Clinical trial NCT05687474: Baby Detect : Genomic Newborn Screening
Official title: Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Adrenal Hyperplasia
Familial Hyperinsulinemic Hypoglycemia 1
Phosphoglucomutase 1 Deficiency
Maturity Onset Diabetes of the Young
Cystic Fibrosis
Hypophosphatasia, Infantile
Congenital Hypothyroidism
Deficit in Anterior Pituitary Function and Variable Immunodeficiency
Pituitary Hormone Deficiency, Combined
Diamond Blackfan Anemia
Wiskott-Aldrich Syndrome
Fanconi Anemia
Hemophilia A
Hemophilia B
Glucose 6 Phosphate Dehydrogenase Deficiency
Alpha-Thalassemia
Sickle Cell Disease
Shwachman-Diamond Syndrome
Alpha 1-Antitrypsin Deficiency
Inflammatory Bowel Disease 25, Autosomal Recessive
Wilson Disease
Progressive Familial Intrahepatic Cholestasis
Crigler-Najjar Syndrome
Familial Chylomicronemia
Lysosomal Acid Lipase Deficiency
Familial Hemophagocytic Lymphocytosis
Griscelli Syndrome
Chediak-Higashi Syndrome
Severe Congenital Neutropenia
Severe Combined Immune Deficiency
Chronic Granulomatous Disease
Menkes Disease
Adrenoleukodystrophy
Smith-Lemli-Opitz Syndrome
Ataxia With Vitamin E Deficiency
Thiamine Metabolism Dysfunction Syndrome 5 (Episodic Encephalopathy Type)
Thiamine Metabolism Dysfunction Syndrome 4 (Bilateral Striatal Degeneration and Progressive Polyneuropathy Type)
Thiamine-Responsive Megaloblastic Anemia
Thiamine Metabolism Dysfunction Syndrome 2
Deficiency of GOT2
Cerebral Folate Transport Deficiency
Segawa Syndrome, Autosomal Recessive
Congenital Myasthenic Syndrome
Metachromatic Leukodystrophy
Sepiapterin Reductase Deficiency
Dopamine Beta Hydroxylase Deficiency
Glut1 Deficiency Syndrome
Late-Infantile Neuronal Ceroid Lipofuscinosis
Aromatic L-amino Acid Decarboxylase Deficiency
Charcot-Marie-Tooth Disease, Type 6C
Hereditary Hyperekplexia
Brain Dopamine-Serotonin Vesicular Transport Disease
Very Long Chain Hydroxy Acyl Dehydrogenase Deficiency
Tyrosinemia, Type I
Disaccharide Intolerance I
Beta Ketothiolase Deficiency
Phosphoglycerate Dehydrogenase Deficiency
Succinyl-Coa:3-Ketoacid Coa-Transferase Deficiency
Pyridoxine-5'-Phosphate Oxidase Deficiency
Pyridoxine-Dependent Epilepsy
Propionic Acidemia
Pompe Disease
Phenylalanine Hydroxylase Deficiency
Ornithine Transcarbamylase Deficiency
N Acetyl Glutamate Synthetase Deficiency
Riboflavin Deficiency
Maple Syrup Urine Disease
Medium Chain Acyl CoA Dehydrogenase Deficiency
Malonic Acidemia
Long-chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency
Isovaleric Acidemia
Phosphoserine Aminotransferase Deficiency
Phosphoserine Phosphatase Deficiency
Hyperornithinemia-Hyperammonemia-Homocitrullinuria
S-Adenosylhomocysteine Hydrolase Deficiency
Mucopolysaccharidosis VII
Mucopolysaccharidosis VI
Mucopolysaccharidosis IV A
Mucopolysaccharidosis II
Mucopolysaccharidosis I
Transcobalamin Deficiency
Isolated Methylmalonic Acidemia
Cobalamin Deficiency
Homocystinuria
Holocarboxylase Synthetase Deficiency
Fanconi Bickel Syndrome
Glycogen Storage Disease
Glycine Encephalopathy
Glutaric Acidemia I
Glucose Galactose Malabsorption
Gaucher Disease, Type 1
Galactosemias
Fructosemia
Fructose-1,6-Diphosphatase Deficiency
Carbamoyl Phosphate Synthase 1 Deficiency
Citrullinemia Type II
Citrullinemia 1
Creatine Deficiency Syndrome
Systemic Primary Carnitine Deficiency
Carnitine Palmitoyltransferase Deficiency 2
Carnitine Palmitoyltransferase Deficiency 1
Carnitine Acylcarnitine Translocase Deficiency
Riboflavin Transporter Deficiency
Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency
Andersen Tawil Syndrome
Timothy Syndrome
Jervell-Lange Nielsen Syndrome
Catecholaminergic Polymorphic Ventricular Tachycardia
Familial Hypertrophic Cardiomyopathy Type 4
Pseudohypoaldosteronism, Type II
Pseudohypoaldosteronism Type 1
Primary Hyperoxaluria
X Linked Hypophosphatemia
Hereditary Nephrogenic Diabetes Insipidus
Cystinosis
Congenital Nephrotic Syndrome, Finnish Type
Alport Syndrome
Hereditary Retinoblastoma
Biotinidase Deficiency
Aciduria, Argininosuccinic
Argininemia
Acyl-CoA Dehydrogenase Family, Member 9, Deficiency of
3-Hydroxy 3-Methyl Glutaric Aciduria
3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency
Lead sponsor: Centre Hospitalier Universitaire de Liege
Sponsor class: OTHER
Collaborators: name: Centre Hospitalier Régional de la Citadelle
name: University of Liege
name: Sanofi
name: Orchard Therapeutics
name: Takeda
name: Zentech-Lacar Company
name: Leon Fredericq Foundation
First posted: 2023-01-18
Enrollment: 6000
Sex: ALL
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborns whose mothers and/or the second-parents meet the inclusion criteria and have provided their consent to take part in the study

