ABSTRACT
The present study aimed to examine the value of ultrasonic soft markers in prenatal screening by analyzing the clinical outcome of fetuses with ultrasonic soft markers during the second trimester of pregnancy.A retrospective analysis was performed to evaluate the outcome of 591 fetuses with ultrasonic soft markers from January 2015 to August 2016 in Zhongnan Hospital of Wuhan University,China.It was found that 591 fetuses showed ultrasonic soft markers in 4927 cases with the occurrence rate being 12.0％.Among them,564 fetuses (95.4％) were delivered and the remaining 27 cases (4.6％) were aborted.Five hundred and sixty-seven cases had single ultrasonic soft marker,including echogenic intracardiac focus (n=343),mild renal pelvis dilatation (n=116),short long bones (n=72),single umbilical artery (n=31),mild lateral ventriculomegaly (n=21),choroid plexus cysts (n=19),and echogenic bowel (n=13),with the disappearing rates in pregnancy being 97.1％ (333/343),77.6％ (90/116),0％ (0/72),0％ (0/31),57.1％ (12/21),89.5％ (17/19) and 61.5％ (8/13) respectively.The rate of pregnancy termination due to single ultrasonic soft marker was 3.4％ (19/567),and that was 33.3％ (8/24) due to two ultrasonic soft markers with the difference being statistically significant (P＜0.05).The reasons of pregnancy termination included malformations (polycystic kidney,cleft lip and palate,congenital heart diseases,pcromphalus,hypospadias,hydrocephalus),chromosome abnormality,and stillbirth.It was concluded that single ultrasonic soft marker is usually transient manifestation in pregnancy.Without the other structural defects,single ultrasonic soft marker usually disappears spontaneously with favorable prognosis in a low-risk population.It is suggested that ultrasonic soft markers should be appropriately interpreted to avoid unnecessary invasive examination.
ABSTRACT
This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA,and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21.Matemal plasma samples were collected from 388 singleton pregnancies,and placental or chorionic villus tissues from 112 of them.Methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme digestion followed by fluorescent quantitative PCR (MSRE + PCR) were employed to detect the maternal-fetal methylation difference in AIRE and RASSF1A.Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in matemal plasma.Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues.Moreover,the differential methylation for each locus could be seen during the whole pregnant period.The positive rates of fetal AIRE and RASSF1A in maternal plasma were found to be 78.1％ and 82.1％ by MSP and 94.8％ and 96.9％ by MSRE + PCR.MSRE + PCR was superior to MSP in the identification of fetal-specific hypermethylated sequences (P＜0.05).Based on the data from 266 euploidy pregnancies,the 95％ reference interval of the fetal AIRE/RASSF1A ratio in maternal plasma was 0.33-1.77,which was taken as the reference value for determining the numbers of fetal chromosome 21 in 102 pregnancies.The accuracy rate in 98 euploidy pregnancies was 96.9％ (95/98).Three of the four trisomy 21 pregnancies were confirmed with this method.It was concluded that hypermethylated AIRE and,RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.