To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening.Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0.With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% (<0.05), in which the positive rate of Down syndrome decreased (<0.05), that of deformity of neural tube increased (<0.05), and that of trisomy 18 syndrome remained the same (>0.05). The median MoMs of free-hCG β and α-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all<0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0.BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.
Adult ; Body Weights and Measures ; standards ; Cephalometry ; standards ; statistics & numerical data ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; standards ; Chromosomes, Human, Pair 18 ; Down Syndrome ; diagnosis ; embryology ; Epidemiologic Measurements ; Female ; Fetal Development ; Gestational Age ; Head ; embryology ; Humans ; Mass Screening ; methods ; standards ; statistics & numerical data ; Menstrual Cycle ; Neural Tube Defects ; diagnosis ; embryology ; Pregnancy ; Prenatal Diagnosis ; methods ; standards ; statistics & numerical data ; Reference Values ; Trisomy ; diagnosis ; Trisomy 18 Syndrome ; alpha-Fetoproteins ; analysis ; standards

The routine prenatal maternal serum testing is widely used for screening of birth defects, including Down syndrome, trisomy 18 syndrome and neural tube defects. The testing results are also associated with other adverse pregnant outcomes such as fetal surface structural abnormalities, gestational hypertension disease, intrahepatic cholestasis of pregnancy, premature rupture of membranes, abortion, stillbirth, intrauterine growth restriction and macrosomia; therefore the abnormal levels of serum markers might be used for predicting these adverse pregnant outcomes.
Biomarkers ; blood ; Chromosomes, Human, Pair 18 ; Down Syndrome ; Female ; Humans ; Neural Tube Defects ; Pregnancy ; Pregnancy Outcome ; Prenatal Diagnosis ; Trisomy

OBJECTIVETo explore the clinical value of screening the serum markers during the second trimester of pregnancy in preventing congenital birth defect and predicting the pregnancy outcome.

METHODSBetween November, 2011 and October, 2013, a total of 25 520 pregnant women (15-20+6 gestational weeks) underwent a screening test of triple serum markers including free beta-human chorionic gonadotrophin (free βhCG), alpha-fetoprotein (AFP), and unconjugated estriol (µE3) during the second semester of pregnancy. The women identified by the screening test as having high risks were referred to invasive prenatal diagnosis by amniocentesis, or to color Doppler ultrasound examination for suspected patent neural tube defect (NTD), and their pregnancy outcomes were followed up.

RESULTSHigh-risk pregnancies were identified by the screening test in 4.91% (1254/25520) of the total cohort. Of the 818 patients receiving invasive prenatal diagnosis, the abnormal rate was 5.75% (47/818). The high-risk pregnancies identified by the screening test was associated with a significantly higher rate of abnormal outcomes compared with the low-risk pregnancies (1.91% vs 0.1%, P<0.01). Of the 210 high-risk cases of NTD, a definite diagnosis was established in 34 cases. We also found that pregnancies at an advanced age (>35 years) was associated with increased risks for trisomy 21 compared with those at younger ages (15% vs 1.65%P<0.01). The detection rate of abnormal karyotypes in pregnancies with an abnormal MoM value of a single marker was 3.17% (6/189).

CONCLUSIONScreening tests of serum markers during the second trimester of pregnancy can be helpful to identify fetal chromosomal and anatomical anomalies, predict unfavorable pregnancy outcomes, and prevent birth defects in pregnancies at an advanced age. The MoM value of a single marker in the second trimester can be indicative of potential chromosomal abnormalities.

Biomarkers ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Chromosome Aberrations ; Down Syndrome ; diagnosis ; Estriol ; blood ; Female ; Humans ; Neural Tube Defects ; diagnosis ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Second ; blood ; Prenatal Diagnosis ; alpha-Fetoproteins ; analysis

Chorionic Gonadotropin, beta Subunit, Human ; blood ; Cost-Benefit Analysis ; Down Syndrome ; blood ; diagnosis ; False Positive Reactions ; Female ; Health Care Costs ; Humans ; Maternal Serum Screening Tests ; economics ; methods ; standards ; Pregnancy ; Pregnancy Trimester, First ; blood ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prenatal Care ; methods ; Prenatal Diagnosis ; economics ; methods ; standards

OBJECTIVETo evaluate the efficiency of first trimester prenatal screening for fetal chromosome abnormality using maternal serum marker test and(or) plus nuchal translucency (NT) in Guangzhou region.

METHODSThe results of prenatal screening were retrospectively analyzed among 43 703 women with singleton pregnancies from January 2007 to September 2012. A total of 43 703 pregnancies between 9 and 13(+6) weeks of pregnancy were collected and analyzed for maternal serum pregnancy-associated plasma protein A (PAPPA), free β -human chorionic gonadotropin (free β -hCG) with or without crown-rump length (CRL). Nuchal translucency was measured by ultrasonographic scan between 11 and 13(+6) weeks of pregnancy. Gestational age was estimated by ultrasonographic scan. The risk values of Down syndrome (DS) and trisomy 18 were calculated using the software Lifcycle. Comparing the difference between the combined screening (PAPPA, free β -hCG and NT) and serum marker screening (PAPPA and free β -hCG).

