Soon after birth, all babies born in the United States have a newborn screening (NBS)
test to check for certain medical conditions. All babies are screened, even if they
appear healthy, because most of these conditions have no obvious physical findings in a
newborn and might otherwise be diagnosed only after the development of serious problems,
such as brain damage, organ damage, or death. In fact, NBS has been an integral part of
preventable health care for over five decades, ever since the discovery that
phenylketonuria is an easily diagnosed, preventable cause of intellectual disability.
Over the past two decades, there have been dramatic advances in screening technology,
with a resulting increase in the number and complexity of disorders on NBS panels. This
enhanced ability to screen brings questions about what types of disorders are appropriate
for NBS. To that end, the Advisory Committee on Heritable Disorders in Newborns and
Children (ACHDNC) was established in 2003 to make evidence-based recommendations at the
national level regarding the suitability of various disorders for NBS. At present, the
Recommended Uniform Screening Panel, or the RUSP, includes 35 core disorders. The RUSP
nomination process uses information about disease incidence and severity, natural
history, benefits of early detection, safety and efficacy of treatment, analytic and
clinical validity of the screening tests, as well as consideration of potential harms
associated with screening and public health impact to determine whether a particular
disorder is appropriate for NBS. However, there are many disorders for which this data is
insufficient or missing. There are other disorders that challenge traditional NBS
criteria by having predominantly later-onset phenotypes, poorly defined natural history,
or unclear treatment outcomes. As these potentially life-threatening disorders might
benefit from early detection, gathering and analyzing this data is both critical and
timely. Accordingly, there is a great deal of interest in pilot NBS studies as a means to
gather objective evidence about whether a disorder is appropriate for widespread
screening.
ScreenPlus is a comprehensive, fluid, pilot NBS program that will screen 100,000
consented infants for specific disorders that are under consideration for universal NBS.
This study will generate critical data about the validity of testing for these candidate
disorders and provide estimates of disease incidence in a large, ethnically diverse
population. The investigators will evaluate different consent and engagement models,
including direct, in-person interaction and the use of a novel E-Consent framework to
educate parents about pilot NBS. The investigators will also collect nuanced information
about the ethical implications of NBS, by conducting qualitative interviews with parents
of children who have received a positive or uncertain NBS result. Parents who are
eligible to participate in ScreenPlus will also have the opportunity to complete a
flexible set of surveys of parent opinions about expanded NBS, research using dried blood
spots, and other relevant topics. Furthermore, newborns who screen positive will be
followed by a ScreenPlus physician. Through thoughtful collaboration with disease
experts, the investigators will help systematically collect disease specific measures
through detailed long-term follow-up which will enable us to critically evaluate how
affected children identified through ScreenPlus are faring, allowing objective assessment
of the impact early diagnosis has on outcome.
The investigators will share this important data with the NBS community, including the
ACHDNC, to help inform objective decision-making about widespread screening
recommendations. The ScreenPlus panel is fluid and disorders may be added/removed as
disorders satisfy the study inclusion criteria or are added to the RUSP and/or the New
York State routine NBS panel. Additionally, recognizing that the NIH, advocacy groups,
academics, and private industry all share a desire for clean, consented pilot NBS data,
the investigators created a unique financial infrastructure. This investigator-driven
arrangement permits all stakeholders to obtain aggregate data of interest in a mutually
beneficial and cost-effective manner. ScreenPlus is guided by Scientific and Community
Advisory Boards, who are comprised of rare disease experts, biochemistry specialists,
physicians, bioethicists, and patient advocates. Overall, the investigators anticipate
that ScreenPlus will become the premier consented pilot NBS program in the United States.
In sum, ScreenPlus will provide critical data about the appropriateness of NBS for
candidate disorders, the feasibility and effectiveness of consented screening models, and
parent informational needs and preferences as they relate to NBS for complex disorders.