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Background: Down syndrome (DS) is the most common known aneuploidy, caused by an extra copy of all or part of chromosome 21. Fetal-specific epigenetic markers have been investigated for non-invasive prenatal detection of fetal DS. The phosphodiesterases gene, PDE9A, located on chromosome 21q22.3, is completely methylated in blood (M-PDE9A) and unmethylated in the placenta (U-PDE9A). Therefore, we estimated the accuracy of non-invasive fetal DS detection during the first trimester of pregnancy using this tissue-specific epigenetic characteristic of PDE9A., Methodology/principal Findings: A nested, case-control study was conducted using maternal plasma samples collected from 108 pregnant women carrying 18 DS and 90 normal fetuses (each case was matched with 5 controls according to gestational weeks at blood sampling). All pregnancies were singletons at or before 12 weeks of gestation between October 2008 and May 2009. The maternal plasma levels of M-PDE9A and U-PDE9A were measured by quantitative methylation-specific polymerase chain reaction. M-PDE9A and U-PDE9A levels were obtained in all samples and did not differ between male and female fetuses. M-PDE9A levels did not differ between the DS cases and controls (1854.3 vs 2004.5 copies/mL; P = 0.928). U-PDE9A levels were significantly elevated in women with DS fetuses compared with controls (356.8 vs 194.7 copies/mL, P<0.001). The sensitivities of U-PDE9A level and the unmethylation index of PDE9A for non-invasive fetal DS detection were 77.8% and 83.3%, respectively, with a 5% false-positive rate. In the risk assessment for fetal DS, the adjusted odds ratios of U-PDE9A level and UI were 46.2 [95% confidence interval: 7.8-151.6] and 63.7 [95% confidence interval: 23.2-206.7], respectively., Conclusions: Our findings suggest that U-PDE9A level and the unmethylation index of PDE9A may be useful biomarkers for non-invasive fetal DS detection during the first trimester of pregnancy, regardless of fetal gender.

Objectives: The aim of this study was to evaluate the role of nasal bone assessment in first-trimester screening for Down syndrome (DS) in the Korean population., Methods: From July 2004 to March 2006, we prospectively evaluated the fetal nasal bones at 11-14 weeks' gestation in the Korean population., Results: A successful evaluation was possible in 6490 of 6787 fetuses (95.6%). Absent, hypoechoic, and short nasal bones were seen in 4 (26.7%), 4 (26.7%), and 1 (6.7%) of 15 fetuses with DS, respectively, whereas in 5 (0.1%), 11 (0.2%), and 246 (3.8%) of 6456 normal fetuses. The incidence of absent and hypoechoic nasal bone showed significant differences between normal fetuses and fetuses with DS (P < 0.0005, both). Screening for DS using an absent or hypoechoic nasal bone resulted in a sensitivity of 53.3%, a specificity of 99.8%, a positive likelihood ratio of 215.2, and a negative likelihood ratio of 0.5., Conclusion: Our study showed that nasal bone abnormality at 11-14 weeks of gestation had a high association with DS in the Korean population. This suggests that nasal bone assessment can be used to supplement the current first-trimester screening for DS in the Korean population., (2007 John Wiley & Sons, Ltd)

Objective: To assess the fetal outcome of three hypertensive women exposed to amlodipine. 5 mg/day, in the first trimester of pregnancy. CASE 1: The patient was treated with amlodipine until 7 weeks of gestation. She was also exposed to levosulpiride, aluminum hydroxide gel, magnesium carbonate, and Ginkgo biloba. At 38(+3) weeks of pregnancy, she delivered a 3750 g healthy female baby, and restarted taking amlodipine, 5 mg/day, while exclusively breastfeeding her daughter. At three months of age, the infant was healthy. CASE 2: The patient was treated with amlodipine from 2(+2) to 3(+4) weeks of pregnancy. Her treatment was modified to atenolol until the week 6(+4 weeks), when she declined any antihypertensive treatment. At 39(+4) weeks of pregnancy, the patient delivered a 2600 g baby. At 20 months old, the baby presented with intellectual delay and weakness in the left arm and hand grasp. These neurological alterations were not attributed to her exposure to amlodipine early in utero. CASE 3: The patient was treated with amlodipine from 7(+6) to 12 weeks of pregnancy. She was also taking sucralfate and lorazepam. At 12 weeks of amenorrhea, ultrasound revealed a 15.3 mm, single fetal pole in the gestational sac without cardiac activity. She underwent dilatation and evacuation of a dead embryo., Conclusion: As reported with other calcium-channel blockers, amlodipine does not appear to be teratogenic and it appears to be compatible with breastfeeding.

Objectives: The aim of this study was to provide reference values for nasal bone length (NBL) scanned at 11-14 weeks' gestation in the Korean population and compare these values with those of the Caucasian and African-American populations., Methods: From April 2004 to July 2004, fetal NBLs were measured in well-dated, non-anomalous fetuses at 11-14 weeks' gestation in the Korean population. Regression analysis was used to assess the relationship between NBL and crown-rump length (CRL), and reference values including the 5th, 50th, and 95th percentile were calculated for each gestational age. The reference values in our study were compared with those of the Caucasian and African-American populations., Results: A total of 982 cases were prospectively included in the study. NBL increased linearly with advance in CRL and was described by the equation; NBL (mm) = 0.433 + 0.022 x CRL (mm), R(2) = 0.37. The median values (5%, 95%) were 1.5 mm (1.2 mm, 1.9 mm), 1.7 mm (1.4 mm, 2.1 mm), 1.9 mm (1.6 mm, 2.3 mm), and 2.1 mm (1.7 mm, 2.6 mm) for 11, 12, 13, and 14 weeks' gestation, respectively. The median values for each gestational age in the Korean population were significantly lower than those in the Caucasian and African-American populations (P < 0.0001)., Conclusion: There is a difference in NBL scanned at 11-14 weeks' gestation between the Korean and the Caucasian/African-American populations, and so racial adjustment is needed in the evaluation of the fetal nasal bone for current first-trimester screening., (Copyright 2006 John Wiley & Sons, Ltd.)