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D A Krantz

Publications and source records attributed to D A Krantz.

18 recordsLinked to original sources
PubMed2000

First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency.

OBJECTIVE: To assess the effectiveness of free beta-hCG, pregnancy-associated plasma protein A, and nuchal translucency in a prospective first-trimester prenatal screening study for Down syndrome and trisomy 18. METHODS: Risks were calculated for Down syndrome and trisomy 18 based on maternal age and biochemistry only (n = 10,251), nuchal translucency only (n = 5809), and the combination of nuchal translucency and biochemistry (n = 5809). RESULTS: The study population included 50 Down syndrome and 20 trisomy 18 cases. Nuchal translucency measurement was done on 33 Down syndrome and 13 trisomy 18 cases. Down syndrome screening using combined biochemistry and ultrasound resulted in a false-positive rate of 4.5% (95% confidence interval [CI] 3.9%, 5.2%) and detection rate of 87.5% (95% CI 47%, 100%) in patients under age 35 years. In older patients, the false-positive rate was 14.3% (95% CI 12.7%, 15. 8%) and detection rate was 92% (95% CI 74%, 99%). For trisomy 18 screening, the false-positive rate was 0.4% (95% CI 0.24%, 0.69%) and detection rate was 100% (95% CI 40%, 100%) in younger patients, whereas in older patients the false-positive rate was 1.4% (95% CI 0. 9%, 2.0%) and detection rate was 100% (95% CI 66%, 100%). Using modeling, at a fixed 5% false-positive rate, the Down syndrome detection rate was 91%. Conversely, at a fixed 70% Down syndrome detection rate, the false-positive rate was 1.4%. CONCLUSION: First-trimester screening for Down syndrome and trisomy 18 is effective and offers substantial benefits to clinicians and patients.

Adult↗
PubMed1998

Comparison of urinary free beta (hCG) and beta-core (hCG) in prenatal screening for chromosomal abnormalities.

To evaluate the potential utility of free beta (hCG) and beta-core (hCG) in a prenatal screening protocol for Down syndrome we analysed these markers in dried maternal urine specimens from 163 control, 13 Down syndrome and 5 trisomy 18 pregnancies from 8 to 25 weeks' gestation. All results are reported after normalization for urinary creatinine determined by modified Jaffe reagent assay. The correlation of urinary free beta (hCG) and urinary beta-core (hCG) was 0.61 in controls and 0.93 in Down syndrome. Median MoM values in Down syndrome were 2.42 for urinary free beta (hCG) and 2.40 for beta-core (hCG). In trisomy 18 the Median MoM was 0.35 and 0.34 for free beta (hCG) and beta-core (hCG), respectively. The degree of elevation observed in DS cases with urinary free beta (hCG) is consistent with previous reports. Studies of beta-core (hCG) in Down syndrome have yielded discrepant results. In this study, beta-core (hCG) in Down syndrome is lower than values observed in early reports but consistent with more recent reports.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1997

First-trimester screening for fetal aneuploidy: biochemistry and nuchal translucency.

Maternal dried whole-blood specimens were collected prospectively from 2010 singleton pregnancies between 9 + 0 and 13 + 4 weeks that included 18 chromosomally abnormal pregnancies (11 Down's syndrome, four trisomy 18, two trisomy 13 and one triploidy). A subset of 744 pregnancies underwent ultrasound nuchal translucency measurement and included seven Down's syndrome, four trisomy 18, two trisomy 13 and one triploidy. Patients were evaluated for risk of Down's syndrome and trisomy 18 based on biochemistry (free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A), nuchal translucency and the combination of both. In prospective biochemical screening, false-positive rates for Down's syndrome and trisomy 18 were 5.1% (66/1297) and 1.9% (25/1297) in women < 35 years of age and 14.2% (99/695) and 1.6% (11/695) in women > or = 35 years of age, respectively. The detection efficiency of aneuploidy was 6/6 (100%) in women < 35 years and 11/12 (92%) in women > or = 35 years. Nuchal translucency measurement alone detected 57% (8/14) of cases of aneuploidy at a 5.8% (42/730) false-positive rate. Modelling with the age distribution of live births, a 5% false-positive rate resulted in Down's syndrome detection efficiency of 61% by biochemistry, 73% by nuchal translucency and 87% by combining both methods. The data in this study demonstrate that combined biochemical and ultrasound evaluation for Down's syndrome and other chromosomal abnormalities in the first trimester of pregnancy yield a detection capability that may exceed that of current second-trimester prenatal screening protocols. The potential for enhanced detection coupled to an earlier alert of fetal complications could represent a substantial advantage to both clinician and patient.

Adolescent↗
PubMed1996

Prenatal maternal dried blood screening with alpha-fetoprotein and free beta-human chorionic gonadotropin for open neural tube defect and Down syndrome.

