Serum Screening For Down's Syndrome Research Articles

Variation in uptake of serum screening: the role of service delivery.

The present study aimed to determine the extent to which variation in the uptake of serum screening for Down syndrome reflects variation in the way the test is offered. A higher uptake of serum screening was seen at hospitals that offered the blood test as part of a routine visit than at those where screening required a separate visit. The type of screening test offered and whether a reminder was sent were not associated with uptake. Given the consensus that undergoing screening should be the result of an informed choice, further research is needed to determine which methods of offering serum screening facilitate and which impede informed choice.

Maternal serum β-hCG levels in screening for Down syndrome are higher in singleton pregnancies achieved with ovulation induction and intrauterine insemination than in spontaneous singleton pregnancies

In pregnancies conceived by assisted reproduction technology (ART), the false-positive rate in maternal midtrimester serum screening for Down syndrome is higher (26.8% to 30%) than in spontaneous pregnancies (5%) (1, 2). In singleton pregnancies conceived after IVF, levels of total or free β-hCG are higher (1, 2) and levels of alpha-fetoprotein (α-fetoprotein) are slightly lower (2) than in spontaneous pregnancies, changes similar to those in Down syndrome pregnancies.

Nuchal translucency screening and antenatal maternal serum screening for Down syndrome: results of a project

Objectives: To asses the implementation of antenatal screening for Down syndrome using individual risk estimates based on maternal age, nuchal translucency and three serum markers; alpha fetoprotein, unconjugated estriol and human chorionic gonadotrophin (hCG) in maternal blood. Women with an estimated risk of 1 in 250 or greater were classified as screen positive and offered diagnostic amniocentesis.Subjects: A total of 1956 women of all ages with singleton pregnancies seen between June 1999 and March 2001.Results: The screening result of combination of first trimester ultrasonographic and serum screening was 85% Down syndrome detection and the false positive rate was 3%. The median gestational age of nuchal translucency was 11 weeks and the time of serum screening was 16 weeks.Conclusion: The combination of nuchal translucency and serum screening increases the Down syndrome detection and decreases the false positive rate. Is very important because the amniocentesis is associated with a risk of pregnancy loss from 0.5 to 1%. Besides, it is cost‐effective and performs better than the selection for amniocentesis on the basis of maternal age only, nuchal translucency only or serum screening.

Inaccurate estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening

AbstractProblems can arise in prenatal screening for Down syndrome when tests are performed in the first and second trimester and some women who have a negative first trimester test have a second trimester serum test. The second test result does not usually take account of the previous one being negative. Even if it does, it is often inaccurate. Using published data the extent of the error was examined. The age‐specific risk of an affected pregnancy in such women will be lower than if no first trimester test had been performed. The distributions of the screening markers in affected and unaffected pregnancies will be different from those in unscreened women. If the appropriate age‐specific risk and marker distributions are not used, error will arise. For example, a 35‐year‐old woman with nuchal translucency (NT), pregnancy‐associated plasma protein‐A (PAPP‐A) and free β‐human chorionic gonadotrophin (hCG) levels at the normal median would have a risk of 1 in 6500. If she then had the Triple Test with alpha‐fetoprotein (AFP), unconjugated oestriol, and hCG levels of 0.7, 0.7 and 1.5 multiples of the median (MoM), respectively, her risk, ignoring the previous result, would be overestimated (1 in 95 compared with the correct estimate of 1 in 705). If the previous result was included, but the age‐specific risk and second trimester marker distributions were not revised, her risk would be underestimated (1 in 820). If the correct age‐specific risk and screening marker distributions were used, risk estimates would be accurate, but two tests would be less efficient than integrating all the screening information into a single test. The practice of offering second trimester serum screening to women who have already been screened is best avoided. Copyright © 2001 John Wiley & Sons, Ltd.

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.

Participation in maternal serum screening for Down syndrome, neural tube defects, and trisomy 18 following screen-positive results in a previous pregnancy.

