Predicting the result of additional second-trimester markers from a woman's first-trimester marker profile: a new concept in Down syndrome screening.

To describe a method for deciding whether an individual's first-trimester Down syndrome screening test result justifies further testing in the second trimester. Statistical modelling was used to estimate the distribution of second-trimester marker profiles for a given first-trimester profile and hence the probability of a final positive result, using a 1 in 250 term cut-off. A multi-variate log Gaussian model was used with published parameters. Markers were maternal serum pregnancy-associated plasma protein-A and free beta-human chorionic gonadotrophin (hCG) at 10 weeks, nuchal translucency at 11 weeks, and second-trimester maternal serum alpha-fetoprotein, total hCG, unconjugated estriol and inhibin-A. To illustrate the method, the model was applied to a published series of 24 Down syndrome and 367 unaffected pregnancies. Modelling predicts that for 63% Down syndrome and 0.4% unaffected pregnancies having first-trimester tests, there is a 50% or more probability of a final positive result. A step-wise sequential screening policy based on immediate prenatal diagnosis for those with high probability and second-trimester testing for the remainder would have a 90% detection rate and 1.7% false-positive rate. Modelling also predicts 8.0% Down syndrome and 89% unaffected pregnancies with probabilities below 3%. A contingent screening policy restricting second-trimester testing to those with 3-49% probabilities would have an 88% detection rate and 1.4% false-positive rate. Predicting the probability of a positive final result from the first-trimester marker profile has potential utility, either as a decision aide for individual women or as a formal part of screening policy in selecting a subset of women for second-trimester testing.

Maymon R ，Cuckle H ，Jones R ，Reish O ，Sharony R ，Herman A ... -  《PRENATAL DIAGNOSIS》

First- and second-trimester screening: detection of aneuploidies other than Down syndrome.

Breathnach FM ，Malone FD ，Lambert-Messerlian G ，Cuckle HS ，Porter TF ，Nyberg DA ，Comstock CH ，Saade GR ，Berkowitz RL ，Klugman S ，Dugoff L ，Craigo SD ，Timor-Tritsch IE ，Carr SR ，Wolfe HM ，Tripp T ，Bianchi DW ，D'Alton ME ，First and Second Trimester Evaluation of Risk (FASTER) Research Consortium ... -  《OBSTETRICS AND GYNECOLOGY》

First-trimester or second-trimester screening, or both, for Down's syndrome.

It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates.

Malone FD ，Canick JA ，Ball RH ，Nyberg DA ，Comstock CH ，Bukowski R ，Berkowitz RL ，Gross SJ ，Dugoff L ，Craigo SD ，Timor-Tritsch IE ，Carr SR ，Wolfe HM ，Dukes K ，Bianchi DW ，Rudnicka AR ，Hackshaw AK ，Lambert-Messerlian G ，Wald NJ ，D'Alton ME ，First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium ... -  《-》

Comparison of serum markers in first-trimester down syndrome screening.

Canick JA ，Lambert-Messerlian GM ，Palomaki GE ，Neveux LM ，Malone FD ，Ball RH ，Nyberg DA ，Comstock CH ，Bukowski R ，Saade GR ，Berkowitz RL ，Dar P ，Dugoff L ，Craigo SD ，Timor-Tritsch IE ，Carr SR ，Wolfe HM ，D'Alton ME ，First and Second Trimester Evaluation of Risk (FASTER) Trial Research Consortium ... -  《OBSTETRICS AND GYNECOLOGY》

Three-stage contingent screening for Down syndrome.

To demonstrate the potential value of three-stage sequential screening for Down syndrome. Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free beta-human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum alpha-fetoprotein, free beta-hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies.

Wright D ，Bradbury I ，Cuckle H ，Gardosi J ，Tonks A ，Standing S ，Benn P ... -  《PRENATAL DIAGNOSIS》