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M J Mahoney

Publications and source records attributed to M J Mahoney.

At least 19 recordsLinked to original sources
PubMed2000

Combined ultrasound biometry, serum markers and age for Down syndrome risk estimation.

OBJECTIVE: To compare Down syndrome screening efficiency of the standard serum triple analyte screen to that of a four-component screen consisting of ultrasound biometry and serum markers in the second trimester. METHODS: The Down syndrome screening efficiency of the triple screen, i.e. alpha-fetoprotein (AFP), unconjugated estriol (E3), hCG and maternal age, was compared with the four-marker algorithm, i.e. humerus length, nuchal thickness, AFP and hCG plus maternal age. A quadrivariate Gaussian algorithm was used to calculate individual Down syndrome odds. Receiver operating characteristic (ROC) curves plotting sensitivity against false-positive rate were constructed for each algorithm and the areas under the curves were compared to determine which was superior. Sensitivity and false-positive rates at different Down syndrome risk thresholds were also compared. RESULTS: There were 46 cases of Down syndrome (1.9%) with 2391 normal singleton pregnancies in a referral population in which triple screen, fetal biometry and karyotype had been done. The gestational age range for the study was 14-24 completed weeks. The median maternal age for the study group was 35.0 years (14.0-46.0 years). The areas (SE) under the ROC curves were 0.75(0.04) and 0.93(0.02) for the standard triple and the four-marker screen, respectively (P < 0.001). At a 10% false-positive rate, detection was 45.7% for the triple and 80.4% for the four-marker screen. CONCLUSIONS: A new algorithm combining humerus length and nuchal thickness measurement with serum AFP, hCG and maternal age substantially improved Down syndrome screening efficiency compared with the traditional triple screen. The model appears promising and should be evaluated in an independent data set.

Adolescent↗
PubMed2000

Cytogenetical diagnosis in paraffin-embedded fetoplacental tissue using comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a FISH-related technique used to assess global chromosomal aberrations in a variety of human tumours. Recently CGH has been applied to cytogenetic analysis of fresh frozen fetoplacental tissues. Here we report the application of CGH to paraffin-embedded placental samples. Ten samples from paraffin-embedded blocks of 6 control placentas and fetoplacental tissue from 10 aneuploidies, and 2 unbalanced aberrations were evaluated. Balanced karyotype profiles were obtained from samples of healthy placentas and all samples from the same placenta appeared to have similar confidence intervals. CGH analysis of four cases of trisomy 21, three cases of trisomy 18, one case of trisomy 13, one case of trisomy 15 and one case of trisomy 7 all showed overrepresentation of the respective trisomic chromosome. The CGH profile was also in accordance with the karyotyping of a case with isochromosome 21. The CGH profile of a case with der (2)t(2;6)(q37.3;q22.2) revealed partial trisomy for chromosome 6 between q21 and q27. CGH may be a useful adjunct in prenatal genetic diagnosis when retrospective diagnosis is needed from archival samples.

Chromosome Aberrations↗
PubMed1999

Millimeter-scale positioning of a nerve-growth-factor source and biological activity in the brain.

Toxicity prevents the systemic administration of many therapeutic proteins, and attempts at protein targeting via the circulatory system (i.e., "magic bullets") have failed in all but a few special cases. Direct administration at the target site is a logical alternative, particularly in the central nervous system, but the limits of direct administration have not been defined clearly. Nerve growth factor (NGF) enhances survival of cholinergic neurons and, therefore, has generated considerable interest for the treatment of Alzheimer's disease. We tested the effectiveness of local delivery by implanting small polymer pellets that slowly released NGF into the central nervous system of adult rats at controlled distances from a target site containing transplanted fetal cholinergic cells. NGF-releasing implants placed within 1-2 mm of the treatment site enhanced the biological function of cellular targets, whereas identical implants placed approximately 3 mm from the target site of treatment produced no beneficial effect. Effective NGF therapy required millimeter-scale positioning of the NGF source, and efficacy correlated with the spatial distribution of NGF concentration in the tissue; this result suggests that NGF must be delivered within several millimeters of the target to be effective in treating Alzheimer's disease. Because the human brain is divided into functional regions that are typically several centimeters in diameter and often irregular in shape, new methods for sculpting larger-scale drug fields are needed. We illustrate a concept, called pharmacotectonics, in which drug-delivery systems are arranged spatially in tissues to shape concentration fields for potent agents.

