Relationships between cell-free DNA and serum analytes in the first and second trimesters of pregnancy.
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.


CONCLUSIONS
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.


METHODS
II.
Vora
Neeta L
NL
From the Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, Massachusetts; the Division of Genetics, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts; the Department of Pathology and Laboratory Medicine, Women and Infants Hospital and the Alpert School of Medicine at Brown University, Providence, Rhode Island; the Institute of Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts; and the Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York.
Johnson
Kirby L
KL
Lambert-Messerlian
Geralyn
G
Tighiouart
Hocine
H
Peter
Inga
I
Urato
Adam C
AC
Bianchi
Diana W
DW
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D004247:DNA / Q000097:blood*; D005260:Female; D006801:Humans; D008403:Mass Screening; D011247:Pregnancy / Q000097:blood*; D011248:Pregnancy Complications / Q000175:diagnosis; D011261:Pregnancy Trimester, First / Q000097:blood*; D011262:Pregnancy Trimester, Second / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism
D015415:Biomarkers; D004247:DNA; D011266:Pregnancy-Associated Plasma Protein-A