title: Incorporation of dried blood alpha fetoprotein into traditional first trimester Down syndrome screening service.
abstract: OBJECTIVE
  The aim of this study was to determine whether incorporation of dried blood alpha fetoprotein (AFP) into first trimester screening using the biochemical markers free Beta human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein A (PAPP-A) can improve screening performance.
  
  
  METHODS
  A retrospective study of 34 Down syndrome and 1185 unaffected dried blood specimens. First trimester dried blood AFP was performed using in-house immunofluorometric time-resolved assay. False positive and detection rates were determined from modeling.
  
  
  RESULTS
  The multiple of the median in Down syndrome cases was 0.73. At a fixed 5% false positive rate, incorporating AFP into a free Beta hCG, PAPP-A, and nuchal translucency protocol adds 2% detection resulting in detection rates of 92% to 94% depending on the gestational age of the blood draw. At a fixed 90% detection rate, AFP reduced the false positive rate by 1.0 to 1.6 percentage points depending on gestational age. Using a cutoff of 1/1000, the combination of free beta hCG, PAPP-A, AFP, and nuchal translucency achieved a detection rate of 96% with a false positive rate of 8.4% to 9.9%. Adding in nasal bone increased detection to 98% while reducing false positive rates to 4.1% to 4.7%.
  
  
  CONCLUSIONS
  Inclusion of dried blood AFP into traditional first trimester screening improves detection while optimizing contingent protocols so that cell-free fetal DNA testing may be offered in a more cost effective manner.
authors.affiliation: PerkinElmer Laboratories, Melville, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Carmichael
authors.affiliation: PerkinElmer Laboratories, Melville, NY, USA.
authors.forename: David
authors.identifier: http://orcid.org/0000-0003-2310-6003
authors.initials: D
authors.lastname: Krantz
authors.affiliation: PerkinElmer Laboratories, Melville, NY, USA.
authors.forename: Hsiao-Pin
authors.initials: HP
authors.lastname: Liu
authors.affiliation: PerkinElmer Laboratories, Melville, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Janik
authors.affiliation: PerkinElmer Laboratories, Melville, NY, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: Hallahan
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004314:Down Syndrome / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests; D015233:Models, Statistical; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D012189:Retrospective Studies; D000509:alpha-Fetoproteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D000509:alpha-Fetoproteins; D011266:Pregnancy-Associated Plasma Protein-A
references.citation: N Engl J Med. 2005 Nov 10;353(19):2001-11
references.pmid: 16282175
references.citation: Annu Rev Med. 1977;28:453-65
references.pmid: 67821
references.citation: Prenat Diagn. 1999 Jun;19(6):505-12
references.pmid: 10416963
references.citation: Am J Obstet Gynecol. 1996 Feb;174(2):566-72
references.pmid: 8623786
references.citation: Am J Obstet Gynecol. 1988 Nov;159(5):1209-13
references.pmid: 2461080
references.citation: Lancet. 1988 Oct 8;2(8615):851-2
references.pmid: 2902296
references.citation: Lancet. 1987 Aug 15;2(8555):389
references.pmid: 2441219
references.citation: Lancet. 1986 Jul 19;2(8499):165-6
references.pmid: 2425203
references.citation: Lancet. 1984 Apr 28;1(8383):926-9
references.pmid: 6201687
references.citation: Clin Chem. 1982 May;28(5):1207-10
references.pmid: 6176368
references.citation: Ultrasound Obstet Gynecol. 2015 Jan;45(1):74-83
references.pmid: 25315699
references.citation: Am J Obstet Gynecol. 1984 Apr 1;148(7):886-94
references.pmid: 6201071
references.citation: J Obstet Gynaecol Can. 2008 Oct;30(10):918-49
references.pmid: 19038077
references.citation: Am J Perinatol. 2011 Jan;28(1):13-8
references.pmid: 20607646
references.citation: Am J Obstet Gynecol. 2011 Mar;204(3):205.e1-11
references.pmid: 21310373
references.citation: Genet Med. 2011 Nov;13(11):913-20
references.pmid: 22005709
references.citation: Obstet Gynecol. 2012 May;119(5):890-901
references.pmid: 22362253
references.citation: J Obstet Gynaecol Can. 2013 Feb;35(2):177-83
references.pmid: 23470070
references.citation: Prenat Diagn. 2011 Sep;31(9):869-74
references.pmid: 21692092
references.citation: Ultrasound Obstet Gynecol. 2013 Jul;42(1):41-50
references.pmid: 23744626
references.citation: Prenat Diagn. 2013 Jul;33(7):636-42
references.pmid: 23674341
references.citation: Prenat Diagn. 2014 Apr;34(4):350-6
references.pmid: 24395030
references.citation: PLoS One. 2014;9(4):e93559
references.pmid: 24714162
references.citation: Obstet Gynecol. 2000 Aug;96(2):207-13
references.pmid: 10908764
references.citation: Lancet. 2001 Nov 17;358(9294):1665-7
references.pmid: 11728540
references.citation: Ann Clin Biochem. 2002 Nov;39(Pt 6):567-76
references.pmid: 12564838
references.citation: Ultrasound Obstet Gynecol. 2004 Mar;23(3):218-23
references.pmid: 15027007
references.citation: Ultrasound Obstet Gynecol. 2005 Mar;25(3):221-6
references.pmid: 15736186