Serum PAPP-A Research Articles

302: Relationship between first trimester maternal serum PAPP-A levels and placental lesions in twin gestations

302: Relationship between first trimester maternal serum PAPP-A levels and placental lesions in twin gestations

Screening for triploidy by the risk algorithms for trisomies 21, 18 and 13 at 11 weeks to 13 weeks and 6 days of gestation

To examine the effectiveness in screening for triploidy at 11 weeks to 13 weeks and 6 days of gestation by the combined use of the risk algorithms for trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and maternal serum free beta-hCG and PAPP-A. Prospective screening for trisomy 21, including 56 376 normal singleton pregnancies and 31 cases with triploidy (24 digynic and 7 diandric). Patient-specific risks for trisomies 21, 18 and 13 were calculated by multiplying the age related risk for trisomies 21, 18 and 13 with the likelihood ratio (LR) for fetal NT and with a combined LR for FHR, free beta-hCG and PAPP-A, respectively. Detection rates (DRs) and false positive rates (FPRs) for triploidy were calculated by taking the proportion with risks above a given risk threshold and standardized for maternal age according to the distribution of pregnancies in England and Wales in 2000 to 2002. In digynic triploidy, free beta-hCG was 0.16 (range 0.02-0.95) MoM and PAPP-A was 0.06 (range 0.02-0.47) MoM and the respective values for diandric triploidy were 8.74 (range 2.83-47.0) and 0.74 (range 0.32-1.51) MoM. Use of the trisomy 21 algorithm identified 5 of the 7 diandric cases and 3 of the 24 digynic ones at a 3% FPR. Combined use of the risk algorithms for trisomies 18 and 13 identified 20 of the 24 cases with the digynic triploidy at the FPR of 0.2%. When screen positivity was defined by a 3% FPR using the algorithm for trisomy 21 and an additional 0.2% FPR using the algorithms for trisomies 18 and 13, the total FPR was 3.1% and the DR was 84%. A beneficial side-effect of first trimester combined screening for trisomies is the detection of a high proportion of fetuses with triploidy.

Comparison of the New PRC Software with the Established Algorithm of the FMF UK for the Detection of Trisomy 21 and 18/13

Objective: The aim of this study was to compare the newly developed Prenatal Risk Calculation (PRC) software and the established Fetal Medicine Foundation (FMF) UK algorithm for their detection and false-positive rates in prenatal screening of trisomy 21 or 18/13. Methods: Nuchal translucency was measured by FMF-certified sonographers in 39,004 pregnancies. Risks for trisomy 21 and 18/13 were calculated together with serum PAPPA and free beta-hCG in all cases. Overall, 109 cases of trisomy 21 and 39 cases of trisomy 18 or 13 occurred. The detection rates were calculated for all 109 trisomy 21 cases using both PRC and ASTRAIA, software based on the official algorithm of the FMF UK. The false-positive rate was calculated on the basis of all 39,004 cases for ASTRAIA and on the basis of 3,620 additional cases for PRC. The comparison of the algorithms was performed by the calculation of receiver-operating characteristic (ROC) curves. Results: The detection rates for trisomy 21 for a 5% false-positive rate were 91% (99/109) for PRC and 90% (98/109) for ASTRAIA. The difference was not significant. ROC curve analysis showed an area under the curve (AUC) of 0.976 for PRC and 0.975 for ASTRAIA (p = 0.80). At a cutoff of 1:300, PRC showed a slightly (nonsignificantly) higher, but nonsignificant false-positive rate (3.8% for ASTRAIA, version since 2005, 5.1% for PRC) associated with a slightly (nonsignificantly) higher, but nonsignificant detection rate of 91% (PRC) versus 88% (ASTRAIA). The false-positive rate of the biochemical risk (without NT) in PRC was significantly higher (17.7%) than with the FMF UK algorithm (9.0%) at a common risk cutoff of 1:300. A reason for the higher false-positive rates in PRC may be the missing correction for maternal weight, smoking status, and ethnicity. The detection rates for trisomy 18/13 at a risk cutoff of 1:150 were 79% for PRC and 77% for ASTRAIA. False-positive rates for trisomy 18/13 at a cutoff of 1:150 were 1.5% for PRC and 0.6% for ASTRAIA (differences were nonsignificant). Conclusion: For a 5% false-positive rate, the new PRC software detects as many trisomy 21 and trisomy 18/13 cases as the established algorithms of the FMF UK. In order to reduce the false-positive rate for the biochemical risk, the algorithm of the PRC software should be redesigned to include the maternal weight, smoking status of the mother, and the ethnicity.

