Noninvasive prenatal testing could be secondary screen

SAN FRANCISCO – Using noninvasive prenatal DNA testing as a secondary screen after conventional prenatal testing could decrease the number of amniocenteses by more than 90%, reduce fetal losses, and improve the ratio of Down syndrome cases detected per amniocentesis, according to Dr. Mary E. Norton.

On the other hand, using noninvasive prenatal testing as the primary screen would increase the rate of detecting trisomy 13, 18, or 21 by a bit, but many women will have unsuccessful test results and will go on to have amniocentesis, negatively affecting the fetal loss rate and the ratio of Down syndrome detected per amniocentesis, she said.

For these and other reasons, it’s premature to abandon current prenatal screening for noninvasive prenatal testing, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

She used available data to compare three hypothetical scenarios in which 2.9 million pregnant women would be screened and 5,110 pregnancies would be affected by trisomy 13, 18, or 21. The women would be screened by conventional prenatal testing alone, by current screening methods followed by noninvasive prenatal testing, or solely by the noninvasive Digital Analysis of Selected Regions (DANSR) assay that can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA.

Approximately 145,000 of the women would have a positive screen under current testing or with current testing plus noninvasive testing as a secondary screen, but only 45,710 would have a positive screen with noninvasive testing as the primary screen, she estimated. The number of trisomy 13, 18, or 21 cases identified would be 4,667 under scenario one or two and slightly higher – 5,100 – using the noninvasive screening test primarily, said Dr. Norton, professor of obstetrics and gynecology at the university. Current screening can detect many more problems than can noninvasive screening, so 2,004 other abnormalities would be detected using current methods, compared with none using noninvasive testing.

A proportion of patients undergoing noninvasive prenatal screening would have no test result because the sequencing failed to work or not enough DNA was present to get a result – 4,350 women undergoing noninvasive testing as a secondary screen and 87,000 women with noninvasive testing as the primary screen, she estimated.

The total number of amniocenteses would be 145,000 under current testing (one for every positive screen), but would be reduced to 11,047 if noninvasive testing was used as a secondary screen to detect aneuploidies. With noninvasive testing as the primary screen, 67,460 women would undergo amniocentesis. That would result in 435 fetal losses with current testing alone, 33 with current testing and secondary noninvasive prenatal testing, or 202 fetal losses with noninvasive testing as the primary screen.

Eighteen amniocenteses would have to be performed to detect one case of Down syndrome with current prenatal testing alone. With noninvasive testing as a secondary screen, every two amniocenteses would detect a case of Down syndrome. With noninvasive testing as the primary screen, 13 amniocenteses would be needed to detect one case of Down syndrome, Dr. Norton said.

The relative benefits of each scenario remain controversial and may vary by each patient’s level of risk. Further study is needed before the standard of care in prenatal screening is changed.

"Prenatal screening is changing at a rapid pace," Dr. Norton said. Even experts are struggling with how best to incorporate all the new information and new tools. "It’s very exciting times, but confusing even for those of us who practice in the field," she commented.

Dr. Norton has received research funding from Ariosa Diagnostics and CellScape, which are involved in prenatal diagnosis products.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Using noninvasive prenatal DNA testing as a secondary screen after conventional prenatal testing could decrease the number of amniocenteses by more than 90%, reduce fetal losses, and improve the ratio of Down syndrome cases detected per amniocentesis, according to Dr. Mary E. Norton.

On the other hand, using noninvasive prenatal testing as the primary screen would increase the rate of detecting trisomy 13, 18, or 21 by a bit, but many women will have unsuccessful test results and will go on to have amniocentesis, negatively affecting the fetal loss rate and the ratio of Down syndrome detected per amniocentesis, she said.

For these and other reasons, it’s premature to abandon current prenatal screening for noninvasive prenatal testing, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

She used available data to compare three hypothetical scenarios in which 2.9 million pregnant women would be screened and 5,110 pregnancies would be affected by trisomy 13, 18, or 21. The women would be screened by conventional prenatal testing alone, by current screening methods followed by noninvasive prenatal testing, or solely by the noninvasive Digital Analysis of Selected Regions (DANSR) assay that can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA.

Approximately 145,000 of the women would have a positive screen under current testing or with current testing plus noninvasive testing as a secondary screen, but only 45,710 would have a positive screen with noninvasive testing as the primary screen, she estimated. The number of trisomy 13, 18, or 21 cases identified would be 4,667 under scenario one or two and slightly higher – 5,100 – using the noninvasive screening test primarily, said Dr. Norton, professor of obstetrics and gynecology at the university. Current screening can detect many more problems than can noninvasive screening, so 2,004 other abnormalities would be detected using current methods, compared with none using noninvasive testing.

