Yun-Xiao Zhu

Accuracy, Agreement, and Reliability of Fetal Cardiac Measurements Using 4-Dimensional Spatiotemporal Image Correlation

The purpose of this study was to evaluate the accuracy, agreement, and reliability of 4‐dimensional sonography using spatiotemporal image correlation (STIC) in fetal cardiac measurements during the second and third trimesters.

Fetal persistent left superior vena cava in cases with and without chromosomal anomalies

The objectives of this study are to determine and compare the prevalence of persistent left superior vena cava (PLSVC) in chromosomally normal and abnormal fetuses and to evaluate the potential of PLSVC as a screening marker for chromosomal abnormalities.

Clinical Outcomes after Selective Fetal Reduction of Complicated Monochorionic Twins with Radiofrequency Ablation and Bipolar Cord Coagulation.

Aims: To review pregnancy outcomes, complication rates and neonatal neural development of selective termination procedures for complicated monochorionic (MC) twins. Methods: This was a retrospective review of the pregnancies that underwent selective reduction with radiofrequency ablation (RFA) and bipolar cord coagulation (BCC) in our institution. Results: Forty-eight cases underwent selective reduction with BCC and the remaining 45 with RFA. Overall survival was not statistically different between the RFA and BCC groups (71.1 and 62.5%, p = 0.379). With regard to the indications, the survival rates were not significantly different for twin to twin transfusion syndrome, twin reversed arterial perfusion, discordant anomalies and selective intrauterine growth restriction. Preterm premature rupture of membrane was not statistically different between the BCC and RFA groups (47.9 and 33.3%, p = 0.153). Five foetuses presented with abnormal middle cerebral artery-peak systolic velocity in the BCC group and 4 in the RFA group (p = 0.829). In the BCC group, neurological injury was detected in 2 neonates, presenting with cerebral dysplasia on MR scanning. In the RFA group, intracranial haemorrhage Grade III was detected in one neonate with cranial ultrasound (p = 0.607). Conclusions: Overall survival and complication rates following selective reduction in complicated MC twin pregnancies is similar irrespective of whether the reduction was performed using RFA or BCC. Key Message: It seems that selective reduction in MC pregnancies with RFA does not carry a significant decrease in the overall survival and complication rates than the cases with BCC. According to our data, neurodevelopmental impairment of the co-twins is relatively seldom after selective reduction.

Date-Independent Parameters: an Innovative Method to Assess Fetal Cerebellar Vermis

The objectives of this paper were to identify gestational age-independent parameters for cerebellar vermis (CV) evaluation and examine their use in CV integrity assessments. Using three-dimensional ultrasonography, we obtained the following measurements from 217 pregnant women carrying 18–37-week-old fetuses: the largest area of the CV, vermal craniocaudal distance (VCC), vermal anterior to posterior diameter, and vermal perimeter (VP). In addition, fetal growth parameters (biparietal diameter, head circumference femoral length [FL], humeral length, transverse cerebellar diameter, and abdominal circumference) were evaluated. The ratios of the CV dimensions to each other and to the fetal growth parameters were calculated. Ratios showing no significant correlation with gestational age and acceptable internal validity in subsequent bootstrap analyses were chosen. The normal ranges of the specific parameters were compared with cases identified with posterior fossa anomalies (PFA). The ratios VP/FL (mean 1.20, SD 0.09), VCC/FL (mean 0.36, SD 0.03), and VCC/VP (mean 0.3, SD 0.03) were chosen using our protocol. These parameters were not significantly different between normal fetuses and those with PFA and an intact vermis. However, VP/FL and VCC/FL values were abnormal in cases of hypoplastic vermis or vermian agenesis, while the VP/VCC value was abnormal only in cases of vermian agenesis. The VP/FL, VCC/FL, and VCC/VP ratios are gestational age-independent parameters in evaluation of CV integrity.

Four-Dimensional Sonography With Spatiotemporal Image Correlation and Tomographic Ultrasound Imaging in the Prenatal Diagnosis of Anomalous Pulmonary Venous Connections

To determine whether the use of 4‐dimensional (4D) sonography with spatiotemporal image correlation (STIC) and tomographic ultrasound imaging (TUI) can provide additional information with respect to 2‐dimensional (2D) echocardiography in the prenatal diagnosis of anomalous pulmonary venous connections.

Harlequin ichthyosis: a novel compound mutation of ABCA12 with prenatal diagnosis

Harlequin ichthyosis (HI) is the most severe form of recessive congenital ichthyosis, and is frequently lethal. We describe a family with prenatal diagnosis of HI in two siblings. We applied genomic capture and massively parallel sequencing to detect all mutations in 20 genes, including ABCA12, with inherited mutations that predispose to congenital ichthyosis. Sequence analysis of the ABCA12 gene identified two mutations, c.5232 G>A (p.Trp1744*) in exon 34 and c.6443 C>A (p.Pro2148Gln) in exon 44, each in a heterozygous state. Sanger sequencing confirmed that each parent was a heterozygous carrier for one of the variants. The spectrum of mutations identified in this study and previous studies reveals a novel compound mutation of ABCA12.

