Da-Chang Chu

Elevated second-trimester dimeric inhibin A levels identify Down syndrome pregnancies ☆ ☆☆ ★

OBJECTIVE Our purpose was to determine whether second-trimester dimeric inhibin A levels distinguish Down syndrome pregnancies from euploid pregnancies. STUDY DESIGN With use of a commercially available enzyme-linked immunosorbent assay (Serotec, Oxford) inhibin A medians were established in stored sera from 40 to 50 euploid pregnancies at each week of gestation from 14 to 20 weeks and from 33 Down syndrome pregnancies. Maternal serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin levels measured in each sample before storage were retrieved. The performance of inhibin A in the multiple-marker screening test was evaluated. RESULTS The mean inhibin A multiple of the median was significantly higher in the Down syndrome group than in the euploid group (2.84 +/- 2.0 vs 1.22 +/- 1.0, p = 0.0001). An inhibin A level > or = 1.6 multiples of the median identified 70% of all Down syndrome pregnancies at a false-positive rate of 22%. Replacing estriol with inhibin A in the multiple-marker screening test resulted in a higher Down syndrome detection rate at a lower screen-positive rate. CONCLUSION Elevated second-trimester maternal serum inhibin A levels identify Down syndrome pregnancies; replacing estriol with inhibin A in the multiple-marker screening test improves test performance.

CNS malformation in a child with Kabuki (Niikawa-Kuroki) syndrome: Report and review

Kabuki (Niikawa-Kuroki) syndrome (KS) comprises characteristic facial changes, developmental delay, skeletal anomalies, mental retardation, and abnormal dermatoglyphics. We report on a 5-year-old Caucasian boy with KS who required surgery for a giant left temporoparietal subarachnoid cyst at age 5 1/2 years. Review of the 143 published cases shows that while malformations may be found in the endocrine, cardiac, genitourinary and skeletal systems, this is the first case of Kabuki syndrome with a major central nervous system malformation.

α-Fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A produce the best results in a three-analyte, multiple-marker screening test for fetal Down syndrome

Abstract Objective: The purpose of this study was to determine, among six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection. Study Design: With use of commercially available assay kits, medians for free β-human chorionic gonadotropin, CA 125, and dimeric inhibin A were established in stored sera from 45 to 50 euploid pregnancies at each week of gestation from 14 to 22 weeks and from 33 Down syndrome pregnancies. Maternal serum α-fetoprotein, unconjugated estriol, and intact human chorionic gonadotropin levels measured in each sample before storage were retrieved. All 20 possible three-analyte combinations were evaluated in the multiple-marker screening test for Down syndrome. Results: The mean maternal age of the study population was 35.6 ± 5.3 years. The best three-analyte combination was maternal serum α-fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A: 97% of Down syndrome cases were detected at a false-positive rate of 16%. At a slightly higher false-positive rate (18%) maternal serum α-fetoprotein, estriol, and intact human chorionic gonadotropin detected only 79% of cases. Conclusions: Of six second-trimester maternal serum analytes, the best three-analyte combination for fetal Down syndrome detection was maternal serum α-fetoprotein, free β-human chorionic gonadotropin, and dimeric inhibin A. This retrospective analysis should now be confirmed prospectively.

Prospective evaluation of free β-subunit of human chorionic gonadotropin and dimeric inhibin A for aneuploidy detection

