Jin-Chung Shih

Role of three‐dimensional power Doppler in the antenatal diagnosis of placenta accreta: comparison with gray‐scale and color Doppler techniques

To assess the role of three‐dimensional (3D) power Doppler in the antenatal diagnosis of placenta accreta and compare its diagnostic performance with gray‐scale and color Doppler ultrasonography.

Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies

Sir, We read with great interest your recent publication by Lee et al. on the use of array comparative genomic hybridisation (CGH) for prenatal diagnosis: a cohort study of 3171 pregnancies. Such a large cohort is an important contribution to the existing literature. It is important then to compare and contrast the results of Lee’s study with those of other recently published cohorts. The abstract states that when array CGH is performed for a fetus with a congenital anomaly apparent on prenatal ultrasound, the test was effective in identifying submicroscopic genomic imbalances (i.e. that are unidentifiable by conventional G-band karyotyping) in 33 of 194 (17%) cases. However, on reviewing data within table 2 (and later on in the abstract) this rate is recorded as 16/194 (8.2%). We attempted to extract data on submicroscopic copy number changes from table 2, but there appeared to have been formatting errors (e.g. in the row ‘pathogenic karyotyping reports’ the columns appear to be shifted a space to the right). It is unclear within the table how the calculated total of pathogenic karyotype and array CGH reports are constructed. We assume that pathogenic karyotype reports would be made up of those with numerical abnormality plus those with large chromosomal deletions and duplications, whereas pathogenic array reports would be made up of the former plus microscopic chromosomal deletions and duplications, plus variants of unknown significance. This, however, is not made clear. It is not certain whether there may have been instances where the array CGH test failed to identify a chromosomal anomaly detected by conventional karyotyping, and indeed whether both types of karyotype testing were performed for all fetuses included in the study. The authors state within the discussion that ‘when array CGH was performed alone no significantly pathological results were missed’, but without a reference test how could one be sure? Two array CGH platforms were used within this study: a 1-Mb bacterial artificial chromosome (BAC) and a 60-kb oligonucleotide array. It appears that there was a switch to the higher resolution 60-kb array towards the end of the cohort study. However, table 3 is not transparent to which array was used to detect which abnormal result. When extrapolating using the coordinates of the oligonucleotide probes in comparison with those of BAC probes aligned to the reference genome in ensembl, and in BlueGnome’s bluefuse multi database software, we predict that only one of the abnormal results detected by the higher resolution 60-kb array within Lee et al.’s cohort would have been missed by the 1-Mb BAC. This point should be commented on, as the lower resolution BAC would be predicted to produce less variants of unknown significance (VOUS), an important point to consider when using this technology on prenatal samples. The authors did not however state which array contributed to the five VOUS recorded. Finally, the authors conclude that there is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal ultrasound examination. The authors conclude that prenatal array CGH is a recommended additional test in pregnant women undergoing invasive testing, but do not comment on the additional VOUS results that such testing could reveal, and the problems of interpretation and counselling of these variants in the prenatal setting. Before we can think about using this technology, even as an adjunct to conventional karyotypic testing, this issue must be addressed and the additional costs to overall pregnancy health care must be considered. j

Cesarean scar pregnancy: diagnosis with three‐dimensional (3D) ultrasound and 3D power Doppler

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Antenatal Depiction of the Fetal Ear With Three-Dimensional Ultrasonography

Objective To evaluate the feasibility of examining the fetal ear with three-dimensional ultrasound. Methods In 125 pregnancies between 19 and 38 weeks of gestation, fetal ears were evaluated by three-dimensional ultrasound. The volume images with surface rendering were analyzed to depict the morphology, lying axis, orientation, and cranial location of the fetal ears. Results Three-dimensional images of one or both ears were successfully reconstructed in 105 fetuses. Among them, 18 fetuses had anomalous ears. The anomalous ears, including microtia, low-set ear with slope axis, abnormal ear orientation, and edematous ear, were confirmed after delivery. Three-dimensional ultrasound consistently displayed fetal ear abnormalities with greater accuracy and clarity. Conclusion Because anomalous ears may be a part of complex fetal malformations, it is important to recognize ear abnormalities. Due to the complexity of the fetal ear, three-dimensional ultrasound offers more important information than two-dimensional ultrasound, which simply gives auricular geometry. We suggest that three-dimensional ultrasound can be used better to examine the fetal ear and may prove to be useful for prenatal diagnosis and genetic counseling.

Two-Dimensional and Three-Dimensional Power Doppler Sonographic Classification of Vascular Patterns in Cervical Lymphadenopathies

Vascular patterns may reflect some pathologic behaviors of tumors and lymph nodes. Power Doppler ultrasonography, with improved sensitivity and better noise contrast, were used to depict vasculature in 289 cases of cervical lymphadenopathy. Four patterns of vasculature, in addition to avascular nodes, were classified. Benign lymphadenopathies represented 89% and 83% of avascular and hilar type nodes, respectively. However, malignant lymphadenopathies dominated in nodes that were of spotted (72%), peripheral (60%), and mixed type (80%). Correlation between nodal sizes and chronologic changes of vascular patterns in malignant lymphadenopathies implied a reasonable classification. Three‐dimensional power angiography, with the advantage of less plane‐sampling bias, was further used to validate our classification.

