ScreenPlus: A Comprehensive, Flexible, Multi-disorder Newborn Screening Program

NCT ID: NCT05368038

Last Updated: 2025-09-12

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 100000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-10
• Study Completion Date: 2029-08-31

Brief Summary

ScreenPlus is a consented, multi-disorder pilot newborn screening program implemented in conjunction with the New York State Newborn Screening Program that provides families the option to have their newborn(s) screened for a panel of additional conditions. The study has three primary objectives: 1) define the analytic and clinical validity of multi-tiered screening assays for a flexible panel of disorders, 2) determine disease incidence in a large newborn population, and 3) assess the impact of early diagnosis on health outcomes. Over a nine-year period, ScreenPlus aims to screen 100,000 infants born in eight high birthrate hospitals in New York for a flexible panel of rare genetic disorders. This study will also evaluate the Ethical, Legal and Social issues pertaining to NBS for complex disorders, which will be done via online surveys that will be directed towards ScreenPlus parents who opt to participate and qualitative interviews with families of infants who are identified through ScreenPlus.

Detailed Description

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 (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 newborn population. The investigators will evaluate different consent and engagement models, including direct, in-person interaction and the use of an electronic 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 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. 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.

Conditions

Acid Sphingomyelinase Deficiency; Ceroid Lipofuscinosis, Neuronal, 2; Cerebrotendinous Xanthomatosis; Fabry Disease; GM1 Gangliosidosis; Gaucher Disease; Lysosomal Acid Lipase Deficiency; Metachromatic Leukodystrophy; Mucopolysaccharidosis II; Mucopolysaccharidosis III-B; Mucopolysaccharidosis IV A; Mucopolysaccharidosis VI; Mucopolysaccharidosis VII; Niemann-Pick Disease, Type C

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Newborn infants born at a ScreenPlus pilot hospital

Parents who give permission will have their infant's sample screened for the ScreenPlus panel. Infants who screen positive after multi-tiered testing will be referred to a ScreenPlus doctor for confirmatory testing and care coordination.

Confirmatory Testing

Intervention Type: DIAGNOSTIC_TEST

All positive screens will be referred using standard notification procedures, where the New York State NBS reporting team contacts the ScreenPlus site medical geneticist, who will contact the newborn's pediatrician and family. The initial evaluation will include a clinical examination and confirmatory molecular studies, enzymatic and biomarker studies, when available. All aspects of the confirmatory testing will be at no cost to the participants. If confirmed to have a ScreenPlus disorder, the investigators will counsel the family and help connect them with treatment, clinical trials and disease specialists. The investigators will also provide emotional and social support resources to help in this journey.

Interventions

Confirmatory Testing

All positive screens will be referred using standard notification procedures, where the New York State NBS reporting team contacts the ScreenPlus site medical geneticist, who will contact the newborn's pediatrician and family. The initial evaluation will include a clinical examination and confirmatory molecular studies, enzymatic and biomarker studies, when available. All aspects of the confirmatory testing will be at no cost to the participants. If confirmed to have a ScreenPlus disorder, the investigators will counsel the family and help connect them with treatment, clinical trials and disease specialists. The investigators will also provide emotional and social support resources to help in this journey.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• All newborn infants born at a ScreenPlus pilot hospital
• Infants who are less than four weeks old, regardless of sex, gestational age, or health status.

Exclusion Criteria

• A newborn screening sample is unavailable
• Infants who are more than four weeks old

• Maximum Eligible Age: 4 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Alexion Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: collaborator

Cure Sanfilippo Foundation

UNKNOWN

Sponsor Role: collaborator

Dana's Angels Research Trust (DART)

UNKNOWN

Sponsor Role: collaborator

Mirum Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Orchard Therapeutics

INDUSTRY

Sponsor Role: collaborator

Passage Bio, Inc.

INDUSTRY

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Sio Gene Therapies

INDUSTRY

Sponsor Role: collaborator

Takeda Pharmaceuticals North America, Inc.

INDUSTRY

Sponsor Role: collaborator

The FireFly Fund

UNKNOWN

Sponsor Role: collaborator

The Noah's Hope - Hope 4 Bridget Family Foundations

UNKNOWN

Sponsor Role: collaborator

Travere Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: collaborator

Ara Parseghian Medical Research Fund

UNKNOWN

Sponsor Role: collaborator

New York State Department of Health

OTHER_GOV

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melissa Wasserstein, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

Maimonides Medical Center

Brooklyn, New York, United States

NYU Langone Hospital - Brooklyn

Brooklyn, New York, United States

North Shore University Hospital

Manhasset, New York, United States

NYU Langone Health - Tisch Hospital

New York, New York, United States

Mount Sinai West

New York, New York, United States

Mount Sinai Hospital

New York, New York, United States

Long Island Jewish Medical Center

Queens, New York, United States

Jack D. Weiler Hospital

The Bronx, New York, United States

ScreenPlus Coordinating Core, Children's Hospital at Montefiore

The Bronx, New York, United States

Countries

United States

References

Kelly NR, Orsini JJ, Goldenberg AJ, Mulrooney NS, Boychuk NA, Clarke MJ, Paleologos K, Martin MM, McNeight H, Caggana M, Bailey SM, Eiland LR, Ganesh J, Kupchik G, Lumba R, Nafday S, Stroustrup A, Gelb MH, Wasserstein MP. ScreenPlus: A comprehensive, multi-disorder newborn screening program. Mol Genet Metab Rep. 2023 Dec 14;38:101037. doi: 10.1016/j.ymgmr.2023.101037. eCollection 2024 Mar.

Reference Type: BACKGROUND

PMID: 38173711 (View on PubMed)

Calonge N, Green NS, Rinaldo P, Lloyd-Puryear M, Dougherty D, Boyle C, Watson M, Trotter T, Terry SF, Howell RR; Advisory Committee on Heritable Disorders in Newborns and Children. Committee report: Method for evaluating conditions nominated for population-based screening of newborns and children. Genet Med. 2010 Mar;12(3):153-9. doi: 10.1097/GIM.0b013e3181d2af04.

Reference Type: BACKGROUND

PMID: 20154628 (View on PubMed)

Wasserstein MP, Caggana M, Bailey SM, Desnick RJ, Edelmann L, Estrella L, Holzman I, Kelly NR, Kornreich R, Kupchik SG, Martin M, Nafday SM, Wasserman R, Yang A, Yu C, Orsini JJ. The New York pilot newborn screening program for lysosomal storage diseases: Report of the First 65,000 Infants. Genet Med. 2019 Mar;21(3):631-640. doi: 10.1038/s41436-018-0129-y. Epub 2018 Aug 10.

Reference Type: BACKGROUND

PMID: 30093709 (View on PubMed)

Related Links

https://einsteinmed.edu/research/screenplus/

Official ScreenPlus information page on the Albert Einstein College of Medicine website.

Other Identifiers

R01HD073292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2019-10774

Identifier Type: -

Identifier Source: org_study_id