无创产前复筛可使羊膜穿刺减少九成

旧金山——加州大学旧金山分校妇产科教授Mary E. Norton博士在该校主办的产前与产时处置会议上报告称，应用无创产前DNA检测作为传统产前检查后的复筛方法，可使羊膜穿刺次数减少90%以上，减少妊娠丢失，并可改善每次羊膜穿刺的唐氏综合征检出率。

此外，无创产前检测作为复筛方法可略微增加13、 18或21三体检出率，但许多女性检测结果并不成功，仍需羊膜穿刺，会对妊娠丢失率和每次羊膜穿刺唐氏综合征检出率造成不利影响。基于上述和其他原因，Norton博士认为目前放弃现行产前检测方法而采用无创产前检测还为时尚早。


Mary Norton博士

研究者利用可用数据对3种假设性情景进行了比较分析，共计涉及290万例待筛查孕妇和5,110例13、18或21三体受累孕妇。这些孕妇将分别接受单纯传统产前筛查、传统筛查+无创产前复查以及无创产前筛查。这种无创性特定片段数字分析(DANSR)通过对母体游离DNA 特殊片段分析可确定染色体异常。

研究者预计，应用现行检测方法或现行检测方法+无创检测复筛，约145,000例女性筛查结果将为阳性，但如采用无创检测方法作为初筛，仅有45,710例结果阳性。采用前2种方法13、18或21三体病例数将为4,667例，而采用无创检测方法作为初筛，病例数略有增加，为5,100例。先行筛查方法比无创筛查方法可检出更多疾病，2,004例其他异常情况将会被检出。

部分患者通过无创产前筛查结果为阴性，因为该筛查方法无效或DNA含量不足，难以以得到阳性结果。无创检测方法作为复筛和初筛将分别有4,350例和87,000例患者结果阴性。

应用现行检测方法筛查非整倍体，总羊膜穿刺次数将为145,000次(每例阳性筛查穿刺1次)，而以无创检测作为复查，穿刺次数则可减至11,047次。以无创检测作为初筛，接受羊膜穿刺的孕妇为67,460例。单纯现行检测可导致435例妊娠丢失，而现行检测+无创检测复筛和无创检测初筛分别为33例和202例。

单纯采用现行产前检测方法筛查唐氏综合症，每检出1例需进行18次羊膜穿刺；以无创检测作为复筛，每2次羊膜穿刺即可检出1例唐氏综合症；以无创检测作为初筛，每检出1例则需进行13次羊膜穿刺。

研究者指出，每种方法相对获益仍存在争议，且因患者风险程度不同而异。如要改变目前标准产前筛查方法，尚需进一步研究。尽管专家们努力整合所有最新信息和方法，但产前筛查技术进展快速，即使是从事这一领域的医生，也仍面临困惑。

Norton博士接受了产前诊断产品生产商Ariosa诊断公司和CellScape公司的研究经费资助。

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By: SHERRY BOSCHERT, Ob.Gyn. News Digital Network

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.