Brief summary: Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life.

Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

Detailed description: Every year, thousands of children around the world are born with rare genetic diseases leading to death or lifelong disability. With technological advancements in the field of genetics and medicine, the rate of introduction of treatments for these rare conditions has grown remarkably.

However, timing is of great importance for medication administration. The benefit that can be measured in a patient who has already suffered from a long irreversible degenerative disorder is small and, sometimes, it hardly justifies the cost and the burden of the treatment. Early diagnosis is, thus, of primary importance both to obtain the best effect of the innovative medications and to accelerate their development.

The investigators are pioneered in the field of genetic newborn screening (NBS) in rare diseases by funding, designing, and leading an innovative genetic NBS program initiated in March 2018 in Southern Belgium for Spinal Muscular Atrophy (SMA) that allowed, so far, for 11 children to be detected and treated early and avoid the terrible fate of the disease. The program was disseminated in 17 countries and included public dissemination and health-economic analysis since the very beginning \[1\]. (www.facebook.com/sunmayariseonsma).

Drawing upon our experience with SMA screening, the investigators have designed a project to screen up to 40,000 newborns/year progressively in 3 years for virtually all the rare diseases that can benefit from treatment or a pre-symptomatic clinical trial.

The methodology of Baby Detect includes sequencing of target genes on dried blood spots collected from the NBS cards in a timely and cost-efficient manner, and its high dynamicity allows for any newly treatable rare disease to be included in its scheme in no longer than 6 months.

Baby Detect, as a multidisciplinary newborn screening program, involves expertise in areas from genetics and medicine to laboratory studies, computer science, Data Protection, Ethics, and health economy. It will constitute the proof of concept that is needed before moving to a whole region-scale population.

Eligibility criteria: Inclusion Criteria:

* newborn between birth and 28 days of life
* consent of parent

Exclusion Criteria:

* + 28 days
* Non consent of parent

Primary outcomes:
measure: Acceptability
timeFrame: through study completion, an average of 1 year
measure: Feasibility - timing
timeFrame: through study completion, an average of 1 year
measure: Feasibility - reliability
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Consequence of NBS on early treatment access - timing
timeFrame: through study completion, an average of 1 year
measure: Consequence of NBS on early treatment access - frequency
timeFrame: through study completion, an average of 1 year
measure: To improve the detection technique for disease related mutations that are not detected in classical screening by improving the classification of unspecified variants.
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
city: Liege
country: Belgium
facility: CRMN, Hôpital La Citadelle
state: Wallonia
Study officials:
affiliation: Centre Hospitalier Universitaire de Liege
name: Laurent Servais
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boemer F, Hovhannesyan K, Piazzon F, Minner F, Mni M, Jacquemin V, Mashhadizadeh D, Benmhammed N, Bours V, Jacquinet A, Harvengt J, Bulk S, Dideberg V, Helou L, Palmeira L, Dangouloff T; BabyDetect Expert Panel; Servais L. Population-based, first-tier genomic newborn screening in the maternity ward. Nat Med. 2025 Apr;31(4):1339-1350. doi: 10.1038/s41591-024-03465-x. Epub 2025 Jan 28.
citation: Dangouloff T, Hovhannesyan K, Mashhadizadeh D, Minner F, Mni M, Helou L, Piazzon F, Palmeira L, Boemer F, Servais L. Feasibility and Acceptability of a Newborn Screening Program Using Targeted Next-Generation Sequencing in One Maternity Hospital in Southern Belgium. Children (Basel). 2024 Jul 30;11(8):926. doi: 10.3390/children11080926.