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P A Benn

Publications and source records attributed to P A Benn.

At least 19 recordsLinked to original sources
PubMed2004

Preliminary estimate for the second-trimester maternal serum screening detection rate of the 45,X karyotype using alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin.

OBJECTIVE: To estimate the detection rate for 45,X pregnancies through second-trimester screening using maternal serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol. METHODS: Twenty-two cases of 45,X were ascertained through a cytogenetics database and an additional 51 cases were identified through publications. Serum analyte concentrations were reviewed for cases with fetal hydrops, cystic hygroma alone, and no evidence of edema. Using the statistical characteristics of this sample of affected pregnancies, computer simulations were carried out to determine the proportion of 45,X pregnancies that should be screen-positive for Down syndrome and trisomy 18. The extent to which additional cases of 45,X might be identified using a protocol specifically designed to detect 45,X pregnancies was also estimated. RESULTS: Approximately 54% of all 45,X pregnancies should be identifiable through screening for Down syndrome and trisomy 18. The detection rate for cases with hydrops and/or cystic hygroma was 60%, and without edema 33%. If offered with screening for Down syndrome and trisomy 18, 45,X screening could identify approximately 7% more of the affected pregnancies with an incremental rise of 0.2% in the false-positive rate. CONCLUSIONS: A screening algorithm for 45,X could be developed. However, the number of additional affected pregnancies identified would appear to be too small to justify this screening.

Algorithms↗
PubMed2003

Cost analysis of Down syndrome screening in advanced maternal age.

OBJECTIVE: To analyze the potential cost and efficacy of Down syndrome screening in the population with advanced maternal age. METHODS: Three screening methods defining Down syndrome risk for women with advanced maternal age were analyzed: advanced maternal age; advanced maternal age and maternal serum triple screen; and advanced maternal age, maternal serum triple screen and genetic sonogram. Costs for all tests and procedures were estimated. Procedure-related loss for amniocentesis was assumed to be 1:200. Efficacy was defined as: number of amniocenteses performed, number of Down syndrome cases detected, procedure-related losses, Down syndrome cases detected per fetal loss, cost per Down syndrome case detected and total cost of screening. RESULTS: In 1999 in the USA, there were 530,610 women with advanced maternal age at 16 weeks' gestation carrying an estimated 4,043 fetuses with Down syndrome. Screening by maternal age alone would result in the 100% detection of Down syndrome cases, but would require over 530,000 amniocenteses and result in 2,653 procedure-related losses. Combining age with serum screen and genetic sonogram would detect 97.6% of Down syndrome cases, but would require only 119,791 amniocenteses and result in 599 procedure-related losses. The projected cost per Down syndrome case detected using age screening is 219,109 dollars versus 155,992 dollars using serum screen and genetic sonogram. CONCLUSIONS: The combination of advanced maternal age, maternal serum screen and genetic sonogram would result in the fewest procedure-related losses and lowest cost per Down syndrome case detected.

Adult↗
PubMed2002

Extreme second-trimester serum analyte values in down syndrome pregnancies with hydrops fetalis.

OBJECTIVE: To compare second-trimester maternal serum analyte values in Down syndrome pregnancies with, and without, hydrops fetalis. METHODS: Seven hydropic and 85 non-hydropic Down syndrome pregnancies were identified among women with positive second-trimester maternal serum screening results. Values for maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), unconjugated estriol and inhibin-A, and risks for Down syndrome were compared using the non-parametric Mann-Whitney statistical test. RESULTS: Hydropic Down syndrome pregnancies had significantly lower MSAFP and estriol concentrations, while hCG levels were higher. For subgroups of five hydropic and 42 non-hydropic cases, no statistically significant difference in the inhibin-A levels could be demonstrated. CONCLUSION: Second-trimester Down syndrome screening risks are significantly higher in affected pregnancies that are complicated by fetal hydrops.

Adult↗
PubMed2001

Second trimester maternal serum analytes in triploid pregnancies: correlation with phenotype and sex chromosome complement.

