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.

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.

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.

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.

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.