Every parent wants a healthy baby. The purpose of prenatal screening and testing is risk stratification and diagnosis of pregnancies affected by an anatomic or genetic abnormality. Results from prenatal testing help inform parents about the health of their baby, as well as guide pregnancy management. Historically, prenatal screening and testing primarily focused on the detection of Down syndrome, as the incidence increases with maternal age and accounts for almost half of all cases of aneuploidy. Newer screening modalities such as cell-free DNA focus mostly on detecting Down syndrome. However, with recent advances in ultrasound, genetics and bioinformatics, the paradigm of prenatal screening and testing is now shifting.
While it is well known that the risk of aneuploidy increases with age, there are other structural chromosomal abnormalities that occur at a steady rate, irrespective of maternal age. What is somewhat less appreciated is the fact that while the common aneuploidies occur in approximately 1 in 500 pregnancies, significant structural chromosomal abnormalities have been reported in up to 1 in 100 pregnancies. Chromosomal microarray allows evaluation of the chromosomes at a higher resolution than karyotype and detects not only aneuploidy but small copy number variants, such as microdeletions, as well. In fact, in women under the age of 35 years, the risk of having a baby affected by one of the common trisomies is less than the risk of having a baby with a pathogenic copy number variant. As a result, prenatal screening technologies identify 20% (at most) of the chromosomal anomalies detectable by diagnostic testing with microarray. In the setting of ultrasound abnormalities, the use of chromosomal microarray yields a pathogenic result in approximately 6% of cases with a normal karyotype. Among patients with a normal ultrasound and normal karyotype, chromosomal microarray will detect a pathogenic copy number variant in approximately 1% of cases. The American Congress of Obstetricians and Gynecologists as well as the Society of Maternal-Fetal Medicine now recommend that chromosomal microarray be the first-line diagnostic test in the setting of ultrasound abnormalities and that it be offered to all women undergoing diagnostic testing.
In the era of chromosomal microarray, a screening and testing paradigm focused only on the detection of age-related common aneuploidies is antiquated. The reproductive goals and values of the parents are paramount. In other words, are the parents concerned primarily about Down syndrome or are they concerned about any underlying chromosomal abnormality that can potentially impact neurodevelopment and quality of life for their unborn child? Alternatively, the parents may not be interested in uncovering genetic abnormalities prior to birth at all and prefer to forego screening and testing altogether. Studies have shown that women view the small risk of pregnancy loss from a diagnostic procedure versus having a child with an undetected chromosomal abnormality differently. It is now incumbent upon all providers of prenatal care to engage in a discussion with parents regarding options for prenatal screening and testing, highlighting what conditions can and cannot be screened for or diagnosed, the accuracy and limitations of each test and that most importantly, there is no test that can identify all conditions.
Not only should all women have the option for diagnostic testing in pregnancy, but they should be guided to choosing the test that most adequately meets their reproductive needs.