Diagnostic yield and psychological outcomes among women pursuing trio-exome sequencing: Do women with recurrent anomalous fetal phenotypes experience more negative psychological outcomes?

Purpose: To describe psychological outcomes among people with recurrent anomalous pregnancies pursuing trio-exome sequencing (exome sequencing (ES)) compared to those with one affected.

Methods: We analyzed data from a prospective ES cohort, enrolling patients with major fetal anomaly and normal microarray. Participants completed validated scales before and after ES. We (1) compared responses of those with multiple anomalous pregnancies to those with one affected and (2) conducted linear regression to examine associations between multiple affected pregnancies and post-ES constructs.

Results: Of 166 trios, 61 (37%) received results from ES. Forty (24%) had more than one affected pregnancy and 45% of those received a result explaining the fetal phenotype. All participants had clinically significant presequencing generalized psychological distress. For the 93 who completed the post-ES surveys, those with multiple affected pregnancies had higher psychological adaptation scores but worse test related distress scores (9.3 (6.2) versus 7.1(5.6), p = 0.12) and (14.3 (1.5) versus 15.4 (1.4), p = 0.01). In linear regression models, there were no significant differences in post-ES constructs after adjusting for clinically relevant covariates.

Conclusions: All individuals experienced significant generalized psychological distress in the pre-ES period, extending our knowledge of how pregnancy history contributes to parental sequencing outcomes.