Animals↗
PubMed1999

Cultures of cells from fetal rat brain: methods to control composition, morphology, and biochemical activity.

Fetal tissue transplantation is a promising new approach for the treatment of neurodegenerative diseases, but the optimal conditions for preparing cells for transplantation have not been defined. The growth of a population of septal brain cells, primarily containing cholinergic neurons and glia, was characterized after seeding at densities from 5 x 10(4) to 6 x 10(5) cells/cm2, on polystyrene-, collagen-, laminin-, and fibronectin-coated surfaces, in the presence of serum and/or serum-free medium. Differentiated glial cells were selected by culture on fibronectin or laminin surfaces, in the presence of low amounts of serum (2.5% FBS) and G5, a soluble factor containing EGF and insulin. Differentiated neuronal cells were selected by culture on laminin, in the presence of low amounts of serum (2.5% FBS) and N2, a soluble factor containing supplemental hormones. In each case, a minimum seeding density of 1 x 10(5) cells/cm2 was required. Neuronal growth could be maintained long term (21 days) with high levels of neuronal activity (ChAT activity).

Animals↗
PubMed1999

Urinary screening tests for fetal Down syndrome: I. Fresh beta-core fragment.

Variable results have been reported using urine beta-core fragment as a marker for fetal Down syndrome. Initial studies by Cuckle et al. (1994) and Canick et al. (1995) indicated that beta-core fragment was an outstanding marker, detecting >80 per cent of Down syndrome cases. Since these reports, widely varying results have been published, indicating between 20 per cent and 66 per cent detection of cases at 5 per cent false-positive rate. The wide variation in the reported data has led to a loss of enthusiasm for this marker as a useful test for Down syndrome screening. Here we report the results of a three-year prospective study in which urine samples were collected daily from women undergoing fetal karyotype analysis for advanced maternal age. Samples were tested within one week of collection and then frozen. We also investigated the likely causes of the variability observed in beta-core fragment data. We collected 1157 urine samples over 955 days. Beta-core fragment levels were measured. A regression line was calculated for the weekly medians of the 1134 control samples and multiples of the control median (MoM) were determined. The median MoM for the controls was 1.0 and the logarithmic standard deviation (log SD) was 0.41. The median MoM for the 23 Down syndrome cases was 5.44 and the log SD was 0.45. Over the study period, 65 per cent of Down syndrome cases exceeded the 95th centile of the control group. The median MoM of control samples and the proportion of Down syndrome cases detected by the test was relatively constant during the study period. The unaffected cases were divided into three equal divisions, corresponding to approximately the first, second and third year of sample collection. No trend was found in the median control MoM values in three sample collection periods (r2=0.04). A similar number of cases exceeded the 95th centile of control samples in the three sample collection periods, 63 per cent, 66 per cent and 66 per cent. Consistent results were indicated during the three years of sample testing. Levels of total oestriol were determined in urine samples and MoM statistics derived. The median oestriol level in Down syndrome cases was 0.59 MoM. Only 12 per cent of cases had MoM levels below the fifth centile. Gaussian models were prepared combining biochemical data and maternal age distribution. While beta-core fragment by itself detected 65 per cent of Down syndrome cases, beta-core fragment modelled with maternal age detected 66 per cent, and modelled with age and total oestriol levels detected 82 per cent of cases at 5 per cent false-positive rate. At the completion of the study, we thawed and reassayed 20 random urine samples (10 control and 10 Down syndrome) collected at different times during the study period. While the control samples (74-1700 ng/ml) had slightly increased values when reassayed (mean value 137 per cent of original prospective value), the Down syndrome samples (360-20,500 ng/ml) all had decreased values when reassayed (mean=53 per cent, t-test, controls versus cases, p = 0.0003). The Down syndrome samples were decreased to between 93 per cent and 12 per cent of the original value. A relationship was identified between the magnitude of the original beta-core fragment value and the change in immunoreactivity when reassayed (r2=0.998). The higher the initial beta-core fragment value the greater the loss of immunoreactivity. We considered the possibility that the beta-core fragment molecules aggregate upon storage in the freezer. We repeated the assay of the 20 samples after treatment with a high salt buffer. Down syndrome samples recovered half of the lost beta-core fragment immunoreactivity (mean increase in beta-core fragment levels 56 per cent, t-test, controls versus cases, p=0.004). We infer that aggregation of beta-core fragment upon storage interferes with beta-core fragment measurements. This may be the cause of the poor beta-core fragment screening performance reported using sto

Biomarkers↗
PubMed1999

A high-sensitivity alternative to "routine" genetic amniocentesis: multiple urinary analytes, nuchal thickness, and age.

