Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome,using a sialic acid-specific lectin immunoassay

In a series of 54 cases of pregnancies complicated by Down syndrome and 224 unaffected pregnancies we examined maternal serum levels of hyperglycosylated human chorionic gonadotrophin (HhCG) in samples collected in the first trimester (11–13 weeks) using a sialic acid-specific lectin immunoassay. We compared these levels with those of other potential first trimester serum markers [free β-hCG, pregnancy-associated plasma protein A (PAPP-A) and total hCG (ThCG)] and modeled detection rates and false-positive rates of various biochemical markers in conjunction with fetal nuchal translucency (NT) and maternal age using an maternal age standardized population. Maternal serum HhCG in cases of Down syndrome were significantly elevated (median MoM 1.97) with 24/54 (44%) of cases above the 95th centile for unaffected pregnancies. Free β-hCG was also elevated (median MoM 2.09) with 33% of cases above the 95th centile. PAPP-A levels were reduced (median MoM 0.47) with 38% below the 5th centile. ThCG levels, whilst elevated (median MoM 1.34), had only 20% of cases above the 95th centile. Maternal serum HhCG levels were not correlated with fetal NT but showed significant correlation with ThCG and free β-hCG and with PAPP-A in the Down syndrome group (r=0.536). Maternal serum HhCG levels in cases with Down syndrome had a significant correlation with gestational age, increasing as the gestation increased. When HhCG was combined together with fetal NT, PAPP-A and maternal age, at a 5% false-positive rate the modeled detection rate was 83%, some 6% lower than when free β-hCG was used and some 4% better than when ThCG was used. Maternal serum HhCG is unlikely to be of additional value when screening for Down syndrome in the first trimester. Copyright © 2002 John Wiley & Sons, Ltd.     

First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18

Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (β-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10–13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (p<0.0001) than in the control group (1.00 MoM). In the trisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free β-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free β-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free β-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free β-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free β-hCG. Copyright © 2001 John Wiley & Sons, Ltd.     

Second trimester two-step trisomy 18 screening using maternal serum markers

Trisomy 21 maternal serum marker screening has led to screening for other anomalies, including trisomy 18. Trisomy 18 is generally prenatally diagnosed because of major morphological defects. However, in up to 30% of cases ultrasound signs are unclear, and in most cases diagnosis is performed late in pregnancy. Of the different maternal serum markers, PAPP-A is now considered as the best for trisomy 18 screening. However, pregnancy-associated plasma protein A (PAPP-A) is of value in first trimester screening for trisomy 21, but not in the second trimester. We therefore propose a two-step screening strategy. Based on 45 trisomy 18 cases, we confirm the values of alpha-fetoprotein (AFP) (median 0.61 MoM), free β-human chorionic gonadotrophin (β-hCG) (median 0.24 MoM) and of PAPP-A (median 0.08 MoM). In the first step, a 0.5 MoM cut-off for AFP or for free β-hCG resulted in detection of 37/45 trisomy 18 cases (82%) with a 10% false-positive rate. The second step consisted of the measurement of PAPP-A for all these false-positive cases. Using a PAPP-A cut-off of 0.5 MoM, all the 37 trisomy 18 cases were detected, but now with a 0.1–0.2% false-positive rate. Amniocentesis was only offered to these few patients. This two-step second trimester screening will be of value for patients who have not been included in first trimester screening based on nuchal translucency (NT) measurement combined with the first trimester markers, PAPP-A and free β-hCG. Copyright © 2002 John Wiley & Sons, Ltd.     

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness,maternal serum free β-hCG and PAPP-A

This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free β-hCG and PAPP-A at 11–14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free β-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11–14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21. Copyright © 2002 John Wiley & Sons, Ltd.     