OBJECTIVE: Our purpose was to evaluate second-trimester prenatal screening for open neural tube defects and Down syndrome by use of dried blood specimen collection and transport. STUDY DESIGN: A prospective study of 7497 dried blood specimens from patients <35 years old was performed. Specimens were assayed for maternal blood alpha-fetoprotein and free beta-human chorionic gonadotropin. Patient-specific risks for both disorders were calculated and used to determine whether further evaluation was indicated. The study included an evaluation of the median and SD of analyte multiple of the median levels. RESULTS: The initial positive rate for open neural tube defect was 4.4% adjusted to 2.7% after ultrasonographic revision and collection of a second sample. The initial positive rate for Down syndrome was 3.6% adjusted to 2.8% after ultrasonographic revision. All seven cases of open neural tube defect were detected within the increased risk group. Six of 8 (75%) cases of Down syndrome were detected. The median alpha-fetoprotein multiple of the median was 3.5 in open neural tube defect cases and 0.6 in Down syndrome cases. The median free beta-human chorionic gonadotropin multiple of the median was 2.4 in Down syndrome cases. The SD (log e) of alpha- fetoprotein and free beta-human chorionic gonadotropin in 5868 unaffected white patients was 0.4022 and 0.5635, respectively. CONCLUSION: Second-trimester dried blood screening for open neural tube defects and Down syndrome can achieve screening efficiency comparable to serum-based protocols with distinct advantages over the conventional method of blood collection.

Adult↗
PubMed1996

First-trimester Down syndrome screening: free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A.

OBJECTIVE: Our purpose was to determine the feasibility of a first-trimester Down syndrome screening protocol including free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. STUDY DESIGN: First-trimester maternal blood samples from 22 Down syndrome and 483 control cases were assayed for free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A by enzyme-linked immunosorbent assay procedures. False-positive and detection rates were determined on the basis of Down syndrome risks calculated from the levels of biochemical markers and maternal age. Because 11 of the 22 Down syndrome cases were from older pregnancies (> or = 35 years old), rates were recalculated with the United States age distribution of live births to get a more representative estimate of false positives and detection efficiency. RESULTS: The median free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A levels in cases of Down syndrome was 2.09 (95% confidence interval 1.69 to 2.62) and 0.405 multiples of the median (95% confidence interval 0.28 to 0.67), respectively. At a 5.0% false-positive rate, 15 (68.2%) Down syndrome cases were detected. By the use of the age distribution of live births, 63% of cases could be expected to be detected at a 5.0% false-positive rate. CONCLUSION: First-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A screening for Down syndrome can achieve detection rates as high as those associated with alpha-fetoprotein and human chorionic gonadotropin or alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol screening in the second trimester. Prospective studies are needed to further assess first-trimester screening.

Biomarkers↗
PubMed1995

Enhanced twin pregnancy detection within an open neural tube defect and Down syndrome screening protocol using free-beta hCG and AFP.

We have applied our multimarker approach of maternal serum alpha-fetoprotein (AFP) and free-beta human chorionic gonadotropin (hCG) for Down syndrome screening to multiple gestations to assess its efficacy for improved detection of twin and triplet pregnancies. This study matched 225 cases of twin pregnancy and 39 cases of triplet pregnancy each with ten singleton pregnancies based on gestational week, race, time to receive sample, time of year of sample, and geographical area. The ratios of the MOM for each group at the tenth, 50th, and 90th percentiles were compared by the Wilcoxon test. Risks for twins were calculated using Bayes' rule, the age-related incidence of twins, and the levels of AFP and free-beta hCG. The tenth, 50th and 90th percentiles of free-beta hCG MOMs in twin and triplet cases were 0.85, 1.99, and 4.51, and 1.38, 2.78, and 4.07, respectively. For AFP, the MOMs at these percentiles were 1.26, 1.91, and 2.99, and 2.02, 2.68, and 5.30, respectively. The twin and triplet distributions for each marker were statistically significantly different from the singleton distributions (P < 0.0001) and from each other (P = 0.0012). At a twin risk cut-off of 1 in 50, 77.4 per cent of all twin gestations can be detected in a second-trimester AFP and free-beta hCG screening protocol with 5.1 per cent of singleton pregnancies falsely identified as at risk for twins. Our dual marker protocol for mid-trimester pregnancy screening combining AFP and free-beta hCG can identify over 77 per cent of twin pregnancies in women less than 35 years of age. This benefit may contribute to an improved outcome of pregnancy by early detection of multiple gestation.

Biomarkers↗
PubMed1993

Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole-blood filter-paper spots: impact on screening for Down syndrome by measurement of free beta-hCG subunit.

