ICoNS has contributing partners worldwide

 

ICoNS is harmonizing international newborn sequencing for preventive genomics, which can reduce suffering and save lives.

The BabySeq Project led by Robert Green at Brigham and Women’s Hospital, the Broad Institute and Harvard Medical School was the first randomized clinical trial designed to measure the medical, behavioral and economic outcomes of using comprehensive genomic sequencing in newborns. The first phase of this project revealed unanticipated monogenic disease risks in 11% of apparently healthy newborn babies.

BabySeq is currently enrolling 1,000 families from diverse populations and using whole genome sequencing to assess clinical utility and cost effectiveness.

Headquarters: Boston, MA, USA • Principal Investigators: Robert Green, Ingrid Holm • Recruitment Goal: 500 • Funded: Yes • IRB Approved: Yes • Currently Enrolling: Yes

BeginNGS, a consortium spearheaded by Stephen Kingsmore at Rady Children’s Institute for Genomic Medicine (RCIGM) in collaboration with Alexion Pharmaceuticals, Travere Therapeutics, Inozyme Pharma, Fabric Genomics, Genomenon, Illumina, and TileDB, wants to provide a platform for implementing whole-genome sequencing for newborn screening, disease management and interventions, and rare disease drug development for use by partners around the world.

BeginNGS plans to enroll about 2,000 infants at seven or more sites in the US and Greece and expand to 500 disorders.

Headquarters: San Diego, CA, USA • Principal Investigator: Stephen Kingsmore

The Newborn Genomes Programme will co-design and run an ethically approved research study, the Generation Study embedded in the NHS to explore the benefits, challenges, and practicalities of sequencing babies’ genomes to accelerate diagnosis and access to treatments for rare genetic conditions.

Headquarters: London, United Kingdom • Principal Investigator: Richard Scott • Recruitment Goal: 100,000 • Funded: Yes • IRB Approved: Yes • Currently Enrolling: Yes • Aims: 1) Evaluating the utility and feasibility of screening newborns for a larger number of childhood-onset rare genetic conditions in the NHS using whole genome sequencing. 2) Understanding how babies’ genomic data could be used for research, focusing on developing new treatments and diagnostics for NHS patients 3) Exploring the potential risks, benefits, and broader implications of storing a baby’s genome over their lifetime

The Early Check study is a statewide, consented newborn screening pilot project conducted in North Carolina. Early Check is led by RTI International (Holly Peay, PI) in partnership with the University of North Carolina at Chapel Hill (Cindy Powell, PI) and the North Carolina State Laboratory of Public Health. In 2018, the project began screening a small number of genetic conditions with a goal of informing newborn screening (NBS) policy and practice. By early 2023, Early Check had returned results to over 25,000 babies; demonstrated successful recruitment, education, and electronic consent approaches across a diverse state; and evaluated genetic counseling, confirmatory testing, and follow up protocols.

Early Check is now poised to study the acceptability, feasibility, implementation, and impact of integrating genome sequencing in NBS. Beginning in late 2023, parents in North Carolina will be offered screening for a large panel of pediatric-onset, actionable genetic conditions. Parents will have options to accept a second panel of less-actionable conditions and a genetic risk score for type 1 diabetes (T1D). Our protocol includes community engagement, formative research, the selection of gene/condition pairs by an expert committee using a customized semi-quantitative framework, and extensive evaluation. Our collaboration with the North Carolina State Laboratory of Public Health ensures that our study answers critical questions about the potential for genome sequencing as a first-tier test in public health newborn screening. Our novel integration of genetic risk scores informs longer-term precision public health practice.

The Early Check sequencing study is currently supported by The Juvenile Diabetes Research Foundation, Helmsley Charitable Trust, Janssen Pharmaceuticals, and Travere Therapeutics.

Headquarters: Durham, NC, USA • Principal Investigators: Holly Peay, Cindy Powell • Recruitment Goal: 10,000 • Funded: Yes • IRB Approved: Yes • Currently Enrolling: Yes • Aims 1) Implement and evaluate the use of genome sequencing to screen newborns for childhood-onset, monogenic conditions. 2) Determine uptake and acceptability of genome sequencing newborn screening among parents of eligible newborns. 3) Implement and evaluate short-term follow-up procedures to inform public health application. 4) Assess 12-month outcomes for children with positive results and their caregivers.

The GUARDIAN project (Genomic Uniform-screening Against Rare Diseases in All Newborns), led by Wendy Chung at Columbia University Irving Medical Center in partnership with New York-Presbyterian, the New York Department of Health, Sema4’s GeneDx, and Illumina, hopes to enroll 100,000 newborns over the next four years.