OBJECTIVE: Our purpose was to evaluate the Down syndrome screening efficiency of a new algorithm consisting of multiple urinary biochemical and ultrasound markers for use in high-risk groups such as women of advanced maternal age. STUDY DESIGN: The urinary beta-core fragment of human chorionic gonadotropin (beta-core fragment) and total urinary estriol, along with fetal nuchal thickness, were measured prospectively in pregnant women who were undergoing genetic amniocentesis at midtrimester (15 to 24 weeks). The most common indication for amniocentesis was advanced maternal age (90.2%). An analyte ratio (beta-core fragment/total estriol ratio) was developed. The values were expressed as multiples of the normal median. An increase in the observed nuchal thickness (delta nuchal thickness) above that expected on the basis of the biparietal diameter was calculated. On the basis of the mean and standard deviations of the urinary analyte ratio in normal fetuses and also Down syndrome, we calculated individual Down syndrome likelihood ratios for each of the two parameters, using gaussian analysis. The product of the likelihood ratios, based on delta nuchal thickness and urinary beta-core fragment-total estriol values times the maternal age-related risk, gave the overall Down syndrome risk. The screening efficiency of our algorithm at various risk thresholds was determined. RESULTS: There were 13 (2.8%) cases of Down syndrome in a total study population of 457. At a risk threshold of >1 in 70, the sensitivity was 92.3% for a false-positive rate of 4.5%. Corresponding values at a risk threshold of >1 in 78 were a sensitivity of 100% with a false-positive rate of 5.2%. CONCLUSION: By combining urinary analyte, nuchal thickness, and maternal age data, we achieved a high Down syndrome detection rate with a low false-positive rate. This algorithm would be attractive as an alternative to "routine" amniocentesis based solely on advanced maternal age. The potential benefits of this protocol could include a significant reduction in the rate of amniocentesis, along with substantial savings in medical expenditures.

Adult↗
PubMed1999

Nuchal thickness, urine beta-core fragment level, and maternal age for down syndrome screening.

OBJECTIVE: Our purpose was to report the midtrimester Down syndrome screening efficiency of a 2-analyte algorithm, urine beta-core fragment (a metabolite of human chorionic gonadotropin) and nuchal thickness, along with maternal age in a high-risk population undergoing genetic amniocentesis. METHOD: Nuchal thickness, humerus length, and maternal urine beta-core fragment levels were measured prospectively before genetic amniocentesis in 1360 singleton pregnancies, 21 (1.5%) of which had fetal Down syndrome. All analyte levels were expressed as multiples of the normal medians based on biparietal diameter. Backward-stepwise logistic regression was used to determine whether the markers were significant independent predictors of fetal Down syndrome. Matrix analysis was used to calculate an adjusted Down syndrome likelihood ratio for each patient based on the significant screening markers. Multiplication by age-related midtrimester risk gave the adjusted Down syndrome risk. The sensitivity and false-positive rates at different Down syndrome screening thresholds were used to generate a receiver-operator characteristics curve. The area under the curve was used to assess the value of this screening test. RESULTS: On the basis of logistic regression, beta-core fragment level (P 1/60 the sensitivity and false-positive rate for Down syndrome were 85.7% and 4.9%, respectively, when beta-core fragment level, nuchal thickness, and maternal age were used. Correspondence screening values at a risk threshold > 1/150 were 95.2% and 10.8%, respectively. The area under the receiver-operator characteristics curve was 0.9357 (SE = 0. 0137), indicating that the algorithm is excellent for Down syndrome screening. CONCLUSION: In this study, a combination algorithm consisting of nuchal thickness, urine beta-core fragment level, and maternal age had a high screening efficiency for Down syndrome. This algorithm should be investigated as a new option for women at high risk of having a fetus with Down syndrome.

Adolescent↗
PubMed1999

Elevated maternal urine level of beta-core fragment of human chorionic gonadotropin versus serum triple test in the second-trimester detection of down syndrome.