Second trimester maternal serum alpha-fetoprotein (MS-AFP), human chorionic gonadotrophin (hCG), unconjugated estiol (uE3), and inhibin-A (INH-A) levels were evaluated in pregnancies complicated by triploidy. In addition to seven new triploid pregnancies, the results for 67 published cases were reviewed. All cases appear to fall into two major groups. First, those identifiable as screen-positive for both Down syndrome and an open neural tube defect (ONTD) with elevated MS-AFP, grossly elevated hCG, low/normal uE3, and probably elevated INH-A. Pregnancies in the second group are identifiable as screen-positive for trisomy 18 with low/normal MS-AFP, and very low hCG, uE3 and INH-A. Triploid pregnancies with high maternal serum hCG nearly always show a placenta with partial mole (25/27 or 93%), a high frequency of ONTDs or ventral wall defects (VWDs) (8/28 or 29%) and have either an XXX or XXY karyotype (observed ratio 6:10, respectively). Low hCG is infrequently associated with a molar placenta (1/11 or 9%), does not appear to be associated with ONTDs or VWDs (0/29 or 0%), and shows an excess of XXX over XXY karyotypes (observed ratio 17:2). There were 16 cases with either a molar placenta, an ONTD or a VWD that received the MS-AFP and hCG tests. All 16 were screen-positive for an ONTD (MS-AFP> or =2 multiples of the median). In addition, all 31 cases that received MS-AFP, hCG, uE3 (and where available INH-A) were screen-positive for either Down syndrome or trisomy 18. The findings are discussed in the context of expected differences between digynic and diandric triploidy. It is suggested that the sex chromosome complement in triploidy is an important factor in determining risk for partial mole development and in utero survival.

Adult↗
PubMed2001

Role of ultrasound for Down syndrome screening in advanced maternal age.

OBJECTIVE: To determine the sensitivity and false-positive rate of Down syndrome screening by use of maternal serum screen and the genetic sonogram in women > or =35 years of age. STUDY DESIGN: We searched our perinatal databases retrospectively from January 1992 to January 2000 for the following criteria: known Down syndrome fetus or newborn, advanced maternal age, and genetic sonogram from 14-24 weeks' gestation. The a priori maternal age or maternal serum screen risk was modified by likelihood ratios for ultrasound markers. Without markers the risk was reduced by 50%. The cut-off was 1:270. RESULTS: Age and maternal serum screen had a sensitivity of 90.5% and a false-positive rate of 27.1%. Age and ultrasound had a 95.2% sensitivity and 43.5% false-positive rate, whereas the combination of age, maternal serum screen, and ultrasound had a 97.6% sensitivity and a 22.0% false-positive rate. CONCLUSION: The combination of age, maternal serum screen, and ultrasound improves the sensitivity for Down syndrome detection in the advanced maternal age population.

Adult↗
PubMed2001

Evaluation of effect of analytical imprecision in maternal serum screening for Down's syndrome.

Formulae to evaluate the effect of inter-assay analytical imprecision (expressed as the coefficient of variation) in maternal serum screening for Down's syndrome have been developed. Experimentally determined imprecision in Down's syndrome risk (based on maternal serum alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotrophin) was found to be consistent with predicted values. Imprecision in the measurement of analytes becomes amplified when risk is calculated using the values of these analytes. A large separation between the means and small standard deviations for normal and affected pregnancies are the characteristics of the tests most useful in screening, but these attributes also result in the most imprecision in risk. In addition, the relative imprecision associated with Down's syndrome risk is not the same for all women screened. Combining tests for multivariate analyses results in a complex compounding of the errors. The need for strict quality control and test reproducibility is emphasized. The effect of analytical imprecision should be of particular concern to laboratories that provide screening for women of advanced maternal age.

Analysis of Variance↗
PubMed2001

Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustment for cross-identification and double-positive results.

