Offering pregnant women different levels of genetic information from prenatal chromosome microarray: a prospective study

Abstract

This study aimed to examine the choice pregnant women make about the amount of fetal genetic information they want from chromosome microarray. Women having invasive prenatal testing in the absence of fetal structural abnormality were recruited in Victoria, Australia. A decision aid for women described 'targeted' analysis as reporting only copy number variants implicated in a highly penetrant and well-described phenotype and 'extended' as additionally reporting variants of uncertain or unknown significance. Participant's choice and demographics were collected by survey before chorionic villus sampling or amniocentesis; psychological data were also collected then and again about 10 days after receiving results. High-resolution single-nucleotide polymorphism array analysis was performed, and a clinical review committee assessed variants for reporting before returning results to participants. Sixty-six participants (59.5%) chose extended analysis and 45 (40.5%) targeted. Choosing extended information was associated with (1) indication for prenatal diagnosis: maternal age alone (adjusted odds ratio (adjOR) 9.6, 95% confidence interval (CI): 1.4-66.0, p= 0.02), or 'other' indication (adjOR 7.1, 95% CI: 1.5-33.1, p= 0.01)); (2) >12 months to conceive (adjOR 4.1, 95% CI: 1.0-17.7, p= 0.05); and (3) Asian background (adjOR 4.67, 95% CI: 1.0-21.0, p= 0.04). No adverse psychological impact occurred in either group. We conclude that offering pregnant women different levels of fetal genetic analysis is warranted, alongside decision support.

Maternity health care professionals' views and experiences of fetal genomic uncertainty: A review

“…Similarly, the United Kingdom has developed written resources to improve the quality and consistency of pretest counseling with a national sample consent form and information sheet for prenatal CMA . Other notable measures to address the challenges of genomic uncertainty include the formation of national databases and committees to discuss ambiguous cases and provide reporting recommendations, and decision aids to augment clinical consultations …”

Detection of copy number variants with chromosomal microarray in 10 377 pregnancies at a single laboratory

“…The frequency observed in our study was lower, which could possibly be related to the less complicated ultrasound findings and larger number of cases studied (Table 4). The incomplete penetrance of sCNV provide difficult prenatal dilemmas, as not all women are interested in such results 16 and counseling in these situations is difficult 17‐20 …”

Current controversies in prenatal diagnosis 2: The 59 genes ACMG recommends reporting as secondary findings when sequencing postnatally should be reported when detected on fetal (and parental) sequencing

“…Evidence from the prenatal diagnosis setting is limited, but suggests that at least 40% of women having prenatal diagnosis wish to limit the amount of genetic information about their fetus that is returned to them. 19 More research has been undertaken in the postnatal setting, in which it is clear that parental attitudes vary greatly, with subsets of parents wanting all information, some information, or no information. 20 Newborn genomic screening research shows that more than one third of parents choose not to receive additional findings, for reasons that include feeling overwhelmed, concern about abnormal results, insurance and privacy, and discomfort with genetic testing more broadly.…”