We thank Dr Singh for his interest in our study on aneuploidy detection using noninvasive prenatal testing. Details of the 31,030 tests received for analysis, including 17,885 available for clinical follow-up, and cases excluded from the study, are presented in the article’s Figure 1 and Supplemental Tables 2 and 3. Follow-up information was available for 84% of high-risk cases, with a positive predictive value (PPV) of 83% calculated for cases that had cytogenetic confirmation. The proportion of miscarriages (16%; 58 of 356) was less than expected, and it is likely that some of the cases with missing follow-up were actually pregnancy losses.

Dr Singh referred to the Boston Globe article that reported 22 termination cases (6.2%) with unconfirmed abnormal noninvasive prenatal screening test (NIPT) results, implying that termination was based only on the NIPT result. Because the clinical data for these cases were incomplete, these observations need to be interpreted cautiously; in reality the decision to terminate could have been based on substantial additional corroborating evidence. Two patients had major anomalies on ultrasound prior to the NIPT, and others may have shown anomalies after the NIPT. That information was not comprehensively provided to us. If, for example, a patient had a positive NIPT for trisomy 13, holoprosencephaly was subsequently observed, and she elected to terminate without waiting additional weeks for amniocentesis results, would that be considered unreasonable?

Our follow-up data were presented in the most transparent and conservative way possible. Estimates of PPV included only those cases with genetic test confirmation. We acknowledged the unlikely possibility that all cases without follow-up were false-positive results and provided a theoretical lowest possible PPV, which was 60% for trisomy 21 (Table 5 of the original article), still much better than the first-trimester screen, and consistent with validation studies. Finally, high-risk cases confirmed by chorionic villus sampling to be aneuploid, but that had normal amniocentesis results, were interpreted as false-positive results.

Women 35 years old and older are considered high risk for aneuploidy. Because PPVs for those 35 years old and older and those younger than 35 years were similar (83% and 87%, respectively), this was important to report. The criteria and numbers of patients that were high or low risk for aneuploidy were defined in the text and in Table 3 of the original article, based on either International Classification of Diseases , ninth revision, codes or maternal age.

For practical reasons, follow-up on all low-risk patients was not performed. Therefore, we did not claim that the 2 false negative results voluntarily reported were the only false-negative results in the study group, and a negative predictive value was not provided.