Extended first-trimester screening using multiple sonographic markers and maternal serum biochemistry: A five year prospective study in Chinese population

• Main Authors: Ching-Hua Hsiao, 蕭慶華
• Other Authors: Woei-Chyn Chu
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/hwnmyc

博士 === 國立陽明大學 === 醫學工程研究所 === 102 === Objective: The aim is to examine the performance of first-trimester (11+0–13+6 gestation weeks) screening test combining several maternal serum biochemical and trisomy 21 fetal sonographic markers for major aneuploidy in a Chinese population. The first aim of this research was to compare the fetal frontomaxillary facial (FMF) angle between normal and trisomy 21 fetuses in a Chinese population. Another ultrasound soft maker was to evaluate and compare the fetuses’ posterior fossa between normal fetuses and the fetuses with chromosomal abnormalities in the Chinese population. Materials and Methods: This is a prospective study performed over five years between January 2005 and December 2010 in Taiwan, with 20586 cases that had combined a variety of sonographic markers and maternal serological β-hCG and PAPP-A levels assessed at first trimester screening between 11+0 and 13+6 weeks of gestation. The risk of aneuploidy was calculated using the software developed by Fetal Medicine Foundation, London (FMF). Fetal karyotyping was performed when the prenatal screening showed a risk of 1/300 or higher. All cases were followed for fetal outcome. Another, a prospective observational study was performed that included 640 euploid and 45 trisomy 21 singleton pregnancies undergoing first trimester ultrasound screening between 11 and 13+6 weeks of gestation. The FMF angle was measured in the midsagittal plane using the standard technique. In 518 normal fetuses referred to first trimester screening fetal brain stem (BS) and brain stem to occipital distance (BSOB) were measured prospectively. The BS and BSOB were also measured on stored images in fetuses with confirmed trisomy 21 (N=38), Trisomy 18 (N=26), Trisomy 13 (N=8), and monosomy X (N=8). Results: The 20586 cases study was divided to four groups according to screening strategy performed. Combination of maternal serological biochemistry and nuchal translucency measurement had 66.7% detection rate of Trisomy 21. Additional use of nasal bone increased the detection rate of Trisomy 21 to 88.2%. Inclusion of tricuspid regurgitation flow showed 87.5% detection rate of Trisomy 21. Further inclusion of Ductus venosus flow increased the detection rate of Trisomy 21 to 100%. Incorporating more markers greatly increased the detection rate and decreased the false-positive rate (FPR). The FMF angle ultrasound soft marker results showed that the fetal mean FMF angle decreased with the increasing crown-rump length (CRL) from 88.6 at a CRL of 45 mm to 78.5 at a CRL of 84 mm (FMF angle = 100.212 - 0.258 x CRL, R2 = 0.222, p<0.001). The overall mean FMF angle in the euploid population was 82.9 ± 4.1o and in trisomy 21 cases, 92.3± 5.2o. The study posterior fossa of fetal brain ultrasound soft marker result revealed the BS diameter and BSOB distance correlated linearly with fetal crown-rump length (CRL) by regression analysis. The BS to BSOB ratio was below the 5th percentile in 2(5.26%), 11(44%), 4(50%) and 4(50%) fetuses with trisomy 21, trisomy 18, trisomy 13 and monosomy X, respectively. The BS and BS/BSOB ratio were significantly lower in trisomy 13, trisomy 18 and monosomy X fetuses than those of the normal fetuses when compared to reference range but not in fetuses with Trisomy 21. Conclusions: Extension of first trimester (11–13+6 gestation weeks) screening to include more sonographic markers greatly increased the sensitivity and decreased FPR for detection of chromosomal abnormalities. Such screening strategy is effective in clinical practice for the Chinese ethnic population. The fetal FMF angle ultrasound soft maker is affected by gestational age in a Chinese population, although it remains a significant predictor of fetal trisomy 21. The fetuses’ posterior fossa ultrasound soft maker reveals that the fetuses of the trisomy 13, 18, and monosomy X had lower BS/BSOB ratios. But trisomy 21 fetuses did not show significant differences in posterior fossa compared to normal in the Chinese population.