Unaffected Pregnancies (unaffected + pregnancy)

Distribution by Scientific Domains

Selected Abstracts

Risk prediction for Down's syndrome in young pregnant women using maternal serum biomarkers: determination of cut-off risk from receiver operating characteristic curve analysis

Hsiao-Lin Hwa MD PhD
Abstract Objective, The aim of this study was to establish a predictive model for Down's syndrome using maternal age as well as maternal serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG), and to identify an optimal cut-off risk in women under the age of 35 years to improve sensitivity. Methods, Logistic regression models were utilized to predict fetal Down's syndrome as a function of maternal age and logarithm of levels of AFP as well as hCG using training data of 20 pregnancies with fetal Down's syndrome and 9730 unaffected pregnancies. Validation was performed using data of another nine affected pregnancies and 3496 unaffected pregnancies. Receiver operating characteristic (ROC) curves were plotted. Results, Based on the newly established logistic regression equations, the optimal cut-off risk from the ROC curve analysis was at 1:499, with a 17.8% false-positive rate and a 90.0% sensitivity. A suboptimal cut-off risk was estimated at 1:332, with a 12.0% false-positive rate and an 80% sensitivity. Conclusion, A predictive model for Down's syndrome was developed using logistic regression. By ROC curve analysis and clinical consideration, the cut-off risk for young pregnant women could be determined. [source]

Sequential and contingent prenatal screening for Down syndrome

Nicholas J Wald
Abstract Objective To compare the Integrated test in three policies for prenatal Down syndrome screening: Integrated screening for all women, sequential screening (first-trimester tests allowing early completion of screening for high-risk pregnancies), and Contingent screening (early completion of screening for high- and low-risk pregnancies). Design and Methods Estimation of detection rates (DRs) and false-positive rates (FPRs) using Monte Carlo simulation and cost effectiveness for each method. Setting and Population Down syndrome affected and unaffected pregnancies studied in the Serum Urine and Ultrasound Screening Study (SURUSS). Results and Main Outcomes Integrated screening has the best screening performance. The performance of the other two policies approached that of Integrated screening as the first-trimester test FPR decreased. If the first-trimester FPR is set to 0.5% (risk , 1 in 30) with an overall DR of 90%, sequential and contingent screening yield overall FPRs of 2.25% and 2.42%, respectively, and 66% of the affected pregnancies are detected by the first-trimester test. The Integrated test on all women yields an FPR of 2.15%. With sequential screening, 99.5% of women would proceed to an Integrated test, or 30% with contingent screening if those with first-trimester test risks of ,1 in 2000 are classified screen-negative and receive no further testing. About 20% of affected pregnancies identified in the first trimester using sequential or contingent screening would have unnecessary terminations (they would miscarry before the early second trimester). Contingent screening is the most cost-effective if there is no alphafetoprotein screening for neural tube defects, otherwise Integrated screening is more cost-effective. Conclusions Integrated screening for all women is the simplest, most effective, and the safest policy. Contingent screening is the most complex with the lowest screening performance. Making an earlier diagnosis with sequential and contingent screening has adverse consequences that are sufficient to discourage their use. Copyright 2006 John Wiley & Sons, Ltd. [source]

Age-standardisation when target setting and auditing performance of Down syndrome screening programmes

Howard Cuckle
Abstract Objective To describe and illustrate a method of setting Down syndrome screening targets and auditing performance that allows for differences in the maternal age distribution. Methods A reference population was determined from a Gaussian model of maternal age. Target detection and false-positive rates were determined by standard statistical modelling techniques, except that the reference population rather than an observed population was used. Second-trimester marker parameters were obtained for Down syndrome from a large meta-analysis, and for unaffected pregnancies from the combined results of more than 600 000 screens in five centres. Audited detection and false-positive rates were the weighted average of the rates in five broad age groups corrected for viability bias. Weights were based on the age distributions in the reference population. Results Maternal age was found to approximate reasonably well to a Gaussian distribution with mean 27 years and standard deviation 5.5 years. Depending on marker combination, the target detection rates were 59 to 64% and false-positive rate 4.2 to 5.4% for a 1 in 250 term cut-off; 65 to 68% and 6.1 to 7.3% for 1 in 270 at mid-trimester. Among the five centres, the audited detection rate ranged from 7% below target to 10% above target, with audited false-positive rates better than the target by 0.3 to 1.5%. Conclusion Age-standardisation should help to improve screening quality by allowing for intrinsic differences between programmes, so that valid comparisons can be made. Copyright 2004 John Wiley & Sons, Ltd. [source]

Cost-effectiveness of prenatal screening for thalassaemia in Hong Kong

K. Y. Leung
Abstract Objectives To determine the cost effectiveness of a universal prenatal screening program for ,- and ,-thalassaemia. Methods We retrospectively reviewed our program from 1998 to 2002, and calculated the direct and indirect costs of various components. Results 18 936 women were screened at our prenatal clinic and 153 couples were subsequently referred to our Prenatal Diagnostic Centre for counselling and further investigations. In addition, there were 238 tertiary referrals and 157 self-referrals. After investigations, 84 fetuses were at risk of ,-thalassaemia major/,-E thalassaemia, 19 of them were affected and 18 were aborted. The total expenditure on our program (HK$10.0 million) would be less than the postnatal service costs (HK$40.4 million) for 18,-thalassaemia major fetuses if they were born. Of 361 women at risk of carrying a homozygous ,0 -thalassaemia fetus, 311 (86.2%) opted for the indirect approach (using serial ultrasound examinations to exclude Hb Bart's disease), and 76 (24.5%) subsequently underwent an invasive test for a definitive diagnosis. The sensitivity and false positive rate of this indirect approach was 100.0% and 2.9% respectively. Conclusion It is cost effective to run a universal prenatal screening program in an area where both ,-thalassaemia and ,-thalassaemia are prevalent. The indirect approach can effectively avoid an invasive test in unaffected pregnancies. Copyright 2004 John Wiley & Sons, Ltd. [source]