The effect of a 'vanishing twin' on biochemical and ultrasound first trimester screening markers for Down's syndrome in pregnancies conceived by assisted reproductive technology

Previous studies have found that 1 in 10 in vitro fertilization (IVF) singletons originates from a twin gestation. First trimester Down's syndrome screening markers are altered in assisted reproductive techniques (ART) pregnancies compared with spontaneously conceived pregnancies. The presence of a perished embryo may further complicate prenatal screening among women pregnant after ART. The aim of this study was to assess the impact of a 'vanishing twin' on first trimester combined biochemical and ultrasound screening in pregnancies conceived after IVF and intracytoplasmatic sperm injection. From a national prospective cohort study concerning first trimester combined screening among women pregnant after ART, 56 cases of pregnancies with a vanishing twin were identified. As control group 897 cases of ART singleton pregnancies were used. All women completed a first trimester combined ultrasound and biochemical screening programme comprising serum PAPP-A and free beta-hCG together with nuchal translucency (NT) measurement. There were no significant differences in geometric mean MoM free beta-hCG and PAPP-A between pregnancies with an early (gestational week <9, EVT) or late vanishing twin (gestational week 9-13, LVT) or singleton pregnancies (0.98, 1.13 and 0.95 for free beta-hCG and 0.84, 0.80 and 0.74 for PAPP-A, respectively). Likewise, no difference was seen for NT measurements. The gestational age at the time of blood sampling and NT scan was similar for the three groups. The proportion of EVT pregnancies with a PAPP-A and free beta-hCG log(10)MoM value below the 5th%iles and above the 95th%iles of the value in the singleton pregnancies were 4.3%, 4.3%, 6.4% and 8.5%, respectively, which did not constitute a significant difference from singletons. The corresponding values for LVT pregnancies were 0%, 22.2%, 0% and 11.1%, respectively; however, these numbers were too small to allow for statistical calculations. First trimester biochemical screening markers in women pregnant after ART, and with a vanished twin diagnosed at early ultrasound, do not differ from those of other ART singleton pregnancies. In cases where the fetal demise was first diagnosed at the time of the NT scan, it is doubtful whether the serum risk assessment is as precise as it is in singleton ART pregnancies. No difference was seen for NT measurements.

First trimester maternal serum PAPP-A and uterine flow velocity waveforms in the prediction of adverse pregnancy outcome. – Preeclampsia, IUGR and preterm delivery represent main risk factors in today‘s obstetrics

This study investigates the early prediction of Preeclampsia (PIH), IUGR and prematurity using first trimester uterine artery doppler waveform analysis (UAD) and maternal serum PAPP-A analysis in a group of singleton pregnancies at 10–16 weeks‘gestation. A retrospective study was performed on two independent samples of singleton pregnancies using Brahms Kryptor analysis and color coded doppler flow waveform analysis (GE Voluson 730E). The pregnancies undergoing PAPP-A analysis (n=66) were grouped respectively according to normal and pathological birth results (IUGR&lt;10th centile, prematurity&lt;38 weeks, APGAR 5rsquor; &lt;7, umbilical artery pH&lt;7.2). PAPP-A levels from pregnancies with pathological birth results were compared to those with normal birth results using the Chi²- and Fisher‘s exact- test. The cutoff level was MoM PAPP-A (10th centile). For the doppler cohort (n=114) mean Pulsatility- and Resistance-Index of the uterine arteries were calculated using the system built-in algorithm. The correlation of PI and RI with PIH and pathological birth result was calculated using logistic regression. Lower PAPP-A values were associated with pathological birth result, but the PAPP-A levels within subgroups (normal/pathological birth result) differed without reaching statistical significance (p=0.068). This difference reached statistical significance in the subgroup of primaparae with a sensitivity of 67% (p=0,01). Results for first trimester UAD did not correlate with adverse pregnancy outcome. PAPP-A levels below 10th centile are associated with preterm delivery and IUGR and seemed to be a stronger first trimester predictor of adverse pregnancy outcome compared to first trimester UAD.