To determine whether women who have had a positive serum screening result for Down syndrome or neural tube defect in 1 pregnancy have a lower rate of participation in screening in their next pregnancy. A triple-marker screening program at a university hospital. Pregnancy and screening information was collected from laboratory and hospital databases to compare subsequent screening participation of women who were screen-negative and screen-positive for the risk of a fetus with Down syndrome or a neural tube defect. In an age-matched comparison, 108 women who had a previous screen-positive result were significantly less likely than 108 women who were screen-negative to participate in maternal serum screening in their next pregnancy. When examined according to the type of screen-positive result, the effect was significant for both those who were screen-positive for Down syndrome and those who were screen-positive for neural tube defect. The degree of risk in screen-positive women did not significantly affect their participation in screening in the next pregnancy. Anxiety related to a screen-positive result probably causes decreased participation in maternal serum screening in the next pregnancy. Reducing the screen-positive rate in prenatal serum screening would alleviate maternal anxiety and would probably lead to more stable participation.

Maternal Serum Screening for Down Syndrome by Using Alpha-Fetoprotein and Human Chorionic Gonadotropin in an Asian Population

The purpose of the present study is to evaluate the efficacy of second-trimester maternal serum screening program by using α-fetoprotein (AFP) and total human chorionic gonadotropin (hCG) in an Asian population. During June 1994 to July 1998, we conducted a prospective study of serum screening protocol for Down syndrome. The cut-off point for a positive result in this analysis was a risk of ≥1/270. A total of 17,742 pregnant women with singleton pregnancy were screened, and 1,153 (6.5%) had positive result. Sixteen of the 17,742 pregnancies had Down syndrome, and 10 of them had positive result. The positive rate and detective rate for Down syndrome were 6.5 and 62.5%, respectively. However, the detective rate will reduce to 47.6% after being adjusted by age-specific risk. It is indicated that the double-marker test using AFP and total hCG is an effective screen strategy for second-trimester detection of Down syndrome in Asian women.

Serum screening for Down syndrome and adverse pregnancy outcomes: a case‐controlled study

The relationship between adverse perinatal outcomes in women with false positive biochemical screening test for Down syndrome was investigated in a retrospective case-controlled study. A cohort of 4000 women who booked for routine antenatal care and opted for biochemical screening over a 22 month period was obtained. The pregnancy outcome data of 272 women with a false positive screening test for Down syndrome (risk >1 in 250) at 15-18 weeks of gestation (study group) were compared with data from 272 age and gestation matched controls with a negative Down syndrome screening test from the same population. The frequency of normal and adverse perinatal outcomes, including pre-eclampsia, isolated intrauterine growth restriction, spontaneous preterm labour and stillbirth was recorded. The incidence of adverse pregnancy outcomes was 11.9% in the study group and 8.6% in the control group. The estimated odds ratio of an abnormal outcome in the study group was 1.41 (95% CI-0.790, 2.55). The observed difference between proportion was 0.0324 (95% CI-0.022, 0.083; p=0.40). These data identify no evidence for a strong association between a false positive Down syndrome screening test result and subsequent adverse perinatal outcomes in the general population.

Serum screening for Down syndrome and adverse pregnancy outcomes: a case‐controlled study

The relationship between adverse perinatal outcomes in women with false positive biochemical screening test for Down syndrome was investigated in a retrospective case-controlled study. A cohort of 4000 women who booked for routine antenatal care and opted for biochemical screening over a 22 month period was obtained. The pregnancy outcome data of 272 women with a false positive screening test for Down syndrome (risk >1 in 250) at 15–18 weeks of gestation (study group) were compared with data from 272 age and gestation matched controls with a negative Down syndrome screening test from the same population. The frequency of normal and adverse perinatal outcomes, including pre-eclampsia, isolated intrauterine growth restriction, spontaneous preterm labour and stillbirth was recorded. The incidence of adverse pregnancy outcomes was 11.9% in the study group and 8.6% in the control group. The estimated odds ratio of an abnormal outcome in the study group was 1.41 (95% CI—0.790, 2.55). The observed difference between proportion was 0.0324 (95% CI—0.022, 0.083; p=0.40). These data identify no evidence for a strong association between a false positive Down syndrome screening test result and subsequent adverse perinatal outcomes in the general population. Copyright © 2000 John Wiley & Sons, Ltd.

Serum screening for Down syndrome and adverse pregnancy outcomes: a case-controlled study

Serum screening for Down syndrome and adverse pregnancy outcomes: a case-controlled study

How women deal with the results of serum screening for Down syndrome in the second trimester of pregnancy.

