Antenatal screening for Down's syndrome

BACKGROUND: In 1968 the first antenatal diagnosis of Down's syndrome was made and screening on the basis of selecting women of advanced maternal age for amniocentesis was gradually introduced into medical practice. In 1983 it was shown that low maternal serum alpha fetoprotein (AFP) was associated with Down's syndrome. Later, raised maternal serum human chorionic gonadotrophin (hCG), and low unconjugated oestriol (uE3) were found to be markers of Down's syndrome. In 1988 the three biochemical markers were used together with maternal age as a method of screening, and this has been widely adopted. PRINCIPLES OF ANTENATAL SCREENING FOR DOWN'S SYNDROME: Methods of screening need to be fully evaluated before being introduced into routine clinical practice. This included choosing markers for which there is sufficient scientific evidence of efficacy, quantifying performance in terms of detection and false positive rates, and establishing methods of monitoring performance. Screening needs to be provided as an integrated service, coordinating and managing the separate aspects of the screening process. SERUM MARKERS AT 15-22 WEEKS OF PREGNANCY: A large number of serum markers have been found to be associated with Down's syndrome between 15 and 22 weeks of pregnancy. The principal markers are AFP, hCG or its individual subunits (free alpha- and free beta-hCG), uE3, and inhibin A. Screening performance varies according to the choice of markers used and whether ultrasound is used to estimate gestational age (table 1). When an ultrasound scan is used to estimate gestational age the detection rate for a 5% false positive rate is estimated to be 59% using the double test (AFP and hCG), 69% using the triple test (AFP, hCG, uE3), and 76% using the quadruple test (AFP, hCG, uE3, inhibin A), all in combination with maternal age. Other factors that can usefully be taken into account in screening are maternal weight, the presence of insulin dependent diabetes mellitus, multiple pregnancy, ethnic origin, previous Down's syndrome pregnancy, and whether the test is the first one in a pregnancy or a repeat. Factors such as parity and smoking are associated with one or more of the serum markers, but the effect is too small to justify adjusting for these factors in interpreting a screening test. URINARY MARKERS AND FETAL CELLS IN MATERNAL BLOOD: Urinary beta-core hCG has been investigated in a number of studies and shown to be raised in pregnancies with Down's syndrome. This area is currently the subject of active research and the use of urine in future screening programmes may be a practical possibility. Other urinary markers, such as total oestriol and free beta-hCG may also be of value. Fetal cells can be identified in the maternal circulation and techniques such as fluorescent in situ hybridisation can be used to identify aneuploidies, including Down's syndrome and trisomy 18. This approach may, in the future, be of value in screening or diagnosis. Currently, the techniques available do not have the performance, simplicity, or economy needed to replace existing methods. DEMONSTRATION PROJECTS: Demonstration projects are valuable in determining the feasibility of screening and in refining the practical application of screening. They are of less value in determining the performance of different screening methods. Several demonstration projects have been conducted using the triple and double tests. In general, the uptake of screening was about 80%. The screen positive rates were about 5-6%. About 80% of women with positive screening results had an invasive diagnostic test, and of those found to have a pregnancy with Down's syndrome, about 90% chose to have a termination of pregnancy. ULTRASOUND MARKERS AT 15-22 WEEKS OF PREGNANCY: There are a number of ultrasound markers of Down's syndrome at 15-22 weeks, including nuchal fold thickness, cardiac abnormalities, duodenal atresia, femur length, humerus length, pyelectasis, and hyperechogenic bowel. (ABSTRA     

