Clinical significance of combining second trimester serum and ultrasound screening for Down syndrome / 临床儿科杂志

objectives To explore the clinical significance of the triple screening method and fetal sonographic markers in Down syndrome screening. Methods The retrospective study included maternal blood serum triple-marker screening per-formed in normal singleton pregnancies at 14+1 to 19+6 weeks and ultrasonography screening for fetal chromosomal trisomy at 18+1 to 23+6 weeks from 2010 to 2013. Results In 24 368 pregancies, Karyotype analysis reveal 35 Down syndromes, the incidence is 0.14%(35/24 368). 25/35 were pregnancies with an expected date of delivery lower than 35 years old and 10/35 were pregnan-cies with an expected date of delivery higher than 35 years old. In 1 215 pregnancies, second-trimester serum screening showed high risk (cutoff>1:380), 14 were confirmed as Down syndromes ( sensitivity 40%;specificity 95.06%). In 1 142 pregnant women showed ultrasonography abnormalities, of which 11 were found to have Down syndrome (sensitivity 60%;specificity 91.09%). In 112 pregnancies, second-trimester serum screening and ultrasonography showed high risk, 4 were conformed as Down syn-drome (sensitivity 11.43%;specificity 99.56). Conclusions The most effective method of screening for Down syndrome is by maternal serum biochemistry. Ultrasonography is important in screening fetal trisomy 21. combined screening methods can improve the detection rate of trisomy 21.

Amniotic Chromosomal Analysis in Pregnant Women Identified by Triple-Marker Testing as Screen Positive / 대한진단검사의학회지

BACKGROUND: Maternal serum triple marker screening (alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol) can detect 60-70% of Down syndrome and 60% of Edwards syndrome. Previous studies have reported that positive serum screening is related to other fetal chromosomal abnormalities, pregnancy complications, and adverse outcomes. We determined the incidence and karyotype of chromosomal abnormalities in screen positive women and evaluated a relationship between chromosomal and ultrasonographic abnormalities. METHODS: Of the 49,806 pregnant women between 15 and 23 weeks' gestational age who received prenatal serum screening with a cut-off value (a risk of 1:270 for Down and 1:100 for Edwards syndrome), 2,116 (4.2%) and 196 (0.4%) were screen positive for Down syndrome and for Edwards syndrome, respectively. Chromosomal analysis in amniotic fluid was performed for 1,893 (89.5%) of the Down positive and 140 (71.4%) of the Edwards positive pregnant women. Ultrasonographic examination was performed to detect fetal abnormalities. RESULTS: Eighty-three cases of chromosomal abnormalities including 40 trisomy 21 (2.1%) and 43 other chromosomal abnormalities (2.3%) were identified in the Down screen positive. Other chromosomal abnormalities included 9 numerical and 34 structural abnormalities. Ten cases of chromosomal abnormalities (9 trisomy 18 and 1 trisomy 9) were detected in the Edwards screen positive. Ultrasonographic abnormalities were found more frequently in the women who had chromosomal aberrations. CONCLUSIONS: These data suggest that 4.4% of the Down screen and 7.1% of the Edwards screen positive pregnancy have fetal chromosomal abnormalities. Positive Down screening results reflect a relatively high probability of other abnormalities except trisomy 21. Edwards screen positive group show a low frequency of other chromosomal abnormalities except trisomy 18. A simultaneous use of maternal serum screening and ultrasonograms could be useful for the diagnosis of fetal abnormalities.

Difference of the Results of Two Visits in Down Syndrome Screening Test / 임상검사와정도관리

INTRODUCTION: Estimation of the risk of Down syndrome pregnancy by the triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age. The triple marker test is based on the distribution of the alpha-fetoprotein (AFP), chorionic gonadotropin (CG) and unconjugated estriol (uE3) of the different pregnancy. In spite of the logical excellencies, various factors can affect the result of the test in practical field. We compared differences of the risk of Down syndrome pregnancy based on the specimen obtained from two visits during the 15-21 weeks of gestational age. METHOD: We measured the AFP, CG and uE3 with Access (Beckman Coulter, USA) from the sera of 104 pregnant women who visited two times about 2 weeks of interval during 15-21 weeks of gestational age. We calculated log (MoM) of AFP, CG and uE3 of each marker between two visits, and compared differences of each biochemical marker and difference of risk of Down syndrome pregnancy between two visits. RESULT: Mean+/-SD of log (MoM) of AFP, CG, uE3 of the 1st visit were 0.019+/-0.156, -0.016+/-0.224, 0.002+/-0.138, respectively, and those of AFP, CG, uE3 of the 2nd visit were 0.010+/-0.140, -0.076+/-0.205, 0.057+/-0.138, respectively. CG and uE3 showed statistically significant difference (P<0.001, P<0.001, respectively) but AFP did not (P=0.328). Risk of Down syndrome pregnancy of the 1st visit was 8.017x10(-4)+/-1.6241x10(-3), and that of the 2nd visit was 5.667x10(-4)+/-1.6241x10(-3), with no significant difference statistically (P=0.094). CONCLUSION: The risk of Down syndrome based on the sera of woman who visited two times about 2 weeks of interval between 15-21 weeks of gestational age did not show significant difference. It is resonable that triple marker test is performed on women once at anytime during the 15-21 weeks of gestational age in practical base.