Second trimester screening for fetal Down syndrome and trisomy 18 is available through separate protocols that combine the maternal age-specific risk and the analysis of maternal serum markers. We have determined the extent to which additional Down syndrome affected pregnancies may be identified through trisomy 18 screening, and the extent to which additional cases of trisomy 18 may be screen-positive for Down syndrome. The combined false-positive rate, taking into consideration those pregnancies that are screen-positive by both protocols, has also been determined. Sensitivity and false-positive rates were determined by computer simulation of results that incorporated previously published statistical variables into the model. Using second trimester risk cut-offs of 1:270 for Down syndrome and 1:100 for trisomy 18, it was found that few additional cases of Down syndrome are identified through trisomy 18 screening. However, approximately 6-10% of trisomy 18 affected pregnancies will be screen-positive for Down syndrome but screen-negative for trisomy 18. For women aged 40 or more, the false-positive rate for trisomy 18 exceeds 1% and approximately half of these cases will also be screen-positive for Down syndrome. For a population with maternal ages equivalent to that in the United States in 1998, after adjusting for the cross-identification, the sensitivity for three-analyte trisomy 18 screening is 78%. If this testing is performed in conjunction with Down syndrome "triple" screening, the Down syndrome sensitivity is 75% and the combined false-positive rate is 8.5%. If the three-analyte trisomy 18 screening is performed with the Down syndrome "quad" screen, the trisomy 18 sensitivity remains at 78%, the Down syndrome sensitivity is 79%, and combined false-positive rate is 7.5%. Sensitivity and false-positive rates are also provided for other widely used Down syndrome and trisomy 18 risk cut-offs. Sensitivity and false-positive rates that take into consideration cross-identification and double-positives should be helpful for pre-test counseling and the evaluation of serum screening programs.

Adolescent↗
PubMed1999

Predictive value of the triple screening test for the phenotype of Down syndrome.

Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are routinely measured in the second trimester ("triple" test) and combined with maternal age to evaluate risk for fetal Down syndrome. Triple test results and clinical findings were retrospectively reviewed for 30 newborns with Down syndrome to determine whether analyte values or second trimester risks for Down syndrome were more extreme in affected pregnancies where cardiac or other severe congenital malformations were present compared to those cases where major anatomical abnormalities were absent. Mean MS-AFP, uE3, maternal age, and second trimester Down syndrome risk were all similar in the two groups of pregnancies. However, hCG concentrations did appear to be higher in the group of Down syndrome pregnancies with anatomical anomalies (mean 1.74 MoM versus 1.19 MoM) (P<0.05). Overall, there was no significant difference in the incidence of major anomalies in patients with screen-positive test results versus those cases that were not identified by the triple test. Prenatal counseling should therefore reflect the general expectations of the Down syndrome phenotype that have been established from live-born infants with this disorder.

Abortion, Spontaneous↗
PubMed1999

Maternal serum screening for fetal trisomy 18: a comparison of fixed cutoff and patient-specific risk protocols.

OBJECTIVE: To compare the effectiveness of two widely used protocols for second-trimester screening for fetal trisomy 18. METHODS: Second-trimester screening results for 41,565 women were reviewed to determine whether pregnancies could be considered to be at high risk for trisomy 18. The screening test was considered positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3) fell below defined levels, or the second-trimester patient-specific risk (based on maternal age and serum analytes) was greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes for the two protocols were compared. RESULTS: The fixed-cutoff method showed a 23% detection rate and a 0.19% false-positive rate for trisomy 18. These low rates were in close agreement with a theoretical expectation for fixed-cutoff trisomy 18 screening. The risk-based approach resulted in a 69% detection rate and a 0.45% false-positive rate. Both methods identified pregnancies with other fetal anomalies. CONCLUSION: Overall, the risk-based method is more effective than the fixed-cutoff approach to trisomy 18 screening.

Abnormalities, Multiple↗
PubMed1999

Cost-effectiveness of estimating gestational age by ultrasonography in Down syndrome screening.