Taking account of vaginal bleeding in screening for Down's syndrome

OBJECTIVE: To derive a method for revising the risk of Down's syndrome in maternal serum marker screening when there is vaginal bleeding. The effect on screening performance of routinely allowing for the presence or absence of bleeding in all women is also assessed. DESIGN: Overview of published studies on the rate of reported vaginal bleeding in pregnancies with Down's syndrome, on the rate according to maternal age and on the association of bleeding with alpha-fetoprotein (AFP) level. The publications are supplemented with data on unconjugated oestriol (uE3), human chorionic gonadotrophin (hCG) and AFP levels in a consecutive series of screened women. SETTING: Routine Down's syndrome screening tests carried out on women having antenatal care at the St James's University Hospital, Leeds. SUBJECTS: Eight hundred and nine screened women. RESULTS: In five studies the rate of vaginal bleeding in Down's syndrome pregnancies was 1.7 times that in unaffected pregnancies on average. In three studies, the vaginal bleeding rate increased proportionally by 2.2% on average for each year of maternal age. Three studies and our own data were consistent with a 10% increase in the mean AFP level associated with vaginal bleeding, but it did not appear to materially alter uE3 and hCG levels or the standard deviations and correlation coefficients for any of the three analytes. An individual woman's risk was calculated by multiplying her age-specific odds of Down's syndrome by two likelihood ratios, one relating to the vaginal bleeding itself and one from the marker levels. Routine allowance for the presence or absence of vaginal bleeding was estimated to increase the detection rate by less than 1%. CONCLUSION: Our method is of clinical value in revising the risk when there is concern that vaginal bleeding might be responsible for a negative maternal serum Down's syndrome screening result. A policy of routinely incorporating information on vaginal bleeding in risk estimation for all women would have too small an effect on overall screening performance to recommend it.     

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.     

NG-nitro-L-arginine methyl ester inhibits bone metastasis after modified intracardiac injection of human breast cancer cells in a nude mouse model

A retrospective evaluation of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) levels in maternal blood in the second trimester was conducted for cases of aneuploid pregnancies identified from a series of women who underwent amniocentesis. Blood samples were collected from 1078 women just before genetic amniocentesis was performed, mainly for individuals of advanced maternal age (greater than 35 years). Twenty-five maternal serum samples from pregnant women with an aneuploid fetus, including 14 with Down's syndrome, were available for analysis of all three parameters. An algorithm to detect Down's syndrome was used for this analysis with a risk of > or = 1:299 classified as screen-positive, this being found for 20.4 per cent of the cases (220/1078). The actual Down's syndrome detection rate was 85.7 per cent (12/14), whereas the detection rate for all aneuploidies was 72.0 per cent (18/25). Those that were not detected were two cases of trisomy 21, one trisomy 18, two trisomy 13, three sex chromosome abnormalities, and one case of an additional marker chromosome. The data indicate that this tri-analyte test should be provided after thorough genetic counselling and informed decision-making regarding maternal serum screening for women who wish for a prenatal diagnosis.     

Coping with serum screening for Down syndrome when the results is given as a numeric value

Forty-six pregnant women undergoing second-trimester biochemical screening for Down syndrome were asked to fill in the State-Trait Anxiety Inventory (STAI) questionnaire to assess their anxiety level at two different moments: when recruited to the study (at 11-13 weeks' gestation), and after the test result was communicated. The test result was given as a numeric value of risk (1/x), rather than as positive/negative. There were 10 women in whom the risk after biochemical screening increased (median delta risk = +1/535, range = 1/69 to 1/1083), whereas in the remainder the risk decreased (median delta risk = -1/1576; range = -1/142 to -1/4947) compared with the baseline value calculated on maternal age alone. Although only in a minority of women the STAI score after biochemical screening exceeded the reference range, the change in the STAI score was significantly higher when the risk increased, and the change in the risk estimate correlated significantly with the change in this index of anxiety. Three out of seven women with a 'negative' test, but increased risk estimate and increased anxiety after biochemical screening chose to undergo amniocentesis. A policy of providing the result of biochemical screening for Down syndrome as a numeric value, even for 'negative' tests, may cause some women to experience anxiety and request amniocentesis.     