To gain insight into how pregnant women experience serum screening for Down syndrome, we sent questionnaires to two groups of relevant subjects in the north of the Netherlands. The questionnaires addressed the following issues: decision-making process, knowledge and opinions. Questionnaire A was sent to women of 36 years of age and older (n=99) (group A) who were all 20 to 36 weeks pregnant at that time. In the Netherlands prenatal diagnosis is routinely available to these women. Questionnaire B was sent to women of younger than 36 years (n=69) (group B) who had received a screen-positive result and had subsequently undergone amniocentesis. About half of these women were still pregnant at that time. For these women, serum screening is only available on the basis of opting-in. The two questionnaires were largely identical. The response rates to questionnaires A and B were 82% and 91%, respectively. Group A (women of 36 years and older) considered that second trimester serum screening made a welcome contribution to the decision-making process about whether to undergo amniocentesis. Moreover, it reduced the amniocentesis rate considerably. The vast majority said they would apply for serum screening in a following pregnancy, but favoured the idea of first trimester screening. In group B (women of younger than 36 years), reassurance was the most commonly mentioned reason for undergoing serum screening. Almost all the women experienced some degree of anxiety when they were informed about the screen-positive result and 13% continued to be anxious, even after the favourable result of the amniocentesis. The majority of the respondents would also apply for serum screening in a following pregnancy and were of the opinion that this screening should be offered to all pregnant women in the Netherlands.

Utilization of Amniocentesis by Women Screening Positive for Down Syndrome on the Second-Trimester Triple Test

Objective: Second-trimester maternal serum screening for Down syndrome has become widely accepted in the United States. However, many women with screen-positive results forgo definitive diagnostic testing that involves chromosomal analysis of amniotic fluid cells. We have reviewed 2,879 cases of women with screen-positive results in an effort to identify determining factors for the utilization of amniocentesis. Methods and Results: The lowest rate of utilization of amniocentesis was seen among very young women, with peak utilization among women of age 33. Although all women in the study had screen-positive results, amniocentesis was most likely to be performed when the patient-specific risk for an affected pregnancy was high. Black or Hispanic women were less likely to receive amniocentesis than white or Asian women. Amniocentesis utilization was also negatively associated with gestational age, maternal weight and an ultrasound examination prior to screening. A sharp decline in the utilization of amniocentesis was noted between 1993 and 1998. A logistic regression model was estimated to assess the independent effect of the variables. The model predicted 67% of the observed amniocenteses and had 66.6% concordance in the evaluation of paired cases with different response values. Conclusions: Our observations indicate that there are multiple medical, social and demographic factors that influence the utilization of amniocentesis by women with screen-positive results. Early screening and a prompt response to screen-positive results, together with accessible and appropriate genetic counseling, should assist women in making an informed choice.

Maternal serum screening for down syndrome in pregnancies conceived by intra-uterine insemination.

The purpose of our study was to assess the influence of intra-uterine insemination (IUI) on the results of maternal serum Down syndrome screening. 43 women with IUI pregnancies and 4507 healthy women who conceived were studied. Ovulation in IUI pregnancies was induced by clomiphene and/or human menopausal gonadotrophin (hMG). Maternal serum levels of free beta-human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) were measured for Down syndrome screening. It was considered screen-positive when the risk of Down syndrome was 1 in 270 or greater in the second trimester. The value of maternal serum AFP was significantly lower in the IUI group (median=0.760 MoM) than in the control group (median=1.050 MoM). However, the value of free beta-hCG was not significantly different between the two groups. The positive rate of maternal serum Down syndrome in IUI pregnancies was similar to that of the control group. Our results indicate that IUI pregnancy may be associated with a lower level of AFP, although the mechanism for this difference remains unknown.

Prenatal diagnosis of trisomy 20 mosaicism by maternal serum screening for Down syndrome

We report two cases of prenatally diagnosed trisomy 20 mosaicism associated with positive Down syndrome screening at 16 weeks’ gestation. Both infants exhibited normal growth and mental development.These cases suggest that the multiple-marker screening test may play an important role in prenatal detection and diagnosis of chromosomal anomalies in addition to Down syndrome.

Prenatal tests: how are women deciding?