The study, funded by Sema4, Illumina, and philanthropic sources, plans to use whole-genome sequencing to assess risk for an initial 250 conditions, the majority of them treatable, a number that will increase over time.

Headquarters: New York City, NY, USA • Principal Investigator: Wendy Chung

BabyBeyond is a completed project that ran from 2016-2019 and offered 106 parents predictive health information for childhood conditions for their new babies diagnosed with hearing loss. One third of parents declined predictive health information, two thirds opted to have this additional information. Some wanted as much information as possible including about untreatable childhood diseases. There were low rates of decision regret amongst all participants providing evidence that predictive health information in newborns is unlikely to cause harm.

Screen4Care, coordinated by Alessandra Ferlini and Nicolas Garnier, is a private-public partnership funded by the European Union, the pharmaceutical industry, and academic institutions plans to generate targeted or whole-genome sequencing data for at least 18,000 infants and look for treatable as well as otherwise actionable diseases.

In addition, it wants to use new algorithms to detect early disease symptoms in babies’ electronic health records.

Status: Headquarters: Ferrara, Italy • Principal Investigator: Alessandra Ferlini

The ScreenPlus study is a consented, multi-disorder, multi-sponsored pilot newborn screening program. Implemented in partnership with the New York State Newborn Screening (NBS) Program, ScreenPlus aims to screen over 100,000 babies from diverse populations for an initial panel of 14 rare, treatable disorders in addition to the those already on the routine NBS panel.

Parents who give birth at nine pilot hospitals in NY are invited to enroll their newborns in ScreenPlus at no cost, using no extra blood. ScreenPlus uses an analyte-first, multi-tiered screening platform to improve accuracy. Babies identified with ScreenPlus disorders will be followed over time, providing critical data about the natural history of pre-symptomatic disease. 

Additionally, we are using our ScreenPlus infrastructure to perform mixed-methods studies focused on the complex ethical, legal and social issues associated with screening newborns for complex disorders.  Through these studies, we will engage thousands of parents whose opinions will generate critical, objective data to guide the future expansion of NBS in an ethically sound manner.

Headquarters: Bronx, NY, USA • Principal Investigator: Melissa Wasserstein

BabyScreen+ is a research study investigating the use of genomic testing as an add-on to standard newborn screening. Using clinically accredited whole genome sequencing, this will increase the number of treatable, childhood-onset conditions that can be detected from around 25 to over 500. The study is conducted in parallel with standard newborn screening, using the same dried bloodspot samples already collected routinely at birth. It focuses on implementation and feasibility to establish the best way to deliver genomic newborn screening for babies across Victoria, Australia.

Headquarters: Melbourne, Australia • Principal Investigators: Sebastian Lunke, Zornitza Stark • Recruitment Goal: 1000 • Funded: Yes • IRB Approved: Yes • Currently Enrolling: Yes • Aims: 1) Design and implement a genomic newborn screening program which will enrol 1,000 Victorian babies. 2) Evaluate the genomic newborn screening program and compare it with standard newborn screening. 3) Explore the value and ethical considerations of using genomic data generated at birth as a lifelong healthcare resource.

The NewbornsInSA research study is offering genomic newborn screening to South Australian families. In addition to regular newborn screening, enrolled newborns will have access to metabolite screening and genomic screening for over 600 genetic conditions using the same bloodspot card. Up to 40,000 families can enrol for metabolite screening and 1000 families can enrol for genomic screening. Genomic results will be returned to families by our study’s genetic counsellor. Newborns with high-chance genomic screening results will be referred to clinicians for confirmatory testing and clinical management of the condition. Clinical and process outcomes will be assessed through a cost-effectiveness analysis. The research program is being informed by stakeholder consultation activities with patient advocacy groups, families, and health care professionals to assess acceptability and feasibility of the model.

Headquarters: Adelaide, Australia • Principal Investigator: Karin Kassahn • Recruitment Goal: 40,000 (metabolomics); 1,000 (genomics/WGS) • Funded: Yes • IRB Approved: Yes • Currently Enrolling: No • Aims: 1) Validate metabolomics and genomics for use in newborn screening. 2) Perform metabolomic and genomic screening on a prospectively enrolled cohort in South Australia. 3) Evaluate the effectiveness (clinical, cost) of the model against current standard-of-care.

BabyDetect project aims to conduct a pilot program in Southern Belgium to explore the feasibility and acceptability of first-tier genomic NBS.

We have developped a targeted NGS (tNGS) approach to screen neonates. A board of dedicated professionals, both scientists and medical doctors, succeeded in compiling a list 126 early-onset, severe, treatable genetic disorders. A tNGS panel of 363 genes was then designed and synthesized using Twist Bioscience technology. Our ethics committee approved the study, allowing electronic consenting.

