Female ; Humans ; Maternal Age ; Maternal Serum Screening Tests ; methods ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; methods

Female ; Humans ; Maternal Age ; Maternal Serum Screening Tests ; methods ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; methods

INTRODUCTION: It is reported that analytical precision in maternal serum screening tests for Down's syndrome has a direct effect on the precision of the risk estimation. Recently, an automatic immunoassay analyzer, which can measure the alphafetoprotein (AFP), chorionic gonadotropin (CG) and unconjugated estriol (uE3) was introduced, and we evaluated the analytical characteris-tics and defined the median value in healthy pregnant women. METHOD: We measured the AFP, CG and uE3 with Access(R) (Beckman Coulter, Fullerton, CA, USA) and evaluated the precision, the low detection limit, the linearity and we defined the median value in the women who were in 15-20 weeks of pregnant. RESULT: Between-run precisions of AFP, CG, uE3 were 1.12%, 2.01%, and 2.59%, respectively. The lower detection limit of AFP, CG, uE3 was 0.08 ng/mL, 0.16 mIU/mL, and 0.015 ng/mL, respec-tively. All three items passed the lack of fit test of the linear regression. Median values for the gesta-tional period (15- 20 week) of AFP, CG, uE3 were 37.47- 69.01 ng/mL, 41.44- 29.10 IU/mL, and 0.871- 2.008 ng/mL, respectively. CONCLUSION: The automatic immunoassay analyzer used for screening for Down's syndrome was satisfactory for the analytical features and showed median values similar to that of the Wald's. We conclude that Access(R) could be used for screening pregnant women for Down's syndrome with better precision and convenience.
Chorionic Gonadotropin ; Down Syndrome* ; Estriol ; Female ; Humans ; Immunoassay* ; Limit of Detection ; Linear Models ; Mass Screening* ; Maternal Serum Screening Tests ; Pregnant Women

Although conventional prenatal screening tests for Down syndrome have been developed over the past 20 years, the positive predictive value of these tests is around 5%. Through these tests, many pregnant women have taken invasive tests including chorionic villi sampling and amniocentesis for confirming Down syndrome. Invasive test carries the risk of fetal loss at a low but significant rate. There is a large amount of evidence that non-invasive prenatal test (NIPT) using cell free DNA in maternal serum is more sensitive and specific than conventional maternal serum and/or ultrasound screening. Therefore implementing NIPT will increase aneuploidy detection rate and concurrently decrease fetal loss rate accompanying invasive test. More than 1,000,000 NIPT were performed globally since 2011. The uptake rate of NIPT is expected to increase more rapidly in the future. Moreover, as a molecular genetic technique advances, NIPT can be used for not only common aneuploidy screening but single gene disorder, microdeletion, and whole fetal genome sequencing. In this review, I will focus on the NIPT for common aneuploidies such as trisomy 13, 18, and 21.
Amniocentesis ; Aneuploidy ; Chorionic Villi Sampling ; DNA* ; Down Syndrome ; Female ; Genome ; Humans ; Mass Screening ; Maternal Serum Screening Tests ; Molecular Biology ; Pregnancy ; Pregnant Women ; Prenatal Diagnosis ; Trisomy ; Ultrasonography

Non-invasive prenatal testing using next generation sequencing technology with cell free fetal DNA from the blood of pregnant women has been rapidly adopted as a screening test for the detection of disorders involving chromosomal aneuploidy, especially Down syndrome. However as part of a prenatal recommendation in high-risk group, this laboratory assessment should be accompanied by informed counseling at both pre-test and post-test stages. In low-risk group and multifetal pregnancies, only conventional maternal serum screening tests in the first trimester and/or second trimester in addition to measurement of nuchal translucency should be recommended, until this potential tool has been incorporated into current screening strategic modalities on the basis ofsufficient published data.
Aneuploidy ; Counseling ; DNA* ; Down Syndrome ; Female ; Humans ; Mass Screening ; Maternal Serum Screening Tests ; Nuchal Translucency Measurement ; Pregnancy ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Pregnant Women

