Genomic Newborn Screening: Are We Ready?

Elizabeth H. Dorfman; Robert C. Green, MD, MPH


December 18, 2012

In This Article

Editor's Note:
Newborn screening is a mandated, state-administered public health program designed to identify children with conditions that require immediate medical action to avoid death or severe disability. Newborn screening began in the 1960s with screening for phenylketonuria, and the number of conditions included in newborn screening panels has increased over the years. A federal panel currently recommends screening for 31 core conditions,[1,2] but states can -- and many do -- screen for other conditions.[3] The evolution of states' newborn screening panels has occurred in part as a result of advances in technology that increased the number of testable conditions. Whole genome sequencing is a new technology that could dramatically expand the number of conditions tested, and efforts to explore how to apply this technology to newborn screening are underway.[4]

On behalf of Medscape, Elizabeth H. Dorfman, a graduate student at the University of Washington Institute for Public Health Genetics, Seattle, Washington, interviewed Robert C. Green, MD, MPH, Associate Professor of Medicine and Director of the G2P Research Program ( in the Division of Genetics at Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, about ethical issues associated with the use of genomic sequencing technologies in voluntary and state-mandated newborn screening efforts.

Newborn Screening Programs: How Does Genomics Fit In?

Ms. Dorfman: Let's start with some general questions. In the last few years, a national dialogue has begun to emerge regarding the use of whole genome sequencing technology in newborn screening. What do you think are the main factors driving this discussion? In broad terms, how might whole genome sequencing improve upon the current system, and are there any potential downsides?

Dr. Green: Clearly, one of the main drivers is the reduction in cost of whole exome and whole genome sequencing technology, which is making this technology available in situations where it could not have been contemplated before. Of course, people are already using sequencing in the diagnosis of rare diseases and in the treatment of cancer, with the expectation that it will soon be useful to guide medication choices as well as to detect preconception carrier states and even in newborn screening. The problem is that sequencing provides an enormous range of information, from information that is highly reliable, accurate, and actionable to information that is simply confusing. The potential deluge of information that could be available through sequencing technologies would strain the culture and the fabric of the newborn screening world.

Ms. Dorfman: State newborn screening programs include educational components, screening, diagnosis, case management, follow-up, and evaluation. Where and how do you think that whole genome sequencing is likely to integrate into this system, and do you think that it would complement or replace the current screening and diagnostic tests?

Dr. Green: There are many questions embedded here, and one of the most important ones is whether we are thinking in the near term or in the long term. Remember that current newborn screening is a state-mandated program that is extremely cost-effective, and it is able to continue to be cost-effective in part because it offloads some of the cost for secondary diagnosis, case management, follow-up, and evaluation on to the clinical care system. Newborn screening programs do some education, they do some screening, and they often take preliminary steps in diagnosis, but they tend to identify individuals, in many cases, who must then be further evaluated and treated in metabolic clinics or other appropriate clinical situations.

Current newborn screening has a long, slowly evolving history of familiarity with these conditions, and generally there are resources available, at least in specialized centers, to manage them. For example, most specialized centers have a pediatric metabolic clinic. No similar infrastructure is currently in place to interpret the results of newborn sequencing.

Setting aside cost considerations, some of the tests that are administered in current newborn screening panels could theoretically be replaced with genome sequencing, but because similar mutations can give rise to diseases with very different clinical presentations, the sequence alone will not quickly replace metabolic screening. And tests for some conditions, such as hypothyroidism, would not lend themselves to replacement with genomic screening at all.

Ms. Dorfman: Under the framework that was used to develop newborn screening, "benefit" has explicitly and exclusively related to direct improvement in an infant’s health. How do you see the use of whole genome sequencing fitting into this framework? Do you see it contributing to a possible reconceptualization of benefit for newborn screening?

Dr. Green: That definition of benefit is already being strained by groups who believe that some untreatable disorders should nonetheless be screening for in order to allow parents to anticipate what lies ahead for their child. I think it is going to be difficult to keep that framework intact in the face of pressure from advocacy groups. As newborn screening with sequencing develops, it may expand these boundaries even further. But if either conventional screening or genomic screening expands too far beyond what states can mandate and afford, we may see a parallel framework that develops in the private sector for parents who are willing to cover the costs on their own.

Ms. Dorfman: Many states currently limit parents' ability to request an exemption from newborn screening. This is justified by the states' interest in protecting vulnerable individuals from preventable harm and the presumptive benefit to children undergoing testing. How valid are fears that through more expansive testing, newborn screening will veer so far from its original public health aims as to threaten the moral and political defensibility of this mandated screening?

Dr. Green: There are some people who believe that newborn screening already goes too far in terms of mandating cooperation from parents. But, as you say, this is justified in most situations by the ethical balance of alleviating preventable harm. As both conventional newborn screening and the possibility of genomic screening offer broader and broader newborn information, including, inevitably, information that is not related to preventable harm but may be related to surveillance, later-onset disease, or carrier states in the parents, I think it is going to be harder to justify a legal mandate. One option is that newborn screening evolves into 2 tracks. One track could represent the states' interest in addressing imminent harm to the newborn that is essentially preventable, somewhat like the way we mandate car seats for infants. There could then be another track that is available to parents and pediatricians with understanding and permission of the parents.