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Jonathan P Bestwick

Publications and source records attributed to Jonathan P Bestwick.

3 recordsLinked to original sources
PubMed2006

Cross-trimester marker ratios in prenatal screening for Down syndrome.

OBJECTIVE: To examine the performance of Integrated Down syndrome screening (first- and second-trimester measurements integrated into a single screening test) when ratios of the levels of the same serum markers measured in both these trimesters (cross-trimester ratios) are added as new screening markers. METHODS: Using data from Serum Urine and Ultrasound Screening Study (SURUSS), second-trimester concentrations (in multiples of the median, or MoM) of pregnancy associated plasma protein A (PAPP-A), alphafetoprotein (AFP), unconjugated oestriol (uE(3)), human chorionic gonadotrophin (hCG) (free beta and total), and inhibin-A were divided by the first-trimester concentration to obtain a cross-trimester (CT) ratio for each analyte in 74 Down syndrome and 492 unaffected pregnancies. We identified CT ratios that improved screening performance and then, using Monte Carlo simulations, estimated the efficacy and cost effectiveness of adding them to the Integrated and serum Integrated tests. RESULTS: All the median CT ratios differed significantly between Down syndrome and unaffected pregnancies. Setting the Integrated test to achieve a 90% detection rate, the false-positive rate (FPR) was 0.7% with CT ratios for PAPP-A, uE(3), inhibin-A, and total hCG compared with 2.2% without CT ratios, a reduction of about two-thirds. Using the serum Integrated test to achieve the same 90% detection rate and the first-trimester measurements made at 11 completed weeks of pregnancy, the corresponding FPRs were 2.4 and 8.1%, a similar proportional reduction. The AFP CT ratio had little effect on screening performance. Using CT ratios did not increase the cost per Down syndrome pregnancy detected. CONCLUSION: The addition of CT ratios to an Integrated test substantially improves the efficacy and safety of prenatal screening for Down syndrome. It is cost effective and could be usefully introduced into screening programmes.

Biomarkers↗
PubMed2006

Sequential and contingent prenatal screening for Down syndrome.

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 >or= 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 <or=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.

Cost-Benefit Analysis↗