Early identification of these genetic conditions is intended to enable interventions that substantially improve symptoms of the condition when initiated in the first year of life.

Inclusion criteria were derived from the International Consortium on Newborn Sequencing (ICoNS) consensus recommendations and adapted for a public health screening context.

Genetic conditions screened in BRIDGES-NBS meet all of the following criteria:

1. An established gene–disease relationship associated with a condition affecting health or development.
   

2. Actionability within the first year of life, defined as a clinically approved treatment ora published surveillance guideline that can be initiated before age 1 and is expected to substantially improve health or development.
   

3. Availability of non-genetic confirmatory evidence, such as a laboratory biomarker, imaging finding, physical sign, or diagnostic criterion that can support diagnosis, or an available surveillance method that is considered to be low risk and potentially high benefit.
   

4. Technical feasibility, meaning reliable detection of likely pathogenic and pathogenic variants using short-read whole genome sequencing.

The goal of BRIDGES-NBS is to find genetic conditions early, so that care can begin in the first year of life, when it can make the biggest difference for a child’s health.

A genetic condition is included if it meets all of the following criteria:

• The condition affects a child’s health or development.

• There is a treatment or medical monitoring plan that can start before age 1 and is expected to meaningfully improve health or prevent serious complications.

• There are other ways, beyond the genetic test itself, to help confirm the diagnosis or guide care, such as blood tests, imaging, physical findings, or safe monitoring strategies.

• The condition can be reliably detected using the type of genome sequencing used in BRIDGES-NBS.

A condition was considered actionable if early identification enables:

• A clinically available treatment that meaningfully alters medical management or outcomes

• Avoidance of harmful interventions (e.g., ionizing radiation, live vaccines)

• A surveillance strategy targeting a specific disease sequela within the first year of life, with favorable risk–benefit balance

The following examples, in isolation, were not considered to be sufficiently actionable:

• Avoidance of a diagnostic odyssey

• Access to clinical trials or experimental therapies

• Initiation of supportive services, such as physical therapy or speech therapy

• Personal, psychosocial, family, or economic utility

• Reproductive decision-making

• Information relevant only to parental medical care

Consistent with the consensus recommendations from the International Consortium on Newborn Sequencing (ICoNS), both relatively common conditions (e.g., G6PD deficiency) and ultra-rare disorders were included. Prevalence alone was not a determining factor.

We did not specifically consider disease penetrance (i.e., the likelihood that someone with a disease causing variant or variants will show the associated symptoms of the condition) when selecting genes and conditions for inclusion in this list of conditions. We acknowledge that the variable penetrance and expressivity of many conditions on the list may result in identification of asymptomatic infants. However, this decision reflects both: 

• Data on penetrance in the general population are unavailable 

• The ethical position that families may reasonably choose to pursue non-molecular confirmatory testing or low-risk surveillance interventions even when penetrance is uncertain

We did exclude genes for which reported penetrance was so low that the gene–disease relationship was uncertain (e.g., DUOX2). Additionally, variants associated with mild, minimally penetrant, or adult-onset phenotypes will be excluded from reporting.

Yes.

Many genes on the list are associated with conditions that can present at different ages and with a wide range of symptom severity. We included conditions for which a severe infantile form is known, even if the onset may occur in early childhood or adolescence. For genes with both infant-onset autosomal recessive and adult-onset autosomal dominant conditions, only biallelic variants will be reported. 

Consistent with traditional newborn screening, we also included conditions that may present in the first days of life, recognizing that age of onset is often variable and that genetic information can guide treatment decisions in the first weeks or months of life even when the first symptoms present immediately after birth.