Elevated levels of total (maternal and fetal) beta globin DNA in maternal blood from first trimester pregnancies with trisomy 21.
BACKGROUND Elevated levels of circulating fetal DNA have been observed in maternal plasma when a trisomy 21 fetus is confirmed. However, these studies have been limited to pregnancies carrying a male fetus. We sought to quantify total (fetal and maternal) DNA from dried blood spots (DBS) for use as an additional factor in multi parameter prenatal screening for aneuploidy. METHODS Maternal DBS were obtained from the NICHD sponsored multi center cohort (BUN) study. Seventeen confirmed trisomy 21 (mean gestational age 12.23 0.77 weeks) cases were each matched by gestational age to euploid controls (n 30) DNA was extracted and quantitative PCR was performed to measure four non chromosome 21 loci, including glyceraldehyde 3 phosphate dehydrogenase (GAPDH) (12p13) beta globin (11p15.5) beta actin (7p15 12) and p53 (17p13.1) RESULTS Beta globin DNA levels were significantly elevated (P 0.003) in 13 of 17 trisomy 21 cases (4.08 1.78 Geq/ml x 10(5) compared with matched controls (2.35 1.84 Geq/ml x 10(5) Following conversion of beta globin concentrations into multiples of the median (MoM) MoM for trisomy 21 cases was 2.8 compared with 1.0 in euploid cases. No significant differences in levels of circulating GAPDH, beta actin and p53 sequences were detected. CONCLUSIONS This work demonstrates differential levels of circulating beta globin DNA in maternal blood of euploid and trisomy 21 cases. Sequence specific quantification could provide an additional measure to improve non invasive methods of prenatal screening to detect trisomy 21 using dried blood. Beta globin in particular is an attractive biomarker that could contribute to enhance multiple serum parameter testing in the first trimester.
Human reproduction