Effect of routine screening for Down's syndrome on the significance of isolated fetal hydronephrosis

OBJECTIVE: To determine the risk of Down's syndrome in fetuses with isolated hydronephrosis at 18-23 weeks in an unselected general population after routine screening for Down's syndrome, using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. POPULATION: All pregnant women undergoing a routine 18-23 week ultrasound scan, from a population who had been offered screening for Down's syndrome. SETTING: A district general hospital serving a low risk obstetric population. METHODS: Prospective study of all routine 18-23 weeks ultrasound scans. The prevalence of isolated hydronephrosis and Down's syndrome was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings. RESULTS: 10,971 women were scanned at 18-23 weeks during the study period. Down's syndrome was diagnosed in 14 of 20 cases before this stage using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. Isolated fetal hydronephrosis was diagnosed in 423 pregnancies (3.9%); none of these pregnancies were affected by Down's syndrome. The relative risk for Down's syndrome was 0.18 (95% CI 0.06-0.53) for women with a normal scan (n = 9983). When multiple ultrasound markers were found (n = 565), the relative risk for Down's syndrome was 2.00 (95% CI 0.18-22.10) and 9.00 (95% CI 1.14-71.30) for all other aneuploidies. CONCLUSION: The finding of isolated fetal hydronephrosis does not significantly increase the age-related risk for Down's syndrome. The presence of multiple ultrasound markers is associated with an increased risk of aneuploidies other than Down's syndiome. These findings are explained by the reduced prevalence of Down's syndrome as a result of prior screening and diagnosis of this condition.     

Maternal serum screening for Down syndrome and neural tube defects

OBJECTIVE: Evaluation of maternal serum screening for Down's syndrome (DS) and neural tube defects (NTDs). DESIGN: Longitudinal study. SETTING: Department of Obstetrics and Gynaecology, University Hospital Utrecht, the Netherlands. METHOD: 6362 pregnant women underwent serum screening for DS and (or) NTD between the 15th and 21st weeks of pregnancy between March 1991 and March 1996. Screening was performed using alpha-foetoprotein, unconjugated oestriol, human chorionic gonadotrophin and maternal age. The result of each individual test was a calculated risk for delivering a child with DS and (or) NTD. RESULTS: Nine out of 12 singleton pregnancies of a foetus with DS were detected. To this purpose, 573 women who, according to the serum screening had an increased risk of a child with the abnormality, were offered amniocentesis, which was performed in 471 of them. Two twin pregnancies with a total of 3 DS affected foetuses were also detected; one twin pregnancy of a DS foetus was screen-negative. The one case of spina bifida was screen-positive. The proportion of women eligible for invasive prenatal diagnosis because of maternal age increased from 9% to 25% in the course of the study. Of 1118 women aged > or = 36 years 913 (82%) declined invasive investigation compared with 40% in the general population. CONCLUSION: The results of the maternal serum screening program in Utrecht were comparable with other studies. Maternal serum screening is accepted as an alternative by women above 36 years, and allows to decrease the need for amniocentesis without a significant loss in detection rate.     

Testing for fetal abnormality in routine antenatal care

The detection of fetal abnormality is a major component of routine antenatal care. A variety of techniques are now in use, although these are constantly being modified in the pursuit of more accurate and earlier detection. In this paper we draw attention to the distinction between screening and diagnostic tests, and describe the techniques which have been most commonly used in the UK: serum-screening for neural tube defects; screening for Down's syndrome; ultrasound scanning; amniocentesis and chorionic villus sampling.     

Effect of allowing for ethnic group in prenatal screening for Down's syndrome

We conducted a study to investigate ethnic group differences in levels of serum markers used in screening for Down's syndrome [serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha- and free beta-hCG, and dimeric inhibin-A], to estimate the extent to which maternal weight differences between ethnic groups explain these differences, and to estimate the effect of adjusting for ethnic group and maternal weight on screening performance. Serum measurements were taken from women who were screened prenatally for Down's syndrome. AFP, uE3, and hCG concentrations were available from 9462 white, 4215 black, and 4392 South Asian women with singleton pregnancies without Down's syndrome or neural tube defects between 15 and 22 weeks' gestational age. Frozen serum samples were available from a subset of 922 white, 449 black, and 135 South Asian women and were used for measurement of free alpha-hCG, free beta-hCG, and inhibin. Values were expressed as multiples of the median (MOM) for women of the same gestational age. There were statistically significant differences in the serum marker levels between ethnic groups that were not explained by differences in maternal weight. The main differences were found in black women compared with white women; black women had serum AFP levels 22 per cent higher (95 per cent confidence interval 20-24 per cent), total hCG levels 19 per cent higher (16-22 per cent), and free beta-hCG levels 12 per cent (3-21 per cent) higher. The other differences were less than 10 per cent. Adjusting for ethnic group only had a small estimated effect on screening performance: a maximum of about 0.5 per cent extra detection at a 5 per cent false-positive rate. At a fixed risk cut-off level, the false-positive rate will not be materially different between different ethnic groups. Adjusting serum markers for ethnic groups improves Down's syndrome screening performance to a very small extent. It is worthwhile because of its established value in AFP screening for open neural tube defects.     

