First trimester noninvasive fetal RHD genotyping using maternal dried blood spots

OBJECTIVE: This study was aimed to evaluate whether maternal dried blood spots could be a potential source for the noninvasive fetal RHD genotyping, serving as a combined one-step test for both the First Trimester Screen and the fetal RHD genotyping. METHOD: Both the maternal dried blood spots and the peripheral blood samples from 19 RhD-negative pregnant women were obtained during the First Trimester Screen. DNA was extracted and sequential real-time PCRs were performed to determine the fetal RHD genotypes. Fetal RhD serological types were obtained after delivery. This study was approved by the Institutional Review Board, and informed consents were obtained. RESULTS: A total of 19/19 fetal RHD genotyping with maternal DBS were consistent with the follow-up serological RhD test results after birth. Eleven were RhD positive, and eight were RhD negative (RHD deletion or RHD-CE-D = 6, RHD pseudogene = 1, RHDVI = 1). Sensitivity = 100%, specificity = 100%, positive predictive value = 100%, negative predictive value = 100%. A total of 18/19 fetal gender were determined correctly with maternal DBS. One female fetus was falsely determined as male. Sensitivity = 100%, specificity = 91.6%, positive predictive value = 87.5%, negative predictive value = 100%. CONCLUSION: Maternal dried blood spots, with the benefits of flexible sample transportation and processing, could be utilized for the noninvasive prenatal fetal RHD genotyping and potentially be incorporated into the routine First Trimester Screen. Larger scale study is in progress to implement fetal RHD genotyping in routine prenatal care. © 2017 John Wiley & Sons, Ltd.