From September 2022, we have started consenting and enrolling newborns in frame of this project. In a period of 6 months we obtained digital informed consent from more than 1200 neonates born in one pilot maternity at Citadelle Hospital (CHR) in Liege. Sequencing and analyzing of these samples was ensured using Illumina platforms and Alissa Interpret interpretation software.

Headquarters: Liège, Belgium • Principal Investigators: Laurent Servais, François Boemer • Recruitment Goal: 40,000 • Funded: Yes • IRB Approved: Yes • Currently Enrolling: Yes • Aims: Explore the feasibility and acceptability of a population-based first-tier genomic NBS using targeted-NGS (tNGS)

Genomic sequencing offers an unprecedented opportunity to detect inherited variants that are implicated in rare Mendelian disorders, yet there are many challenges to overcome before this technology can routinely be applied in the healthy population. The Age-Based Genomic Screening (ABGS) study is investigating a novel alternative to genome-scale sequencing at birth that aims to provide highly actionable genetic information to parents over the course of their child’s routine health care. ABGS utilizes an established metric to identify conditions with high clinical actionability and incorporates information about the age of onset and age of intervention to determine the optimal time to screen for any given condition. Ongoing partnerships with parents and providers throughout the study will inform the co-creation of educational resources and strategies to address potential implementation barriers. Implementation science frameworks and informative empirical data will be used to evaluate strategies to establish this unique clinical application of targeted genomic sequencing. A pilot project conducted in primary care pediatrics clinics will assess patient and implementation outcomes, parent and provider perspectives, and feasibility of ABGS. Ultimately, a validated, stakeholder-informed, and practical ABGS program will include hundreds of conditions that are actionable during infancy and childhood, setting the stage for a longitudinal implementation that can assess clinical and health economic outcomes.

NEW_LIVES is an interdisciplinary research group, funded by Germany's Federal Ministry of Education and Research, that unites researches from the fields of medical ethics, law, medical psychology, human genetics, and pediatrics at the Universities of Heidelberg and Mannheim.

Headquarters: Heidelberg, Germany • Principal Investigators: Eva Winkler (ethics); Ralf Müller-Terpitz (law); Beate Ditzen (psychology); Christian Schaaf (genetics); Stefan Kölker (pediatrics) • Funded: Yes • IRB Approved: Yes • Currently Enrolling: No • Aims: focus group studies, quantiative surveys, clinical implementation study aimed at defining and testing a scalable workflow for a future screening program, and normative (ethical, legal) analysis. overarching goal: development of normative guidelines for the implementation of a genomic newborn screening program in Germany, with a focus on issues such as defining selection criteria for target diseases, determining the requirements of family genetic counseling and informed consent, and assessing the ethical-legal framework for the secondary use of patient data in research and related data protection needs.

PERIGENOMED project, a large-scale project aiming to provide initial concrete evidence on the relevance of genomic NBS in France (analytical validity, clinical validity, clinical utility and psychosocial, ethical and economic issues). It includes a therapeutic trial, PERIGENOMED-CLINICS. PERIGENOMED-CLINICS will be led in two steps. The first pre-pilot step (PERIGENOMED-CLINICS 1) aims to evaluate the feasibility and acceptability of genomic NBS in France (2500 inclusions) by solo-GS with targeted analysis of two lists of genes responsible for treatable (list 1) or actionable (list 2) rare diseases of early onset in 5 health establishments in France, and return in less than 3 weeks. It will also provide an understanding of the optimum information and analysis circuits, and the possible organisational repercussions of NBS using panel-based GS (pGS-NBS). Two ancillary studies in the humanities and social sciences (HSS) will also be attached to PERIGENOMED-CLINICS 1. PERIGENOMED-CLINICS 1 will be followed by a second step, called PERIGENOMED-CLINICS 2, aiming at evaluating the clinical utility, performance, relevance and economic sustainability of genomic NBS in France on a larger scale, and to analyse the associated ethical, regulatory, psychosocial and economic issues in greater depth.

Headquarters: Dijon, France • Principal Investigator: Laurence Faivre • Recruitment Goal: 2,500 for phase 1 (faisability, acceptability) ; 20,000 for phase 2 (clinical utility, performance, relevance and economic sustainability) • Funded: Yes • IRB Approved: No • Currently Enrolling: No

The FirstSteps initiative is a newborn genome screening program in Greece. It aims to establish universal newborn genome screening (NGS) as the standard of care within five years. Additionally, it aims to establish Greece as a hub for drug development and discovery in rare diseases.

