fetal chromosome abnormalities.
Karyotypes have limitations. Technicians must grow the sample cells in a lab culture for several weeks, and some cultures fail due to contamination or other snags. Cells from the mother may be mixed in with the fetal tissue sample, so the karyotype may actually display the mother’s chromosomes instead of the fetus’s. The results of the test are then useless.
Natera’s test can sort out the fetal DNA from the mother’s, Pettersen says. Rather than relying on the physical appearance of the chromosomes, Natera uses a microarray or “gene chip” to identify variations in specific sequences of DNA, both from the fetal sample and another from the mother for comparison.
The Natera test can detect not only entire missing chromosomes or extra copies, but can also find abnormalities within the fetal chromosomes. For example, there might be missing or duplicated sections in a chromosome. The results can help women plan for their next attempt to conceive.
“If we know the chromosomal abnormality, we can give her risk factors for the future,” Pettersen says. Natera has a staff of 16 genetic counselors available to discuss the results of all its tests and their implications with both patients and their doctors, she says.
Identifying a genetic cause for a miscarriage can also help rule out other reasons for the pregnancy loss, including the shape of the uterus, maternal hormonal imbalances, antibody reactions, and clotting, Pettersen says. This can spare the woman from an extensive series of further tests, as well as save money for the healthcare system, she says.
For a young woman who has had a single miscarriage caused by a non-inherited chromosomal abnormality, the risk of another miscarriage may be only slightly higher, Pettersen says. During the woman’s next pregnancy, she could opt for prenatal tests to find out if the fetus again has genetic problems that could prevent a successful pregnancy or cause birth defects.
The risk of fetal chromosomal abnormalities is higher in older mothers—who may consider choosing in vitro fertilization after a first miscarriage.
Parents who have had multiple miscarriages may be able to trace back the causes with the Natera test if the tissues containing fetal DNA have been properly preserved, Pettersen says. The doctors most likely to order collection of tissue from a miscarriage are IVF specialists and physicians treating women who have lost more than one pregnancy, she says. (Women can collect the sample themselves if they miscarry at home, and know they are interested in having the test. Natera instructs women to place the sample in a sterile container such as a new Ziploc bag and refrigerate it. If the woman’s doctor then orders the test, Natera ships a collection kit to the woman for transport of the sample to the company for analysis.)
Although many miscarriages come from random genetic abnormalities that may never recur, the Natera test can detect problems that may pose continuing challenges in pregnancy.
For example, some couples have a 50-50 chance of miscarriage or a baby with birth defects if one parent has a “balanced chromosome rearrangement,” a condition that affects one out of 500 people in the healthy population, Pettersen says. This can occur when chromosomes “swap” sections with each other.
All the genes are retained in such balanced re-arrangements, and the parent is usually healthy. But when the chromosomes of the parent and partner are re-shuffled and combined in the process of conception, the chromosomes of the fetus may end up with missing parts. The Natera test can reveal that the fetus ended up with missing chromosome sections. Further testing might be needed to determine which of the parents has the balanced chromosome rearrangement.
“They don’t know they have it,” Pettersen says.
Another genetic accident of conception—a rare one—may have a profound impact on the mother’s health. Called “uniparental disomy,” this is a situation in which both copies of each of the 23 chromosomes in the fetus come from either the father alone or the mother alone, Pettersen says. If the father is the sole source of the fetal chromosomes, this can lead to a form of uterine cancer called choriocarcinoma, which is often curable when doctors diagnose it early. The Natera test can detect the chromosomal abnormality in the fetal tissue.
Natera has not conducted clinical trials on its miscarriage test, but the company in 2012 published a joint paper with the Stanford Fertility & Reproductive Medicine Center. In the study analyzing tissue from 30 miscarriages, the results of the Natera test agreed with traditional karyotype results in 93 percent of all findings of chromosomal abnormalities that were relevant to clinical treatment decisions. At the time, the Natera test didn’t detect certain rare genetic abnormalities, the authors pointed out. But they noted advantages of the Natera test: its quicker turnaround time; its elimination of the cell culture process needed for karyotyping; its ability to distinguish maternal from fetal chromosomes; and its identification of uniparental disomy.
Natera continously reviews the scientific literature for new insights on the impact of chromosomal variations on miscarriage and the health of the fetus, Pettersen says. The company has not changed the 317,000 locations called single nucleotide polymorphisms, or SNPs, that it tests across the chromosomes. But it has updated its bioinformatic algorithms to pick up smaller changes in DNA sequences that are now seen as significant, she says.
As a private company, Natera doesn’t disclose revenues for its products. But the company views miscarriage testing as a good business bet. For one thing, home pregnancy tests are making more women aware about a pregnancy early, Pettersen says. They are therefore more likely to realize that they are having a miscarriage if they begin bleeding, she says. In the past, an early miscarriage might have been mistaken for a heavy period.
Health plans are often willing to cover the cost of a miscarriage test for women who have had more than one miscarriage, for IVF clients, and for older women, Pettersen says. But younger women are increasingly eager to know the cause of a miscarriage—even when it’s their first, Pettersen says. Aside from the insights they may gain about planning another pregnancy, women may benefit from knowing the miscarriage was just a fairly common “accident of nature,” she says.
“There’s nothing they did to cause that,” Pettersen says. “That can help them.”
[Corrected 2/12/14. Due to a typographical error on Natera’s website, a previous version of this story misspelled Barbara Pettersen’s surname. It is Pettersen, not Petterson.]