A proportion of patients undergoing noninvasive prenatal screening would have no test result because the sequencing failed to work or not enough DNA was present to get a result – 4,350 women undergoing noninvasive testing as a secondary screen and 87,000 women with noninvasive testing as the primary screen, she estimated.

The total number of amniocenteses would be 145,000 under current testing (one for every positive screen), but would be reduced to 11,047 if noninvasive testing was used as a secondary screen to detect aneuploidies. With noninvasive testing as the primary screen, 67,460 women would undergo amniocentesis. That would result in 435 fetal losses with current testing alone, 33 with current testing and secondary noninvasive prenatal testing, or 202 fetal losses with noninvasive testing as the primary screen.

Eighteen amniocenteses would have to be performed to detect one case of Down syndrome with current prenatal testing alone. With noninvasive testing as a secondary screen, every two amniocenteses would detect a case of Down syndrome. With noninvasive testing as the primary screen, 13 amniocenteses would be needed to detect one case of Down syndrome, Dr. Norton said.

The relative benefits of each scenario remain controversial and may vary by each patient’s level of risk. Further study is needed before the standard of care in prenatal screening is changed.

"Prenatal screening is changing at a rapid pace," Dr. Norton said. Even experts are struggling with how best to incorporate all the new information and new tools. "It’s very exciting times, but confusing even for those of us who practice in the field," she commented.

Dr. Norton has received research funding from Ariosa Diagnostics and CellScape, which are involved in prenatal diagnosis products.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – Using noninvasive prenatal DNA testing as a secondary screen after conventional prenatal testing could decrease the number of amniocenteses by more than 90%, reduce fetal losses, and improve the ratio of Down syndrome cases detected per amniocentesis, according to Dr. Mary E. Norton.

On the other hand, using noninvasive prenatal testing as the primary screen would increase the rate of detecting trisomy 13, 18, or 21 by a bit, but many women will have unsuccessful test results and will go on to have amniocentesis, negatively affecting the fetal loss rate and the ratio of Down syndrome detected per amniocentesis, she said.

For these and other reasons, it’s premature to abandon current prenatal screening for noninvasive prenatal testing, she said at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.

She used available data to compare three hypothetical scenarios in which 2.9 million pregnant women would be screened and 5,110 pregnancies would be affected by trisomy 13, 18, or 21. The women would be screened by conventional prenatal testing alone, by current screening methods followed by noninvasive prenatal testing, or solely by the noninvasive Digital Analysis of Selected Regions (DANSR) assay that can identify chromosome abnormalities by evaluating specific fragments of maternal cell-free DNA.

Approximately 145,000 of the women would have a positive screen under current testing or with current testing plus noninvasive testing as a secondary screen, but only 45,710 would have a positive screen with noninvasive testing as the primary screen, she estimated. The number of trisomy 13, 18, or 21 cases identified would be 4,667 under scenario one or two and slightly higher – 5,100 – using the noninvasive screening test primarily, said Dr. Norton, professor of obstetrics and gynecology at the university. Current screening can detect many more problems than can noninvasive screening, so 2,004 other abnormalities would be detected using current methods, compared with none using noninvasive testing.

A proportion of patients undergoing noninvasive prenatal screening would have no test result because the sequencing failed to work or not enough DNA was present to get a result – 4,350 women undergoing noninvasive testing as a secondary screen and 87,000 women with noninvasive testing as the primary screen, she estimated.

The total number of amniocenteses would be 145,000 under current testing (one for every positive screen), but would be reduced to 11,047 if noninvasive testing was used as a secondary screen to detect aneuploidies. With noninvasive testing as the primary screen, 67,460 women would undergo amniocentesis. That would result in 435 fetal losses with current testing alone, 33 with current testing and secondary noninvasive prenatal testing, or 202 fetal losses with noninvasive testing as the primary screen.

Eighteen amniocenteses would have to be performed to detect one case of Down syndrome with current prenatal testing alone. With noninvasive testing as a secondary screen, every two amniocenteses would detect a case of Down syndrome. With noninvasive testing as the primary screen, 13 amniocenteses would be needed to detect one case of Down syndrome, Dr. Norton said.

The relative benefits of each scenario remain controversial and may vary by each patient’s level of risk. Further study is needed before the standard of care in prenatal screening is changed.

"Prenatal screening is changing at a rapid pace," Dr. Norton said. Even experts are struggling with how best to incorporate all the new information and new tools. "It’s very exciting times, but confusing even for those of us who practice in the field," she commented.

Dr. Norton has received research funding from Ariosa Diagnostics and CellScape, which are involved in prenatal diagnosis products.

[email protected]

On Twitter @sherryboschert