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Optimization Of The Maternal Serum Screening Programs For Down Syndrome

Posted on:2011-02-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z W XieFull Text:PDF
GTID:1114360305958175Subject:Obstetrics and gynecology
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Chapter One Contingent triple-screening for Down syndrome in the second trimester:a feasibility study in Mainland Chinese population1. BackgroundThe detection rate of second trimester maternal serum triple-screening (AFP+freeβ-hCG+uE3) program is higher than that of double-screening (AFP+freeβ-hCG). But the costs for triple-screening increased too due to one more detection index added in. In order to improve the detection rate of Down syndrome and reduce the costs just based on current routine double-screening program in China, and taking into account of the actual situation of Chinese economy& technology and the cost-effectiveness of program, we proposed a contingent triple-screening program, which performing triple-screening in pregnant women with DS risks between 1/270 and 1/1000 at routine double-screening. 2. ObjectivesThis study was designed for the following purposes:(1) to determine whether the DS risks between 1/270 and 1/1000 at routine double-screening is a feasible range of contingent triple-screening program; (2) to explore the efficacy of contingent triple-screening compared with routine double-screening in the second trimester; (3) to evaluate the economic value of the contingent triple-screening compared with routine triple-screening in the second trimester.3. Methods30 maternal serum samples of double-screening false-negative cases were collected and 24 of them had DS risks between 1/270 and 1/1000 at routine double-screening. Maternal serum concentrations of AFP, free P-hCG and uE3 were measured by time-resolved fluoroimmunoassay in 24 double-screening false-negative (DSFN) and 322 double-screening true-negative (DSTN) pregnancies with DS risks between 1/1000- 1/270 at routine double-screening performed at 15-20 weeks of gestation. DS risk of each pregnancy was calculated by computer software. The detection rate (DR), false positive rate (FPR), and costs of contingent triple-screening were calculated and compared to routine double-screening and triple-screening methods.4. Results80% double-screening false-negative cases had DS risks between 1/270 and 1/1000 at routine double-screening.6 of 24 DSFN and 3 of 322 DSTN were contingent triple-screening positive. Compared to routine double-screening, DR of contingent triple-screening increased by 10%(from 50% to 60%) without a significant increase of FPR (p>0.05). When compared to routine triple-screening, uE3 costs in contingent triple-screening were reduced by more than 84.3%.5. ConclusionsSecond trimester maternal serum contingent triple-screening could not only improve the efficacy of screening but also reduce the health care costs. It could be effective and suitable for prenatal care in Mainland China. Governments and Health Agencies of other developing countries may also find this strategy cost-effective.This was the first introduction of the concept of "contingent triple-screening program" in the world. Our results has been published in'Prenatal Diagnosis'(Prenat Diagn.2010 Jan; 30(1):74-6.), a core journal in the field of prenatal care. Chapter Two Second-trimester maternal serum free-β-human chorionic gonadotropin and a-fetoprotein levels in normal twin and singleton pregnancies1. BackgroundTwin pregnancies are frequent in China and the incidence of having at least one Down Syndrome (DS)-affected fetus in twin pregnancies was higher than that of singleton pregnancies, thus it is important to carry out prenatal screening for twin pregnancies. However, the value of maternal serum screening in twin pregnancies is still controversial. In current prenatal screening for twin pregnancies, the estimated risk of DS in twin pregnancies was calculated based on the theory that maternal serum concentration of markers in twins would be twice of that in singletons. We may suggest that the current maternal serum screening programs, which are based on the data collected from singleton pregnancies seem to be unreasonable for DS screening in twin pregnancies. It is necessary to establish special gestational age-specific mid-trimester normal medians of maternal serum freeβ-hCG and AFP for DS screening in twin pregnancies.2. ObjectivesThe study was designed to explore the changing trends of the levels of maternal serum freeβ-hCG and AFP used in second-trimester DS screening for twin pregnancies. And to confirm whether there are differences between Chinese normal twin and singleton pregnancies in the levels of maternal serum freeβ-hCG and AFP.3. MethodsThe concentrations of maternal serum markers of 456 twin pregnancies and 12,067 singleton controls in gestational 15 to 20 weeks were measured by time-resolved fluoroimmunoassay, and the levels of markers were compared between the twins and singletons in each gestational week. 4. ResultsAll cases had been