OBJECTIVE: This study was undertaken to compare the Down syndrome screening efficiency of elevated maternal urine level of the beta-core fragment of human chorionic gonadotropin with that of the traditional serum triple test. STUDY DESIGN: Urinary beta-core fragment and serum analyte levels were measured prospectively in women with singleton pregnancies who were undergoing second-trimester genetic amniocentesis. Urinary analyte levels were measured within a week of specimen collection. In some cases only alpha-fetoprotein was measured initially and human chorionic gonadotropin and unconjugated estriol levels were subsequently determined from the stored serum specimens. The Down syndrome screening efficiency of urinary concentration of beta-core fragment plus maternal age was compared with that of the traditional triple test. Receiver operating characteristic curves were generated for each algorithm and the areas under the curves were compared to determine which algorithm was superior. RESULTS: There were a total of 926 study patients, of whom 21 (2.3%) carried fetuses with Down syndrome. The mean (+/-SD) gestations at amniocentesis were 16.6 +/- 1.5 weeks for the fetuses without Down syndrome and 17.7 +/- 2.3 for the fetuses with Down syndrome. A total of 539 women (4 of whom carried fetuses with Down syndrome) had serum alpha-fetoprotein alone measured initially. Urinary concentration of beta-core fragment had a 61.9% detection rate with a 4.9% false-positive rate for Down syndrome, whereas the values for the triple screen were 57. 1% and 11.2%, respectively. The areas under the receiver-operating characteristic curves were 0.8744 for elevated urinary beta-core fragment level and 0.7504 for the triple screen (P =.1116). When the false-positive rate was fixed at an ideal threshold value (</=5%) the urine test was superior (area under the curve, 0.0212 vs 0.0133, P <.05). Similarly, when we considered only cases in which the complete triple screen was performed prospectively (17 fetuses with Down syndrome and 431 fetuses without Down syndrome), the urine test was significantly better (area under the curve, 0.873 vs 0.624, P =.012). CONCLUSION: In this first reported direct comparison we consistently observed higher sensitivity values for screening with urinary levels of beta-core fragment than for serum triple screen, suggesting an equivalent or superior Down syndrome screening performance for the urinary analyte. It is important that freezing and prolonged urine storage before testing be avoided. The reduced cost (single- versus triple-analyte testing) and excellent screening performance support large-scale testing and evaluation of maternal urinary beta-core fragment measurement as an alternative to the traditional serum triple test.

Adult↗
PubMed1999

Cystic hygroma in the fetus and newborn.

Cystic hygromas are developmental abnormalities of the lymphoid system that occur at sites of lymphatic-venous connection, most commonly in the posterior neck. They are frequently associated with karyotypic abnormalities, various malformation syndromes, and several teratogenic agents. The disease course of an infant with cystic hygroma is unpredictable. When diagnosed prenatally, the overall prognosis is poor. Cystic hygroma diagnosed after birth is usually associated with a good prognosis. This article reviews the embryologic, genetic, and pathologic correlates of these lymphatic system abnormalities, as well as the clinical course and outcome of the fetus and newborn with a cystic hygroma. Management strategies are reviewed, including newer nonsurgical therapies for the neonate with a cystic hygroma.

Chromosome Aberrations↗
PubMed1999

Intracranial delivery of recombinant nerve growth factor: release kinetics and protein distribution for three delivery systems.

PURPOSE: Three different polymeric delivery systems, composed of either poly(ethylene-co-vinyl acetate) (EVAc) or poly(lactide-co-glycolide) (PLGA), were used to administer recombinant human nerve growth factor (rhNGF) intracranially in rats. METHODS: The delivery systems were characterized with respect to release kinetics, both in the brain and in well-stirred buffer solutions. RESULTS: During incubation in buffered saline, the delivery systems released rhNGF in distinct patterns: sustained (EVAc), immediate (PLGA1) and delayed (PLGA2). One 10-mg delivery system was implanted in each rat and an ELISA technique was used to determine the amount of rhNGF in 1-mm coronal brain slices produced immediately after removal of the delivery system. High levels of rhNGF (as high as 60,000 ng in a brain slice of approximately 50 microliters) were recovered from the brain tissue at 1, 2, and 4 weeks after implantation. With all three delivery systems, the amount of rhNGF in each brain slice decreased exponentially with distance from the implant site: the distance over which concentration decreased by 10-fold was 2-3 mm for all delivery systems. When rhNGF release was moderate (10 to 200 ng rhNGF/day), the total amount of rhNGF in the brain increased linearly with release rate, suggesting an overall rate of rhNGF elimination of 0.4 hr-1 or a half-life of 1.7 hr. With higher release rates (500 to 50,000 ng rhNGF/day), total amounts of rhNGF in the brain were considerably higher than anticipated based on this rate of elimination. CONCLUSIONS: Polymeric controlled release can provide high, localized doses of rhNGF in the brain. All of the experimental data were consistent with penetration of rhNGF through the brain tissue with a diffusion coefficient approximately 8 x 10(-7) cm2/s, which is approximately 50% of the diffusion coefficient in water.

