP and 86 normal controls. The images were examined to determine if a maxillary gap was present, in which case its size was measured. RESULTS: In 37 (43.0%) cases of CLP the defect was isolated and in 49 (57.0%) there were additional fetal defects. In the isolated CLP group, the diagnosis of facial cleft was made in the first trimester in nine (24.3%) cases and in the second trimester in 28 (75.7%). In the group with additional defects, the diagnosis of facial cleft was made in the first trimester in 46 (93.9%) cases and in the second trimester in three (6.1%). A maxillary gap was observed in 96% of cases of CLP with additional defects, in 65% of those with isolated CLP and in 7% of normal fetuses. There was a large gap (>1.5 mm) or complete absence of signals from the maxilla in the midline in 69% of cases of CLP with additional defects, in 35% of those with isolated CLP and in none of the normal controls. CONCLUSIONS: The maxillary gap is a new simple marker of possible CLP, which could increase the detection rate of CLP, especially in isolated cases.

Cranial and cerebral signs in the diagnosis of spina bifida between 18 and 22 weeks of gestation: a German multicentre study.

OBJECTIVE: The aim of this article is to study secondary cranial signs in fetuses with spina bifida in a precisely defined screening period between 18 + 0 and 22 + 0 weeks of gestation. METHOD: On the basis of retrospective analysis of 627 fetuses with spina bifida, the value of indirect cranial and cerebral markers was assessed by well-trained ultrasonographers in 13 different prenatal centres in accordance with the ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) guidelines on fetal neurosonography. RESULTS: Open spina bifida was diagnosed in 98.9% of cases whereas 1.1% was closed spina bifida. Associated chromosomal abnormalities were found in 6.2%. The banana and lemon signs were evident in 97.1% and 88.6% of cases. Obliteration of the cisterna magna was seen in 96.7%. Cerebellar diameter, head circumference and biparietal diameter were below the 5th percentile in chromosomally normal fetuses in 72.5%, 69.7% and 52%, respectively. The width of the posterior horn of the lateral ventricle was above the 95th percentile in 57.7%. The secondary cranial and cerebral signs were dependent on fetal chromosome status and width of the posterior horn. Biparietal diameter was also dependent on the chromosome status with statistical significance p = 0.0068. Pregnancy was terminated in 89.6% of cases. CONCLUSION: In standard measuring planes, lemon sign, banana sign and an inability to image the cistern magna are very reliable indirect ultrasound markers of spina bifida. © 2014 John Wiley & Sons, Ltd.

Differential and linear insertion of atrioventricular valves: a useful tool?

OBJECTIVE: The differential insertion of the atrioventricular valves is the ultrasonographic representation of the more apical attachment of the tricuspid valve to the septum with respect to the mitral valve. A linear insertion is present when both valves form a linear continuum and has been suggested as a marker for atrioventricular septal defects (AVSDs). The objective of this study was to evaluate the anatomical substratum of differential and linear insertions of the atrioventricular valves in normal fetal hearts and fetal hearts with an AVSD. METHODS: The extent and position of the fibrous skeleton and attachment of the atrioventricular valves to the septum were studied in histological sections of 17 normal hearts and four hearts with an AVSD from 10 + 0 weeks' gestation to 3 days postpartum with various immunohistochemical tissue markers. In addition, spatiotemporal image correlation (STIC) volumes of 10 normal hearts and STIC volumes of eight hearts with an AVSD at 13 + 6 to 35 + 5 weeks' gestation were examined. RESULTS: The differential insertion of the atrioventricular valves was visible in normal hearts in the four-chamber plane immediately beneath the aorta, but nearer the diaphragm a linear insertion was found. In hearts with an AVSD, a linear appearance was observed in the four-chamber plane immediately beneath the aorta. Towards the diaphragm, however, first a differential insertion and, more caudally, a linear insertion was found. CONCLUSIONS: Both differential and linear insertions can be found in normal fetal hearts and fetal hearts with AVSD, depending on the plane in which the four-chamber view is visualized. Therefore, measurement of the differential insertion is likely to be useful only in experienced hands.