followed-up till 1 month after childbirth and no childbirth with DS was found. Significant differences were found between the levels of freeβ-hCG in twins and twice of those in singletons in 16,17 and 19 gestational weeks (p< 0.05 for all). While considering AFP, significant differences were found in 16 and 19 gestational weeks (p< 0.05 for both). In singleton pregnancies there were significant correlations between the levels of makers and maternal weights in most gestational week, while no correlations were found in twins between the levels of markers and maternal weights in most gestational weeks.5. ConclusionsThe Chinese gestational age-specific levels of maternal serum markers in normal twins are not twice as those in singletons. The current weight-correction model for DS screening may be not feasible for twins. It is necessary to establish special gestational age specific mid-trimester normal medians of the freeβ-hCG and AFP and special weight-correction model for DS screening in twin pregnancies. Our study for medians of freeβ-hCG and AFP in Chinese twin pregnancies will help to establish specific second trimester DS screening model for Chinese twin-prenatal care and the results has been published in'Prenatal Diagnosis'(Prenat Diagn.2008 Aug; 28(8):735-8.), a core journal in the field of prenatal care. Chapter Three Maternal serum freeβ-hCG, PAPP-A, and ADAM 12 levels in local Chinese population during the first trimester1. BackgroundFirst trimester prenatal screening has not yet carried out widespread in China, but it is undoubtedly the tendency of the future clinical work with prenatal screening. So, it is necessary to gradually carry out basic research related to first trimester screening. Among all screening programs in first trimester, the combined screening (Freeβ-hCG+PAPP-A+NT) is the best. But NT measurement is so difficult and it couldn't be performed as a routine screening program in current China. A Disintegrin and Metalloproteinase 12 (ADAM 12) is a recently discovered new serum marker, which is considered increasing the detection rate of DS screening significantly. It is rarely reported about freeβ-hCG, PAPP-A and ADAM 12 in the Chinese population of large sample study of first trimester pregnancy.2. ObjectivesTo explore maternal serum freeβ-hCG, PAPP-A and ADAM 12 levels in the first trimester in local Chinese population, in order to provide a theoretical basis for establishment of first trimester screening program in local Chinese pregnant women.3. MethodsFrom July 2007 to February 2010,685 maternal serum samples(1 DS pregnancy and 684 non-DS pregnancies) were collected from women with singleton pregnancy who received first trimester (7-13 gestational weeks) examination in the Affiliated Women's Hospital, College of Medicine, Zhejiang University. Levels of freeβ-hCG, PAPP-A and ADAM 12 were measured by commercial time-resolved fluoroimmunoassay. Statistical analysis was performed using SPSS 16.0 software to evaluate the relationship between each serum marker and weight, gestational age, and the correlations between markers were analyzed too.4. ResultsAfter statistical analysis, there was no significant differences were found between the maternal ages and weights in each gestational week, and no correlations were found between the maternal weights and gestational weeks either (P>0.01 for all). From 9th gestational week to 13th gestational week, the median of maternal serum PAPP-A concentration in non-DS was 876.00,1365.00,2380.00,3995.00 and 5305.00 mU/L respectively. While the median of maternal serum ADAM 12 concentration in non-DS was 282.55,376.80,436.36,547.43 and 634.08 ng/ml respectively.The concentrations of both serum markers above were increased with the gestational weeks increased. The median of maternal serum freeβ-hCG concentration in non-DS was 87.30,86.45,70.40, 59.45 and 42.10 ng/ml respectively, and it was significantly decreased after 10 gestational weeks. Relationship could be found between each serum marker and gestational weeks, maternal weights (P<0.01 for all), and correlation could be found between PAPP-A and ADAM 12 too (P<0.01), while there was no relationship between maternal serum freeβ-hCG and PAPP-A, ADAM 12 (both P>0.01).5. ConclusionThe maternal serum PAPP-A and ADAM 12 concentration were increased with the gestational age increased during the first trimester pregnancy in local Chinese population, while the maternal serum freeβ-hCG concentration was significantly decreased after 10 gestational weeks. There was relationship between ADAM 12 and PAPP-A, so the potency of combined screening with ADAM 12 and PAPP-A need further investigation. Our study could provide a theoretical basis for establishment of first trimester screening program in local Chinese pregnant women.
Keywords/Search Tags:Down syndrome, maternal serum screening, second trimester, triple-screening, double-screening, maternal serum screening, Down syndrome, twin pregnancies, free-β-human chorionic gonadotropin, α-fetoprotein, Freeβ-human chorionic gonadotropin
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