OBJECTIVE: To compare and analysis the result of second trimester maternal serum triple marker screening test for Down syndrome and open neural tube defects in singleton pregnancies conceived by conventional in vitro fertilization- embryo transfer (IVF-ET) with that of the naturally conceived pregnancies. METHODS: Maternal serum screening tests during the second trimester in 49 singleton pregnancies conceived by IVF-ET and 813 singleton pregnancies conceived naturally of whom delivery outcome was normal in each other were analyzed from April 1997 to June 2000. RESULTS: 4 (8.2%) out of 49 cases of IVF-ET singleton pregnancies compared with 62 (7.6%) out of 813 cases of naturally conceived pregnancies had a positive RESULTS: for Down syndrome or open neural tube defects. The median level of the triple markers were 1.03 0.47 multiples of the median (MoM) in IVF-ET pregnancies vs 1.05+/-0.39 MoM in natural pregnancies for alpha-fetoprotein (AFP), 1.11+/-0.64 vs 1.19+/-1.13 MoM for unconjugated estriol (uE3) and 1.21+/-0.56 vs 1.11+/-0.59 MoM for human chorionic gonadotropin (hCG). CONCLUSION: The positive rate of triple test and the median values of triple markers for Down syndrome and open neural tube defect between two groups were not different in terms of statistical significance. To provide an objective assessment of an individual patient's risk of fetal abnormality, the impact of IVF-ET on triple marker biochemistry should be studied further in larger samples and adjustments made if appropriate.
alpha-Fetoproteins ; Biochemistry ; Chorionic Gonadotropin ; Down Syndrome ; Embryo Transfer ; Estriol ; Female ; Fertilization in Vitro* ; Humans ; Mass Screening* ; Maternal Serum Screening Tests ; Neural Tube Defects ; Pregnancy Trimester, Second ; Pregnancy*

OBJECTIVETo assess the value of droplet digital PCR (ddPCR) for non-invasive prenatal diagnosis of single gene disease in two families.

METHODSPaternal mutation in cell-free DNA derived from the maternal blood and amniotic fluid DNA was detected by ddPCR. Suspected mutation in the amniotic fluid DNA was verified with Sanger sequencing.

RESULTSThe result of ddPCR and Sanger sequencing indicated that the fetuses have carried pathogenic mutations from the paternal side in both families.

CONCLUSIONDroplet digital PCR can accurately detect paternal mutation carried by the fetus, and it is sensitive and reliable for analyzing trace samples. This method may be applied for the diagnosis of single gene diseases caused by paternal mutation using peripheral blood sample derived from the mother.

Fathers ; Female ; Genetic Diseases, Inborn ; diagnosis ; Humans ; Male ; Maternal Serum Screening Tests ; Mutation ; Polymerase Chain Reaction ; methods ; Prenatal Diagnosis ; methods ; Sequence Analysis, DNA

INTRODUCTIONFirst trimester screening (FTS) is a validated screening tool that has been shown to achieve detection rates of 84%-90% for trisomies 21, 18 and 13. However, its effectiveness for different maternal ages has not been assessed. The present study aimed to assess the performance of FTS in an Asian population, and to compare its effectiveness in older (≥ 35 years) and younger (< 35 years) women. The potential use of noninvasive prenatal test (NIPT) as a contingent screening test is also examined.

METHODSData on cases of FTS performed on singleton pregnancies over a six-year period was collated from two Singapore maternal centres, National University Hospital and Singapore General Hospital. Cases that had a 1:250 risk of trisomy were considered to be screen-positive. Pregnancy outcomes were obtained from birth records or karyotype test results.

RESULTSFrom 10,289 FTS cases, we obtained a sensitivity of 87.8%, a specificity of 97.6%, a false positive rate of 2.4% and a false negative rate of 0.06% for the detection of aneuploidy. The overall detection rate for trisomy 21 was 86.5%-85.7% for older women and 87.5% for younger women. The mean number of invasive tests required per case of trisomy 21 was 9.3 in younger women, 8.6 in older women and 13.5 in women with intermediate risk (1:250-1,000).