Women offered prenatal tests should be given sufficient information to enable them to make an informed decision. We compared the decision-making of 261 women who underwent serum screening for Down syndrome with 63 who did not. A questionnaire completed at 16 weeks' gestation assessed systematic decision-making (the weighing up of pros and cons on the basis of information presented), knowledge, anxiety and demographic information. Those undergoing screening were older but, with age partialled out, they had more knowledge about the test and made decisions less systematically than those not screened.

Cost-Effectiveness of Estimating Gestational Age by Ultrasonography in Down Syndrome Screening

In Brief 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. First-trimester ultrasonography to confirm gestational age can be justified economically on the basis of improved efficiency of Down syndrome screening.

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.

Maternal serum screening for Down syndrome in the first trimester: experience from Belarus.

We have carried out a large retrospective study of alpha-fetoprotein (AFP), free-beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein (PAPP-A) in the first trimester of pregnancy. Unlike other studies all women had routine ultrasound dating, carried out during a nuchal translucency measurement project. A total of 13,477 serum samples were tested for AFP and 11,659 for free beta-hCG. A subset of 1564 samples from unaffected pregnancies were also tested for PAPP-A on a case-control basis. All three markers were also determined in 31 samples from pregnancies with Down syndrome. Equations were derived to express results in multiples of the median using both gestational age and crown rump length and to adjust for maternal weight. Statistical modelling with Gaussian distribution parameters obtained in the study were used to predict the detection rate for a 5 per cent false-positive rate. The predicted rates were: 73.7 per cent for all three markers; 69.1 per cent for PAPP-A and free beta-hCG; 47.4 per cent for PAPP-A and AFP; 57.6 per cent for free beta-hCG and AFP. As these rates are similar to those in the second trimester, health planners may now want to consider a change in policy from second-trimester to first-trimester screening with biochemical markers.

Risk factors for placenta accreta

Objective: To identify risk factors associated with placenta accreta in a large cohort study. Methods: Data for this study came from the Taiwan Down Syndrome Screening Group, an ongoing project on feasibility of serum screening in an Asian population. Women who had serum screening for Down syndrome at 14–22 weeks’ gestation using alpha-fetoprotein (AFP) and free β-hCG between January 1994 and June 1997, and delivered in the same institution, were included ( n = 10,672). Those who had multiple gestations ( n = 200), overt diabetes ( n = 11), or fetal malformations ( n = 101) were excluded. If a woman was involved more than once, one randomly selected pregnancy was included in the analysis ( n = 9349). Twenty-eight pregnancies were complicated by placenta accreta, diagnosed by clinical presentation ( n = 26) or histologic confirmation ( n = 2). Multiple logistic regression with adjustment for potentially confounding variables was used to identify independent risk factors for placenta accreta. Results: Women who had placenta previa (odds ratio [OR] 54.2; 95% confidence interval [CI] 17.8, 165.5) and second-trimester serum levels of AFP and free β-hCG greater than 2.5 multiples of the median (OR 8.3; 95% CI 1.8, 39.3 and OR 3.9; 95% CI 1.5, 9.9, respectively), and were 35 years and older (OR 3.2; 95% CI 1.1, 9.4) were at increased risk of having placenta accreta. Conclusion: Risk factors for placenta accreta include placenta previa, abnormally elevated second-trimester AFP and free β-hCG levels, and advanced maternal age.

Prenatal screening for down syndrome: a dilemma for the unsupported midwife?

Objective: to explore the personal and professional concerns of midwives in relation to their experiences with women undergoing serum screening for Down syndrome. Design: semi-structured interviews. Setting: a consultant-led maternity unit in the south of England. Participants: ten midwives based in areas which most commonly support women undergoing this test. Methods: interviews were recorded and transcribed and a grounded theory approach involving coding was used to identify categories which were analysed. Findings: themes identified were: education needs on introduction of the test and in relation to current research about the test; strategies for explaining the concept of ‘risk’; personal and professional conflict in relation to the dilemmas raised. Key conclusions: accurate information (including psychosocial aspects) should be available to midwives prior to the introduction of potentially complex investigations. Continuing education should prepare midwives to meet the challenges related to prenatal screening for Down syndrome. Some strategies which could be considered include the use of reflection sheets, prompt cards and case studies or vignettes. Interprofessional education could provide the opportunity to increase understanding of individual roles and the conflicts experienced.