Program seeks Council approval for renewal of an initiative titled “Natural History of Disorders Screenable in the Newborn Period.” State newborn screening programs screen nearly four million infants every year to identify those at risk for the 38 core and 26 secondary congenital disorders that comprise the Recommended Uniform Screening Panel (RUSP).
Adding a new condition to the RUSP requires an evidence-based review process overseen by a federal advisory committee (the Advisory Committee on Heritable Disorders in Newborns and Children). This review process evaluates the natural history of the disorder, the robustness of the screening test, and the effectiveness of available treatments, among other considerations. However, it is difficult to receive NIH funding for natural-history studies to support the evidence base for conditions nominated for addition to the RUSP, as often these studies are not hypothesis-driven.
There has been a rapid expansion of the number of conditions included in state newborn screening panels and the RUSP, including many with late-onset forms. For many of these conditions, a comprehensive understanding of their natural history is still lacking, representing a knowledge gap that threatens the ability to develop and evaluate the most effective interventions for infants identified via newborn screening, particularly as they age.
The goal of this initiative is to improve our clinical understanding of disorders detectable through newborn screening by supporting natural-history studies that will help to characterize the sequence and timing of the onset of symptoms and complications of the conditions. Furthermore, these natural-history studies will inform the development of targeted, age-appropriate, and disease stage-relevant treatments for individuals identified through newborn screening for conditions that currently are, or may become, part of the RUSP.
This proposed concept aligns with the NICHD mandate to carry out, coordinate, and expand research in newborn screening as part of the Hunter Kelly Newborn Research Screening Program authorized by the Newborn Screening Saves Lives Act of 2008 (reauthorized in 2014).
This proposed concept aligns with the IDDB research priorities focusing on newborn screening tests and their translation into clinical care. It also addresses the Strategic Planning Research Theme #4: Identifying Sensitive Time Periods to Optimize Health Interventions.
The original RFA (FY 2011) funded two applications. Both projects were highly successful: the first defined the natural history of inborn errors of metabolism through a prolific longitudinal study, and the second identified and followed up with infants with spinal muscular atrophy (SMA), laying the groundwork for the addition of SMA to the RUSP. The second iteration of the PAR funded three applications, including natural-history studies of sex chromosome trisomy conditions (47, XXY; 47, XXX; 47, XYY), succinic semialdehyde dehydrogenase deficiency, and long-chain-3-hydroxyacyl-CoA dehydrogenase retinopathy. The third – and current – iteration of the PAR (PAR-21-115) has received multiple meritorious applications; so far, one has been funded: a continuation of the sex chromosome trisomy study. While this PAR has not made many awards, the applications funded to date have been impactful and have advanced our understanding of rare diseases.
Program Contact
Kathleen Huntzicker
Intellectual Development and Disabilities Branch (IDDB)
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