RESULTSAmong the 43 703 pregnant women, screening showed that 1385 (3.17%) were Down syndrome positive and 55 (0.13%) were trisomy 18 positive. The final outcomes of pregnancy showed that 142 cases presented chromosomal abnormalities, of which 54 cases suffered from Down syndrome, 13 had trisomy 18, and 75 had other chromosome abnormalities. The total detection rate of Down syndrome and trisomy 18 were 83.33% and 76.92%, respectively.The positive rate is lower, and the detection rate is higher in combined screening group than serum marker screening group. The median PAPPA MoM was lower and the median free β -hCG MoM and NT measured value was higher in Down syndrome pregnancies than control group. The median PAPPA and free β -hCG MoM were lower and the median NT measured value was higher in trisomy 18 pregnancies than control group.

CONCLUSIONThe first trimester prenatal screening can effectively detect Down syndrome and trisomy 18 pregnancy. The combined screening method is superior to the serum marker screening and is the preferred strategy in the first trimester prenatal screening.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Biomarkers ; blood ; China ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Down Syndrome ; diagnosis ; genetics ; Female ; Fetal Diseases ; diagnosis ; ethnology ; genetics ; Genetic Testing ; methods ; Humans ; Middle Aged ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy-Associated Plasma Protein-A ; metabolism ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity ; Trisomy ; diagnosis ; genetics ; Trisomy 18 Syndrome ; Young Adult

OBJECTIVETo investigate the value of a disintegrin and metalloproteinase 12 secreting form (ADAM12-S) as a maternal serum marker in second trimester screening for trisomy 21 (Down syndrome, DS), and to develop an appropriate prenatal DS screening protocol.

METHODSSerum samples were collected from 53 pregnant women carrying a trisomy 21 fetus and 621 pregnant women with matched gestational age and weight carrying a healthy fetus. ADAM12-S concentrations were determined with a time-resolved fluorescence immunoassay (TRFIA). Curve fitting by weighted regression and other statistical methods were conducted, and the model was optimized for prenatal trisomy 21 screening program in second trimester. ADAM12-S alone or in combination with other two- or three-combination test was selected as a serum marker for prenatal second-trimester screening of trisomy 21 by calculation of detection rate (DR) and false positive rate (FPR).

RESULTSBy comparison, the median multiple of the median (MoM) value of ADAM12-S in DS pregnancy group was higher than that of the control group (P< 0.01). When FPR = 5%, the DR of ADAM12-S was 28.3%, and the positive and negative likelihood ratios were 5.66 and 0.75, respectively. The DR of three-combination test of ADAM12-S, alpha-fetoprotein (AFP) and free beta subunit of human chorionic gonadotropin (β-HCG) has increased to 52.80% from 39.62% of the conventional two-combination test (AFP and free β-HCG). For women with a risk between 1/300 and 1/1000 by two-combination test for DS, the DR has increased from 39.62% to 47.12%, but FPR only increased by 0.8% after adding ADAM12-S as a maternal serum marker.

CONCLUSIONConsidering the increased DR of pregnancies with a risk between 1/300 and 1/1000 in second trimester, ADAM12-S may provide a feasible maternal serum maker when combined with AFP and free β-HCG. The cost-effectiveness ratio is reasonable.

ADAM Proteins ; blood ; ADAM12 Protein ; Biomarkers ; blood ; Disintegrins ; blood ; Down Syndrome ; blood ; diagnosis ; enzymology ; Female ; Humans ; Membrane Proteins ; blood ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; methods

OBJECTIVETo provide basis for selecting the suitable method of Down's syndrome biochemical screening in the second trimester pregnancy.

METHODSA total of 30 547 singleton pregnancies between 14 and 20(+ 6) weeks of pregnancy were collected and analyzed for maternal serum alpha-fetoproteins (AFP) and human chorionic gonadotrophin, free beta subunit (beta-HCG) with or without unconjugated estriol (uE3). The screening risks were calculated using the software Lifecycle. The detection rates and the cost of per Down's syndrome detected were calculated and compared. And four different methods were compared in a series of 64 serum samples from Down's syndrome pregnancies.

RESULTS(1) Among the 64 affected cases, the detection rate of Down's syndrome was improved no matter in the double test (DT) or in the triple test (TT) if software Lifecycle (LC) was used to evaluate risks. And it was not suitable to evaluate risks with software 2T-Risks in the triple tests. (2) In the cohort of 30 547 singleton pregnancies, the detection rate of Down's syndrome with project DT-LC, which was double test using AFP and free beta-HCG together with software Lifecycle, and project TT-LC, which was triple test using AFP, free beta-HCG and uE3 together with software Lifecycle, was 56.25% and 57.14%, respectively. The former project was better because it decreased the false positive rate at a lower running cost.