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.     

Evaluation of boys with marked breast development at puberty

OBJECTIVE: The purpose of this study was to investigate the efficiency of second-trimester maternal serum screening for Down's syndrome and open neural tube defects using alpha-fetoprotein and free beta-human chorionic gonadotropin as serum markers. METHODS: 3, 188 women underwent testing between 14th and 22nd week of pregnancy. Of all tested patients, 25.4% were >/=35 years old. A cut-off risk of >/=1:250 for Down's syndrome and MS-AFP >/=2.0 MoM for open neural tube defect were considered screen-positive. RESULTS: The detection rate for Down's syndrome was 77.8% (7/9) with 8.2% screen-positive rate (7.9% false-positive rate). When evaluated separately, in patients younger than 35 and in those >/=35 years old, the screen-positive rates were 3.1 and 23.3%, respectively. A total of 52 (1.6%) were found screen-positive for open neural tube defect; 2 cases of encephalocela and 1 case of gastroschisis were confirmed prenatally. CONCLUSION: The respectable number of cases with trisomy 21 identified in this study confirms that routine mid-trimester screening for Down's syndrome including MS-AFP, free beta-hCG and maternal age is useful in identifying pregnancies at increased risk.     

Antenatal diagnosis of congenital heart disease and Down's syndrome: the potential effect on the practice of paediatric cardiology

OBJECTIVE: To predict the effect of antenatal ultrasound screening for congenital heart disease and maternal serum screening of Down's syndrome on the practice of paediatric cardiology and paediatric cardiac surgery. DESIGN: A retrospective and prospective ascertainment of all congenital heart disease diagnosed in infancy in 1985-1991. SETTING: One English health region. PATIENTS: All congenital heart disease diagnosed in infancy by echocardiography, cardiac catheterisation, surgery, or necropsy was classified as "complex", "significant", or "minor" and as "detectable" or "not detectable" on a routine antenatal ultrasound scan. RESULTS: 1347 infants had congenital heart disease which was "complex" in 13%, "significant" in 55%, and "minor" in 32%. 15% of cases were "detectable" on routine antenatal ultrasound. Assuming 20% detection and termination of 67% of affected pregnancies, liveborn congenital heart disease would be reduced by 2%, infant mortality from congenital heart disease by 5%, and paediatric cardiac surgical activity by 3%. Maternal screening for Down's syndrome, assuming 75% uptake, 60% detection, and termination of all affected pregnancies, would reduce liveborn cases of Down's syndrome by 45%, liveborn cases of congenital heart disease by 3.5%, and cardiac surgery by 2.6%. CONCLUSIONS: Screening for congenital heart disease using the four chamber view in routine obstetric examinations and maternal serum screening for Down's syndrome is likely to have only a small effect on the requirements for paediatric cardiology services and paediatric cardiac surgery.     

