Testing normality of fetal DNA concentration in maternal plasma at 10-12 completed weeks' gestation: A preliminary approach to a new marker for genetic screening

Objectives: To test the distribution of fetal DNA in maternal plasma expressed as gen/eq in a population of normal pregnancies. Methods: Peripheral blood samples were obtained from 63 women (85% ≥35 years of age at delivery) bearing a euploid male fetus. Each patient underwent chorionic villus sampling (CVS) for karyotype analysis and/or β-thalassemia screening. Ultrasound scanning was used to determine gestational age. At 10-12 weeks' gestation, a peripheral blood sample was collected followed by CVS. To detect the Y chromosome-specific sequences (SRY) quantitative polymerase chain reaction (PCR) analysis was used. Normal distribution of the data was tested by means of the Kolmogorov-Smirnov (KS) test. A Symmetry test (reliability p > 0.05) was used to evaluate the reliability of the median. Results: Only after natural logarithmic transformation did the data display a normal distribution. The median value of fetal DNA was 23.3 gen/eq (range 2.08-195), interquartile range 18.57-45.4. A Pearson test showed a significant correlation between gestational age and fetal DNA concentration (r=0.25, p = 0.045). Conclusion: The present finding is a preliminary step towards a possible integration of fetal DNA with other variables (biochemical and/or ultrasound). It may serve to improve the discrimination of the screening for genetic diseases in the first trimester. Because of the relatively high dispersion, adjustments for possible covariates would appear to be necessary in further studies. Copyright © 2002 John Wiley & Sons, Ltd.