We thank Drs Grati, Ferreira, and Bajaj for their insightful comments regarding the resolution of the discordant results that were reported in our recent study of noninvasive prenatal screening for the common aneuploidies by massively parallel sequencing (MPS) of cell-free DNA in maternal blood. Their recent publication of a retrospective audit of >50,000 chorionic villi specimens documented that confined placental mosaicism and true fetal mosaicism may be potential explanations for discordant findings from noninvasive MPS screening technology. With regard to our own study, 4 of the 5 false-negative results from noninvasive screening for Trisomies 18 and 13 were from patients in whom amniocentesis was the invasive procedure that permitted study inclusion; accordingly, the laboratory method for placental karyotyping would not be relevant in understanding whether the possibility of true fetal mosaicism (true fetal mosaicism 5: cytotrophoblast normal, fetus abnormal) might be an explanation for these results. The 3 false-positive MPS screening results for Trisomy 21 (including the patient with an early twin loss) also were from amniocentesis-included patients, precluding any judgment regarding whether confined placental mosaicism might be an explanation for this finding. We agree that the biologic reality of fetoplacental mosaicism undermines the potential for current technology to lead to a truly diagnostic noninvasive prenatal testing scheme.