Animals↗
PubMed1999

The meanings and correlates of spirituality: suggestions from an exploratory survey of experts.

There has been an increasing interest in spirituality among health care professionals over the last several decades. Specialists in the areas of trauma, grief, and death and dying have been among those who have shown particular interest in religious and spiritual issues. Recent efforts to distinguish religiosity from spirituality have stimulated inquiries into the changing meanings of these dimensions. Drawing on prior and parallel works, the authors created a questionnaire and asked for responses to it from convenience samples of experts in death studies (n = 22) and spiritual studies (n = 13). Our findings are suggestive of possible lines of convergence and divergence. Both groups considered themselves to be spiritual but not religious, and there was consensus that the meaning of the term spirituality is currently changing. There was also general agreement that spiritual experiences are meaningful learning opportunities and that spiritual individuals tend to be more hopeful and to experience more meaning or purpose in life than their nonspiritual peers. The themes most strongly associated with spirituality in both groups were charity, community or connectedness, compassion, forgiveness, hope, meaning, and morality. Future research should be directed toward clarifying what people mean by "spiritual" and how they experience and express this dimension of their lives.

Health Knowledge, Attitudes, Practice↗
PubMed1999

Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG.

Hyperglycosylated hCG is a form of hCG with more complex oligosaccharide side chains. A specific immunoassay was developed to measure hyperglycosylated hCG. Levels were measured in urine samples from 1157 women between 11 to 22 weeks of gestation, undergoing genetic analysis because of advanced maternal age. Values were normalized to urine creatinine concentration and plotted against gestational age, median values were determined and multiples of the control median (MoM) calculated. The median MoM and log standard deviation (log SD) of the 1134 control samples was 1.0 and 0.47, and of the 23 Down syndrome cases was 7.8 and 0.48, respectively. This indicated a 7.8-fold increase in hyperglycosylated hCG levels in Down syndrome cases. In the accompanying article, a stability problem was found with beta-core fragment measurements in frozen urine samples. In anticipation of similar problems, nine urine samples were tested for hyperglycosylated hCG fresh and after storage in the freezer. No clear difference was found in hyperglycosylated hCG values. In addition, no trend was found in hyperglycosylated hCG MoM values or in Down syndrome detection rates in urine samples stored for one, two or three years in the freezer. Samples were split into five equal groups according to creatinine concentration. A trend was observed, hyperglycosylated hCG MoM values decreasing with advancing creatinine concentration (1.77, 1.08, 1.01, 0.73 and 0.60 at 0.25, 0.50, 0.79, 1.11 and 1.73 mg/ml, respectively). An error was noted. This was corrected with a regression equation. After correction, the median MoM and log SD of the control samples was 1.0 and 0.44, and of Down syndrome samples was 7.3 and 0.42, respectively. Correction of this error, while reducing the elevation of Down syndrome cases, tightened the spread of samples. Samples were ranked and centiles determined. 18 of 23 Down syndrome cases (78 per cent) exceeded the 95th centile of the control population. ROC analysis indicated 79 per cent detection at 5 per cent false-positive rate. Urine samples were collected during two periods of gestation, an early period (11th to 14th completed week) and the period when chemical screening is normally performed (15th to 21st week). ROC analysis indicated 80 per cent and 78 per cent detection rates, respectively, at 5 per cent false-positive rate, in the two gestational periods. Hyperglycosylated hCG values were modelled with beta-core fragment values, total oestriol values and maternal age. ROC analysis indicated 97 per cent detection rate at 5 per cent false-positive rate. This detection rate and this level of Down syndrome and control patient discrimination surpasses that of any other serum, urine or ultrasound screening protocol. Hyperglycosylated hCG should be considered as a new screening test for aneuploid pregnancies, with the potential of detecting almost all cases of Down syndrome. Evaluation is needed by other centres in order to bring hyperglycosylated hCG into clinical practice.