OP11.03: Can the severity of the maternal anti‐angiogenic state of pre‐eclampsia be detected by Doppler velocimetry?

statistically significant correlation between maternal serum PAPP-A, free β-hCG and uterine artery resistance indices. Conclusions: The present study demonstrates a positive correlation between first trimester uterine artery resistance, pulsatility indices and second trimester MSAFP. Uterine artery Doppler measurement during the first trimester prenatal sonography may be a prognostic screening method. The potential application of first trimester uterine artery blood flow in conjunction with maternal biochemistry such as MSAFP for prediction of adverse pregnancy outcomes will be further evaluated with increasing number of patients in the current study.

First Trimester Combined Screening in Hong Kong, China: outcome first 10000 cases

Objective: To examine the effectiveness of first trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency (NT), maternal serum fb-hCG and PAPP-A and levels in a predominantly Chinese population in Hong Kong.

Subcutaneous continuous glucose monitoring system in assessment of a dynamics of the glycemia during and after physical activity in patients with diabetes

Our study was designed to determine serum PAPP-A and MMP-9 after renal transplantation (RTx) and to correlate them with renal function. Methods: Serum PAPP-A and MMP-9 were determined at 0, 6, and 12 months post-RTx in 80 pts 49/31 M/F, age 48.7 (22–76) years and in 22 healthy controls 10/12 M/F, age 51.0 (22–76) years. Renal function was determined as inulin clearance, and serum PAPP-A and MMP-9 by ELISA. Results: Serum PAPP-A was significantly increased at time 0 post-RTx compared with controls (24.4 12.1 vs. 9.6 1.7 mlU/l; p 0.01) and we noted a significant inverse correlation between inulin clearance and serum PAPP-A (r 0.569; p 0.01). Serum MMP-9 was significantly raised at 1 year post-RTx as against controls: median 602 vs. 355 ng/ml; p 0.01. The correlation between increased MMP-9 levels and renal function was not significant. Conclusion: The serum levels of PAPP-A are the highest prior to RTx, and their decline correlates with developing graft function. In contrast, serum MMP-9 increases in the late post-RTx period; further research is needed to explain its rise, not due to a change in renal function. Supported by grant NR/9398-3 IGA MH Czech Republic.

Implementation of an NHS First Trimester Screening Clinic

We aimed to improve trisomy 21 and maternal screening by introducing a 'one-stop' NHS first trimester screening clinic (FTSC). We offered first trimester ultrasound assessment of nuchal translucency (NT), measurement of serum free βHCG and Papp-A, along with maternal screening tests (full blood count, rubella, hepatitis B, syphilis, HIV and midstream urine culture). We restructured antenatal clinics, developed clear algorithms, provided detailed patient information and consent leaflets, ensured high standards of ultrasound and serum biochemistry measurement. After one year, completion of screening improved (60–91%) whilst maintaining a high trisomy 21 detection rate (89%) along with a 23% reduction in number of invasive procedures. A reliable FTSC can be introduced which complements existing NHS maternity care.

OP25.05: First trimester combined screening for trisomy 21 in a predominantly Chinese population

To examine the effectiveness of first-trimester fetal Trisomy 21 (T21) screening using a combination of maternal age, nuchal translucency (NT), maternal serum free beta-hCG and PAPP-A levels in a predominantly Chinese population in Hong Kong. A prospective study performed in a university fetal medicine unit over a three and a half-year period. Consecutive women who underwent the combined screening for T21 between 11 and 13 + 6 weeks of gestation were recruited. NT was measured according to the criteria set by the Fetal Medicine Foundation (FMF). Maternal serum biochemistry was measured by Kryptor analyzer. Risk of T21 was calculated using FMF's algorithm. Fetal karyotyping was advised when the risk was 1 : 300 or above for T21, or 1 : 150 for T13/18. All subjects were followed up for pregnancy and fetal outcome. Among the 9333 women who underwent the screening program, 99% were Chinese and 173 women had a twin pregnancy, with a total of 9506 fetuses. 27.1% of the women were at or above 35 years old. 558 fetuses were screened positive (5.98%) for T21 (with or without increased risk for T13/18). Another 18 cases were positive for T13/18 only, making a total of 576 (6.17%). There were a total of 26 cases of T21, of which two were screened negative (detection rate of 92.3%). There were five cases of T13, 12 cases of T18, 10 cases of monosomy X, and six cases of other chromosomal abnormalities; all were screened positive. The overall positive predictive value for chromosomal abnormality was 1 in 9.9. First-trimester combined screening for fetal T21 is highly effective among Chinese subjects.

