Ming-Jie Yang

An overview of a 30-year experience with amniocentesis in a single tertiary medical center in Taiwan.

OBJECTIVE Amniocentesis is a popular and effective prenatal diagnostic tool for chromosomal disorders. It is well-established that the risk of chromosomal abnormalities increases with maternal age; however, other related indications are seldom reported. Herein, we report our 30-year experience with amniocentesis from a single medical center, focusing on the indications and rates of abnormality. MATERIAL AND METHODS A retrospective review of 16,749 pregnant women in the mid-trimester between January 1981 and December 2010 was conducted. The medical records were analyzed. RESULTS The indications for amniocentesis were advanced maternal age (≥ 34 years old) (n=10,970, 65.5%), increasing-risk maternal triple-marker Downs screening test (≥ 1/270) (n=2090, 12.5%), history of abnormal offspring birth (n=792, 4.7%), abnormal ultrasound findings (n=484, 2.9%), parent with abnormal karyotype (n=252, 1.5%), family history of chromosomal abnormality (n=183, 1.1%), drug and radiation exposure (n=165), abnormal chorionic villus sampling (CVS) results (n=25), intrauterine fetal death (n=50), and other non-specific causes (n=1662, 9.9%). The rate of abnormality for each indication was 16% in the abnormal CVS group, 12% in the intrauterine fetal death group, 11.5% for parental chromosomal abnormality, 8.7% in the abnormal ultrasound finding group, 3.0% in the increasing-risk maternal triple-marker Downs screening test group, 2.5% in the advanced maternal age group, 1.5% for other non-specific causes, 1.4% for history of abnormal offspring birth, and 1.1% for family history of chromosomal abnormality. CONCLUSIONS Both parents with abnormal karyotype and abnormal ultrasound findings are indications for which consideration of further amniocentesis is highly recommended.

Lamivudine Therapy in the Treatment of Chronic Hepatitis B with Acute Exacerbation During Pregnancy

We report a case of chronic hepatitis B carrier gravida who had acute exacerbation during pregnancy. She had been taking lamivudine 100 mg/qd for 17 months when hepatitis B virus (HBV) DNA in the YMDD region of the polymerase gene (YMDD motif) mutant was noted. After discontinuing lamivudine, she became pregnant. HBeAg became positive again and liver enzymes were elevated during the first trimester of pregnancy. She received the hepatoprotective agent silymarin 150 mg bid at 13+2 gestational weeks. Serum aspartate aminotransferase (AST) dropped to 757 U/L at 15+0 gestational weeks, but serum alanine aminotransferase (ALT) flared up to 2,230 U/L and AST to 2,250 U/L at 17+1 gestational weeks. Serum HBV-DNA test revealed serum HBV-DNA concentration of 7.31 x 10(8) copies/mL. Lamivudine 100 mg/qd and silymarin 150 mg/bid were initiated at 17+1 gestational weeks. Liver function showed gradual decline to ALT 341 U/L and AST 91 U/L at 21+0 gestational weeks, while HBeAg(+) converted to (-) and anti-HBe(-) converted to (+). Further treatment with lamivudine 100 mg/qd continued for 3 months. Serum HBV-DNA concentrations decreased to 3.19 x 10(2) copies/mL at 36+6 gestational weeks. Spontaneous delivery of a male baby weighing 3314 g occurred at 38+3 gestational weeks. The neonatal physical check-up revealed no congenital anomalies, and fetal growth was within normal reference ranges, suggesting that lamivudine may be safely used in the treatment of chronic hepatitis B with acute exacerbation during the second trimester of pregnancy.

Prevalence of maternal group B streptococcus colonization and vertical transmission in low-risk women in a single institute

Background: Intrapartum administration of antibiotics lowers the risk of neonatal group B streptococcus (GBS) infection based on recommended guidelines (a risk‐based approach and a culture‐based screening approach). However, many pregnant women do not undergo culture‐based screening, nor treatment with prophylactic antibiotics after a GBS risk‐based approach. Therefore, the value of GBS detection in asymptomatic low‐risk pregnant women is controversial. Methods: A cohort study of 354 asymptomatic pregnant women at more than 37 weeks’ gestation who were planning to undergo vaginal delivery, and 118 neonates (107 paired samples of both mother and newborn), was conducted to evaluate the GBS colonization rate of these pregnant women and the subsequent vertical transmission rate, using a culture method. Results: The positive rate for GBS culture was 6.2% (22/354). Among 107 paired samples, six maternal samples and one neonatal sample were positive for GBS culture, with an estimated vertical transmission rate of 16.7% (1/6). Conclusion: Although the positive rate of GBS culture was lower in asymptomatic low‐risk pregnant women, the possibility of vertical transmission might be high. This finding is worthy of further investigation.

Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare. Only seven cases have been documented, and among those three cases were diagnosed prenatally. We reported on another prenatal diagnosis of a de novo mosaic sSMC in an apparently normal female fetus whose mother had conceived with assisted reproductive technology (ART) procedures. G‐banding analysis of amniotic cells was performed. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies with chromosome 10‐specific alphoid satellite DNA probe were used to identify the chromosome 10 origin of the sSMC. Further FISH study with telomeric sequence probes showed that the sSMC lacked a hybridization signal, suggesting that the marker could be a ring chromosome. FISH studies using BAC clone probes specific for the regions within 10p11.2, 10q11.1, and 10q11.2 showed that the short arm breakpoint was located between 29.8 and 30.7 Mb from the 10p telomere, and that the long arm breakpoint was located less than 43.6 Mb from the 10p telomere. The karyotype of the fetus was 47,XX,+mar. ish der(10)(SKY+ CEP 10+, CTD‐2130I7+, RP11‐89J23−)/46,XX. Oligonucleotide microarray‐based copy number variations (CNV) analysis was also performed and showed a 6.7 Mb duplication from 10p11.2 to 10q11.2 (36.2–42.9 Mb) with Affymetrix SNP‐array 6.0 genotype: arr cgh. 10p11.2q11.2(CN_519687 → CN_541524) X 3. At the 1‐year follow‐up, the baby did not have any findings of the trisomy 10p syndrome. This observation provided further credence to the concept that additional chromosome material of proximal 10p11.2 may not contribute to the trisomy 10p syndrome phenotype.

Robertsonian translocations: An overview of a 30-year experience in a single tertiary medical center in Taiwan

Background: Advanced maternal age (AMA) is the most frequent indication for amniocentesis in predicting balanced reciprocal translocations, and abnormal ultrasound findings are indications in predicting unbalanced reciprocal translocations; however, to date, no studies have focused on Robertsonian translocations. Methods: A retrospective review was conducted on 16,749 pregnant women who underwent midtrimester amniocentesis between January 1981 and December 2010. Robertsonian translocations were identified in 39 cases. Results: The percentage of Robertsonian translocations in all amniocentesis cases was 0.23% (39/16,749); 31 were balanced and eight were unbalanced. De novo abnormality occurred in 17 cases, or in 43.6% of all Robertsonian translocations. The two major indications for amniocentesis with a diagnosis of Robertsonian translocations were AMA (41.0%, n = 16) and a parent with abnormal karyotypes (18.0%, n = 7). The highest percentage of Robertsonian translocations was found in parents with abnormal karyotypes (2.8%, 7/252), but neither of the indications were clearly superior for detecting de novo Robertsonian translocations. Conclusion: Although AMA is an indication for amniocentesis in approximately two‐fifths of cases with Robertsonian translocations, the indication of parent with abnormal karyotypes was more likely to lead to the detection of non‐de novo Robertsonian translocations, suggesting that parents with abnormal karyotypes need careful prenatal consultation.

Changes in maternal serum insulin-like growth factor-I during pregnancy and its relationship to maternal anthropometry.

Background: Insulin‐like growth factor (IGF)‐I is primarily produced by the liver under the stimulation of growth hormone, and has systemic growth effects. Placental growth hormone in maternal circulation increases from early pregnancy and is responsible for the increment in maternal serum IGF‐I. The purpose of this study was to evaluate the changes in maternal serum IGF‐I during pregnancy and their relationship to maternal anthropometry, including body weight (BW) and body mass index (BMI). Methods: We obtained 332 blood samples from 114 expectant mothers at different gestational ages (Gas) without adverse medical history. Serum IGF‐I levels were measured by immunoradiometric assay. Linear regression analysis for continuous variables and t test for comparisons of categorical variables were used to test for significance. Results: Maternal serum IGF‐I during pregnancy was significantly correlated not only to GA (p < 0.001, r = 0.358), but also to maternal BW (p = 0.001, r = 0.202), and maternal BMI (p < 0.001, r = 0.263). The mean maternal IGF‐I was highest in the third trimester [1st vs. 2nd, p < 0.001, 95% confidence interval (CI) = −70.17 to −28.22; 1st vs. 3rd, p < 0.001, 95% CI = −138.02 to −76.94; 1st vs. 3rd, p < 0.001, 95% CI = −88.86 to −27.71]. Conclusion: Maternal serum IGF‐I is significantly related to GA, maternal BW, and BMI during pregnancy.

Uterine arterial embolization in the management of severe post-partum hemorrhage: a successful rescue method to avoid peripartum hysterectomy.

Background: Although the effects of uterine arterial embolization (UAE) for the control of post‐partum hemorrhage on menstruation, fertility and future pregnancy have been reported before, domestic reports on long‐term outcomes are lacking. Methods: From April 2001 to March 2005, 9 patients who underwent UAE for post‐partum hemorrhage were evaluated retrospectively. The analyses included both immediate and long‐term outcome, including menstruation, future fertility and subsequent pregnancies. Results: The median follow‐up was 82 months, ranging from 63 months to 108 months. All the women had regular menstruation after UAE treatment, but 5 had hypomenorrhea. Four women attempted pregnancy, and 3 had successful term deliveries. One woman was infertile. Conclusion: UAE appeared to be a safe procedure. Hypomenorrhea was common after UAE treatment (55.6%), although regular menstruation returned successfully. Future pregnancy seemed possible, and without complications.

