Impact of the introduction of Non-invasive prenatal genetic testing on invasive tests: A single-center study in Japan.

Abstract

Non-invasive prenatal genetic testing (NIPT) using massively parallel sequencing of cell-free DNA is a technique to screen for fetal aneuploidies by evaluating the amount of cell-free DNA of target chromosomes in maternal blood (Chiu et al. 2008). NIPT demonstrates a sensitivity and specificity of higher than 99% for fetal trisomy 21 (Palomaki et al. 2011). NIPT was first introduced in 2011 in the United States, and since then there have been a report on the decrease in invasive prenatal procedures (Larion et al. 2014). NIPT was introduced in Japan in April 2013 as a nationwide clinical research (Sago and Sekizawa 2015). A decrease in the proportion of invasive testing among pregnant women who underwent prenatal genetic testing was reported, although the total number of invasive testing did not decrease at a single center after one year (Akaishi et al. 2015). Notably, the impact of NIPT on invasive testing in Japan has not been elucidated. Table 1 shows the numbers and clinical indications of amniocentesis (AC) and chorionic villus sampling (CVS), and the numbers of quadruple test (QT) and NIPT between April 2011 and March 2015. The number of AC increased before the introduction of NIPT, then decreased remarkably after the introduction of NIPT, whereas the change in the number of CVS was relatively small. The number of QT showed similar changes to that of AC, that is, increased before the introduction of NIPT then decreased remarkably after the introduction of NIPT. The number of NIPT was high compared with that of other prenatal tests. AC owing to advanced maternal age (AMA), abnormal ultrasonography (USG) findings and positive QT at the second trimester decreased after the introduction of NIPT. When comparing the numbers of AC and CVS in the first year after the introduction of NIPT with those in the year before the introduction of NIPT, AC and CVS decreased 38% (from 347 to 216) and 11% (from 82 to 73), respectively. In the second year after the introduction of NIPT, AC and CVS decreased 58% (from 347 to 147) and 28% (from 82 to 59), respectively. The change in the number of AC after the introduction of NIPT in our hospital was similar to that in the United States (52.5% reduction) (Larion et al. 2014), while the change in the number of CVS was smaller than that in the United States (77.2% reduction) (Larion et al. 2014). In a population in which first and second trimester prenatal screening tests are widely prevalent, both AC and CVS may decrease because NIPT can reduce the rate of “screen-positive” which can be confirmed by AC or CVS; this would be the main reason for the decrease in invasive tests in the United States. In Japan, prenatal screening tests are not widely accepted due to ethical issues. Obstetricians are reluctant to offer prenatal screening tests for fetal aneuploidies to pregnant women without their request. Thus, the rate of prenatal genetic testing in Japan remained low at about 3%, with AC being the main invasive diagnostic procedure (Sasaki et al. 2011). The most frequent indication for AC was AMA in the pre-NIPT period (Nishiyama et al. 2015). Many pregnant women who wanted to have prenatal genetic testing for AMA have chosen NIPT instead of AC. This would be the main reason for the decrease in AC in our hospital. The decrease of AC owing to positive QT or USG abnormality was suspected to be a reflection of the decrease in the number of QT or NT measurement performed in the post-NIPT period. A possible reason for the relatively small change in the number of CVS is that the indication criteria for CVS has been limited for women at higher risk for genetic disorders or USG abnormality, which implies chromosomal abnormality in the first trimester. Therefore, CVS could not be replaced by NIPT for trisomy 21, 18 and 13. In conclusion, the number of AC decreased remarkably after the introduction of NIPT, whereas the change in the number of CVS was relatively small. The impact of NIPT on prenatal testing may vary among populations with different prenatal screening situations in which screening tests are widely accepted or not. The authors would like to thank Dr Julian Tang of the National Center for Child Health and Development for his valuable and excellent support. None.