References

" Worldwide published prospective data exist on almost a quarter of a million pregnancies in which protocols cited by Kellner et al... have been used.  It is clear that the dual-analyte free beta-human chorionic gonadotropin-maternal serum AFP biochemical screen has a 21% greater detection efficiency than the triple screen of Kellner et al.  Recent data from Cuckle et al., however, indicate that this pattern (triple screen) has reversed and currently fewer than half as many patients are screened with the triple marker.  ...Indeed, in the United Kingdom there remain only 6 of 67 screening laboratory using triple screening...analytes chosen rather that the number (single, double, or triple) are critical to maximizing detection efficiency." James N. Macri, PhD., Kevin Spencer, MS. Am J Obstet Gynecol, Vol 174 No.5:1668-1669 1996.

"The use of free beta hCG combined with maternal serum AFP and maternal age-related risk for Down syndrome in a screening popluation (i.e., women under 35 years) yields an improved detection efficiency over other protocols." James N. Macri, Kevin Spencer, Kenneth Garver, Philip D. Buchanan, Burhan Say, Nancy J. Carpenter, Francoise Muller and Andre Boue. Maternal Serum FreeBeta hCG Screening:  Results of Studies Including 480 Cases of Down Syndrome.   Prenatal Diagnosis, Vol. 14: 97-103 1994.

"Second-trimester dried blood screening for open neural tube defects and Down syndrome can achieve efficiency comparable to serum-based protocols with distinct advantages over the conventional method of blood collection." James N. Macri, PhD., Robert W. Anderson, MS, David A. Krantz, BS, John W. Larsen, MD, and Philip D. Buchanan, PhD.  Prenatal Maternal Dried Blood Screening with alpha-fetoprotein and free beta-human Chorionic Gonadotropin for Open Neural Tube Defect and Down Syndrome.   Am J Obstet Gynecol, Vol. 174 No. 2: 566-572 1996.

"Compared to total hCG, alpha-fetoprotein and unconjugated estriol, use of free beta-hCG and alpha-fetoprotein represents a better second-trimester screening test for Down's Syndrome, because it significantly decreases the false postive rate at a lower running cost." PH Estermann, P. Bischof, F. Beguin.  Second-Trimester Maternal Serum Screening for Down's Syndrome: Comparision of Free Beta-hCG and Alpha-Fetoprotein with Total hCG, Alpha-Fetoprotein and Unconjugated Estriol. Society of Perinatal Obstetricians Sixteenth Annual Meeting, Kamuela, Hawaii, No. 463, 1996.

"By use of existing methods, double screening is equally as effective as triple screening, so that the expense of estriol is unnecessary... Changing to DADs and eliminating estriol should achieve higher specificity for the same sensitivity and save, conservatively, about $900,000 in this series.  Extrapolated nationally, if confirmed, the annual savings could approach $72,000,000."  Mark I. Evans, MD, Lawrence Chik, PhD, Joseph E. O'Brien, MD, Bernadette Chin, MT, ASCP, Elena Dvorin, MD, PhD, Mazin Ayoub, BS, Eric L. Krivchenia, MS, Joel W. Ager, PhD, Mark P. Johnson, MD, and Robert J. Sokol, MD. MOMs (multiples of the median) and DADs (discriminat aneuploidy detection): Improved specificity and cost-effectiveness of biochemical sreening for aneuploidy with DADs.   Am J Obstet Gynecol, Vol. 172 No. 4: 1138-1149 1995.

"There is now a firm body of evidence that free beta-hCG has better detection efficiency than total hCG and that this applies earlier in the second trimester (14-16 weeks).  This earlier screening opportunity has obvious benefits for counseling, amniocentesis and the delays in obtaining results of karyotyping...wider screening period of 14 to 22 weeks...beta-hCG and AFP can be used in first trimester." K. Spencer.  The Measurement of hCG Subunits in Screening for Down's Syndrome. Screening for Down's Syndrome,  Cambridge University Press, pgs. 85-100,1994.

"On the basis of current evidence a case for the inclusion of uE3, in Down's syndrome screening programmes has not and is unlikely to be proved. "  K. Spencer. Measurement of Unconjugated Oestriol. Screening for Down's Syndrome,  Cambridge University Press, pgs. 141 - 159,1994.

"First-trimester free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A screening for Down syndrome can achieve detection rates as high as those associated with µ-fetoprotein, human chorionic gonadotropin, and unconjugated estriol screening in the second trimester."  David A. Krantz, BS,  John W. Larsen, MD,  Philip D. Buchanan, PhD, James N. Macri, PhD. First-Trimester Down Syndrome Screening: Free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A.   Am J Obstet Gynecol, Vol. 174 No. 2: 612-616 1996

"First-trimester screening is thus clearly superior to screening in the second trimester. The gap would probably widen if assessment of the nasal bone becomes incorporated in risk estimates. Although the FASTER group did not find assessments of the nasal bone helpful, the experience of others is different.  First-trimester screening is practical."  Simpson J.L.; N ENGL J MED 353;19;2005.

"Pregnancy terminations are earlier, more private, and far safer than in the second trimester. The maternal death rate for first-trimester abortions is 1.1 per 100,000 abortions, as compared with 7 to 10 per 100,000 in the second trimester. Earlier is clearly better." Simpson J.L.; N ENGL J MED 353;19;2005.

"Why not first-plus-second-trimester screening? A key finding of the FASTER trial was...the estimated detection rate for trisomy 21with sequential screening - 95 to 96 percent...however, the detection rate with the use of sequential screening was no better than first-trimester detection rates of Avgidou et al and Nicolaides (93 to 97 percent)." Simpson J.L.; N ENGL J MED 353;19;2005.

"Sequential screening...precludes safer, earlier terminations. Another problem is that an uncertain number of patients will return to complete the protocol. In the SURUSS trial, one third of subjects failed to return in the second trimester...the fear of litigation is obvious." Simpson J.L.; N ENGL J MED 353;19;2005.

"Why not proceed directly to chorionic-villus sampling or amniocentesis? In experienced hands, neither procedure seems to be as risky as once thought. In the FASTER trial, the procedure-related loss rate from amniocentesis was 0.15 percent." Simpson J.L.; N ENGL J MED 353;19;2005.