Chorionic Gonadotropin↗
PubMed1999

Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational Down syndrome screening.

BACKGROUND: Serum human chorionic gonadotropin (hCG) and hCG free beta-subunit tests are used in combination with unconjugated estriol and alpha-fetoprotein in the triple screen test, and with the addition of inhibin-A in the quadruple marker test for detecting Down syndrome in the second trimester of pregnancy. These tests have a limited detection rate for Down syndrome: approximately 40% for hCG or free beta-subunit alone, approximately 60% for the triple screen test, and approximately 70% for the quadruple marker test, all at 5%, or a relatively high, false-positive rate. New tests are needed with higher detection and lower false rates. Hyperglycosylated hCG (also known as invasive trophoblast antigen or ITA) is a new test. It specifically detects a unique oligosaccharide variant of hCG associated with Down syndrome pregnancies. We evaluated this new Down syndrome-directed test in prenatal diagnosis. METHODS: Hyperglycosylated hCG was measured in urine samples from women undergoing amniocentesis for advanced maternal age concerns at 14-22 weeks of gestation, 1448 with normal karyotype and 39 with Down syndrome fetuses. RESULTS: The median hyperglycosylated hCG value was 9.5-fold higher in Down syndrome cases (9.5 multiples of the normal karyotype median). The single test detected 80% of Down syndrome cases at a 5% false-positive rate. Urine hyperglycosylated hCG was combined with urine beta-core fragment (urine breakdown product of serum hCG free beta-subunit), serum alpha-fetoprotein, and maternal age-related risk. This urine-serum combination detected 96% of Down syndrome cases at a 5% false-positive rate, 94% of cases at a 3% false-positive rate, and 71% of cases at a 1% false-positive rate. These detection rates exceed those of any previously reported combination of biochemical markers. CONCLUSIONS: Hyperglycosylated hCG is a new base marker for Down syndrome screening in the second trimester of pregnancy. The measurement of hyperglycosylated hCG can fundamentally improve the performance of Down syndrome screening protocols.

Adult↗
PubMed1998

Renal tubular dysgenesis, absent nipples, and multiple malformations in three brothers: a new, lethal syndrome.

We report on three brothers with renal tubular dysgenesis and absent nipples, each also had other malformations including pre-auricular pits and a preauricular tag, branchial clefts, choanal atresia, pulmonary lobation anomaly, ventricular septal defect, type IIB interrupted aortic arch, absent gallbladder, absent thymus, parathyroid gland, accessory spleen, imperforate anus, clinodactyly, and broad digits and small nails. All three infants died neonatally. This pattern of clinical malformations appears to be a previously unreported syndrome.

Abnormalities, Multiple↗
PubMed1998

An alternative for women initially declining genetic amniocentesis: individual Down syndrome odds on the basis of maternal age and multiple ultrasonographic markers.

OBJECTIVE: Our purpose was to develop a method of calculating the individual odds of Down syndrome on the basis of a combination of maternal age and multiple ultrasonographic parameters that can be used to counsel women at high risk who initially decline amniocentesis. STUDY DESIGN: Maternal age and ultrasonographic biometry data were collected prospectively on 3254 normal and 30 Down syndrome singleton fetuses between 15 and 24 weeks' gestation. Humerus length data were expressed as multiples of the normal median. Log transformation of the humerus length data permitted their expression in gaussian frequency distributions and the calculation of likelihood ratios for Down syndrome on the basis of humerus length. We also developed likelihood ratios on the basis of the degree of nuchal skinfold thickening and the presence or absence of hyperechoic fetal bowel and hypoplastic fifth digit. RESULTS: The ultrasonographic parameters and maternal age did not significantly correlate with each other and were significant independent predictors of Down syndrome. We therefore calculated the individual odds of Down syndrome by using the product of the age-related risk and the likelihood ratios associated with nuchal thickening, humerus length shortening, and the presence or absence of hyperechoic fetal bowel or fifth digit hypoplasia, respectively. At a Down syndrome risk level of >1:50, a 60.0% detection rate with 4.5% false-positive rate was observed with a screen-positive rate of 5.5%, positive predictive value of 1:10, and odds ratio (95% confidence interval) of 28.4 (12.8 to 64.0). CONCLUSION: This is the first report of individual odds calculation based on multiple midtrimester biometry parameters and maternal age. The screening efficiency is similar to that reported with triple-analyte serum screening. These data are useful for counseling women who are at increased Down syndrome risk and initially decline amniocentesis.

