Abstract

Definition of problem Newborn screening (NBS) is an internationally successful program for the secondary prevention of rare congenital diseases. At present, most of the target conditions in NBS are diagnosed by biochemical markers. Recent advances in genomic sequencing and in the bioinformatic evaluation of genetic variants will soon make it feasible however to expand NBS significantly by testing newborns directly for pathogenic variants. Yet, genomic newborn screening (gNBS) raises important ethical issues that require resolution, given that several pilot studies on gNBS implementation are already underway. Given a rapidly growing scholarly engagement with the ethics of gNBS, a more systematic and comprehensive mapping of the ethical issues and considerations relevant to gNBS is needed to move the debate forward at this point. - Methods In this integrative review, we survey the literature with the aim of delineating a conceptual framework for the ethics of gNBS, which organizes the ongoing debate and thereby provides guidance for further research. Here in Part I, we focus primarily on an exposition of the ethical issues and questions involved in gNBS program design. - Conclusion The ethical issues divide into issues regarding (1) the test itself and the selection of target conditions, (2) informed consent, and (3) genomic data generation, storage, and use. Regarding (1) we discuss several dimensions along which potential target conditions can differ and their ethical implications, and formulate some requirements on appropriate selection criteria with special regard to minimizing diagnostic and therapeutic uncertainty. Regarding (2) we discuss the need for informed consent, the structure and content of pre-test counseling (when, who, what, how), the suggestion of a tiered testing offer, and familial conflict. Regarding (3) we discuss liberal versus restrictive approaches to genomic data generation, parental consent to genomic raw data storage for further uses beyond the test, some candidate further uses, and the risk of abuse.