Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project: A Randomized Clinical Trial

Abstract

Importance: Newborn genomic sequencing (nGS) may provide health benefits throughout the life span, but there are concerns that it could also have an unfavorable (ie, negative) psychosocial effect on families.

Objective: To assess the psychosocial effect of nGS on families from the BabySeq Project, a randomized clinical trial evaluating the effect of nGS on the clinical care of newborns from well-baby nurseries and intensive care units.

Design, setting, and participants: In this randomized clinical trial conducted from May 14, 2015, to May 21, 2019, at well-baby nurseries and intensive care units at 3 Boston, Massachusetts, area hospitals, 519 parents of 325 infants completed surveys at enrollment, immediately after disclosure of nGS results, and 3 and 10 months after results disclosure. Statistical analysis was performed on a per-protocol basis from January 16, 2019, to December 1, 2019.

Intervention: Newborns were randomized to receive either standard newborn screening and a family history report (control group) or the same plus an nGS report of childhood-onset conditions and highly actionable adult-onset conditions (nGS group).

Main outcomes and measures: Mean responses were compared between groups and, within the nGS group, between parents of children who received a monogenic disease risk finding and those who did not in 3 domains of psychosocial impact: parent-child relationship (Mother-to-Infant Bonding Scale), parents' relationship (Kansas Marital Satisfaction Scale), and parents' psychological distress (Edinburgh Postnatal Depression Scale anxiety subscale).

Results: A total of 519 parents (275 women [53.0%]; mean [SD] age, 35.1 [4.5] years) were included in this study. Although mean scores differed for some outcomes at singular time points, generalized estimating equations models did not show meaningful differences in parent-child relationship (between-group difference in adjusted mean [SE] Mother-to-Infant Bonding Scale scores: postdisclosure, 0.04 [0.15]; 3 months, -0.18 [0.18]; 10 months, -0.07 [0.20]; joint P = .57) or parents' psychological distress (between-group ratio of adjusted mean [SE] Edinburgh Postnatal Depression Scale anxiety subscale scores: postdisclosure, 1.04 [0.08]; 3 months, 1.07 [0.11]; joint P = .80) response patterns between study groups over time for any measures analyzed in these 2 domains. Response patterns on one parents' relationship measure differed between groups over time (between-group difference in adjusted mean [SE] Kansas Marital Satisfaction Scale scores: postdisclosure, -0.19 [0.07]; 3 months, -0.04 [0.07]; and 10 months, -0.01 [0.08]; joint P = .02), but the effect decreased over time and no difference was observed on the conflict measure responses over time. We found no evidence of persistent negative psychosocial effect in any domain.

Conclusions and relevance: In this randomized clinical trial of nGS, there was no persistent negative psychosocial effect on families among those who received nGS nor among those who received a monogenic disease risk finding for their infant.

Trial registration: ClinicalTrials.gov Identifier: NCT02422511.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Pereira, Smith, Christensen, Waisbren, Beggs, Green, and McGuire and Ms Blout Zawatsky reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Pereira reported receiving grants from the NIH and the US Department of Defense outside the submitted work. Dr Smith reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Human Genome Research Institute during the conduct of the study. Dr Christensen reported receiving grants from the NIH and Sanford Health outside the submitted work; and royalties from UpToDate for work on genomic secondary findings. Dr Beggs reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study; grants and personal fees from Audentes Therapeutics; grants from Dynacure SAS, Alexion Pharmaceuticals, Pfizer, Muscular Dystrophy Association, and the NIH; personal fees from F. Hoffmann-La Roche AG, Biogen, Asklepios BioPharmaceutical, Gerson Lehrman Group, Guidepoint Global LLC, and Kate Therapeutics; and equity in Ballard Biologics and Kate Therapeutics outside the submitted work. Dr Green reported receiving compensation for advising the AIA, Genomic Life, Grail, Humanity, Kneed Media, OptumLabs, Plumcare, Verily, and VibrentHealth and is co-founder of Genome Medical. Dr Holm reported receiving grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Human Genome Research Institute; and personal fees from Perceptive Informatics, Alexion Pharmaceuticals, Novartis Pharmaceuticals, and F. Hoffmann-La Roche AG during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Study Flow Diagram

Families lost to follow-up (LTFU) submitted a survey for the immediately previous time point, did not submit a survey for this time point, and did not return to any subsequent time point. nGS indicates newborn genomic sequencing; ICU, intensive care unit. aPassive withdrawal: neither parent completed a baseline survey within 2 weeks of enrollment and the family was therefore withdrawn. bMissing: did not submit a survey for this time point but may have returned at a subsequent time point; includes LTFU.

Figure 2.. Parents’ Scores on Vulnerable Baby Scale and Edinburgh Postnatal Depression Scale (EPDS) by Study Group Over Time

A, Vulnerable Baby Scale score by study group over time. Group × time interaction joint P = .25. See eTable 13 in Supplement 2 for generalized estimating equation results. Higher scores indicate greater concern or worry about a child’s vulnerability and health. Shaded areas indicate pointwise 95% CIs. B, Edinburgh Postnatal Depression Scale, anxiety subscale by study group over time. Group × time interaction joint P = .80. See eTable 19 in Supplement 2 for generalized estimating equation results. Higher numbers indicate more anxiety-related symptoms. Shaded areas indicate pointwise 95% CIs. nGS indicates newborn genomic sequencing.