Identification by whole-exome sequencing of novel mutation c.64C > G in the BTK gene of a fetus with X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) or Bruton’s disease is a rare genetic disorder, discovered in 1952, that mitigates the immune response to infections1. Early studies have associated mutations in the Bruton tyrosine kinase (BTK) gene (GDB 120542) with XLA development2,3. The BTK gene, spanning 37.5 kilobases (kb) with 19 exons, is located on the X chromosome at Xq21.3–Xq22 and encodes Bruton agammaglobulinemia tyrosine kinase (Btk), a 77-kiloDalton (kDa) protein. Btk plays an essential role in the maturation of B cells within the bone marrow. Its mutation often stalls differentiation of immature pro-B into pre-B lymphocytes, decreasing the number of peripheral mature B cells4. We report the identification of a new mutation in a fetus with XLA, identified prenatally by whole-exome sequencing, predicted to cause a drastic alteration in BTK gene function. A 26-year-old primigravida was referred to our center after detection by ultrasound screening at 25 + 6 weeks’ gestation of fetal brain abnormalities (ventriculomegaly, cerebral calcification and intracranial space-occupying lesion) (Figures 1a and b), which were confirmed by magnetic resonance imaging at 28 weeks (Figures 1c and d). Lymphocyte immunophenotyping of the fetus by flow cytometry at 28 weeks showed that 97.6% of its lymphocytes were CD3+ (T-cells) (Figure S1), but B-cell and NK-cell levels were almost undetectable. Peripheral venous blood of the mother and umbilical cord blood from a normal pregnancy were used as controls. Both samples were found to have normal lymphocyte counts (Figure S1). Exome sequencing of the fetal BTK gene revealed a homozygous missense mutation, c.64C > G, caused by substitution of a single amino acid (p.Pro22Ala) in the Btk protein (Figure S2). This mutation has not yet been identified in the BTK database (http://structure.bmc.lu.se/ idbase/BTKbase/). Exome sequencing of the mother found her to be a carrier of the mutation. To confirm further the presence of this mutation, we amplified the DNA fragment that contained the mutation by polymerase chain reaction (PCR) and subsequently performed Sanger sequencing on the PCR product. In addition, the DNA fragment from 50 healthy donors was amplified and sequenced and no c.64C > G mutations were detected in these cases. This finding implicated the c.64C > G mutation as a novel XLA-relevant mutation. We have shown a novel mutation in the BTK gene of a fetus with a severe phenotype, including B-cell deficiency. The central message of this case is to emphasize the contribution of whole-exome sequencing in the diagnosis of complex human disease, especially in the context of prenatal screening. In addition, the BTK gene mutation demonstrated in this study expanded the spectrum of known XLA-causing mutations.

Prenatal diagnosis of prevalence of the right heart: associated anomalies and outcome predictors.

To analyze the characteristics, associations, and outcomes of prevalence of the right heart and to evaluate the use of sonography to predict the risk of a poor prognosis in fetuses with this condition.

OP26.01: Prenatal diagnosis of trisomy 18 with sonogram index scoring system

pregnancy outcomes. The current sensitivity and positive predictive value of this association has, however, not yet justified initiation of increased antenatal surveillance in these patients. This study was carried out to identify if 3D placental evaluation enhances the performance of this serum marker as a predictor of adverse pregnancy outcomes. Methods: 62 patients with PAPP-A levels lower than 0.4 multiples of median (MoM) were evaluated between 11 weeks to 13 weeks 6 days of gestation with 3D power Doppler studies in this prospective study. Placental volume, Vascularisation Index (VI), Flow Index and Vascularisation Flow Index (VFI) were computed with standardised equipment settings and correlated with pregnancy outcomes. Results: 38 patients had an uneventful pregnancy outcome. 29 of these had normal 3D placental parameters. Of the 24 patients with adverse outcomes 19 had a small volume placenta, impaired 3D placental vascularisation indices or both. Conclusions: 3D and 3D power Doppler evaluation of the placenta in the late first trimester improves the prediction of adverse outcomes in patients with low PAPP-A levels.

OC032: Study on the fetal cerebellar vermis of Dandy-Walker Syndrome with the third plane image of three-dimensional ultrasonography

ROI direction on the lateral aspect; then, the inversion visualization mode was activated and the threshold increased until the voxels started to bleed into the vermis, highlighting the fissures, paying no attention to the surrounding structures. Finally, it was analysed if the primary and/or additional fissures could be confidently detected. Results: The primary fissure was consistently detected at 20 weeks of gestation on 3DUS vs 28 weeks on 2DUS. The earliest recognition of the primary fissure was by transvaginal approach with 6–12 MHz probe at 16 weeks. By 26 weeks, both the primary and the secondary fissures were recognisable at least in part in all cases of normalcy, MCM and BPC. At 32 weeks of gestation, fissures were recognisable in all volumes, if of good quality. Abnormal or absent fissures were seen in case of DW and DWv. Conclusions: 3DUS can identify vermian fissures more reliably and earlier than 2DUS in normal and abnormal PF conditions. This technique may contribute to the differential diagnosis of vermian abnormalities.