Influence of maternal systemic lupus erythematosus on first‐trimester combined screening for chromosomal abnormalities

To explore the effect of maternal systemic lupus erythematosus (SLE) on first-trimester screening markers for Down syndrome. A retrospective study was conducted on 1150 normal singleton fetuses that underwent first-trimester combined screening for Down syndrome. Fetal delta nuchal translucency (NT), maternal serum PAPP-A and free beta-hCG were compared between pregnancies with SLE (n = 10) and without preexisting maternal disease (n = 1140). The medians +/- SD for delta NT, log(10) MoM of PAPP-A and free beta-hCG +/- SD in pregnancies with SLE and without maternal disease were - 0.18 +/- 0.29 versus - 0.18 +/- 0.33, 0.005 +/- 0.32 versus 0.02 +/- 0.26, and 0.22 +/- 0.19 versus - 0.014 +/- 0.28, with a p value of 0.7, 0.98 and 0.03, respectively. Patients with preexisting SLE have increased maternal serum-free beta-hCG levels in the first-trimester. But, because of the multimodal procedure of risk calculation there is no significant difference in the screen-positive rate after the combined first-trimester screening for trisomy 21.

Aneuploidy screening in the first trimester

This article reviews the performance of first trimester screening for chromosomal anomalies using various combinations of ultrasound and maternal serum biochemical modalities. Detection rates in excess of 90% can be routinely achieved for Trisomy 21, Trisomy 13, Trisomy 18 using a combination of fetal nuchal translucency (NT) thickness and maternal serum free ss-hCG and PAPP-A at 11 + 0 to 13 + 6 weeks of gestation.

Implications cliniques de l'hCG dans les résultats de l'assistance médicale à la procréation au cours des cycles de transfert d'embryons frais et cryoconservés

Does mode of conception influence placental volume and other first-trimester outcomes?This retrospective single-centre case-control study led in Dijon University Hospital included 252 singleton pregnancies (84 IVF with either fresh embryo transfer or frozen-thawed embryo transfer [FET] and 168 natural conceptions). First-trimester placental volume, uterine artery pulsatility index and maternal serum PAPP-A and beta-HCG were measured. Statistical analyses were adjusted for gestational age, the newborn’s gender, maternal age, parity, body mass index and smoking status.Placental volume was significantly greater in the FET group than in the control group (P = 0.043) and fresh embryo transfer (P = 0.023) groups. At birth, fresh embryo transfer newborns were significantly smaller than controls (P = 0.01) and FET newborns (P = 0.008). Postpartum haemorrhage was far more frequent in FET than in controls and fresh embryo transfer group (38.1%, 2.6% and 1.9%, respectively; P < 0.0001). Placental volume positively correlated with PAPP-A, beta-HCG and the newborn’s birth weight, and negatively correlated with uterine artery pulsatility index.Placental volume and other first-trimester parameters are modified by IVF with fresh embryo transfer and FET compared with natural conception, but with opposite trends. Given the different protocols used for these techniques, hormonal treatment per se may have a major effect on pregnancy outcomes through the modification of placental invasiveness.

