Universal newborn screening programs are usually designed to detect serious conditions in asymptomatic infants in order to provide treatment that can greatly ameliorate a disease or even prevent it from occurring. The medical, financial, and social costs and benefits of such programs can be evaluated using standard public health criteria1,2, and recent commentaries3,4 present a strong case for why we need to collect large-scale trial data that will enable us to do such evaluations.

Discussions of genomic newborn screening often focus on sequencing all of the protein-coding genes, but the function of most human genes is unknown, and sequencing these genes would be of no immediate value. Almost all concrete proposals and pilot projects for genomic newborn screening actually involve bioinformatics analysis of only a panel of genes, usually, just a few hundred, that are known to be associated with serious mendelian diseases that occur in young children and are clinically “actionable”. However, genome sequencing also provides information on single nucleotide polymorphisms (SNPs), the genetic markers that are used in most studies of common adult-onset diseases as well as of traits like IQ, height, and ancestry. The fact that population-based genome sequencing would provide information on thousands of genes that are not the targets of newborn screening and on millions of SNPs in every infant has led to suggestions that genomic newborn screening might be valuable for many purposes beyond detecting potentially treatable childhood-onset genetic diseases in healthy-appearing babies. These “additional benefits” might include shortening the diagnostic odyssey in children who subsequently develop symptoms of a genetic disease or informing a family of the likelihood that an infant will develop a genetic disease for which no effective treatment currently exists. Genomic data could also be used to provide risk stratification for common diseases of later life, pre-emptive pharmacogenomic testing, or heterozygous carrier status for thousands of recessive diseases. In addition, genomic screening of newborn infants could provide information for parents and other family members regarding their own risks for developing a serious genetic disease or for having a child with such a disease.

The costs and benefits of using genomic data for purposes other than screening for serious diseases that can be effectively prevented or treated in infancy cannot be evaluated using the public health criteria that justify conventional newborn screening3,4. Routine genome sequencing for any purpose has the potential to harm some of the infants who are screened5,6, and there is usually no laboratory test or imaging study that can reliably establish the clinical diagnosis of a genetic disease in an asymptomatic child. Thus, it may be necessary to follow children clinically for many years to recognize false positive and false negative newborn screening results for many genetic diseases.

One of the most important reasons that many conventional newborn screening programs have been successful is that they are universal – almost every baby born within the jurisdiction receives newborn screening7,8. An important factor in achieving such inclusive coverage is thought to be the use of implied consent – all parents are assumed to want this screening because of the severity of the diseases included and the urgency and effectiveness of available treatments for the baby7,8. The assumption of potential benefit for all infants may also apply to newborn screening for other genetic diseases that meet standard public health disease screening criteria1,2, and implied consent may also suffice for these conditions. However, genomic newborn screening to achieve additional potential benefits like those listed above is very likely to require explicit parental consent for screening7,8,9. Moreover, many of these additional benefits cannot be achieved without long-term storage of the baby’s genomic data, which would require explicit parental consent in most jurisdictions10.

Long-term storage of genomic data raises a number of legal, ethical, and privacy concerns9,11,12. The benefit of maintaining an electronic record of an individual’s genome sequence is predicated on the assumption that genome sequencing is difficult to obtain and very expensive. This is no longer true, and if genome sequencing were cheap enough for universal genomic newborn screening to be practical, repeat sequencing would probably be less expensive and more informative than storing a person’s genomic data securely for many years. Resequencing a stored newborn screening blood spot or sequencing a sample from concerned individuals or family members when they need or desire the information could provide most, if not all, of the additional benefits suggested for genomic newborn screening without the need for long-term storage of the baby’s sequence data.