Psychosocial Effect of Newborn Genomic Sequencing on Families in the BabySeq Project

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 PARTICIPANTSIn 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 MEASURESMean 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 RELEVANCEIn 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.

Medical Evaluation of Unanticipated Monogenic Disease Risks Identified through Newborn Genomic Screening: Findings from the BabySeq Project

“…A much larger study with a more diverse population would be needed to ascertain whether the anxiety to parents and cost to the healthcare system associated with speciality consultations and surveillance around these risks is worthwhile. However, it is reassuring that in a separate report we recently demonstrated that neither sequencing, nor receiving uMDRs, was associated with significantly greater parental distress or disruption of the parent-child bond, and that parents felt empowered by both positive and negative results 10 . In assessing the reactions of parents in a study like this, it is important to keep in mind that parents self-select to enroll, and their self-selection reflects a desire to receive risk information and may be biased toward greater optimism around the results.…”

“…Genomic sequencing as a screening tool in newborns is being explored 2 and supplementary genomic screening panels are now offered by several commercial laboratories 3 , but there are a number of evidentiary, ethical, and cost concerns that must be considered 1, [4][5][6][7] . The BabySeq Project is a series of randomized clinical trials of newborn screening by genomic sequencing (GS) that has generated empirical data on mechanisms of consent, gene curation, variant interpretation, disclosure methods, as well as medical, behavioral and economic outcomes [8][9][10][11][12][13] . In the initial pilot of the project, we recruited infants from both a well-baby nursery and intensive care units (ICU) who were randomized to receive either standard of care newborn screening (NBS) or NBS plus GS.…”

“…The BabySeq Project is the first rigorous examination of uMDR findings in an unselected cohort of newborns, yet has several limitations. Participation in our project was offered to the parents of several thousand infants born in a tertiary care medical center, and those who enrolled were more educated and of higher socio-economic status than the general population 10,13 . The sample size of infants carrying uMDRs is small and the constellation of unanticipated genetic findings cannot necessarily be presumed to be representative of what might be found in population-level sequencing.…”

Medical Evaluation of Unanticipated Monogenic Disease Risks Identified through Newborn Genomic Screening: Findings from the BabySeq Project

“…A much larger study with a more diverse population would be needed to ascertain whether the anxiety to parents and cost to the healthcare system associated with specialty consultations and surveillance around these risks is worthwhile. However, it is reassuring that in a separate report we recently demonstrated that neither sequencing, nor receiving uMDRs, was associated with significantly greater parental distress or disruption of the parent-child bond, and that parents felt empowered by both positive and negative results 10 . In assessing the reactions of parents in a study like this, it is important to keep in mind that parents self-select to enroll, and their self-selection reflects a desire to receive risk information and may be biased toward greater optimism around the results.…”

“…Genomic sequencing as a screening tool in newborns is being explored 2 and supplementary genomic screening panels are now offered by several commercial laboratories 3 , but there are a number of evidentiary, ethical, and cost concerns that must be considered 1, [4][5][6][7] . The BabySeq Project is a series of randomized clinical trials of newborn screening by genomic sequencing (GS) that has generated empirical data on mechanisms of consent, gene curation, variant interpretation, disclosure methods, as well as medical, behavioral and economic outcomes, with institutional review board approval and informed consent from all participants [8][9][10][11][12][13] . In the initial pilot of the project, we recruited infants from both a wellbaby nursery and intensive care units (ICU) who were randomized to receive either standard of care newborn screening (NBS) or NBS plus GS.…”