OBJECTIVE: To assess the relationship between first- and second-trimester cell-free DNA levels and maternal serum screening markers. METHODS: First- and second-trimester residual maternal serum samples from 50 women were obtained. First-trimester (pregnancy-associated plasma protein A and beta-hCG) and second-trimester serum analytes (beta-hCG, alpha-fetoprotein, unconjugated estriol, and inhibin A) had been measured at the time of sample receipt. All fetuses were male as confirmed by birth records. Cell-free DNA was extracted and measured by real-time quantitative polymerase chain reaction amplification using glyceraldehyde phosphate dehydrogenase and DYS1 as markers of total DNA and fetal DNA, respectively. Determination of linear associations between first- and second-trimester serum markers and cell-free DNA levels using Pearson correlations was performed. RESULTS: Statistically significant correlations between first-trimester pregnancy-associated plasma protein A multiples of the median and both total (r=0.36, P=.016) and fetal (r=0.41, P=.006) DNA in the first trimester were observed. There were no significant correlations between first-trimester serum human chorionic gonadotropin or any second-trimester serum marker with DNA levels. CONCLUSION: Correlation between serum pregnancy-associated plasma protein A and first-trimester circulating cell-free fetal and total DNA levels is a novel finding. Pregnancy-associated plasma protein A is a glycoprotein of placental origin, and its correlation to cell-free fetal DNA in maternal serum suggests a common tissue origin through apoptosis of placental cells. However, because pregnancy-associated plasma protein A and cell-free DNA were only marginally correlated and cell-free DNA can be reliably detected in the first trimester, the addition of cell-free DNA to serum screening strategies may be helpful in predicting adverse pregnancy outcome. LEVEL OF EVIDENCE: II.
OBJECTIVE: To assess the relationship between first- and second-trimester cell-free DNA levels and maternal serum screening markers. METHODS: First- and second-trimester residual maternal serum samples from 50 women were obtained. First-trimester (pregnancy-associated plasma protein A and beta-hCG) and second-trimester serum analytes (beta-hCG, alpha-fetoprotein, unconjugated estriol, and inhibin A) had been measured at the time of sample receipt. All fetuses were male as confirmed by birth records. Cell-free DNA was extracted and measured by real-time quantitative polymerase chain reaction amplification using glyceraldehyde phosphate dehydrogenase and DYS1 as markers of total DNA and fetal DNA, respectively. Determination of linear associations between first- and second-trimester serum markers and cell-free DNA levels using Pearson correlations was performed. RESULTS: Statistically significant correlations between first-trimester pregnancy-associated plasma protein A multiples of the median and both total (r=0.36, P=.016) and fetal (r=0.41, P=.006) DNA in the first trimester were observed. There were no significant correlations between first-trimester serum human chorionic gonadotropin or any second-trimester serum marker with DNA levels. CONCLUSION: Correlation between serum pregnancy-associated plasma protein A and first-trimester circulating cell-free fetal and total DNA levels is a novel finding. Pregnancy-associated plasma protein A is a glycoprotein of placental origin, and its correlation to cell-free fetal DNA in maternal serum suggests a common tissue origin through apoptosis of placental cells. However, because pregnancy-associated plasma protein A and cell-free DNA were only marginally correlated and cell-free DNA can be reliably detected in the first trimester, the addition of cell-free DNA to serum screening strategies may be helpful in predicting adverse pregnancy outcome. LEVEL OF EVIDENCE: II.
Authors: Antonio Farina; Erik S LeShane; Geralyn M Lambert-Messerlian; Jacob A Canick; Thomas Lee; Louis M Neveux; Glenn E Palomaki; Diana W Bianchi Journal: Clin Chem Date: 2003-02 Impact factor: 8.327
Authors: Lorraine Dugoff; John C Hobbins; Fergal D Malone; T Flint Porter; David Luthy; Christine H Comstock; Gary Hankins; Richard L Berkowitz; Irwin Merkatz; Sabrina D Craigo; Ilan E Timor-Tritsch; Steven R Carr; Honor M Wolfe; John Vidaver; Mary E D'Alton Journal: Am J Obstet Gynecol Date: 2004-10 Impact factor: 8.661
Authors: Kirby L Johnson; Kimberly A Dukes; John Vidaver; Erik S LeShane; Idania Ramirez; William D Weber; Farideh Z Bischoff; Sinuhe Hahn; Arun Sharma; Dianne X Dang; Lisa M Hire; Diana W Bianchi; Joe Leigh Simpson; Wolfgang Holzgreve; Sherman Elias; Katherine W Klinger Journal: Clin Chem Date: 2004-01-12 Impact factor: 8.327