Optimisation of sandwich ELISA based on monoclonal antibodies for the specific measurement of pregnancy-associated plasma protein (PAPP-A) in acute coronary syndrome

Objectives: PAPP-A has become the principal biochemical serum marker in first trimester screening for Down syndrome, the original data being based on results of a radioimmunoassay (RIA). Recent observations using sandwich ELISA technology have proposed PAPP-A as a potential marker in patients with acute coronary syndrome (ACS). The aims of the present study were to demonstrate (i) the importance of antibody specificity, (ii) the potential pitfalls in changing assay technology, (iii) the importance of strict definition of technology, and (iv) the application of a well-defined assay technology on sera from patients with ACS. Design and methods: Candidate monoclonal antibodies (Mab) were identified by immunohistochemistry, Western blot and the absence of positive signals (ELISA) with normal, non-pregnant serum as antigen source. The ELISA technology was standardized against the original PAPP-A RIA and the WHO reference preparation (WHO 78/610). Results different from those obtained by the original RIA led to ELISA modifications with respect to dilution buffer and enzymatic digestion of the Mab. Results: The first generation ELISA revealed serum measurements from a pool of non-pregnant ( n = 103) individuals which, compared to the RIA, seemed to be false positive. The false positive reaction was abolished by addition of bovine serum (BS) to the dilution buffer. Subsequent analysis of individual sera ( n = 103) indicated that 7/103 were still false positive. This reaction was eliminated by introduction of F(ab′) 2-fragment of the indicator antibody. This modified ELISA revealed that serum PAPP-A levels in ACS were statistically significantly higher than in controls ( p < 0.001). Moreover, serum PAPP-A in ACS patients with ST-segment elevation (STEMI) were higher ( p < 0.001) compared to patients without ST-segment elevation (NSTEMI). Immunohistochemical analysis failed to identify PAPP-A in the atherosclerotic plaques.

Nasal bone in first-trimester screening for trisomy 21

This study was undertaken to investigate the impact of incorporating assessment of the nasal bone into first-trimester combined screening by fetal nuchal translucency (NT) thickness and maternal serum biochemistry. In this prospective combined screening study for trisomy 21, the fetal nasal bone was also examined and classified as present or absent. A multivariate approach was used to calculate patient-specific risks for trisomy 21 and the detection rate (DR) and false-positive rate (FPR) were estimated. We examined 2 screening strategies; first, integrated first-trimester screening in all patients and second, first-stage screening of all patients using fetal NT and maternal serum free beta-hCG and PAPP-A, followed by second-stage assessment of nasal bone only in those with an intermediate risk of 1 in 101 to 1 in 1000 after the first-stage. The nasal bone was absent in 113 (0.6%) of the 20,165 chromosomally or phenotypically normal fetuses and in 87 (62.1%) of the 140 fetuses with trisomy 21. With combined first-trimester NT and serum screening, the DR of 90% was achieved at a FPR of 5%. Inclusion of the nasal bone, either in all cases or in about 10% of the total in the 2-stage approach, halved the FPR to 2.5%. Inclusion of the nasal bone in first-trimester combined screening for trisomy 21 achieves a DR of 90% for a FPR of 2.5%.

The efficacy of first-trimester PAPP-A and free βhCG levels for predicting adverse pregnancy outcome

To determine whether first-trimester measurements of maternal serum PAPP-A and free beta hCG levels were associated with adverse pregnancy outcomes. First trimester maternal serum free beta hCG and PAPP-A were measured in 490 singleton pregnancies. Pregnancies were followed by the fetal-maternal unit, and predictive efficacy of these markers for small for gestational age (SGA) babies, gestational diabetes mellitus and hypertensive disorders were analyzed by cut-off values determined by using a ROC analysis, and also, by using the fifth percentile as the cut-off value. The sensitivities for PAPP-A in predicting pregnancies with a SGA baby and those complicated by a hypertensive disorder were 49% and 73%, respectively, when optimal cut-off values were used. Specificities were 76% and 65%, respectively. Serum free beta hCG had no predictive value for individual pregnancy outcomes. Efficacy of first trimester maternal serum markers in predicting adverse pregnancy outcome is low. Even after optimization of cut-off values, these markers do not appear to be clinically acceptable as an effective tool for screening for adverse pregnancy outcomes.

Influence of Oral Vitamin E Therapy on Micro-Inflammation and Cardiovascular Disease Markers in Chronic Hemodialysis Patients

Background. The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. Methods. 29 HD patients were randomized into two groups: 15 patients were treated orally with 400mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical – TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. Results. Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23±11.94 vs. 11.41±1.94 mIU/L, p<0.001; CRP: 5.20±3.50 vs. 3.40±3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. Conclusion. Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.