CONCLUSIONThe DT-LC is an effective screening strategy for second trimester detection of fetal Down's syndrome in mainland China.

Adult ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Down Syndrome ; blood ; diagnosis ; Estriol ; blood ; Female ; Genetic Testing ; methods ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; blood ; Prenatal Diagnosis ; economics ; methods ; Young Adult ; alpha-Fetoproteins ; metabolism

OBJECTIVETo investigate the application value of the multiplex ligation-dependent probe amplification (MLPA) technique in diagnosis and prenatal diagnosis of chromosomes 13, 18, 21, X and Y aneuploidy.

METHODSForty-four cases including 30 peripheral blood samples, 10 fetal cord blood samples, and 4 amniotic fluid samples were collected in this study. DNA was isolated from the samples and detected by MLPA, followed by analyzing in ABI310 Genetic Analyzer. Analysis of copy number changes for chromosomes 13, 18, 21, X and Y was carried out with RH-MLPA-analysis software. The routine karyotype analyses were also done for all the samples.

RESULTSOf 44 samples, the results of 42 by MLPA method was consistent with that by chromosome karyotyping. Only one case with trisomy 21 chimerism was failed to reach conclusion. In addition, one case of mark chromosome segment was identified as Y-chromosome segment by MLPA, while karyotyping failed to make judgment. The accurate rate of MLPA was 97.7% (43/44).

CONCLUSIONThe MLPA technique can simultaneously detect dozens of different target sequences and their copy number changes in a single reaction. It showed high specificity, good reproducibility, was fast and high-throughput. The MLPA technique can be applied to diagnosis and prenatal diagnosis of the common chromosomal aneuploidy.

Amniotic Fluid ; chemistry ; Aneuploidy ; Chromosomes, Human, Pair 13 ; DNA ; genetics ; isolation & purification ; DNA Copy Number Variations ; Down Syndrome ; diagnosis ; genetics ; Female ; Fetal Blood ; chemistry ; Humans ; Nucleic Acid Amplification Techniques ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Sensitivity and Specificity

INTRODUCTIONThis study examines the effectiveness of double-marker analysis for α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) combined with measurement of nuchal fold thickness (NT) in the detection of Down's syndrome (DS) in Mainland Chinese subjects during second trimester prenatal screening.

MATERIALS AND METHODSWe examined pregnant women with a singleton pregnancy between 15 and 21 weeks of gestation who underwent second trimester screening for DS using double-marker analysis for AFP and β-hCG combined with ultrasound measurement of NT. The combined risk of DS was calculated. A cut-off of 1/270 was used to define a pregnancy at high-risk of DS. Amniocentesis was offered to all patients with high-risk pregnancies.

RESULTSUsing double-marker analysis for AFP and β-hCG in combination with measurement of NT, the detection rate of DS increased from 66.7% to 77.8% when compared with double-marker analysis alone with similar false-positive rates (4.35%, 4.83% respectively). Using receiver operating characteristic curve (ROC) analysis, we determined that the double-marker analysis combined with measurement of NT exhibited an increased area under the curve (AUC) of 0.835 (95% CI: 0.743 to 0.927) when compared to double-marker analysis alone, which had an AUC of 0.748 (95% CI: 0.635 to 0.860). In addition, both methods were more effective than any other single test such as AFP, free β-hCG or NT measurement.

CONCLUSIONSecond trimester prenatal screening using double-marker analysis for AFP and β-hCG combined with measurement of NT is effective for the detection of DS in Mainland Chinese pregnancies.

Adult ; Biomarkers ; China ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Down Syndrome ; diagnosis ; diagnostic imaging ; Female ; Gestational Age ; Humans ; Mass Screening ; Nuchal Translucency Measurement ; methods ; Pregnancy ; Pregnancy Trimester, Second ; Prenatal Diagnosis ; Risk Assessment ; Young Adult ; alpha-Fetoproteins ; analysis

The purpose of the current study was to propose a Korean-specific parameter set for calculating the risk of Down syndrome in the second trimester of pregnancy and to determine the screening performances of triple and quadruple tests in Korean women. Using the data on triple or quadruple screening from three hospitals in Korea during 7 yr, we re-converted the concentrations of four serum markers to multiple of median values according to gestational age and maternal weight. After re-calculating the risk of Down syndrome in each pregnancy by multiplying maternal age-specific risk by the likelihood ratio values for the serum markers, screening performances and optimal cut-off values of triple and quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with new parameters had improved screening performance. The triple and quadruple tests had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of 5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We have presented a Korean-specific parameter set for Down syndrome screening. The proposed screening test using this parameter set may improve the performance of Down syndrome screening for Korean women.
Adult ; Asian Continental Ancestry Group ; Biological Markers/blood ; Down Syndrome/blood/*diagnosis ; Female ; Genetic Testing/*methods ; Humans ; Predictive Value of Tests ; Pregnancy ; *Pregnancy Trimester, Second ; Prenatal Diagnosis/*methods ; Republic of Korea ; Risk