First trimester screening for Down syndrome and assisted reproduction: no basis for concern

In pregnancies obtained after assisted reproduction the false-positive rate of second trimester Down syndrome (DS) screening is increased by 1.5–3-fold. This may cause an increase in the number of amniocenteses and the fetal loss rate. The present study for the first time examined whether assisted reproductive technologies affect the results of first trimester screening. The markers PAPP-A, free β-hCG and the nuchal translucency (NT) thickness were examined at 12–14 weeks' gestation. Screening markers in 47 in vitro fertilisation (IVF), 63 ovulation induction (OI) and 3026 spontaneously conceived singleton pregnancies were compared. The MoM (multiples of the median) value in the IVF pregnancies was 1.02 (95% CI: 0.85–1.22) for PAPP-A, 1.14 (95% CI: 0.95–1.37) for β-hCG and 0.97 (95% CI: 0.89–1.05) for NT; the MoM value in the OI pregnancies was 0.89 (95% CI: 0.76–1.05) for PAPP-A, 1.08 (95% CI: 0.93–1.25) for β-hCG and 1.02 (95% CI: 0.95–1.11) for NT. The first trimester marker values in assisted reproductive pregnancies and spontaneously conceived pregnancies were not significantly different. Estimated false-positive rates for a risk cut-off of 1:400 varied from 4.7% in IVF pregnancies to 5.1% in OI pregnancies. Therefore the false-positive rate in Down syndrome screening should be independent of the method of conception. Copyright © 2001 John Wiley & Sons, Ltd.     

Accuracy of Down syndrome risks produced in a first-trimester screening programme incorporating fetal nuchal translucency thickness and maternal serum biochemistry

Over the past three years approximately 12 000 women have been screened in the first trimester through our OSCAR programme, which utilizes fetal NT and maternal serum free β-hCG and PAPP-A. During this time 30 cases of Down syndrome were identified either prenatally or postnatally. Using an established procedure the accuracy of predicted risk for Down syndrome was assessed in a population of 30 cases of Down syndrome and 11 758 unaffected pregnancies. The correlation between predicted risk and prevalence of Down syndrome was very high (r=0.9995). It is concluded that risks produced by the Fetal Medicine Foundation combined risk algorithm agree very closely with Down syndrome prevalence and can be used with confidence when counselling women of their risk. Copyright © 2002 John Wiley & Sons, Ltd.     

Maternal serum activin A and inhibin A in trisomy 18 pregnancies at 10–14 weeks

In 45 cases of trisomy 18 and 493 control pregnancies at 10–14 weeks of gestation, maternal serum inhibin A, total activin A, free β-hCG and PAPP-A were measured. In the trisomy 18 pregnancies the median values were 0.74 MoM for inhibin A, 1.23 MoM for activin A, 0.38 MoM for free β-hCG and 0.16 MoM for PAPP-A. The degree of deviation from normal in the levels of inhibin and activin is small in comparison with free β-hCG and PAPP-A and they are therefore unlikely to be of value in improving the sensitivity of 90% for a 1% false-positive rate achieved by screening with fetal nuchal translucency and maternal serum free β-hCG and PAPP-A. Copyright © 2001 John Wiley & Sons, Ltd.     

Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free β-hCG or PAPP-A levels?

In a study of 180 twin pregnancies I have examined the distribution of maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in addition to fetal nuchal translucency thickness (NT), in twins classified as monochorionic or dichorionic, based on ultrasound appearance at 10–14 weeks of gestation. In 45 monochorionic and 135 dichorionic twin pregnancies the median MoM free β-hCG was not significantly different (1.00 vs 1.01), whilst that for PAPP-A was lower (0.89 vs 1.01) but again with no statistical significance. Previous reports of an increased fetal NT in monochorionic twins pregnancies could not be confirmed (1.03 vs 1.00). It is concluded that the existing pseudo risk twin correction algorithm is appropriate for both monochorionic and dichorionic twins in providing accurate first trimester risks for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal serum levels of dimeric inhibin A in pregnancies affected by trisomy 21 in the first trimester