Pregnancy outcomes following false-positive multiple marker screening tests

Pregnancy outcomes in women with a false-positive midtrimester multiple marker screening test (MMST) were reviewed. A genetic database was used to identify all women > or = age 30 who had a MMST at 15-20 weeks of gestation, a targeted ultrasound, and amniocentesis, and complete pregnancy outcome data. All patients with an abnormal fetal ultrasound (US) or karyotype were excluded. The incidence of adverse outcomes (defined as fetal death, preterm delivery, or a birth weight less than the 10th percentile for gestational age), in those women with a positive MMST (risk of Down's syndrome > or = 1:190) was compared to the incidence of adverse outcomes in control women with negative MMST. Chi-square analysis and Fisher's exact tests were used for comparisons as appropriate. Complete data was available from 1135 women. Seventy-seven percent were over age 35. Two hundred and forty-six women (22%) had a positive multiple marker test. No significant differences in outcomes were discovered after comparisons to controls: fetal death 1 of 246 (0.4%) versus 12 of 889 (1.3%), p = 0.32; preterm delivery 32 of 246 (13.0%) versus 147 of 889 (16.5%), p = 0.17; birth weight less than the 10th percentile, 9 of 246 (3.7%) versus 30 of 889 (3.4%), p = 0.83. Our data suggest that women > or = age 30 with a false-positive MMST and a normal midtrimester obstetrical sonogram are not at an increased risk for adverse pregnancy outcomes in later gestation.     

Inclusion of serum marker measurements from a previous pregnancy improves Down syndrome screening performance

A predisposition for high or low levels of serum marker concentrations in second trimester Down syndrome screening reflecting itself in consecutive pregnancies in the same woman has been demonstrated, but hitherto the possible effect of including previous marker results in a current risk evaluation has been considered negligible. Using published data on correlations between the markers AFP, hCG and uE3 in different normal pregnancies in the same women and age-related a priori probabilities we found, that in triple marker screening the inclusion of results from a previous pregnancy in a likelihood ratio based risk calculation could increase the detection rate for women having had an earlier pregnancy from 68.0 per cent to 70.2 per cent at a risk cut-off = 1:250. The screen positive rate for normals for the same population of women, being on average older than the total population, fell from 7.1 per cent to 6.8 per cent. These figures, that are based on an assumption of the same correlations between one normal and one Down syndrome pregnancy as between two normal pregnancies, corresponds to an expected reduction, in the population considered, of the number of children born with Down syndrome of 6.7 per cent and of the number of screen positive normals of 4.7 per cent. Considering that this can be achieved at no extra cost, it is concluded that implementation of a procedure for taking information from previous pregnancies into account in second trimester screening should be considered at centres that can handle the software problems involved in doing so. However, better data on the correlations between a normal and a subsequent Down syndrome pregnancy in the same woman should probably be awaited before this is done.     

Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid

Fetal nuchal translucency can be measured in most pregnant women in the first and early second trimester. The size of translucency varies slightly with gestational age and crown rump length and is independent of maternal age. Most authors have used a nuchal thickness of > or = 2.5 mm or > or = 3 mm to define abnormal, although some have suggested that the normal variation with gestation requires that different thresholds be used at different gestational ages. The accuracy of nuchal translucency measurement varies between examiners and between patients, likely in relation to examiner skill and image resolution. The small size of a nuchal translucency, less than 3 mm in most cases, probably approximates the threshold of normal interexaminer and intraexaminer variability. The presence of a thickened nuchal translucency is associated with chromosomal abnormality and perhaps with structural abnormality even when the karyotype is normal. Because of the reported variations in the populations studied, the methods used, and the results of screening, it is inappropriate at this time to assign a numeric risk to any individual patient with this finding. However, in both high-risk and low-risk groups, the positive predictive value appears to be high enough that patients with increased nuchal translucency should be counseled by their obstetrician and prenatal diagnostic testing should be offered. Because early genetic diagnosis by CVS has a substantially higher procedure-associated loss rate than amniocentesis in the second trimester, many patients may elect to wait for chromosomal testing. If so, disappearance of nuchal thickening should not be taken as reassurance. As a screening test to be widely applied to a general or low-risk population, the utility of fetal nuchal translucency measurement is uncertain. The reported sensitivity for identification of trisomy 21 has ranged from about 40% to 80%, and the sensitivity for identification of other aneuploidies may be lower than for Down's syndrome. From a cost-risk-benefit standpoint, universal first-trimester ultrasound screening has not been appropriately compared with standard risk assessment using maternal age and multiple-marker serum screening, with amniocentesis as the predominant diagnostic method. Also, the issues of availability and reimbursement have not been addressed. Currently, measurement of nuchal translucency is not a substitute for the standard of obstetrical care, which is to offer multiple-marker serum screening to every pregnant woman at 15 to 20 weeks. Similarly, it is inappropriate to substitute nuchal translucency measurement for genetic counseling and CVS or amniocentesis in women above 35 years of age or those with a significant positive history. Finally, the data are not clear as to whether a normal nuchal translucency decreases the likelihood of chromosomal abnormality in a high-risk population, and such women should not be discouraged from invasive testing because of a normal first-trimester ultrasound study. The data supporting the association between thickened nuchal transluency and chromosomal abnormality are compelling, but further study is needed before adopting routine nuchal translucency screening. Combining first-trimester ultrasonography with early serum screening is currently being investigated and may ultimately prove to be the most efficient means of screening for chromosomal anomaly.     