Determination of Reference Level for Triple Marker in Korean Population / 임상검사와정도관리

BACKGROUND: The triple marker test with maternal serum during 15~20 weeks gestation is a useful prenatal screening technique. However established reference level is determined for Caucasians and there has not been Korean reference level determined from triple marker results of normal pregnant women without adverse outcome. We intended to determine the Median for triple marker respectively from results which have been done in Samsung Medical Center (SMC), considering the pregnancy outcome in this study. METHODS: The study population was derived from women undergoing triple marker screening at SMC between January, 2000 and July, 2001. alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) were measured by ACS: CentaurTM (Bayer Diagnostics, Chicago, USA) and unconjugated estriol (uE3) was measured by T21 Screening ELISA (Gamma S.A., Liege-Angleur, Belgium). We reviewed the pregnancy outcome, ultrasonographic finding and amniocentesis result in each case. RESULTS: Eighty two (4.3%) patients of the 1,918 women screened were identified as positive. Two patients with chromosomal abnormalities (trisomy 21) were found in the 64 patients (78%) who underwent chromosomal analysis of amniotic fluid. With reference to total 1,830 cases, we determined the median of AFP, hCG and uE3, categorized by gestational age. Also, we calculated the Multiples of Median (MoM) of each result according to the newly determined median. CONCLUSIONS: Although triple marker test appears to be an effective method detecting chromosomal abnormalities and neural tube defect (NTD), it is most important to determine the median of our own population for the correct prenatal screening.

An Evaluation of Prenatal Triple Marker Screening / 대한진단검사의학회지

BACKGROUND: Maternal serum triple marker screening has become standard in prenatal care to help identify women at risk for neural tube defects (NTDs), trisomy 21 (Down syndrome) and trisomy 18 (Edwards' syndrome). This study was undertaken to evaluate the results of maternal serum triplemarker screening performed in pregnant women visiting Chung-Ang University Hospital and to assess the effectiveness of prenatal triple-marker screening. METHODS: Alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) were measured by radioimmunoassay (Amerlex-M 2nd Trimester Kit, Ortho Clinical Diagnostics, Amersham, Aylesbury, UK) in 506 pregnant women visiting Chung-Ang University Hospital. Women at risk for NTDs, trisomy 21 and trisomy 18 were identified using the computer program (HIT Program). Amniocentesis with chromosome analysis was performed in women who had positive screening results. RESULTS: Positive screening results were found in 41 (8.1%) women among 506 pregnant women who had undergone prenatal triple-marker screening between 14 and 22 weeks of gestation. Of these 41 women, 39 (7.7%) had a positive screening results for Down syndrome and 2 (0.4%) for NTDs. Thirty-two women with positive screening results for Down syndrome chose amniocentesis for chromosomal analysis, of which the results showed normal in 28 (87.5%), inv(9) in 3 (9.4%) and 48, XXY, +18 in 1 (3.1%). Although all but one of the fetuses with normal karyotypes and inv(9) were born with normal phenotypes, one pregnancy with 48, XXY, +18 was terminated due to fetal death in-utero. One of 2 pregnancies affected with NTDs was correctly identified, showing meningocele, abdominal wall defect and scoliosis. CONCLUSIONS: Our data confirm chromosome abnormalities or congenital anomalies in about 5% of the pregnancies with positive triple-marker screening results, suggesting an effective prenatal screening test. It has been found that the presence of inv(9) in fetuses might be accompanied by false-positive results for Down syndrome.

Pregnancy Outcomes in Women with False Positivity of Triple Marker Screening / 대한임상병리학회지

BACKGROUND: The triple marker test with maternal serum during 15-20 weeks gestation, based on AFP, hCG and uE3, is a useful screening technique for detecting chromosomal abnormalities and neural tube defect (NTD). However, the false positive rate has been reported from 4 to 8%. The purpose of this study was to evaluate whether or not women with a false positive result of the triple marker screening are at an increased risk for adverse outcomes other than chromosomal abnor-malities and NTD. METHODS: The study population was derived from 5,622 women undergoing triple marker screening at Mokdong Hospital between January, 1997 and August, 1999. A false positive was defined as a positive result of the triple marker test without further evidence of NTD or chromoso-mal abnormalities. The study group included 83 women whose results were a false positive and the 129 controls whose results were negative. The adverse outcomes included preterm delivery ( 0.05). However, adverse outcomes such as pla-cental abnormalities (8.4% vs 2.3%) and congenital anomalies (7.2% vs 0.8%) were more frequent in the women with a false positive result than women with a negative result s (P < 0.05). CONCLUSIONS: The results suggest that false positive results of the triple marker screening test do not appear to be associated with an increased risk for an adverse pregnancy outcome, but a careful evaluation for the placental and fetal abnormalities is necessary.