Dimeric inhibin A was measured in maternal serum samples from 45 pregnancies affected by trisomy 21 and 493 samples from unaffected pregnancies at 10–14 weeks of gestation. Inhibin A levels in affected pregnancies were compared with levels of free β-hCG and PAPP-A in the same series. In the trisomy 21 group, the median multiple of the median (MoM) inhibin A was not significantly elevated (1.28 vs 1.00) with only 15.5% being above the 95th centile. In contrast, the median MoM free β-hCG was significantly increased (2.05 vs 1.00) with 36% above the 95th centile and PAPP-A was significantly reduced (0.49 vs 1.00) with 42% below the 5th centile. Inhibin A levels in the trisomy 21 group were significantly correlated with gestational age such that median levels rose from 1.04 at 11 weeks to 1.30 at 12 weeks and 1.67 at 13 weeks. These findings suggest that first trimester biochemical screening for trisomy 21, which is currently optimised using maternal serum free β-hCG and PAPP-A and fetal nuchal translucency, will not benefit from the inclusion of inhibin A. Copyright © 2001 John Wiley & Sons, Ltd.     

Association between fetal nuchal translucency thickness in first trimester and subsequent gestational hypertension and preeclampsia

Increased fetal nuchal translucency (NT) in the first trimester is associated with adverse pregnancy outcomes. Whether the increased NT is also associated with an increased frequency of pregnancy-associated hypertension (PAH) is not known. Seven hundred and seventy-nine pregnant women who received NT-based Down syndrome screening and delivered their babies at our hospital by September 2000 were enrolled into this study. Among these women, there are 46 cases of preeclampsia, 68 cases of gestational hypertension (GH); 665 women without any adverse pregnancy outcomes served as controls. Correlation analysis demonstrated that NT MoM (multiples of median) level had a positive association with maternal diastolic blood pressure at the time of admission for delivery (r = 0.104; p < 0.01). The severity of PAH was concordant with the stepwise increase of mean NT MoM level, which was 0.88 in control, 1.07 in gestational hypertension, and 1.13 in preeclampsia (p < 0.001). Using the 95th (1.52 MoM) and 90th (1.31 MoM) percentiles of NT thickness as cut-offs, the sensitivities and odds ratios of the women at risk for developing GH after 20 weeks of gestation were 8.8%, 19.1% and 1.98, 2.15 respectively, while for preeclampsia were 10.9%, 28.3% and 2.49, 3.58 respectively. It is concluded that the pathological changes in the placenta responsible for the development of PAH may also influence the physiological decrease of NT thickness in late first trimester. However, the sensitivity of fetal NT measurement in first trimester is not sufficient as a single marker for predicting the pregnant women at risk for subsequent PAH. Copyright © 2002 John Wiley & Sons, Ltd.     

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

Problems 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.     

Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies

The aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein-A (PAPP-A), and free ß human chorionic gonadotrophin (free ß-hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance. The assumption that proportional differences in serum marker levels in affected and unaffected singleton pregnancies apply to twin pregnancies was not confirmed. Median free β-hCG value in monochorionic affected twin pregnancies (2.63 multiples of the median [MoM]; 95% CI, 1.79-3.22 MoM) was lower than that assuming proportionality (3.76 MoM), and the median PAPP-A value in dichorionic affected twin pregnancies (1.88 MoM; 95% CI, 1.60-2.17 MoM) was higher than that based on proportionality (1.33 MoM). The detection rate was 87% for a 3% false-positive rate in monochorionic twin pregnancies and 74% in dichorionic twin pregnancies compared with 86% in singleton pregnancies. Estimates of screening performance in Down syndrome twin pregnancies do not need to rely on assumptions and can take account of chorionicity and gestational age.     

