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Abstract

The strategy of chromosomal microarray analysis (CMA) for all is attractive due to its high accuracy, giving couples a precise answer regarding a wide variety of potentially devastating genetic diseases/syndromes in their fetus, allowing them to make important choices about the pregnancy, including the option for pregnancy termination.The discovery of ambiguous findings, with the obvious disadvantage of causing anxiety for the family, necessitates pretest genetic counseling for all. Apparently, not all patients who seek 'the best test for the fetus' really understand the robustness and resolution of CMA. One possibility is that, after receiving a thorough explanation regarding the capabilities of CMA, including the identification of variants of uncertain significance and susceptibility loci, couples may choose not to undergo the test or limit the extent of its results. An unwanted scenario in this setup is having an unexpected CMA result for which the couple was not prepared, and this should be prevented by mandatory pretest explanation. Some of these ambiguous CMA findings have the added value of increased vigilance for developmental delay in affected children, with the option, in some instances, for early intervention, which may improve outcome.We believe that the timing of invasive prenatal diagnosis should be relatively early in pregnancy, either by chorionic villus sampling or amniocentesis performed as early as safely allowed. However, as some sonographic signs will appear later in gestation, pathogenic results might be diagnosed by CMA in apparently 'low-risk' cases in which conservative follow-up could have identified anatomical findings requiring prenatal testing according to conventional criteria.As Baert et al. stated, the cost of the procedure is similar to the cost of non-invasive prenatal testing (NIPT), and the total expenditure of a CMA-for-all strategy may be lower than that of a screening-based strategy when taking into account possible postnatal costs. Future policies may provide genome-wide NIPT as the recommended screening test and CMA as the diagnostic test of choice. This discussion does not deal with the capabilities of exome sequencing for low-risk pregnancies, which, to date, is a modality used in the prenatal setup almost exclusively for the investigation of cases of fetal malformation with negative CMA.Despite the many advantages of CMA for all, we agree with Baert et al. that each couple should be offered all the available options for prenatal screening and diagnosis with proper consultation, and choose the most suitable option for them. Some couples, who would not consider pregnancy termination given even severe genetic findings for cultural or religious reasons, may decline an invasive test or even screening, and this is a legitimate choice that should be respected by caregivers.