Maternal serum PP13 and PAPP-A in first trimester, and doppler in second trimester, as markers of pre-eclampsia

To evaluate serum PP-13 and PAPP-A at 11-13 weeks of gestation, and second trimester Doppler, as markers for pre-eclampsia (PET). A nested case-control study of PET Cases vs. Controls matched for gestational age and storage time. Samples were collected as part of a first trimester Prenatal Chromosomal Anomaly screening programme and were routinely tested for PAPP-A. PP-13 was tested blind to pregnancy outcome. All patients also underwent 22-24 week uterine artery Doppler flow velocimetry (mean Pulsatility index). There were 446 Controls and 88 PET Cases in the study. Median PP-13 levels for Controls and Cases were 176.9 and 121.9 (MoMs = 1.00 and 0.69) respectively (P < 0.001). PAPP-A MoMs were 1.0 and 0.89 (P = 0.076) and Doppler PIs were 1.0 and 1.6 (P < 0.001) for Controls and Cases respectively. Receiver operating characteristic (ROC) curve analysis for Cases vs. Controls yielded areas under the curve (AUCs) for PP-13, PAPP-A and Doppler respectively of 0.68 (95% CI: 0.61 to 0.74; P < 0.001), 0.56 (0.49 to 0.63; P = 0.076), and 0.79 (0.72 to 0.87; P < 0.001). Using each marker by itself and setting specificity at 0.80 gave sensitivities of 0.44, 0.24 and 0.73 for PP-13, PAPP-A and Doppler respectively. Combining PP-13 and Doppler using logistic regression yielded an AUC of 0.84 (0.78 to 0.90; P < 0.001) and sensitivity of 0.74. PAPP-A with Doppler gave an AUC of 0.82 (0.76 to 0.89; P < 0.001) and sensitivity of 0.76. Combining all markers did not add significantly to combining each serum marker with Doppler. First trimester PP-13 may be useful in predicting early PET, its accuracy increasing when coupled with second trimester Doppler. First trimester PAPP-A provides some prediction for PET, its prediction similarly increasing when combined with Doppler.

Maternal serum PP13 and PAPP-A in first trimester, and doppler in second trimester, as markers of early pre-eclampsia

Maternal serum PP13 and PAPP-A in first trimester, and doppler in second trimester, as markers of early pre-eclampsia

OC38.03: One stop clinic for assessment of risk (OSCAR) for trisomy 21 in singleton pregnancies at 11 to 13 + 6 weeks of gestation

Objective: To evaluate the performance of first-trimester screening for trisomy 21 using maternal age, fetal nuchal translucency (NT) and maternal serum free s-hCG and PAPP-A at 11 to 13 + 6 weeks. Methods: All women attending between 11 to 13 + 6 weeks of gestation were offered screening for trisomy 21. Assessment of NT was performed by appropriately trained sonographers (Fetal Medicine Foundation Certificate of competence), and maternal serum s-hCG and PAPP-A was measured using the Kryptor analyser. Patients were counselled with regards to their combined estimated risk and the available options for the management of the pregnancy. Data on pregnancy outcome were obtained from the cytogenetics laboratory, and by letters and telephone calls to the patients, their general practitioners or the maternity units in which they delivered. Detection rates and false positive rates were calculated for use of maternal age, maternal age and NT, and maternal age, fetal NT and maternal biochemistry. Results: Screening for trisomy 21 was carried out in 31 904 singleton pregnancies and pregnancy outcome was obtained in 30 564 (95.8%) cases. There were 330 pregnancies affected with a chromosomal abnormality, including 196 cases of trisomy 21. Of these, in 185 cases the diagnosis was made prenatally (178 in the screen positive and seven in the screen negative pregnancies) and 11 where the diagnosis was made postnatally in live births (five in the screen positive pregnancies, in which the parents chose to avoid invasive testing, and six in the screen negative pregnancies). The estimated risk for trisomy 21 was 1 in 300 or greater in 7.5% of the normal pregnancies, in 93.4% of those with trisomy 21 and in 88.8% of those with other chromosomal defects. Conclusion: Currently, the most effective method of screening for trisomy 21 is by a combination of maternal age, fetal NT and maternal serum free s-hCG and PAPP-A at 11 to 13 + 6 weeks.