Please Note that any non-invasive prenatal chromosomal tests could test positive, possibly from cancer present in the mother. “[T]he new findings underscore the need to have any positive result confirmed by amniocentesis or chorionic villus sampling diagnostic test before considering whether to terminate a pregnancy or to plan for a child with developmental disabilities”… “Based on the results of the study, we estimate there is between a 20% and 44% risk of maternal cancer if multiple aneuploidies are detected [in the prenatal tests].“
[Comment: Note this quote from the article: “The unexpected finding emerged in a study involving eight women who initially had abnormal results from the prenatal blood test, but for whom a subsequent assessment showed their babies were normal. When the mothers’ DNA was reanalyzed, researchers said, the anomalies were linked to cancer in each of the women.”
However, a December 2014 NBC News article “Prenatal Tests Have High Failure Rate, Triggering Abortions” (online at: http://www.nbcnews.com/health/womens-health/prenatal-tests-have-high-failure-rate-triggering-abortions-n267301) states:
“But positive results can be wrong 50 percent or more of the time. And an investigation by the New England Center for Investigative Reporting published in the Boston Globe found that “likely hundreds” of women are aborting fetuses based on this new generation of (noninvasive) testing. One company reported a 6.2 percent abortion rate based on screening results alone — and without further testing, there is no way to know how many of those may have been due to a false positive. (emphasis added)”
Having had a daughter Karen with Down Syndrome in 1982, I was often asked if I had had prenatal testing which at that time was primarily amniocentesis. I said no and that the only time I would consider it would be if there seemed to be a problem that hopefully could be corrected.
But the question led me to research prenatal testing and talk to one of the top geneticists in my city.
I also read the first edition of the book “The Tentative Pregnancy: How Amniocentesis Changes the Experience of Motherhood” by Barbara Katz Rothman, ironically a “pro-choice” advocate. The book was an eye-opener for me about how prenatal testing can interfere with the mother/child bonding process during pregnancy even when the results are normal.
So it is ironic that this latest breakthrough in discovering cancer that can save the lives of expectant mothers winds up exposing the risk to those same mothers when, out of fear, they decide to have an abortion after an abnormal or inconclusive prenatal blood test. N. Valko RN, 15 July 2015]
Prenatal Blood Tests Could Detect Cancer in Mothers
Ability to analyze both maternal and fetal DNA at the same time can lead to surprising results
A popular new type of prenatal test intended to find genetic flaws in a fetus can in rare cases also reveal previously undiagnosed cancer in the mother.
The unexpected finding emerged in a study involving eight women who initially had abnormal results from the prenatal blood test, but for whom a subsequent assessment showed their babies were normal.
When the mothers’ DNA was reanalyzed, researchers said, the anomalies were linked to cancer in each of the women.
Researchers said the report, presented Monday at a meeting of the International Society for Prenatal Diagnosis in Washington, D.C., underscores both challenges and opportunities for the tests, which have altered the prenatal testing landscape since they first hit the market in 2011.
Excerpts from the Introduction and Discussion of the JAMA study: “The diagnosis of cancer during pregnancy is relatively uncommon, with an incidence of about 1 in 1000 gestations.15
The most common malignancies observed in pregnant women are breast and cervical cancers, Hodgkin and non-Hodgkin lymphomas, malignant melanoma, leukemia, ovarian cancer, and colorectal cancer.15
“The purpose of this study was to retrospectively examine DNA sequencing data in a series of pregnant women with abnormal NIPT results involving aneuploidies of chromosomes 13, 18, 21, X, or Y, who were diagnosed with cancer after prenatal testing occurred. In addition, to better understand the frequency with which maternal cancer might provide an explanation for abnormal NIPT results that are discordant with the fetal karyotype, all abnormal test results in the clinical laboratory and available clinical outcomes were reviewed.”
[From the Discussion] “The data presented here underscore the necessity of performing a diagnostic procedure to determine the true fetal karyotype whenever NIPT results reveal chromosomal abnormalities. Many genetic counselors and obstetricians are concerned that an NIPT result of multiple aneuploidies or autosomal monosomy may be suggestive of maternal cancer.
When there is discordance between the fetal karyotype and NIPT result, occult maternal malignancy, although very uncommon, may be an explanation for the findings.