First trimester PAPP-A in the detection of non-Down syndrome aneuploidy

Combined first trimester screening using pregnancy associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin, and nuchal translucency (NT), is currently accepted as probably the best combination for the detection of Down syndrome (DS). Current first trimester algorithms provide computed risks only for DS. However, low PAPP-A is also associated with other chromosome anomalies such as trisomy 13, 18, and sex chromosome aneuploidy. Thus, using currently available algorithms, some chromosome anomalies may not be detected. The purpose of the present study was to establish a low-end cut-off value for PAPP-A that would increase the detection rates for non-DS chromosome anomalies. The study included 1408 patients who underwent combined first trimester screening. To determine a low-end cut-off value for PAPP-A, a Receiver–Operator Characteristic (ROC) curve analysis was performed. In the entire study group there were 18 cases of chromosome anomalies (trisomy 21, 13, 18, sex chromosome anomalies), 14 of which were among screen-positive patients, a detection rate of 77.7% for all chromosome anomalies (95% CI: 55.7–99.7%). ROC curve analysis detected a statistically significant cut-off for PAPP-A at 0.25 MoM. If the definition of screen-positive were to also include patients with PAPP-A<0.25 MoM, the detection rate would increase to 88.8% for all chromosome anomalies (95% CI: 71.6–106%). This low cut-off value may be used until specific algorithms are implemented for non-Down syndrome aneuploidy. Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal serum levels of total activin-A in first-trimester trisomy 21 pregnancies

Maternal serum total activin-A concentration was measured in 45 pregnancies affected by trisomy 21 and 493 control unaffected pregnancies at 10–14 weeks of gestation. In the trisomy 21 pregnancies total activin-A concentration was significantly higher (1.36 MoM of the unaffected pregnancies) and in 16% of cases the level was above the 95th centile of normal. The log₁₀ SD for the control group and the trisomy 21 group were 0.17 and 0.22, respectively. The median pregnancy associated plasma protein-A (PAPP-A) in this trisomy 21 series was 0.49 and for free β-hCG was 2.05. In the trisomy group there were significant positive associations between total activin-A and PAPP-A (0.6071) and free β-hCG (0.4255). The low median difference and the high overlap in values between trisomic and unaffected pregnancies make total activin-A of little practical use in first-trimester screening for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

Second-trimester maternal serum alpha-fetoprotein (MSAFP) iselevated in women with adverse pregnancy outcome associated with inherited thrombophilias

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and β subunit of human chorionic gonadotrophin (βhCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or βhCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs 3%, p=0.04). Neither the median MoM βhCG nor the incidence of abnormally elevated βhCG were significantly different between the groups. We conclude that second trimester MSAFP, but not βhCG, is abnormally elevated in patients with thrombophilia and obstetric complications. Copyright © 2001 John Wiley & Sons, Ltd.     

Four-marker serum screening for Down's syndrome

The value of measuring the separate sub-units of human chorionic gonadotrophin (free α-hCG and free β-hCG) instead of total hCG together with alpha-fetoprotein (AFP) and unconjugated oestriol (uE₃) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples relating to 75 singleton pregnancies with fetal Down's syndrome and 367 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the serum sample, supplemented by data from 970 white women with unaffected pregnancies. Using the four serum markers AFP, uE₃, free β-hCG, and free α-hCG, in addition to maternal age, 65 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE₃, total hCG with maternal age). If gestation was based on an ultrasound scan examination, the detection rate was 72 per cent using the four serum markers compared with 67 per cent with the triple test. As an alternative illustration, if the detection rate was kept at 60 per cent and gestation was estimated by an ultrasound scan examination the four-marker test reduced the false-positive rate by one-third from 3 per cent using the triple test to 2 per cent with the four-marker test. Screening performance was hardly affected by adjusting marker levels for maternal weight. The four-marker test is, both from a medical and from a financial perspective, the most effective method of prenatal screening for Down's syndrome suitable for routine use.     

An increase in cost-effectiveness of first trimester maternal screening programmes for fetal chromosome anomalies is obtained by contingent testing

We assessed the discriminatory efficiency and cost-effectiveness of a novel way of organising first trimester screening for Down syndrome (DS), contingent testing, where a serological test (PAPP-A and β-hCG: the double test) is made in early first trimester and followed by nuchal translucency testing (NT) only in women with an intermediate risk, e.g. <1:65 and >1:1000, and not in all women as in normal first trimester screening (NFTS). Using Monte Carlo simulation contingent testing had a detection rate (DR) of 78.9% and a false-positive rate (FPR) of 4.0% for DS with 19.4% of women offered NT testing. The DR of NFTS was 85.5% and the FPR 4.4%. The decrease in NT screening was associated with an increase from 23% to 29% in the proportion of DS cases born. The cost of the contingent testing programme was £53 000 per DS case not born and £91 000 in NFTS. The number of aborted fetuses per DS case were 0.35 and 0.36, respectively. Thus, contingent testing is an organisation of first trimester screening where costs can be reduced with a marginal decrease in performance. Contingent testing is attractive in areas where NT screening is the bottleneck preventing the introduction of first trimester screening. Copyright © 2002 John Wiley & Sons, Ltd.     