CONCLUSIONWhile the performance of FTS was similar in younger and older women, more invasive procedures were required to diagnose trisomy 21 in women with intermediate risk. It may be advantageous to offer contingent NIPT to this group of women to reduce the risk of iatrogenic fetal loss.

Adolescent ; Adult ; Aneuploidy ; Asia ; Cohort Studies ; DNA ; analysis ; Down Syndrome ; diagnosis ; Female ; Humans ; Karyotyping ; Maternal Age ; Maternal Serum Screening Tests ; methods ; Middle Aged ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, First ; Prenatal Diagnosis ; methods ; Risk Factors ; Singapore ; Trisomy ; diagnosis

OBJECTIVES: Amniocentesis is the most commonly used invasive method for prenatal diagnosis of genetic disorders. But this invasive study may induce preterm labor, endanger both the mother and the fetus, cause infection and abortion. This study was performed to clarify the safety and confidency of amniocentesis. MATERIAL AND METHODS: 1,500 amniocentesis cases were performed from 1987 to 1996 at Severance hospital for prenatal diagnosis of genetic disorders. Of 1,500 cases, 499 cases whose pregnancy outcomes were proven were finally analized. We compared incidence of complications such as spontaneous abortion, vaginal spotting, premature rupture of membranes, preterm labor or chorioamnionitis according to placental location, frequency of needle insertion and amniotic fluid color. RESULTS: 1) Indications for amniocentesis were (1) advanced maternal age - 47.3%, (2) positive maternal serum triple test - 13.8%, (3) fetal chromosomal anomaly suspected in ultrasonography - 10.0%. 2) 6.6% of the amniocentesis samples had color changes due to bleedng or meconium passing. 3) 18.8% of the cases were performed at 16th gestational weeks followed by 20th, 18th and 17th weeks. 4) 2.2% had complications such as spontaneous abortion, vaginal bleeding, premature rupture of membranes, preterm labor and chorioamnionitis in 4 weeks after amniocentesis. 5) No correlation was found between the placental location, frequency of needle insertion(below 3 times) and complication rate. The spontaneous abortion rate in the group with amniotic fluid discolorization was 6.1% whose only 0.4% had spontaneous abortion to the group with clear amniotic fluid. 6) Median value of amniotic fluid alphafetoprotein(alphaFP) of pregnant women in midtrimester were 15,769.4ng/ml at 15 weeks, 13,160.3ng/ml at 16 weeks, 11,539.3ng/ml at 17 weeks, 9,569.8 mg/ml at 18 weeks, 8,423.4mg/ml at 19 weeks, 6,527.1ng/ml at 20 weeks, 5,979.3ng/ml at 21 weeks, 4,363.2ng/ml at 22 weeks, 3,555.2ng/ml at 23weeks, respectively. In midtrimester amniotic fluid alphaFP declined gradually as gestational weeks increase. CONCLUSIONS: Fetal loss rate of midtrimester amniocentesis was 0.8%, proving that it outstanding in the aspects of safty and confidency. Since the fetal loss rate significantly increases in case with amniotic fluid discoloration, it is needless to mention the importance of close follow-up.
Abortion, Spontaneous ; Amniocentesis* ; Amniotic Fluid ; Chorioamnionitis ; Female ; Fetus ; Follow-Up Studies ; Humans ; Incidence ; Maternal Age ; Maternal Serum Screening Tests ; Meconium ; Membranes ; Metrorrhagia ; Mothers ; Needles ; Obstetric Labor, Premature ; Pregnancy ; Pregnancy Outcome ; Pregnancy Trimester, Second* ; Pregnant Women ; Prenatal Diagnosis ; Rupture ; Ultrasonography ; Uterine Hemorrhage

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