A Case of Normal Delivery of a Fetus with Prenatally Diagnosed 47,XYY,inv(9)(p11;q13) / 대한주산의학회잡지

A 35-year-old multigravida woman received triple marker screening tests in 16weeks 2days of gestation. MSAFP and MShCG values were increased, whereas MSuE3 value was decreased. So we performed amniocentesis for karyotyping and confirmed male fetus with 47,XYY,inv(9)(p11:q13). A neonatal survey showed the incidence of XYY male to be approximately 1:1000, the majority of cases are phenotypically normal. XYY males are taller than normal and show delayed mental development. A pericenteric inversion of chromosome 9 that extends from p11 to q13 is considered a normal chromosome variant, but the carrier is at high risk to produce abnormal offspring. As she did not want to terminate her pregnancy, she delivered vaginally in 39weeks 6days of gestation. As a result of physical examination, the neonate showed a normal phenotype. We report it with brief review.

Pregnancy Outcomes in Women with Unexplained Elevation of Maternal Serum Human Chorionic Gonadotropin Levels at Midtrimester / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to determine the association between unexplained elevation of maternal serum human chorionic gonadotropin (hCG) in the second trimester and adverse pregnancy outcomes. MATERIAL AND METHODS: Between February 1995 and July 1999, we evaluated 1566 pregnant women who have underwent second trimester triple marker screening tests (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and delivered at Severance Hospital, Yonsei Medical Center. Multiple pregnancies, abnormal fetal karyotypes, fetal anomalies, and abortions were excluded from the study. One hundred twenty-one women with hCG levels greater than 2.0 multiples of the median (MoM) were included in the study group while 1389 women with hCG levels less than 2.0 MoM served as the control group. Pregnancy outcomes were obtained from the delivery and neonatal records in our institution. Adverse pregnancy outcomes between the two groups were compared using chi-square test and Fisher's exact test. RESULTS: Women with unexplained elevation of human chorionic gonadotropin levels were associated with statistically significant increased risks for preeclampsia, preterm delivery, and low birth weight (p<0.05). However, there were no significant differences between the study and control groups with respect to preterm premature rupture of membranes, abnormal fetal heart rate tracing, abruptio placentae, intrauterine fetal death, and neonatal death. CONCLUSION: An unexplained elevation in human chorionic gonadotropin level in the second trimester may increase the risk for preeclampsia, preterm delivery, and low birth weight but not for other adverse pregnancy outcomes such as preterm premature rupture of membranes, abnormal fetal heart rate tracing, intrauterine fetal death, or neonatal death.

Triple marker screening for fetal chromosomal abnormalities in Korean women of advanced maternal age

The purpose of this article is to assess the value of maternal serum triple marker screening of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) for the prenatal diagnosis of fetal chromosomal abnormalities in Korean women of advanced maternal age. Maternal sera were collected from 458 pregnant Korean women aged 35 between 15 and 20 weeks gestation before amniocentesis. A patient- specific second trimester risk for fetal Down's syndrome was calculated using the median values for AFP, hCG, uE3 and maternal age. Twelve fetal chromosomal abnormalities were identified. These included six cases of trisomy 21, one case of 46,XY/47,XY,+21, two cases of trisomy 18, one case of trisomy 13, and two cases of 45, X. A cutoff level of 1:200 detected 85.7% (6/7) of the cases of Down's syndrome and 20% (1/5) of the other aneuploidies, with a 27.3% false positive rate. However, a cutoff level of 1:270 did not result in any gains in detecting Down's syndrome or other aneuploidies at the expense of a false positive rate of 34.3%. Second trimester triple marker testing is an effective screening tool for detecting fetal Down's syndrome in Korean women > or = 35 years old. However, it is not an effective screening tool for non-Down's chromosomal abnormalities.

Analysis of Serum Triple-Marker Screening in In Vitro Fertilization and Naturally Conceived Pregnancy / 대한산부인과학회잡지

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.