Endothelial cell dysfunction and preeclampsia

Preeclampsia is a pregnancy-specific syndrome of hypertension and proteinuria and one of the leading causes of perinatal morbidity and mortality. The pathogenesis of preeclampsia, although not entirely clear, is typically abnormal placental implantation, followed by endothelial dysfunction with subsequently resulting vasospasm, coagulopathy, or changes in capillary permeability; this underscores the importance of successfully established circulation networks between the fetus and mother. These established circulation networks require an ongoing sequential process, and one of the most noteworthy facilitators of this process is the success of angiogenesis. However, angiogenesis is a very complicated procedure because normal physiological function is needed, and many diverse pathologies and disease status indicators also involve an active angiogenesis process. Endothelial progenitor cells (EPCs) were characterized and isolated from peripheral blood by Asahara et al in 1997, and are recruited to vascular lesion sites. EPCs may play a critical role in the repair of blood vessel damage, restoration of endothelial function, or neoangiogenesis after the fetal period. Dysfunction of endothelial cells is a hallmark of many cardiovascular diseases, and there is evidence that reductions in the number and functionality of circulating EPCs might contribute to adult cardiovascular disease. However, the role of circulating EPCs on the development of preeclampsia is not conclusive. The study by Parsanezhad et al in this issue of the Journal of the Chinese Medical Association seems to be the first report to study the differences between three distinct subsets of EPCs of maternal peripheral blood, including circulating angiogenic cells (CAC), colony-forming unit endothelial cells (CFUECs), and endothelial colony-forming cells (ECFCs) in women with and without preeclampsia. They show higher numbers of CACs and ECFCs subsets in the peripheral blood but fewer colony formation capacities in the peripheral blood of pregnant women with preeclampsia compared with that of women with normal pregnancy, suggesting that the functionality of CACs and ECFCs in women with preeclampsia was decreased. By contrast, the number of CACs increases without alternations in colony formation ability was found in women with normal pregnancy. It is unclear why the high numbers of ECFCs in the peripheral blood of women with preeclampsia did not contribute to an elevated number of colony formations, suggesting that ECFCs of women with and without preeclampsia might

Quantitative analysis of normal fetal brain volume and flow by three-dimensional power Doppler ultrasound

Background: Assessment of the fetal brain volume and blood flow is important in the evaluation of fetal growth. We used three‐dimensional (3D) ultrasound and power Doppler to assess the fetal brain volume and the blood flow index during normal gestation. The relationships of these parameters were further analyzed. Methods: We assessed the total volume and the blood flow index of the fetal brain in normal pregnancies using 3D ultrasound (Voluson 730). The bilateral parietal diameter (BPD) plane was measured by a 3D transabdominal probe to scan the fetal brain under the power Doppler mode. Then, we quantitatively assessed the total volume of the fetal brain, mean grey area (MG), vascularization index (VI), flow index (FI), and vascularization‐flow index (VFI) by applying Kretz VOCAL software. Results: The study included 126 fetuses, ranging from 15 to 38 weeks of gestation. The total volume of the fetal brain was highly positively correlated with the gestational age (GA) (correlation coefficient [r] = 0.976, p < 0.0001). The MG, VI, and VFI were negatively correlated with the GA (correlation coefficient [r] = −0.520, p < 0.0001; [r] = −0.421, p < 0.001; [r] = −0.319, p < 0.0001). The FI was positively correlated with the GA (correlation coefficient [r] = 0.483, p < 0.0001). Conclusion: 3D ultrasound can be used to assess the fetal brain volume and blood flow development quantitatively. Our study indicates that the fetal brain vascularization and blood flow correlates significantly with the advancement of GA. This information may serve as a reference point for further studies of the fetal brain volume and blood flow in abnormal conditions.

Gene Set−Based Integrative Analysis Revealing Two Distinct Functional Regulation Patterns in Four Common Subtypes of Epithelial Ovarian Cancer

Clear cell (CCC), endometrioid (EC), mucinous (MC) and high-grade serous carcinoma (SC) are the four most common subtypes of epithelial ovarian carcinoma (EOC). The widely accepted dualistic model of ovarian carcinogenesis divided EOCs into type I and II categories based on the molecular features. However, this hypothesis has not been experimentally demonstrated. We carried out a gene set-based analysis by integrating the microarray gene expression profiles downloaded from the publicly available databases. These quantified biological functions of EOCs were defined by 1454 Gene Ontology (GO) term and 674 Reactome pathway gene sets. The pathogenesis of the four EOC subtypes was investigated by hierarchical clustering and exploratory factor analysis. The patterns of functional regulation among the four subtypes containing 1316 cases could be accurately classified by machine learning. The results revealed that the ERBB and PI3K-related pathways played important roles in the carcinogenesis of CCC, EC and MC; while deregulation of cell cycle was more predominant in SC. The study revealed that two different functional regulation patterns exist among the four EOC subtypes, which were compatible with the type I and II classifications proposed by the dualistic model of ovarian carcinogenesis.