OBJECTIVE: To quantify the financial benefits of using ultrasound estimation of gestational age in maternal serum screening for Down syndrome. METHODS: Maternal age-specific sensitivity and false-positive rates for Down syndrome were derived for the triple test (alpha-fetoprotein, hCG, and unconjugated estriol) using gestational age based on ultrasound dating and also time from the last menstrual period (LMP). These rates were entered into a formula to determine the societal financial net benefit of Down syndrome screening. The average per-case net benefits of ultrasound- and LMP-dated pregnancies were then compared. Average net benefits were also calculated separately with ultrasound versus LMP dating for triple tests referred to our laboratory, and the additional costs associated with any post-test ultrasound scans, repeat testing, or recalculations were estimated. RESULTS: The use of ultrasound dating resulted in higher detection rates for Down syndrome and lower false-positive rates, which translated into an average per-case savings to society of $33.54. For women referred to our program with LMP dating, there was an average reduction of $31.60 in net benefits, plus added costs of $14.39 attributable to extra ultrasound, repeat testing, and recalculation. CONCLUSION: When ultrasound dating is available before serum screening, it should be used preferentially to establish Down syndrome risk. Routine first-trimester ultrasound examination can be justified for women with a known LMP if the cost of the ultrasound examination is less than $46.

Adolescent↗
PubMed1999

X-chromosome abnormalities in women with premature ovarian failure.

OBJECTIVE: To evaluate the significance of X-chromosome abnormalities identified in a series of women with premature ovarian failure (POF). STUDY DESIGN: Karyotypes were reviewed for all women referred to our cytogenetic laboratory over a five-year interval with the diagnosis of POF. Thirty women aged less than 40 with unexplained secondary amenorrhea and elevated follicle-stimulating hormone were included. RESULTS: Of the 30 patients, 26 had a normal karyotype and 4 showed the following X-chromosome abnormalities: 46,Xi(Xq), 45,X/46,XX mosaic, 46,X,der(X)t(X;Y)(q28;q12) mat and 46,X,t(X;5)(q22;q11.2) mat. In the two families with familial translocations, carrier females within each family showed considerable variability in age at onset of menopause. CONCLUSION: Both familial and nonfamilial X-chromosome abnormalities can be identified in women with POF. Cytogenetic studies should not be limited to those patients with very-early-onset POF.

Adolescent↗
PubMed1998

45,X/46,XX mosaicism in patients with idiopathic premature ovarian failure.

OBJECTIVE: To determine whether low-level 45,X/46,XX mosaicism may be present in some women with premature ovarian failure (POF). DESIGN: Slide preparations were made from lymphocyte cultures stimulated with phytohemagglutinin, and fluorescence in situ hybridization (FISH) was then performed using a biotin-labeled X-chromosome probe. SETTING: Cytogenetics laboratory. PATIENT(S): Fifteen women with idiopathic POF, 20 age-matched controls, and an additional 10 older control women with normal reproductive histories. INTERVENTION(S): Blood samples were collected. MAIN OUTCOME MEASURE(S): The number of X chromosomes present in each cell. RESULT(S): In patients with POF, the percentage of cells with a single X chromosome (mean, 5.50) was significantly greater than in the controls of similar age (mean, 2.42). For control subjects, there appeared to be a linear correlation between the number of cells with a single X chromosome and age. CONCLUSION(S): Some cases of POF may be attributable to low-level 45,X/46,XX mosaicism, which can be detected using FISH. In the lymphocytes from normal women, the rate of accumulation of cells with a single X chromosome was approximately 700 per 10(6) cells per year.

Adolescent↗
PubMed1998

Preliminary evidence for associations between second-trimester human chorionic gonadotropin and unconjugated oestriol levels with pregnancy outcome in Down syndrome pregnancies.

