Early Check: Expanded Screening in Newborns

Summary

Early Check provides voluntary screening of newborns for a selected panel of conditions. The study has three main objectives: 1) develop and implement an approach to identify affected infants, 2) address the impact on infants and families who screen positive, and 3) evaluate the Early Check program. The Early Check screening will lead to earlier identification of newborns with rare health conditions in addition to providing important data on the implementation of this model program. Early diagnosis may result in health and development benefits for the newborns. Infants who have newborn screening in North Carolina will be eligible to participate, equating to over 120,000 eligible infants a year. Over 95% of participants are expected to screen negative. Newborns who screen positive and their parents are invited to additional research activities and services. Parents can enroll eligible newborns on the Early Check electronic Research Portal. Screening tests are conducted on residual blood from existing newborn screening dried blood spots. Confirmatory testing is provided free-of-charge for infants who screen positive, and carrier testing is provided to mothers of infants with fragile X. Affected newborns have a physical and developmental evaluation. Their parents have genetic counseling and are invited to participate in surveys and interviews. Ongoing evaluation of the program includes additional parent interviews.

Conditions

• Spinal Muscular Atrophy
• Fragile X Syndrome
• Fragile X - Premutation
• Duchenne Muscular Dystrophy
• Hyperinsulinemic Hypoglycemia, Familial 1
• Diabetes Mellitus
• Adrenoleukodystrophy, Neonatal
• Medium-chain Acyl-CoA Dehydrogenase Deficiency
• Very Long Chain Acyl Coa Dehydrogenase Deficiency
• Beta-ketothiolase Deficiency
• Severe Combined Immunodeficiency Due to Adenosine Deaminase Deficiency
• Primary Hyperoxaluria Type 1
• Congenital Bile Acid Synthesis Defect Type 2
• Pyridoxine-Dependent Epilepsy
• Hereditary Fructose Intolerance
• Hypophosphatasia
• Hyperargininemia
• Mucopolysaccharidosis Type 6
• Argininosuccinic Aciduria
• Citrullinemia, Type I
• Wilson Disease
• Maple Syrup Urine Disease, Type 1A
• Maple Syrup Urine Disease, Type 1B
• Biotinidase Deficiency
• Neonatal Severe Primary Hyperparathyroidism
• Intrinsic Factor Deficiency
• Usher Syndrome Type 1D/F Digenic (Diagnosis)
• Cystic Fibrosis
• Stickler Syndrome Type 2
• Stickler Syndrome Type 1
• Alport Syndrome, Autosomal Recessive
• Alport Syndrome, X-Linked
• Carbamoyl Phosphate Synthetase I Deficiency Disease
• Carnitine Palmitoyl Transferase 1A Deficiency
• Carnitine Palmitoyltransferase II Deficiency
• Cystinosis
• Chronic Granulomatous Disease
• Cerebrotendinous Xanthomatoses
• Maple Syrup Urine Disease, Type 2
• Severe Combined Immunodeficiency Due to DCLRE1C Deficiency
• Thyroid Dyshormonogenesis 6
• Thyroid Dyshormonogenesis 5
• Supravalvar Aortic Stenosis
• Factor X Deficiency
• Hemophilia A
• Hemophilia B
• Tyrosinemia, Type I
• Fructose 1,6 Bisphosphatase Deficiency
• Glycogen Storage Disease Type I
• G6PD Deficiency
• Glycogen Storage Disease II
• Galactokinase Deficiency
• Mucopolysaccharidosis Type IV A
• Galactosemias
• Guanidinoacetate Methyltransferase Deficiency
• Agat Deficiency
• Glutaryl-CoA Dehydrogenase Deficiency
• Gtp Cyclohydrolase I Deficiency
• Hyperinsulinism-Hyperammonemia Syndrome
• Primary Hyperoxaluria Type 2
• 3-Hydroxyacyl-CoA Dehydrogenase Deficiency
• Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency
• Mitochondrial Trifunctional Protein Deficiency
• Sickle Cell Disease
• Beta-Thalassemia
• Holocarboxylase Synthetase Deficiency
• 3-Hydroxy-3-Methylglutaric Aciduria
• Primary Hyperoxaluria Type 3
• Hermansky-Pudlak Syndrome 1
• Hermansky-Pudlak Syndrome 4
• Apparent Mineralocorticoid Excess
• HSDB
• CBAS1
• Mucopolysaccharidosis Type 2
• Mucopolysaccharidosis Type 1
• Severe Combined Immunodeficiency, X Linked
• Severe Combined Immunodeficiency Due to IL-7Ralpha Deficiency
• Diabetes Mellitus, Permanent Neonatal
• Isovaleric Acidemia
• Severe Combined Immunodeficiency T-Cell Negative B-Cell Positive Due to Janus Kinase-3 Deficiency (Disorder)
• Jervell and Lange-Nielsen Syndrome 2
• Hyperinsulinemic Hypoglycemia, Familial, 2
• Diabetes Mellitus, Permanent Neonatal, With Neurologic Features
• Jervell and Lange-Nielsen Syndrome 1
• Lysosomal Acid Lipase Deficiency
• CblF
• 3-Methylcrotonyl CoA Carboxylase 1 Deficiency
• 3-Methylcrotonyl CoA Carboxylase 2 Deficiency
• Waardenburg Syndrome Type 2A
• Methylmalonic Aciduria cblA Type
• Methylmalonic Aciduria cblB Type
• Methylmalonic Aciduria and Homocystinuria Type cblC
• MAHCD
• Methylmalonic Aciduria Due to Methylmalonyl-CoA Mutase Deficiency
• Congenital Disorder of Glycosylation Type 1B
• Mthfr Deficiency
• Methylcobalamin Deficiency Type Cbl G (Disorder)
• Methylcobalamin Deficiency Type cblE
• Usher Syndrome, Type 1B
• N-acetylglutamate Synthase Deficiency
• Ornithine Transcarbamylase Deficiency
• Phenylketonurias
• Waardenburg Syndrome Type 1
• Congenital Hypothyroidism
• Propionic Acidemia
• Usher Syndrome, Type 1F
• Pancreatic Agenesis 1
• Hereditary Hypophosphatemic Rickets
• Glycogen Storage Disease IXB
• Glycogen Storage Disease IXC
• MOWS
• Epilepsy, Early-Onset, Vitamin B6-Dependent
• Pyridoxal Phosphate-Responsive Seizures
• Pituitary Hormone Deficiency, Combined, 1
• Ptsd
• Dihydropteridine Reductase Deficiency
• Severe Combined Immunodeficiency Due to RAG1 Deficiency
• Severe Combined Immunodeficiency Due to RAG2 Deficiency
• Retinoblastoma
• Multiple Endocrine Neoplasia Type 2B
• Pseudohypoaldosteronism, Type I
• Liddle Syndrome
• Biotin-Responsive Basal Ganglia Disease
• SCD
• DIAR1
• GSD1C
• Acrodermatitis Enteropathica
• Thyroid Dyshormonogenesis 1
• Riboflavin Transporter Deficiency
• Waardenburg Syndrome, Type 2E
• SRD
• Congenital Lipoid Adrenal Hyperplasia Due to STAR Deficiency
• Barth Syndrome
• Adrenocorticotropic Hormone Deficiency
• Transcobalamin II Deficiency
• Thyroid Dyshormonogenesis 3
• Segawa Syndrome, Autosomal Recessive
• Autosomal Recessive Nonsyndromic Hearing Loss
• Thyroid Dyshormonogenesis 2A
• Congenital Isolated Thyroid Stimulating Hormone Deficiency
• Hypothyroidism Due to TSH Receptor Mutations
• Usher Syndrome Type 1C
• Usher Syndrome Type 1G (Diagnosis)
• Von Willebrand Disease, Type 3
• Combined Immunodeficiency Due to ZAP70 Deficiency
• Adenine Phosphoribosyltransferase Deficiency
• Metachromatic Leukodystrophy
• Canavan Disease
• Menkes Disease
• Carbonic Anhydrase VA Deficiency
• Developmental and Epileptic Encephalopathy 2
• 17 Alpha-Hydroxylase Deficiency
• Smith-Lemli-Opitz Syndrome
• Krabbe Disease
• Glutathione Synthetase Deficiency
• Mucopolysaccharidosis Type 7
• Rett Syndrome
• Molybdenum Cofactor Deficiency, Type A
• Niemann-Pick Disease, Type C1
• Niemann-Pick Disease Type C2
• Ornithine Aminotransferase Deficiency
• 3-Phosphoglycerate Dehydrogenase Deficiency
• Leber Congenital Amaurosis 2
• Dravet Syndrome
• Mucopolysaccharidosis Type 3 A
• Ornithine Translocase Deficiency
• Carnitine-acylcarnitine Translocase Deficiency
• Glucose Transporter Type 1 Deficiency Syndrome
• Creatine Transporter Deficiency
• Niemann-Pick Disease Type A
• Pitt Hopkins Syndrome
• Tuberous Sclerosis 1
• Tuberous Sclerosis 2
• Ataxia With Isolated Vitamin E Deficiency
• Angelman Syndrome
• Prader-Willi Syndrome
• Homocystinuria
• Permanent Neonatal Diabetes Mellitus
• Transient Neonatal Diabetes Mellitus
• Factor VII Deficiency
• Glycogen Storage Disease Type IXA1
• Glycogen Storage Disease, Type IXA2
• Glycogen Storage Disease IC
• Glycogen Storage Disease Type IB
• Central Hypoventilation Syndrome With or Without Hirschsprung Disease