Correlation of Prenatal Ultrasound and Postnatal Outcome in Meconium Peritonitis

Objectives: To study the relationship between prenatal ultrasound features and postnatal course of meconium peritonitis. Methods: Meconium peritonitis was diagnosed by prenatal ultrasound. Fetuses were treated by intrauterine paracentesis of ascites when indicated, and symptomatic newborns received surgery. Results: Totally 17 cases were enrolled. Prenatal ultrasound findings include abdominal calcification (16/17), fetal ascites (12/17), hydramnios (9/17), pseudocyst (7/17) and dilated bowel loop (6/17). Persistent ascites, pseudocyst or dilated bowel loop are most sensitive (92%) to predict postnatal surgery (p = 0.022). The survivors have a higher gestational age at birth (36.4 vs. 33.3 weeks, p = 0.008). Persistent ascites and postnatal persistent pulmonary hypertension of the newborns significantly correlate with neonatal mortality (p = 0.029 and 0.022). Conclusion: Prenatal ultrasound can predict the neonatal outcome in meconium peritonitis.

A recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapy

To assess the possible correlations between the reported candidate genes (VEGFR3, FOXC2, ITGA9 and ITGB1) and the clinical response in fetuses with severe congenital chylothorax (CC) treated by prenatal OK‐432 pleurodesis.

MUC1 Expression Is Increased During Human Placental Development and Suppresses Trophoblast-Like Cell Invasion In Vitro

Abstract Mucin (MUC)1 is a multifunctional mucin expressed by a variety of reproductive tract epithelia. Trophoblast invasion is essential for normal placental development. However, MUC1 expression in the human placenta throughout pregnancy and the role of MUC1 in trophoblast-like cell invasion are still unclear. In the present study, results from quantitative RT-PCR and Western blot demonstrated that MUC1 mRNA and MUC1 protein expression, respectively, increased with gestational age of the human placenta. Immunohistochemistry revealed that MUC1 in placental villi was mainly expressed by syncytiotrophoblasts throughout pregnancy and increased with gestational age. Interestingly, we found two populations of extravillous trophoblasts, MUC1-positive and MUC1-negative cells, in decidua. The numbers of MUC1-positive extravillous trophoblasts were increased during placental development. Furthermore, MUC1 overexpression significantly (P < 0.01) suppressed matrigel invasion of trophoblast-like JAR cells by 34.6% ± 4.5% compared with control, which was associated with a decrease in MMP9 activity assessed by gelatin zymography. Our results suggest that MUC1 expression in the human placenta is increased during placental development, and its overexpression suppresses trophoblast-like cell invasion in vitro.

Antenatal treatment of chylothorax and cystic hygroma with OK-432 in nonimmune hydrops fetalis.

Objectives: To present our experience of using OK-432 in treating fetal cystic hygroma and chylothorax complicated with nonimmune hydrops fetalis. Methods: OK-432 (Picibanil®) was injected into the fetal pleural cavity or fetal cystic hygroma. Results:Patient 1: A 23-year-old, gravida 2, para 1, was found to have a recurrent fetal chylothorax at GA 29 weeks. Serial amnioreduction and thoracocentesis was performed at GA 31, 32, 33, and 34 weeks. Intrapleural OK-432 injection was performed twice at GA 33 and 34 weeks. Cyanosis and respiratory distress were noted immediately after birth (GA 34 weeks). The baby expired despite of aggressive neonatal resuscitation. Patient 2: A 26-year-old, gravida 2, para 1, was found to have a cystic hygroma of her fetus at GA 17 weeks. Karyotype of the cystic fluid and the amniocytes were 46, XY. Fetal ascites developed at GA 22 weeks. OK-432 injection into the tumour was performed at GA 23 weeks. Stabilization of the cystic hygroma was noted throughout the pregnancy (about 3.5 cm in diameter). Serial fetal paracentesis and/or amnioreduction were performed. Karyotype of the ascites was again 46, XY. Maternal dietary modification with medium chain triglyceride was also prescribed. Chylothorax developed and the baby was born by cesareans at GA 32 weeks. Resolution of pleural effusion, ascites, and regression of cystic hygroma were noted since the 2nd day after birth. The baby had survived beyond 4 months of age at submission. Conclusion: Combination of antenatal OK-432 injection, maternal dietary modification, serial thoracocentesis plus paracentesis, together with amnioreduction and tocolysis, appeared to contribute to the success of antenatal treatment. Fetal pulmonary expansion may determine the immediate neonatal survival.

Experimental treatment of bilateral fetal chylothorax using in‐utero pleurodesis

To assess the use and efficacy of in‐utero pleurodesis for experimental treatment of bilateral fetal chylothorax.