Adult↗
PubMed1998

Subtle ultrasonographic anomalies: do they improve the Down syndrome detection rate?

OBJECTIVE: Our purpose was to determine whether the identification of subtle anomalies further improves Down syndrome detection over standard ultrasonographic biometry and the detection of gross morphologic defects. STUDY DESIGN: The screening efficiency of clinodactyly, dilated renal pelvis (> or =4 mm), echogenic bowel, mild ventriculomegaly (> or =10 to 15 mm), and two-vessel cord was determined prospectively in midtrimester fetuses at amniocentesis. The screening efficiency of increased nuchal thickness and shortened long-bone length (standard biometry) and gross morphologic defects was determined for comparison. Multiple backward stepwise regression analysis was used to determine which subtle anomalies significantly correlated with Down syndrome detection rate and whether they increased Down syndrome detection over that with standard biometry and morphologic defects. RESULTS: Although all subtle anomalies except two-vessel cord correlated with the presence of Down syndrome on univariate analysis, only echogenic bowel (Wald chi2 = 15.0211, p = 0.0001) and clinodactyly (Wald chi2 = 9.4273, p = 0.002) persisted in regression analysis of the subtle anomaly group. When either of the above-described anomalies was present, the detection rate for Down syndrome was 28.6%, p < 0.00001. For the combination of standard biometry (either increased nuchal thickness or short humerus) or gross anatomic defect, Down syndrome detection rate was 53.3% (p < 0.00000001). This increased to 63.2% (p < 0.00000001) when subtle anatomic defects (either echogenic bowel or clinodactyly) were included in the definition of an abnormal sonogram. CONCLUSION: Subtle anomalies, of which echogenic bowel and clinodactyly are the most significant, further increase Down syndrome screening efficiency over standard biometry or the finding of gross anatomic defect. Our data appear to support the addition of subtle anomaly findings to ultrasonographic screening for Down syndrome.

Abnormalities, Multiple↗
PubMed1998

A new screening protocol combining urine beta-core fragment and ultrasonography for Down syndrome detection.

OBJECTIVE: Our purpose was to ascertain the screening efficiency of a new midtrimester Down syndrome detection protocol that combines maternal urine testing and ultrasonographic examination. STUDY DESIGN: In a prospective study, beta-core fragment, the stable end product of human chorionic gonadotropin metabolism, was measured in maternal urine. The results were standardized for urine creatinine levels. The study was performed in women undergoing midtrimester genetic amniocentesis (15 to 24 weeks' gestation). Urine beta-core fragment values were expressed as multiples of the normal median for gestational age. The screening performance of a combination of ultrasonographic parameters and urine beta-core values for Down syndrome detection was determined. RESULTS: A total of 511 singleton pregnancies in women undergoing amniocentesis were studied, 18 of the women (3.5%) had a Down syndrome fetus. A urine beta-core fragment level > or = 97th percentile had a sensitivity of 61.1% and a false-positive rate of 3.2%. An abnormal prenatal screen was defined as a urine beta-core level > or = 97th percentile, increased nuchal thickness (> or = 5 mm), or the presence of gross structural defects. Corresponding values for the screening efficiency of an abnormal prenatal screen were sensitivity of 77.8% and a false-positive rate of 4.1%. With an abnormal prenatal screen the odds ratio is 82.8 (95% confidence interval 22.6 to 364.9) for having a Down syndrome fetus. CONCLUSION: The presence of an abnormal maternal urine beta-core level, a gross ultrasonographic anomaly, or increased nuchal thickness had a high detection rate and a low false-positive rate for Down syndrome. This novel screening algorithm is useful for further delineating the risk status in patients at high risk who are reluctant to undergo or decline genetic amniocentesis.

Adult↗