In vivo model to determine fetal-cell enrichment efficiency of novel noninvasive prenatal diagnosis methods

• Published in: Prenatal diagnosis 2008-06, Vol.28 (6), p.494-502
• Main Authors: Ponnusamy, S., Mohammed, N., Ho, S. S. Y., Zhang, H. M., Chan, Y. H., Ng, Y. W., Su, L. L., Mahyuddin, A. P., Venkat, A., Chan, J., Rauff, M., Biswas, A., Choolani, M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Delivery. Postpartum. Lactation; enrichment; Erythroblasts; Female; Fetal Blood; fetal primitive erythroblasts; Fetal Research; Fetomaternal Transfusion; Fetus; FNRBCs; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Globins; Gynecology. Andrology. Obstetrics; Humans; in vivo model; maternal blood; Maternal-Fetal Exchange; Medical sciences; Models, Biological; Molecular and cellular biology; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis - methods
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.2009

Objective To develop an in vivo model to determine fetal‐cell enrichment efficiency of novel noninvasive prenatal diagnosis methods. Methods Efficiency of our three‐step enrichment protocol was determined in vitro before fetal nucleated red blood cells (FNRBCs) were enriched from first‐trimester maternal blood samples collected from the same patients pre‐ and postsurgical termination of pregnancy (TOP) (n = 10). FNRBCs enriched were identified using embryonic ε‐globin immunocytochemistry and chromosomal fluorescence in situ hybridization. Results We recovered 37% of spiked FNRBCs (95% confidence interval (CI) 28.5–45.6; n = 8) in in vitro experiments. We show a consistent threefold increase in the number of ε + FNRBCs in maternal blood obtained immediately post‐TOP (p = 0.005). A mathematical relationship was derived: observed number of pretermination primitive FNRBCs = 0.6 + 0.31 (coefficient between pretermination/post‐termination primitive FNRBCs, 95% CI 0.12–0.49; p = 0.005) × observed number of post‐termination primitive FNRBCs (R2 = 0.65). Conclusion Our data demonstrate that maternal blood obtained immediately post‐TOP would be a good in vivo model to determine the enrichment efficiency of novel protocols and methods for noninvasive prenatal diagnosis. Copyright © 2008 John Wiley & Sons, Ltd.