Interventions

DIAGNOSTIC_TEST

Confirmatory Testing

If a newborn's screening test is positive, an experienced genetic counselor will contact the infant's mother by phone to explain the positive screening result and arrange for confirmatory testing and a follow-up appointment. If the confirmatory test is positive, then the child receives a diagnosis of the disease. Children identified with a disorder are referred for treatment, their parents receive information and counseling on what a positive diagnosis means for their child, and they are offered participation in follow-up and registry activities for the disorder.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill

  collaborator OTHER

• The John Merck Fund

  collaborator UNKNOWN

• Duke University

  collaborator OTHER

• Wake Forest University

  collaborator OTHER

• North Carolina Department of Health and Human Services

  collaborator OTHER_GOV

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• Cure SMA

  collaborator OTHER

• The National Fragile X Foundation

  collaborator OTHER

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

  collaborator NIH

• Asuragen, Inc.

  collaborator UNKNOWN

• Sarepta Therapeutics, Inc.

  collaborator INDUSTRY

• Muscular Dystrophy Association

  collaborator OTHER

• The Leona M. and Harry B. Helmsley Charitable Trust

  collaborator OTHER

• Juvenile Diabetes Research Foundation

  collaborator OTHER

• Janssen Pharmaceuticals

  collaborator INDUSTRY

• GeneDx

  collaborator UNKNOWN

• Illumina, Inc.

  collaborator INDUSTRY

• RTI International

  lead OTHER

Principal Investigators

• Don Bailey, PhD · RTI International

Eligibility

Min Age

1 Day

Max Age

31 Days

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-10-15

Primary Completion

2025-11-30

Completion

2025-12-31

FDA Device

Yes

Countries

• United States

Study Locations