Improved methods of prenatal testing provide parents with a wealth of data that scientists cannot interpret. Do we really need to know this much?
Four years ago, while about halfway through her pregnancy, Denise Bratina heard disturbing news. Doctors told a 37-year-old woman at the time that the amniocentesis results showed her unborn baby was missing a small fragment of chromosome 15. Missing DNA, she heard, could be responsible for a long list of health problems, including epilepsy, heart defects and developmental delays. While the defect may as well not cause any adverse changes in the baby in the future, Bratina was told. Five months later, a completely healthy baby girl, Ella, was born.
Most future parents would never know about such an anomaly in their child’s DNA, because previous prenatal tests have not been characterized by such precision in the detection of defects. However, Bratina uses microarray technology, which allows doctors to spot the smallest flaws in the fetal DNA.
DNA microarray technology in genetic diagnosis could prove to be a breakthrough in prenatal research, says Ronald Wapner, a specialist in reproductive genetics at NewYork-Presbyterian Hospital. Over the past two or three years, the genetic testing available to expectant parents has developed in an astonishing way. Researchers are learning to associate tiny anomalies detected with DNA microarrays with problems such as learning disabilities, autism and schizophrenia. It seemed a natural step for medicine to move from examining children and adults to performing fetal tests.
In a study published in December in the New England Journal of Medicine, Wapner, the principal investigator in Bratina’s study, compared DNA microarray analyzes to the traditional amniocentesis method to determine the fetal karyotype. The participants of the experiment were 4406 women over 35 years of age, in whom preliminary studies showed an increased likelihood of genetic defects in the fetus. Scientists then showed that the new method is as effective in capturing an abnormal number of chromosomes in a cell (such as in Down’s syndrome) as is the karyotype test. On the other hand, DNA microarray testing has proven to be more effective at identifying those abnormalities that eluded previous tests, later responsible for learning difficulties, autism and schizophrenia, as well as for three rare genetic diseases, Prader-Willi syndrome, Jacobsen syndrome and diGeorge syndrome ‘ and. The karyotype test proved not to be a sensitive tool for this purpose, as it did not identify abnormalities in less than 10 million DNA base pairs. Base pairs are the chemical building blocks of the human genome, and each of us has about three billion of them. The microarray will help to register anomalies regarding a small portion of DNA – only 10. base pairs.
A new type of microarray analysis is recommended for those American parents in whom the karyotype test did not explain the abnormalities in the structure of the fetal heart or brain during ultrasound. Unfortunately, DNA microarray technology is now twice as expensive as traditional prenatal testing, and not everyone will be able to bear this cost – although doctors believe the method should become more affordable over time. Based on his results, Wapner says this path should be accessible to all women. – Why should we give up the knowledge that can be obtained in this way? – he asks.
Parents who are fully aware of what awaits their child in the future may better consider all the options available, including abortion, or be prepared to raise a child who is in need of special care. Moreover, already performed surgical interventions in the womb may, in some cases, increase the chances of survival and health of the baby.
On the other hand, some researchers have warned that DNA microarray testing will provide too much redundant information, such as Denise Bratina, who was told that a genetic abnormality in her baby could result in serious impairment or no appreciable effect on his health. Meanwhile, parents are unlikely to be ready to deal with this type of uncertainty, notes Barbara Bernhardt, a genetics therapist at the Hospital of the University of Pennsylvania. Bernhardt spoke to 23 women participating in the Wapner study. Some of them obtained inconclusive results of analyzes using microarrays. Although future mothers were told that the information obtained in this way about the irregularities could have an impact on the health of their children, none of the women reacted with panic to the news. “People too often expect research to show something in black and white,” Bernhardt observes. – When they hear an ambiguous diagnosis, they cannot interpret it properly.
Bernhardt would like to develop guidelines that should be followed by therapists preparing families to obtain such detailed information. Especially since, for some mothers, the birth of a healthy baby does not put an end to fears. “Ever since I was communicated this ambiguous genetic diagnosis … if anything bad happens to him in the future … I will always agonize over it,” said one of the women Bernhardt. – I, in turn, intend to be much more vigilant now – another mother said, announcing that she would carefully monitor the child’s health and possible delays in its development.
Bratina has a similar approach to testing. The woman appreciates that her daughter will continue to be monitored as part of the Wapner study. So far, the girl has not been diagnosed with any health problems, but the mother is glad that she found out about the incomplete DNA of the child. “If there are any problems in the future, we will at least know the source,” he says.
But with DNA microarray technology, advances in prenatal testing do not stop there. For years, fetal genetic testing has necessitated invasive medical intervention – such as amniocentesis or chorionic villus sampling (CVS) – to obtain DNA material. Now, completely safe methods have emerged to test a baby for three disorders – chromosome 21 trisomy (Down syndrome), chromosome 13 trisomy (Patau’s syndrome) and chromosome 18 trisomy (Edwards syndrome) – based on the analysis of the mother’s plasma. The test known as cell-free fetal DNA testing allows you to test your baby’s DNA from material present in the mother’s bloodstream. These fragments are too small to allow complete genetic testing of the fetus, as with microarrays. The new test is currently available in the MaterniT21, Harmony and Verifi versions.
However, the cell-free fetal DNA test is treated like any other diagnostic test, which means that although it has been proven to be 99% effective in detecting Down’s syndrome. However, in order to be absolutely sure that the baby will be born with a chromosomal aberration, the pregnant woman should undergo amniocentesis or chorionic villus sampling. On the other hand, prenatal analyzes from the mother’s blood give a much more reliable result than an ultrasound or determination of the level of certain proteins and hormones in a woman. Fetal cell-free DNA testing can be performed as early as the ninth week of pregnancy.
While the benefits of these new types of prenatal testing are obvious, Mary Norton, head of the research unit for this type of prenatal testing at Stanford University, makes no mistake: doctors and patients may be too eager to take advantage of this medical advance. Currently, the American Association of Obstetricians and Gynecologists, ACOG, advises prenatal testing only for pregnant women over the age of 35 or for people with a family burden, as we still do not know its effectiveness for women outside risk groups.
In the near future, we may be able to achieve the same precision and reliability of non-invasive prenatal testing that characterize microarray testing today. Undoubtedly, scientists are able to obtain more and more information from the fragments of fetal DNA present in the bloodstream of the pregnant woman. Last year, University of Washington geneticist Jay Shendure used baby DNA samples obtained from the mother’s plasma to completely sequence the fetal genome. The cost of this project was approximately PLN 50. dollars, which means that this type of research will not be shared with a larger group anytime soon, Shendure notes. But the scientist adds that this news should not worry us. Sequencing the child’s genome by simply analyzing the mother’s blood would provide future parents with a detailed knowledge of the offspring, with an amount of data that is currently impossible to obtain even with the help of a DNA microarray that only provides insight into a fragment of the genome. “I think it’s a good thing that such research is not yet common,” said Shendure. Before we make this option available to prospective parents, we need to solve a significant number of problems – and the high cost of the study is just one of them.
Lea Winerman