Detection Of Cell-free Fetal DNA In Maternal Plasma For Noninvasive Prenatal Screening Of Fetal Common Chromosomal Aneuploidy In Women Of Advanced Maternal Age

Background:As the two-child policy was fully liberalized,the number of pregnant women of advanced maternal age has skyrocketed.Primary observation showed that the number already accounted for 33.4-46%of the number of the prenatal diagnostic clinic.Advanced age is a risk factor for fetal aneuploidy.The pregnant women of advanced maternal age should accept invasive prenatal screening according to the management of prenatal diagnosis technology in China.However,invasive prenatal screening exists some disadvantages such as it’s invasive manipulation to fetus,the cell culture cycle is long,the cell culture may fail,high throughput automation detection cannot be realized and there is a risk of fetal loss,coupled with the supply and demand contradiction of medical resources,It is difficult to meet all the high risk and the needs of the pregnant women of advanced maternal age.Consequently,it is excepted that a prenatal screening and diagnostic techniques and programmes are more responsive to clinical needs.The prenatal screening in free fetal DNA is a detection technology based on next generation sequencing,which is noninvasive prenatal screening(NIPS).It can realized high throughput automation analysis.The clinical observation results show that NIPS has performed perfect in the high risk pregnant women and the pregnant women of advanced maternal age.The detection efficiency is far superior to serological screening.However,the evaluation of noninvasive prenatal screening among women of advanced maternal age is still uncommon.It is rare of application in the Chinese population.Therefore,it is of great significance to evaluate the performance of NIPS in Chinese pregnant women of advanced maternal age and to optimize the strategy of prenatal screening and diagnosis.Objectives:To evaluate the effciency of NIPS for women of advanced maternal age(AMA),and to optimize the strategy of prenatal screening and diagnosis.The object and method:1.Object:The datas of 29 385 maternal women who received NIPS were collected in the Women’s Hospital,Zhejiang University School of Medicine and Jiaxing Maternal and Child Health Hospital during February 2015 and September 2016,10 584 of AMA who were completely investigated were recruited.2.Method:The NIPS-positive cases and underwent interventional prenatal diagnosis would consider the fetal karyotyping as the gold standard for diagnosis;while the NIPS-negative cases were validated by the pregnant or fetal outcomes postnatal followed-up.Counted the demographic information of fetal common chromosomal aneuploidy screening in different age groups.(1)Counted the confirmed cases form the high risk pregnant women for trisomy 21,trisomy 18 and trisomy 13 in the study subjects.The sensitivity,specitivity,positive predictive value(PPV)and negative predictive value(NPV)of NIPS were calculated(2)Divided the maternal women as 35 years old,36 years old,37 years old,38 years old,39 years old,40 years old and the women aged than or equal to 41 due date.Compered the high-risk rate and true positive rate of trisomy 21 in different ages.Results:1.The sensitivity,specificity,PPV and NPV of NIPS were 100%,99.96%,91.67%,100%for trisomy 21,100%,99.93%,68.18%,100%for trisomy 18 and 100%,99.97%,25%,100%for trisomy 13.2.We found that high-risk rate and true positive rate of trisomy 21 were increase gradually positively correlated with the maternal age(all P<0.01)from the calculation of the datas of NIPS for trisomy 21 in different ages.There were significant differences in high-risk rate and true positive rate between 35-37 year old groups and 38-40 year old groups(P<0.05).Such difference was also found in high-risk rate between 38-40 year old group and ≥41 year old group(P<0.05),but not in true positive rate between two groups(P>0.05).Conclusions:1.NIPS is effective and suitable for fetal chromosomal aneuploidy screening in women of advanced maternal age.2.The incidence of fetal chromosomal aneuploidy increases with maternal age.For women under 38 years of age,NIPS is preferred;for women of 41 and above,invasive diagnostic methods are suggested;and for women between 38-41 years old,the potion can be determined by themselves after risks and advantages were fully informed.