Maternal serum free α- and free β-human chorionic gonadotrophin in pregnancies with insulin-dependent diabetes mellitus: Implications for screening for Down's syndrome

A study was performed to investigate the concentrations of the α and β free sub-units of human chorionic gonadotrophin (free α-hCG and free β-hCG) in maternal serum between 15 and 22 weeks of pregnancy in 126 pregnancies among 92 women with insulin-dependent diabetes mellitus (IDDM). Each IDDM pregnancy was matched with two control singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar quarter). The median free α-hCG level in the IDDM pregnancies was 0·86 multiples of the median (MOM) for pregnancies without IDDM at the same gestational age (P<0·002) (95 per cent confidence interval 0·80–0·94). The corresponding free β-hCG level was 0·96 MOM (95 per cent confidence interval 0·85–1·09). These results enable free α-hCG values to be adjusted so that antenatal screening for Down's syndrome can be performed using this marker in IDDM pregnancies as well as in non-diabetic pregnancies.     

The first trimester ‘combined test’ for the detection of Down syndrome pregnancies in 4939 unselected pregnancies

The high detection rate (DR) for Down syndrome (DS) pregnancies which can be achieved by measuring fetal nuchal translucency (NT) early in pregnancy can be improved by combining it with placental hormones [pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (fβ-hCG)] and maternal age (‘combined test’). In this study we wanted to assess the DR using the ‘combined test’ in an unselected population of self-referred pregnant women at a false-positive rate (FPR) of about 5%. NT, PAPP-A, fβ-hCG and maternal age were measured in all women with singleton pregnancies who booked for delivery in our hospital from 1 December 1997 to 31 April 2000 and who were between 10 and 13 completed weeks of gestation [crown–rump length (CRL) 35–70 mm]. The specific DS risk was calculated using the computer program Alpha Version 5aa (Logical Medical Systems, London, UK). A total of 4939 women were tested. Out of 14 DS pregnancies that occurred during this period of time, 12 were detected with the test. A total of 246 women had a false-positive test result in a non-DS pregnancy (FPR 5.0%). This makes the ‘combined test’ by far the best test for the detection of DS pregnancies in a low-risk population. The constant increase in maternal age at the time of delivery can also lead to an improved DR if a simple age-dependant protocol for DS detection is used, but only at the price of a much higher number of amniocenteses and subsequent abortions. The DR for DS can be increased much more markedly using the ‘combined test’ with a FPR that still remains at the level as it was in the early 1970s. Copyright © 2002 John Wiley & Sons, Ltd.     

First trimester serum screening for down's syndrome

Screening for Down's Syndrome has been shown to be effective at 10 weeks of pregnancy. A multicentre study (the First trimester serum screening study) has shown that there are two biochemical markers of choice at this time in pregnancy, namely pregnancy associated placental protein A (PAPP-A) and the free β-sub-unit of human chorionic gonadotrophin (free β-hCG). When used together with maternal age these two biochemical markers have an estimated detection rate of 62% and a 5% false-positive rate. The results are consistent with those obtained from a systematic review of the world literature. Other markers are less predictive of Down's syndrome though there is still some uncertainty over the value of dimeric inhibin-A at 10 weeks of pregnancy. Nuchal translucency measurement, from an ultrasound examination performed at about 10 weeks of pregnancy, is associated with Down's syndrome and is emerging as an important potential screening marker. At present there is uncertainty over its quantitative performance and performance when combined with biochemical markers. The resolution of these issues is currently the subject of active research. Ten week screening for Down's syndrome is an advance that is now technically possible though there is still insufficient information to justify its use in routine screening practice.