The value of combined detailed first-trimester ultrasound-biochemical analysis for screening fetal aneuploidy in the era of non-invasive prenatal testing.

PURPOSE: This study aimed to investigate the performance, cost-effectiveness and additional findings of combined detailed ultrasound and biochemical screening for risks of major fetal trisomies in the first-trimester. METHODS: This is a retrospective analysis study, we estimated the risk of trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency thickness, nasal bone, ductus venosus pulsatility index velocity, tricuspid regurgitation, fetal heart rate, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein A in singleton pregnant women, and performed non-invasive prenatal testing for women with risks of trisomy 21 between 1:500 and 1:300. Invasive diagnostic testing was performed for women with positive or failed non-invasive prenatal testing result and in the high-risk group of this screening method. The direct costs were compared between this strategy and the non-invasive prenatal testing which alone used as first-line screening for all pregnant women. RESULTS: Among 25,155 singleton pregnant women who underwent screening, 24,361 were available for analysis, of these, 194 cases underwent non-invasive prenatal testing. Among the 24,361 women, 39, 19, and 7 had trisomies 21, 18 and 13, respectively. The use of this strategy could potentially detect approximately 94.87% of trisomy 21 cases, 100% of trisomy 18 cases, and 100% of trisomy 13 cases, with false-positive rates of 2.49%, 0.41%, and 0.49%, respectively. The overall detection rate and overall false-positive rates were 96.92% and 2.52%, respectively. The detection rate was 100% in the advanced age group and 94.12% in the general age group. Additionally, structural abnormalities were detected in 137 fetuses, and 44 fetuses had other chromosomal abnormalities. The total cost of this strategy was $3,730,843.30, and the cost per person tested was $153.15. The total cost of using non-invasive prenatal testing as the first-line strategy would be $6,813,387.04 and the cost per person tested was $279.68. CONCLUSIONS: Our strategy is an efficient and cost-effective approach for detecting major trisomies and identifying more fetuses with a potential abnormality. Therefore, this strategy is a valuable screening method and highly feasible in the clinical setting.

Clinical Significance of First-Trimester Screening of the Retronasal Triangle for Identification of Primary Cleft Palate.

OBJECTIVE: To investigate the use of the retronasal triangle (RNT) for identification of orofacial cleft (OC) in the first trimester and the clinical application of three-dimensional (3D) ultrasound techniques for confirming the diagnosis of OC. METHODS: A total of 5,054 women with singleton pregnancies underwent first-trimester screening for Down syndrome at 11-13(+6) weeks. The RNT was scanned in each fetus, and 3D volumetric images of cases with abnormal or indeterminate RNT were obtained. RESULTS: Satisfactory images were obtained from all cases. Seven cases (1.4‰) of abnormal RNT were diagnosed as OC in the first trimester, which were confirmed at a 16 weeks scan or at a postmortem examination. One case that was considered a normal RNT was diagnosed with OC at 22(+2) weeks and after term delivery. Six cases of indeterminate RNT were diagnosed as normal by 3D ultrasound. Identification of OC by visualization of the RNT in the first trimester had a sensitivity of 87.5% and a specificity of 99.9%. CONCLUSION: The RNT is an important sonographic landmark that has a high sensitivity and specificity for the detection of OC in the first trimester. 3D ultrasound is an important tool that aids in confirming diagnosis of OC in the first and second trimesters.

SIRT1 regulates trophoblast senescence in premature placental aging in preeclampsia.

INTRODUCTION: Premature placental aging is implicated in a number of complications of pregnancy including preeclampsia. A placenta knockout mouse model has shown a relationship between SIRT1, aging and placental dysfunction. The role of SIRT1 in cellular senescence has been extensively studied in various cell types, but its role in trophoblast senescence is almost unknown. METHODS: Human placental samples were obtained from preeclampsia-affected women and healthy controls. The placental aging profiles were assessed by Doppler ultrasound, placental histopathology, and evaluation of senescence- and ECM-related markers. The SIRT1 expression pattern relevant to placental aging profiles was studied in premature aging placenta with preeclampsia (32-37 weeks gestation, n = 10) and healthy controls (37-40 weeks gestation, n = 10). Using cell culture, the effects of activation and knockdown of SIRT1 or its downstream target molecules in syncytialized BeWo cells were evaluated. RESULTS: SIRT1 was expressed by syncytiotrophoblast across normal gestation. In preeclamptic premature aging placentas, SIRT1 was significantly downregulated, while senescence- and extracellular matrix (ECM) -related protein levels were upregulated compared to controls. Immunohistochemistry showed these changes to be confined to syncytiotrophoblast. In vitro, SIRT1 activation in response to resveratrol (RSV) abrogated senescence in forskolin-induced syncytialization of BeWo cells via regulation of senescence- and ECM-related proteins, and filamentous actin (F-actin). These effects were restored by SIRT1 siRNA. DISCUSSION: The downregulation of SIRT1 may accelerate senescence of syncytiotrophoblast via targets contributing to regulation of the cell cycle, ECM production and cytoskeleton reorganization leading to premature placental aging observed in preeclampsia.