The use of multiple maternal serum biochemical markers in screening for Down syndrome is gaining worldwide acceptance. We sought to study the impact of the potential instability of intact human chorionic gonadotropin (hCG) on free beta-hCG subunit, a marker that has recently been used successfully in such screening. We found that, in practice, any changes in free beta-hCG due to the instability of intact hCG do not inhibit the effectiveness of free beta-hCG as a marker for Down syndrome. This was proven by controlled laboratory experiments at various stress temperatures, freeze-thaw studies, and analysis of a large set of screening data with particular reference to time in transit for individual samples. Data from controlled dissociation studies demonstrate that any apparent increase in free beta-hCG due to the instability of intact hCG cannot be attributed simply to the dissociation of intact hCG. Finally, for large-scale mass population screening in areas of the world where transport delays, safety concerns, and high temperatures preclude the shipment of liquid whole blood, dried whole-blood spots in filter paper provide a suitable delivery system with many advantages.

Blood Specimen Collection↗
PubMed1990

Maternal serum Down syndrome screening: free beta-protein is a more effective marker than human chorionic gonadotropin.

The use of quantitative human chorionic gonadotropin measurement in obstetrics has a long and successful history. Prior studies on the utility of human chorionic gonadotropin in Down syndrome screening have utilized assays that measure the intact human chorionic gonadotropin molecule. This study targeted a distinct marker, the human chorionic gonadotropin free beta-protein, which is present in second-trimester maternal serum at much lower concentrations than is intact human chorionic gonadotropin. Our study of 29 cases of trisomy 21 and 450 control samples shows 80% detection efficiency with maternal serum alpha-fetoprotein, the free beta-protein, and maternal age in pregnancies under 17 weeks' gestation. We conclude that the combination of maternal serum alpha-fetoprotein and the human chorionic gonadotropin free beta-protein will be useful in the prenatal detection of trisomy 21.

Antibodies, Monoclonal↗
PubMed1990

Maternal serum Down syndrome screening: unconjugated estriol is not useful.

Study of 41 known Down syndrome cases and 441 matched controls did not confirm earlier reports that low unconjugated estriol levels can be used to detect fetal Down syndrome. Hence the obstetric community should exercise caution in using unconjugated estriol levels as a marker in prenatal Down syndrome screening.

Down Syndrome↗
PubMed1990

Maternal serum alpha-fetoprotein (MSAFP) patient-specific risk reporting: its use and misuse.

Fundamental to maternal serum alpha-fetoprotein screening is the clinical utility of the laboratory report. It follows that the scientific form of expression in that report is vital. Professional societies concur that patient-specific risk reporting is the preferred form. However, some intermediate steps being taken to calculate patient-specific risks are invalid because of the erroneous assumption that multiples of the median (MoMs) represent an interlaboratory common currency. The numerous methods by which MoMs may be calculated belie the foregoing assumption.

Algorithms↗
PubMed1987

Maternal serum alpha-fetoprotein screening. II. Pitfalls in low-volume decentralized laboratory performance.

Assays of maternal serum alpha-fetoprotein are subject to the phenomenon of assay drift, which may be defined as incorrect increase or decrease of alpha-fetoprotein values from their true values. Low maternal serum alpha-fetoprotein weekly volume (for example, fewer than 500 specimens per week) will result in a greater than 47% probability that 10% assay drift will not be recognized. Further, laboratory reports to clinicians may lead to either misdirecting 43% more pregnant women (with positive drift) into further (possibly invasive) diagnostic procedures or the offer of further diagnostic services to 32% fewer gravidas at increased risk (with negative drift) than should be so managed. We address the problem outlined above and present the reasons for establishment of regional maternal serum alpha-fetoprotein screening programs operating at sufficient volume to permit the identification and control of assay drift.

Clinical Laboratory Techniques↗
PubMed1987

Maternal serum alpha-fetoprotein screening. III. Pitfalls in evaluating black gravid women.

Maternal serum alpha-fetoprotein levels are higher in black women. Misinterpretation of maternal serum alpha-fetoprotein screening results can subject black gravid women to unnecessary invasive diagnostic procedures and their calculable risks. Screening errors for black women can result from the use of normative data bases established with maternal serum samples drawn from other racial groups or the use of such data bases in conjunction with a published correction factor. Because the incidence of open neural tube defects is lower for blacks than for others, excessive false positive results for blacks (estimated to be 8817 to 28,215 cases annually) would be a pernicious misapplication of maternal serum alpha-fetoprotein screening. We address the problem outlined above and recommend independently developed, valid, normative data bases.

Black People↗
PubMed1986

Maternal serum alpha-fetoprotein screening, maternal weight, and detection efficiency.

Various methods of adjusting maternal serum alpha-fetoprotein levels based on maternal weight have been recommended in order to more appropriately assign risk in maternal serum alpha-fetoprotein screening. These adjustments may, however, result in a larger proportion of pregnancies designated as having increased risk and reduction in detection accuracy.

Body Weight↗