Australia, New Zealand develop guidelines for SMA newborn screening
Evidence-based standards prioritize early diagnosis, management of disease
Written by |
- Australia and New Zealand developed SMA newborn screening guidelines for early diagnosis and management.
- Screening involves testing dried blood spots for the SMN1 gene mutation and SMN2 copy number.
- Positive results require a rapid neurological exam, diagnostic confirmation, and immediate treatment.
Evidence-based guidelines have been developed for newborn screening (NBS), diagnosis, and early management of spinal muscular atrophy (SMA) in Australia and New Zealand to help ensure that all affected children are identified and treated as early as possible.
“The study informs best practice within a new diagnostic and therapeutic era for spinal muscular atrophy by providing an evidence-based translational framework to improve the health and well-being of affected children,” researchers wrote.
The study, “Evidence-based multidisciplinary model of care for newborn screening in spinal muscular atrophy,” was published in Genetics in Medicine.
Clinical outcomes in SMA are better when treatment is started early
SMA is a rare genetic neuromuscular disorder characterized by progressive muscle weakness and wasting. The most common disease-causing mutation is the complete loss of exon 7 in both copies of the SMN1 gene. Exons are the segments of a gene that contain instructions to make proteins.
It’s well established that clinical outcomes in SMA are significantly better when treatment is started early, particularly before signs and symptoms develop.
NBS enables diagnosis before symptoms appear, creating a window during which treatment can be initiated at the point of greatest potential benefit. Without screening, many affected children would be identified only after symptoms develop, by which time irreversible nerve cell damage may already have occurred.
In this report, researchers describe how clinical guidelines for NBS for SMA were developed in Australia and New Zealand. They first conducted a review of the published literature and completed online surveys to share their direct clinical observations and experiences.
Two types of recommendations were generated: evidence-based recommendations, supported by the published literature, and consensus-based recommendations, supported by expert agreement where evidence was limited.
Guidelines specifically require culturally safe care
The guidelines strongly recommended that NBS for SMA be performed on routine newborn dried blood spots, small blood samples collected from newborns shortly after birth. The test used to detect the absence of exon 7 in the SMN1 gene should correctly identify affected newborns at least 95% of the time.
The guidelines also recommended determining the SMN2 copy number. SMN2 is a related gene whose copy number is an indicator of disease severity, with more copies generally associated with a milder disease course. However, the SMN2 result should not delay notification of a positive SMN1 screening result.
Newborns who test positive should undergo a neurological examination. Diagnosis should confirm the absence of exon 7 in SMN1 and SMN2 copy number using a whole-blood sample or a repeat dried blood spot. The SMN1 result should be available within seven days of the laboratory receiving the sample, and the full diagnostic result should be available to clinical services within 30 days of the child’s birth.
When a newborn screening result is uncertain, false-positive, or false-negative, the guidelines recommend a case review involving clinical services responsible for screening to determine the cause, with an explanation provided to the family. If uncertainty persists, the child should continue to be followed by a pediatric neurologist until a definitive diagnosis is established.
A screen-positive result should be disclosed to the family within two working days of notification to healthcare services. And the newborn should be offered a clinical review with a pediatric neurology or neuromuscular specialist within two working days of that disclosure.
As implementation of these public health programs [accelerates] globally, this study provides health care professionals and policy makers with a template to develop feasible and equitable newborn screening programs for spinal muscular atrophy.
Culturally safe care is specifically required when disclosing results to families from Aboriginal, Torres Strait Islander, Pacific Islander, Maori, or other culturally and linguistically diverse backgrounds. Where the healthcare practitioner is not bilingual, a professional interpreter must be used.
For newborns who are already showing signs and symptoms of SMA at diagnosis, a pediatric neurologist should discuss immediate treatment with the family. The same applies to presymptomatic newborns with one, two, or three copies of SMN2.
For families of children who cannot access approved and reimbursed treatments, or who choose not to begin treatment immediately, clinical follow-up should include assessments at least every three months for the first two years and at least every six months thereafter. Families should also be offered a referral for genetic counseling and testing of other family members who may carry the genetic defect.
During a public consultation period, individuals or organizations, including consumers, advocates, and those with lived experience of SMA, provided written feedback. The final guideline was approved by the CEO of the National Health and Medical Research Council for five years. It was also endorsed by 11 organizations across Australia and New Zealand.
“As implementation of these public health programs [accelerates] globally, this study provides health care professionals and policy makers with a template to develop feasible and equitable newborn screening programs for spinal muscular atrophy,” the team wrote.