The Phase I clinical trial, sponsored by Greece's National Organization of Public Health (EODY), is currently underway at three leading academic medical institutions across Greece. The trial will involve whole genome sequencing of up to 1,000 newborns, with an analysis of 385 genes covering over 500 genetic diseases where early-life interventions are available.

Headquarters: Athens, Greece • Principal Investigator: Petros Tsipouras

TRAIL Study

Supporting a national effort in the exploration of the potential use of genomics in newborn screening programs.

As the research arm of the Sydney Children’s Hospitals Network (SCHN), Kids Research is jointly leading a study that will provide high quality evidence to inform the potential integration of new models of genomic sequencing in newborn bloodspot screening (NBS) programmes. The study is called the Newborn Gen Seq TRAIL (Newborn Genomic Sequencing: Therapy Ready And Information for Life) study.

Headquarters: Sydney, Australia • Principal Investigators: Bruce Bennetts, Gladys Ho • Recruitment Goal: 1500 • Funded: Yes • IRB Approved: No • Currently Recruiting: No

Global Scope

Project Headquarters Principal Investigator(s) Recruitment Goal Funded IRB Approved Currently Enrolling Aims
BabyDetect Liège, Belgium Laurent Servais, François Boemer 40,000 ✓ ✓ ✓
Explore the feasibility and acceptability of a population-based first-tier genomic NBS using targeted-NGS (tNGS)
BabyScreen+ Melbourne, Australia Sebastian Lunke, Zornitza Stark 1,000 ✓ ✓ ✓
(1) Design and implement a genomic newborn screening program which will enrol 1,000 Victorian babies.
2) Evaluate the genomic newborn screening program and compare it with standard newborn screening.
3) Explore the value and ethical considerations of using genomic data generated at birth as a lifelong healthcare resource.
BabySeq Boston, MA, USA Robert Green, Ingrid Holm 500 ✓ ✓ ✓
BeginNGS San Diego, CA, USA Stephen Kingsmore
EarlyCheck Durham, NC, USA Holly Peay (RTI), Cindy Powell (UNC) 10,000 ✓ ✓ ✓
(1) Implement and evaluate the use of genome sequencing to screen newborns for childhood-onset, monogenic conditions.
2) Determine uptake and acceptability of genome sequencing newborn screening among parents of eligible newborns.
3) Implement and evaluate short-term follow-up procedures to inform public health application.
4) Assess 12-month outcomes for children with positive results and their caregivers.
GUARDIAN Study New York City, NY, USA Wendy Chung
FirstSteps Athens, Greece Petros Tsipouras
Generation Study London, United Kingdom Richard Scott 100,000 ✓ ✓ ✓
(1) Evaluating the utility and feasibility of screening newborns for a larger number of childhood-onset rare genetic conditions in the NHS using whole genome sequencing.
(2) Understanding how babies’ genomic data could be used for research, focusing on developing new treatments and diagnostics for NHS patients.
(3) Exploring the potential risks, benefits, and broader implications of storing a baby’s genome over their lifetime.
NewbornsInSA Adelaide, Australia Karin Kassahn 40,000 (metabolomics); 1,000 (genomics/WGS) ✓ ✓ ✓
(1) Validate metabolomics and genomics for use in newborn screening.
(2) Perform metabolomic and genomic screening on a prospectively enrolled cohort in South Australia.
(3) Evaluate the effectiveness (clinical, cost) of the model against current standard-of-care.
NEW_LIVES Heidelberg, Germany Eva Winkler; Ralf Müller-Terpitz; Beate Ditzen; Christian Schaaf; Stefan Kölker ✓ ✓
Focus group studies, quantiative surveys, clinical implementation study aimed at defining and testing a scalable workflow for a future screening program, and normative (ethical, legal) analysis. overarching goal: development of normative guidelines for the implementation of a genomic newborn screening program in Germany, with a focus on issues such as defining selection criteria for target diseases, determining the requirements of family genetic counseling and informed consent, and assessing the ethical-legal framework for the secondary use of patient data in research and related data protection needs.
PERIGENOMED Dijon, France Laurence Faivre P1: 2,500
P2: 20,000 		✓
ScreenPlus Bronx, NY, USA Melissa Wasserstein
Screen4Care Ferrara, Italy Alessandra Ferlini
TRAIL Study Sydney, Australia Bruce Bennetts, Gladys Ho 1,500 ✓

Do you have a project in the field? You’re invited to join the movement.

“One can imagine the day that 99% of newborns will have their genomes sequenced immediately at birth.”
— Alan Guttmacher / Director NICHD