OBJECTIVE Our goal was to prospectively evaluate the use of the free beta-subunit of human chorionic gonadotropin and dimeric inhibin A for the detection of fetal Down syndrome and other aneuploidies. STUDY DESIGN Women who had a second-trimester multiple-marker screening test (alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin) and genetic amniocentesis from August 1996 to August 1998 were included. Serum was also analyzed for inhibin and the free beta-subunit of human chorionic gonadotropin. Detection and false-positive rates for 4 analyte combinations at 5 different screening risk cutoff points for Down syndrome were determined and compared. RESULTS We evaluated 1256 patients, including 23 with aneuploidy (13 with Down syndrome, 10 others). The maternal age was 35.9 +/- 4.6 years (mean +/- SD). At the optimal risk cutoff point for Down syndrome detection (1:190; false-positive rate, 19%), the multiple-marker screening test plus inhibin was superior, detecting 85% of Down syndrome cases, in comparison with 69% when the multiple-marker screening test alone was used and 62% when the other 2 combinations were used. The multiple-marker screening test plus inhibin also detected 60% of the other aneuploidies. CONCLUSIONS When evaluated prospectively in a high-risk population, the multiple-marker screening test plus inhibin was superior to the traditional multiple-marker screening test and 2 other analyte combinations, with a lower false-positive rate and increased detection of all aneuploidies in a high-risk population.

Maternal serum α-fetoprotein and dimeric inhibin A detect aneuploidies other than Down syndrome

Abstract Objective: Our purpose was to determine whether the combination of maternal serum α-fetoprotein, free human chorionic gonadotropin-β, dimeric inhibin A, and maternal age detects aneuploidies other than Down syndrome. Study Design: We retrieved stored serum from pregnancies complicated by aneuploidies other than Down syndrome from 1988 to 1997 (n = 55, mean maternal age 35.2 ± 5.6 years). α-Fetoprotein levels were obtained from our database, and free human chorionic gonadotropin-β and dimeric inhibin A levels were measured in the thawed serum with use of commercial assays. Analyte values were used in both 3-analyte and 2-analyte multiple-marker screening tests; detection rates were determined at several different Down syndrome risk-positive cutoff values. Results: In the 3-analyte test 58% (32/55) of all aneuploidies were detected with use of both the Down syndrome protocol at a screen-positive risk cutoff value of 1:300 (false-positive rate 17%) and a novel trisomy 18 screening algorithm. However, 67% (37/55) detection was obtained with use of the 2-analyte combination of α-fetoprotein and dimeric inhibin A, with both the Down syndrome protocol (screen positive cutoff value 1:300) and the trisomy 18 algorithm: 12 of 13 trisomy 18 (92%), 9 of 17 Turner’s syndrome (53%), 10 of 17 other sex chromosome aneuploidies (59%), 1 of 1 trisomy 22 (100%), and 5 of 7 trisomy 13 (71%). Conclusions: The combination of maternal serum α-fetoprotein, dimeric inhibin A, and maternal age detects autosomal trisomies other than Down syndrome at a rate superior to that of the traditional analyte combination. (Am J Obstet Gynecol 1998;179:966-70.)

Free β-hCG subunit versus intact hCG in Down syndrome screening

Objective To assess the ability of second-trimester maternal serum free β-hCG to detect fetal Down syndrome and to compare free β-hCG to intact hCG in the multiple-marker screening test for Down syndrome. Methods From our bank of stored maternal sera, we selected 40–50 samples from euploid pregnancies at each week of gestation from 14 to 20 weeks and 31 samples from Down syndrome pregnancies. Free β-hCG was measured by enzyme-linked immunosorbent assay, and week-specific multiples of the median (MoM) were derived. The free β-hCG Down syndrome detection and false-positive rates were determined. Free β-hCG was then substituted for intact hCG in the multiple-marker screening test, and the Down syndrome detection and false-positive rates at various risk cutoffs were compared. Results The mean (± standard deviation) maternal age of all study samples was 35.6 ± 5.3 years. The mean Down syndrome free β-hCG MoM was significantly higher than the mean euploid MoM (2.4 ± 1.1 versus 1.2 ± 1.0; P < .001). A free β-hCG level of at least 1.7 MoM identified 68% of Down syndrome pregnancies at a false-positive rate of 20%. When intact hCG was replaced with free β-hCG in the multiple-marker screening test, a higher Down syndrome detection rate was achieved at a lower false-positive rate at each of several screen positive risk cutoffs. Conclusion Elevated free β-hCG levels identify Down syndrome pregnancies. Replacing intact hCG with free β-hCG in the multiple-marker screening test results in a higher Down syndrome detection rate at a lower falsepositive rate.

