Dilemmas in prenatal chromosomal microarray analysis: how knowledge of a variant of uncertain significance (VUS) impacts regret and psychological outcomes in mothers who chose to terminate
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Abstract
Prenatal genetic testing is a rapidly advancing field of medicine and with the improvements in accessibility and diagnostic ability, testing for abnormalities has become a part of routine prenatal care. Historically, karyotyping was the genetic test of choice that was offered to expecting parents; however, Chromosomal Microarray Analysis (CMA) is rapidly becoming the new standard due to its higher diagnostic yield at no additional risk. CMA detects the presence of copy number variants (CNV) in the fetus’s genotype which can be classified as benign, pathogenic or as a variant of uncertain significance (VUS) based on the presence of a known associated phenotype. With the finding of a benign or pathogenic CNV parents can be better prepared to welcome their child or they can make a choice to terminate the pregnancy. Though a prenatal diagnosis can be a useful tool in allowing parents to make informed decisions, it also has significant psychological implications of the parents, specifically, mothers. Mothers can display symptoms of psychological distress, such as regret, grief, depression and PTSD, throughout their pregnancies that can persist after the child is born or after the pregnancy is terminated.
Variants of Uncertain Significance (VUS) are challenging findings to interpret as there is no knowledge of a phenotype or disease associated with the variant. Because of this uncertainty, VUS results often lead to more confusion. Parents lose the ability to make an informed choice allowing room for doubt, which can have worsening psychological effects on parents. The need for providers to disclose VUS results to patients is highly debated, since this finding can potentially lead to the termination of a healthy fetus or unnecessary psychological distress for parents. Though VUS findings are rare, they are becoming more prominent as CMA popularity increases and deserve more understanding as to how these results can impact patients and the course of their pregnancy.
The aim of this study is to gain further insight into the implications associated with VUS findings so that clinicians and patients can be more aware of the weight of possible results, prior to undergoing prenatal CMA testing. By giving pregnant mothers the choice of whether they would like to be informed of a VUS finding, the impact of the uncertainty associated with a VUS can be identified. Thus, we hypothesize that mothers who choose not to know of a VUS will experience less regret about CMA and have better psychological outcomes post termination than mothers who choose to know of a VUS.