Screening of maternal serum for fetal Down's syndrome in the first trimester

BACKGROUND: Screening of maternal serum to identify fetuses with Down's syndrome is now routinely offered during the second trimester of pregnancy. Prenatal screening by means of serum assays or ultrasonographic measurements, either alone or in combination, may also be possible in the first trimester. METHODS: We measured serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated protein A in 4412 women (82 percent of whom were 35 years of age or older) who came to 16 prenatal diagnostic centers for chorionic-villus sampling or early amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal nuchal translucency were also reported. Fetal chromosomal analysis was performed in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome. RESULTS: A total of 48 pregnancies affected by Down's syndrome and 3169 unaffected pregnancies were identified before 14 weeks of gestation; the rates of detection of Down's syndrome for the five serum markers were as follows: 17 percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy-associated protein A, at false positive rates of 5 percent. The results of the measurements of serum hCG and its free beta subunit were highly correlated. When used in combination with the serum concentration of pregnancy-associated protein A and maternal age, the detection rate was 63 percent for hCG (95 percent confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal translucency varied considerably between centers and could not be reliably incorporated into our calculations. CONCLUSIONS: Screening for Down's syndrome in the first trimester is feasible, with use of measurements of pregnancy-associated protein A and either hCG or its free beta subunit in maternal serum.     

Understanding pregnant women's decision making concerning prenatal screening.

Objective: This study is aimed at enhancing understanding prenatal screening decision making through testing a hypothesized decision model based on decision theory and health behavior theory. Design: We obtained questionnaires from 1,666 pregnant women who were offered prenatal screening for Down's syndrome. Path analysis (using LISREL) resulted in a final model with reasonable model fit, which was verified by split-sample cross-validation. Main outcome measures: These included perceived probability, perceived severity, attitude toward termination, response efficacy, attitude toward prenatal screening, subjective norm, child-related anxiety, and intention to undergo prenatal screening. Results: Attitude toward termination of pregnancy, perceived test efficacy, and subjective norm regarding the desirability of having prenatal screening determined a woman's attitude toward having a prenatal test. Anxiety was influenced by perceived risk and perceived severity of having a child with Down's syndrome, and by subjective norm, but this appeared to be a weak predictor of intention to test. Pregnant women with a positive attitude toward prenatal screening, and who perceived a subjective norm in favor of undergoing prenatal screening, showed a greater intention to have prenatal screening done. Conclusion: These findings suggest that more attention should be paid toward the values and social context of pregnant women during the counseling process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

First trimester screening for Down's syndrome using maternal serum PAPP-A and free beta-hCG in combination with fetal nuchal translucency thickness

The aim of this study was to evaluate the potential effectiveness of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG in combination with nuchal translucency thickness in first trimester screening for Down's syndrome. Maternal serum levels of PAPP-A and free beta-hCG were assayed in stored sera from 32 Down's syndrome and 200 unaffected pregnancies. Fetal nuchal translucency was measured by ultrasound at the time of blood sampling. Screening of Down's syndrome using a combination of maternal age, PAPP-A, free beta-hCG and nuchal translucency would achieve a detection rate of 75.8% for a false positive rate of 5%.