Maternal serum,integrated screening for trisomy 18 using both first- and second-trimester markers

Glenn E. Palomaki
Abstract Objectives To estimate the prenatal screening performance of an integrated serum test for detecting trisomy 18, which combines measurements of first- and second-trimester markers with maternal age to assign patient-specific risks. Methods Published and new observations of maternal serum marker levels in trisomy 18 and unaffected pregnancies are used to derive population parameters. These parameters are then combined in a multivariate Gaussian model to assign patient-specific risks for trisomy 18. Results The best combination of serum markers includes pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein, unconjugated estriol and human chorionic gonadotropin in the second trimester. At a second-trimester risk cutoff of 1 : 100, these 4 markers, in combination with maternal age, detect 90% of trisomy 18 pregnancies at a false-positive rate of 0.1%. The odds of a trisomy 18 pregnancy among screen-positive women are 1 : 4. Without the first-trimester marker, detection is reduced to 67% at about the same false-positive rate. Conclusion The algorithm described here is highly efficient for detecting trisomy 18 and should be considered by programs that offer serum-integrated screening for Down syndrome. Copyright 2003 John Wiley & Sons, Ltd. [source]

Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay

J. A. Talbot
Abstract Aim To assess whether glycoform variants of human chorionic gonadotrophin (hCG) are present in altered concentrations in the maternal serum in pregnancies affected by Down syndrome. Methods In a series of 50 cases of pregnancies complicated by Down syndrome and 278 unaffected pregnancies, we have examined maternal serum levels of hCG glycoforms (GlyhCG) in samples collected in the second trimester (14 to 21 weeks) using a sialic acid binding lectin immunoassay. We have compared these levels with those of other second trimester serum markers (Free ,-hCG, alpha fetaprotein (AFP) and Total hCG) and modelled detection rates and false positive rates of various biochemical markers in conjunction with maternal age using a maternal age standardized population. Results Maternal serum GlyhCG in cases of Down syndrome was significantly elevated (Median MoM 1.81) with 15 of 50 (30%) cases above the 95th centile for unaffected pregnancies. Free ,-hCG was also elevated (Median MoM 2.16) with 18 of 50 (36%) cases above the 95th centile. AFP levels were reduced (Median MoM 0.75) with 9 of 50 (18%) cases below the 5th centile. Total hCG levels whilst elevated (Median MoM 1.88) had only 15 of 50 (30%) cases above the 95th centile. Maternal serum GlyhCG levels showed significant correlation with total hCG and free ,-hCG (r = 0.6880 and 0.6922) in the Down group but not with AFP (r = 0.1237). When GlyhCG was combined together with AFP and maternal age, at a 5% false positive rate, the modelled detection rate was 53%, some 13% lower than when free ,-hCG was used and some 7% lower than when total hCG was used. Conclusion Maternal serum GlyhCG, as measured by the sialic acid,binding lectin immunoassay is unlikely to be of additional value when screening for Down syndrome in the second trimester. Copyright 2002 John Wiley & Sons, Ltd. [source]

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

Kevin Spencer
Abstract 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 ,-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 ,-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 ,-hCG and PAPP-A and fetal nuchal translucency, will not benefit from the inclusion of inhibin A. Copyright 2001 John Wiley & Sons, Ltd. [source]

Assessment of risk for the development of pre-eclampsia by maternal characteristics and uterine artery Doppler

Aris T. Papageorghiou
Objective To develop a method for the estimation of patient-specific risk for the development of pre-eclampsia by combining maternal history and uterine artery Doppler. Design Prospective multicentre observational study. Setting Antenatal clinics in seven hospitals in the UK and three overseas centres. Population Unselected women with singleton pregnancies attending for routine antenatal care. Methods Doppler studies of the uterine arteries were performed using colour flow mapping and pulsed wave Doppler at 23 weeks of gestation. The mean pulsatility index (PI) of the two uterine arteries was calculated. Doppler and maternal history variables were combined to develop a model for risk assessment. The incidence of pre-eclampsia was used to derive the prior risk for this complication. The posterior risk was derived by multiplying the prior odds with likelihood ratios (LRs) derived from independent risk factors identified from the maternal history, and the LR estimated from the heights of the frequency distributions of mean PI in affected and unaffected pregnancies. Main outcome measure Pre-eclampsia. Results There were 17,480 women recruited to the study, in which 17,319 (99.1%) of these Doppler examination of both uterine arteries were completed, and outcome data were available in 16,806 (97.0%). Pre-eclampsia occurred in 369 (2.20%) cases. Significant independent prediction of pre-eclampsia was provided by mean PI, ethnic origin, body mass index (BMI), parity, cigarette smoking, history of hypertension and family or personal history of pre-eclampsia. Models were derived allowing calculation of patient-specific risk for development of pre-eclampsia. For a false-positive rate of 25%, the detection rate of pre-eclampsia by screening using maternal history was 45.3%, with uterine artery Doppler it was 63.1% and with combined assessment it was 67.5%. Conclusions Combining risk factors in the mother's history with Doppler of the uterine arteries allows calculation of patient-specific risk for the development of pre-eclampsia. [source]