Professional forum

Non-invasive prenatal testing involves whole-genome sequencing of cell free DNA (cfDNA) fragments derived from maternal peripheral whole blood samples to screen for common chromosome disorders in singleton and twin pregnancies that can affect the health of a baby, i.e. Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13). The standard NIPT can also screen for common disorders of the sex chromosomes (i.e. Turner syndrome (45,X), Klinefelter syndrome (47,XXY), triple X syndrome (47,XXX) and XYY syndrome (47,XYY)) in singleton pregnancies. Genome-wide NIPT (gNIPT) has more recently become available and is sought by both patients and clinicians, who wish to obtain additional information related to a given pregnancy. While the positive predictive value (PPV) of the genome-wide screen for rare autosomal trisomies (13%) and segmental copy number variants is substantially lower (10-30%) than for the common trisomies (37-92%) (PMID 35608568), there is growing evidence in the literature that the use of the genome-wide component can increase the detection of fetal anomalies, and pregnancies associated with poor prognosis, intrauterine growth restrictions, malformations and adverse fetal outcomes (PMIDs: 28855395, 27362910, 25585704, 29956348). In the context of a busy general practice, the challenge lies in providing sufficient information about the purpose, scope, and outcomes of different non-invasive screening options, as well as in dealing with high-risk results.

There is a strong international move to reproductive carrier screening:
• American College of Medical Genetics & Genomics: “All pregnant patients and those planning a pregnancy should be offered Tier 3 carrier screening” (>100 gene screen)
• American College of Obstetricians & Gynecologists: “Information about carrier screening should be provided to every pregnant woman. Carrier screening and counseling ideally should be performed before pregnancy because this enables couples to learn about their reproductive risk and consider the most complete range of reproductive options”.
• The European Society of Human Genetics has reviewed the need for education among health practitioners about the science of carrier screening and the challenges in ensuring couples make informed choices about carrier screening.
• In India, the proportion of congenital abnormalities that can be attributed to genetic disorders is rising as the proportion due to malnutrition and infectious diseases is falling. As a result, there is growing interest in the role of carrier screening in reducing the incidence of congenital malformations.

1. Contrast the difference between screening test and a diagnostic test
2. Identify the appropriate follow-up testing recommended after a high risk NIPT test
3. Assess the overall performance and utility of NIPT