Fifty-six cases of Down syndrome were identified in a population of women who had undergone maternal serum triple marker screening [alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) analyses]. These affected pregnancies represented all known cases present in the population of 34,368 women screened. Using a 1:270 mid-trimester Down syndrome risk to define the screen-positive group, 42 affected pregnancies were screen-positive (medians: AFP = 0.79 MOM, hCG = 2.13 MOM, uE3 = 0.62 MOM, age 34.6 years) and 14 pregnancies were screen-negative (medians: AFP = 0.82 MOM, hCG = 1.57 MOM, uE3 = 0.92 MOM, age 24.2 years). Four affected pregnancies were associated with in utero death and each of these cases was associated with relatively extreme values of AFP, hCG, and uE3, including the three highest levels of hCG in the entire series of Down syndrome pregnancies. Twenty-nine (15 screen-positive and 14 screen-negative) affected pregnancies resulted in liveborns. Down syndrome pregnancies had a significantly shorter gestational term than controls, and Down syndrome babies were also lighter than controls, even after adjustment for sex and gestational age. In affected pregnancies, a low uE3 level appeared to be associated with a greater chance of a small-for-gestational age baby. No correlations could be demonstrated between AFP or hCG levels and gestational age-adjusted term weight. Based on this small series, it would appear that uE3 may be particularly useful in detecting those Down syndrome cases associated with small-for-gestational age fetuses. A very high hCG value may indicate a higher probability of fetal death.

Chorionic Gonadotropin↗
PubMed1997

Rare trisomy mosaicism diagnosed in amniocytes, involving an autosome other than chromosomes 13, 18, 20, and 21: karyotype/phenotype correlations.

In order to determine the significance of trisomy mosaicism of an autosome other than chromosomes 13, 18, 20, and 21, 151 such cases diagnosed prenatally through amniocentesis were reviewed. These rare trisomy mosaicism cases include 54 from 17 cytogenetic laboratories, 34 from a previous North American mosaicism survey, and 63 from published reports. All were cases of true mosaicism with information available on pregnancy outcome, and with no evidence of biased ascertainment. There were 11 cases of 46/47, +2; 2 of 46/47, +3; 2 of 46/47, +4; 5 of 46/47, +5; 3 of 46/47, +6; 8 of 46/47, +7; 14 of 46/47, +8; 25 of 46/47, +9; 2 of 46/47, +11; 23 of 46/47, +12; 5 of 46/47, +14; 11 of 46/47, +15; 21 of 46/47, +16; 7 of 46/47, +17; 1 of 46/47, +19; and 11 of 46/47, +22. As to the risk of an abnormal outcome, the data showed a very high risk (> 60 per cent) for 46/47, +2, 46/47, +16, and 46/47, +22; a high risk (40-59 per cent) for 46/47, +5, 46/47, +9, 46/47, +14, and 46/47, +15; a moderately high risk (20-39 per cent) for 46/47, +12; a moderate risk (up to 19 per cent) for 46/47, +7 and 46/47, +7 and 46/47, +8; a low risk for 46/47, +17; and an undetermined risk, due to lack of cases, for the remaining autosomal trisomy mosaics. Most cases were evaluated at birth or at termination, so subtle abnormalities may have escaped detection and developmental retardation was not evaluated at all. Comparison of the phenotypes of prenatally diagnosed abnormal cases and postnatally diagnosed cases with the same diagnosis showed considerable concordance. Since the majority of anomalies noted are prenatally detectable with ultrasound, an ultrasound examination should be performed in all prenatally diagnosed cases. In cytogenetic confirmation studies, the data showed much higher confirmation rates in cases with abnormal outcomes than in cases with normal outcomes [81 per cent vs. 55 per cent for fibroblasts (from skin, fetal tissue, and/or cord); 88 per cent vs. 46 per cent for placental cells; 22 per cent vs. 10 per cent for blood cells]. The confirmation rate reached 85 per cent when both fibroblasts and placental tissues were studied in the same case (with trisomic cells found in one or the other, or both). Therefore, one must emphasize that both fibroblasts and placental tissues should be studied. Except for 46/47, +8 and 46/47, +9, PUBS is of limited value for prenatal diagnosis of rate trisomy mosaicism. DNA studies for UPD are suggested for certain chromosomes with established imprinting effects, such as chromosomes 7, 11, 14, and 15, and perhaps for chromosomes 2 and 16, where imprinting effects are likely.

Adolescent↗