Based on the results of the study, we estimate there is between a 20% and 44% risk of maternal cancer if multiple aneuploidies are detected.
However, until further studies are done to assess the clinical implications of discordant NIPT and fetal karyotype results, it is not clear what, if any, follow-up clinical evaluation is appropriate.24 (Amant F, Verheecke M, Wlodarska I, et al.
Presymptomatic identification of cancers in pregnant women during noninvasive prenatal testing [published online June 5, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.1883.)”
JAMA study July 14, 2015, Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies, Vol 314, No. 2, JAMA. 2015;314(2):162-169.
The noninvasive prenatal blood tests can detect evidence of fetal abnormalities in the blood of a pregnant woman.
That enables doctors to determine whether a fetus is at risk for such genetic abnormalities as Down syndrome with a blood test rather than with more invasive amniocentesis or chorionic villus sampling that can, in rare cases, induce miscarriages.
But as the new study shows, the unique ability to analyze both maternal and fetal DNA at the same time can lead to surprising results.
“When the test first came out we didn’t think about cancer being a possibility,” said Diana Bianchi, executive director of the Mother Infant Research Institute at Tufts Medical Center, Boston.
“I’ve been working in this field for 25 years, and it’s something that we never expected to find.”
Dr. Bianchi is lead author of the study, which was also published online by the Journal of the American Medical Association — http://jama.jamanetwork.com/article.aspx?articleid=2389341#tab1
While the noninvasive tests are considered highly accurate, Dr. Bianchi said the new findings underscore the need to have any positive result confirmed by amniocentesis or chorionic villus sampling diagnostic test before considering whether to terminate a pregnancy or to plan for a child with developmental disabilities.
“Most of the time, the results do confirm the screening test,” she said, but it is possible the initial result “may have nothing to do with the fetus.”
The tests are recommended only for women considered at high risk of carrying fetuses with chromosomal abnormalities, but they have been rapidly adopted by clinicians and patients.
Since they first came on the market in 2011, more than 2 million tests have been performed world-wide, Dr. Bianchi said.
Leading marketers of the tests are Illumina Inc., ILMN 0.43 % which funded the study, and Sequenom Inc., SQNM -1.57 % both in San Diego.
The eight cases in the study came from a database of more than 125,000 blood samples submitted to Illumina between 2012 and 2014, of which 3,757, or 3%, were positive for at least one chromosomal abnormality associated with Down syndrome and other conditions.
Among the very small number of instances where follow-up tests showed the fetus was normal, doctors later reported 10 cases of cancer.
Among the eight women studied, three had their cancers diagnosed because of the abnormal findings.
“These women said they feel like their babies saved their lives because that was the finding that prompted the additional workup and treatment,” Dr. Bianchi said.
Unanticipated results from genetic tests, known as incidental findings, are the subject of ongoing debate among genetics experts and clinicians about the ethics of whether and how to divulge such information to patients.
For instance, if a genetic test for a childhood disease turned up evidence of an elevated risk for breast cancer later in life, there is no consensus on when or how to inform the patient.
In the case of maternal cancer, “this is a very interesting incidental finding because it’s something that potentially you need to take immediate action about,” Dr. Bianchi said.
The full implications of the new findings need further study, said Roberto Romero, a perinatology researcher at the National Institute of Child Health and Human Development and colleagues in an editorial accompanying the study.
With the growing popularity of the noninvasive tests, there is increased need “to provide informed advice to potentially affected pregnant women” and to help guide their care, they said.
[13 July 2015, Ron Winslow, http://www.wsj.com/articles/prenatal-blood-tests-could-detect-cancer-in-mothers-1436818819 ; 15 July 2015, Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies, Vol 314, No. 2, JAMA. 2015;314(2):162-169, http://jama.jamanetwork.com/article.aspx?articleid=2389341#tab1 ; N Valko RN, 15 July 2015]
Importance Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care.
To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies.
Design, Setting, and Participants
Case series identified from 125?426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing.
Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation.
Exposures NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y).
Main Outcomes and Measures
Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers.
Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort.
From a cohort of 125,426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y.
From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]).
All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident.
Conclusions and Relevance
In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.
[ http://jama.jamanetwork.com/article.aspx?articleid=2389341#tab1 , and http://jama.jamanetwork.com/article.aspx?articleid=2389341#jpc150004r24 ]