Analysis of Results of Serum Triple Marker Screening test between In Vitro Fertilization and Naturally Conceived Pregnancy / 대한산부인과학회잡지

OBJECTIVE: To evaluate the results of second-trimester maternal serum triple-marker screening test for Down syndrome and open neural tube defects in singleton pregnancies conceived from in vitro fertilization, the screen positive rates and triple-marker level of patients conceiving singleton pregnancies by IVF were compared to those of pregnancies conceived naturally. METHODS: Two hundred singleton pregnancies conceived by IVF and naturally conceived pregnancies who had done maternal serum screening test during the second trimester were analyzed from January 1995 to April 1998. RESULTS: One (0.5%) of the 200 cases of IVF singleton pregnancies had a positive result for Down syndrome compared with 1% of screen positive rate in the 200 cases of naturally conceived pregnancies. The median level of the triple markers were 0.92 multiples of the median(MoM) for alpha-fetoprotein(AFP), 1.44 MoM for unconjugated estriol(E3) and 0.87 MoM for human chorionic gonadotropin(hCG) respectively. CONCLUSION: The positive rate of triple test for Down syndrome and open neural tube defect in the two groups were significantly not different. As additional data are collected, corrected standards should be determined.

A Clinical Study of 1,064 Cases of Midtrimester Genetic Amnicentesis / 대한산부인과학회잡지

Midtrimester genetic amniocentesis has been a gold standard for prenatal diagnosis in antenatal care since last 25 years. After the triple serum marker test was introduced as a prenatal screening method for Down syndrome, the frequency of genetic amniocentesis was increased. OBJECTIVE: To determine the complication, risk of amniocentesis and detection rate of chromosomal abnormality. MATERIAL AND METHODS: A retrospective clinical analysis of 1,064 midtrimester genetic amnicentesis in IL Sin Christian Hospital antenatal clinic from Jan 1995 to Dec 1997. Chi square test was used for the statistical analysis and p value < 0.05 was considered significant. RESULTS: Amnicentesis were significantly increased in the age of 35-39 yrs and 40yrs over. And also the incidence of chromosomal abnormality was higher than younger age group. The indications of amnicentesis were screen positive of triple marker test(43%), advanced maternal age(20.8%), abnormal beta-hCG level, past history of chromosome abnormality or malformed baby and abnormal alpha-FP level in order. Total number of chromosomal abnormalities was 30 and the incidence of chromosomal abnormalities was 2.8%(30/1,064). The complications were developed in 13 cases and fetal loss rate was 0.78%(9/1,064). CONCLUSION: The detection rate of chromosomal abnormality in midtrimester amnicentesis for prenatal diagnosis was high and relatively safe procedure but, we should be attention to more careful manipulation.

Screening of high risk pregnancy using maternal serum triple markers / 대한산부인과학회잡지

OBJECTIVE: Our purpose was to determine whether abnormal triple marker in the second trimester may be associated with adverse pregnancy outcomes. METHODS: Between November 1996 and April 1998, we evaluated 1,158 pregnant women undergoing second trimester triple marker screening tests who delivered at our hospital. The pregnancy outcomes of 48 women with false positive screens were compared with 1,158 screen negative controls. The pregnancy outcomes were obtained from hospital delivery records. RESULTS: Women with abnormal triple marker showed increased risks for low birth weight(p<0.01). But there was no significant differences between study and control groups with respect to preterm labor, pregnancy induced hypertension, oligohydroamnios, premature rupture of membrane, placenta previa, abruptio placenta, fetal death in utero. CONCLUSION: Abnormal triple marker in the second trimester was associated with low birth weight.

Analysis of 200 Cases of Midtrimesteric Amniocentesis / 대한산부인과학회잡지

OBJECTIVE: We analyzed 200 cases of prenatal amniocentesis and compared them with other reported studies. Thus we propose the necessity of metanalysis for prenatal amniocentesis. METHOD: We analyzed 200 cases that have undergone amniocentesis at Masan Samsung hospital from January 1996 to December 1997. The results of our study was compared with other reported studies of amniocentesis by indication and maternal age. The proportion of age-class and indication are compared between previous study subjects and our 200 cases. RESULTS: Triple marker abnormality was the most common indication of amniocentesis(51%) and the most common age distribution was 25-29 years (43.5%). Chromosomal aberration was diagnosed in 20 cases (10%) of which the numerical aberration was 9 cases (4.5%) and the structural aberration was 11 cases (5.5%). 5 cases (2.5%) out of ll cases of the structural aberration were normal variant. There were 7 cases (trisomy 21) of autosomal aberration and 2 cases (Turner syndrome) of sex chromosome aberration. Arnong the structural aberration, there was only one reported case of 46, t(7:10) reciprocal translocation. There were no cases of fetal death except for a little self limited preterm labor. There were no neonatal complications. In the comparison of indication and maternal age with other studies, abnormal triple test was the most common indication of amniocentesis. The number of young pregnant women under 35 years old who underwent genetic amniocentesis was increased year by year. CONCLUSION: Triple maker screening test and genetic amniocentesis become popular method of antenatal diagnosis in Korea. Now, it is the proper time to establish standard indication of prenatal amniocentesis in this country by systemic and objective statistic examination. So we address the need for metanalysis in our country as comparing with other studies.