A unique 502C>T mutation in exon 7 of ABO gene associated with the Bel phenotype in Taiwan

BACKGROUND:  The ABO system includes many variant subgroups. Some of them are difficult to identify serologically, leading to mistyping of blood groups. For example, Bel is often typed as O blood group.

Three missense mutations, including a novel 860C>T transition, and allelic enhancement phenomenon associated with ABO blood subgroups A in Taiwan

BACKGROUND: It was estimated that approximately 25 percent of Taiwanese residents were ABO blood group A. Many subgroups of A, however, revealed ambiguous serologic typing results. This study aimed to delineate the molecular basis of the A3, Ax, and weak A phenotypes.

Non-radioactive southern hybridization for early diagnosis of α-thalassemia with Southeast Asian-type deletion in Taiwan

Alpha-thalassemia has been estimated to account for over 60% of hydrops fetalis cases in Taiwan. The most common genotypic lesion found in alpha-thalassemia-1 cases in Taiwan is deletion of a large segment of the alpha-globin gene cluster, termed the Southeast Asian-type deletion (-SEA/; further referred to as SEA-type deletion). Seven chorionic villus samples (CVS) from pregnancies of couples both heterozygous for SEA-type deletion were studied. Non-radioactive Southern-blot hybridization using the dig-alkaline phosphatase detection system was developed to fulfill this purpose. The results were compared with corresponding polymerase chain reaction (PCR) data to elucidate the effectiveness of these two protocols in the diagnosis of the SEA-type deletion. The data showed that of the seven CVS, three demonstrated a distinctive band pattern, indicating their homozygous status of SEA-type deletion, whereas two showed heterozygous patterns, and the other two were free of the deletion. Homozygosity of the deletion was confirmed by Southern-blot hybridization performed on DNA samples extracted from the abortus tissue. However, two of the three cases with SEA-type deletion showed heterozygous PCR results. Maternal cell contamination could be responsible for the artifacts in the PCR results, but the influence due to the contamination is minimal in non-radioactive Southern-blot hybridization. We concluded that PCR is suitable for screening of carrier adults with SEA-type deletion, and non-radioactive Southern hybridization is ideal for early prenatal diagnosis of the SEA-type deletion.

Insulin-like growth factor binding protein-3 in the detection of fetal Down syndrome pregnancies.

Objective To study the usefulness of maternal serum insulin-like growth factor binding protein-3, a potential cell growth inhibitor, in second trimester prenatal screening for fetal Down syndrome. Methods Three hundred and forty-two samples from normal pregnancies and nine fetal Down syndrome pregnancies were analyzed for insulin-like growth factor binding protein-3 levels by radioimmunoassay. Data were converted to multiples of median (MoM) and analyzed statistically to compare the differences between control and Down syndrome pregnancies. Results The mean insulin-like growth factor binding protein-3 MoM of Down syndrome-affected pregnancies (1.09) was significantly higher than that of the normal pregnancies (1.00) (P < .01). Insulin-like growth factor binding protein-3, in combination with maternal serum alpha-fetoprotein (MSAFP), hCG, and maternal age, detected 89% of Down syndrome pregnancies at a screen positive rate of 2.1%. This compares favorably to the standard combination of MSAFP, hCG, and unconjugated estriol (E3), which had a 66.7% Down syndrome detection rate and a 4.1% screen positive rate in our study samples. Conclusion This retrospective analysis suggested that the inclusion of insulin-like growth factor binding protein-3 into the triple screen program to replace unconjugated E3 might enhance the detection rate of fetal Down syndrome pregnancies. These data need to be confirmed by a larger prospective study.