Premature babies, diagnosed via screening, treated for SMA
Babies born prematurely were diagnosed with spinal muscular atrophy (SMA) through newborn screening programs (NBS) in Germany and, in most cases, started on treatment before disease symptoms emerged, a retrospective study reports.
Doctors, however, waited to initiate treatment until many of the 12 newborns had reached full-term age, as data are lacking on the use of disease-modifying SMA treatments (DMTs) in babies born preterm.
“Premature infants with SMA require interdisciplinary care in close collaboration with the neuromuscular center,” the researchers wrote.
Still, “SMA NBS facilitates early initiation of disease-modifying therapy, ideally during the presymptomatic phase, which significantly influences the prognosis of the newborn,” they added.
Little is known about the safety of SMA therapies in premature newborns
The study, “Postnatal management of preterm infants with spinal muscular atrophy: experience from German newborn screening,” was published in the Orphanet Journal of Rare Diseases.
It’s well-recognized that the earliest possible start to disease-modifying treatments (DMTs) leads to better clinical outcomes for babies with SMA, a rare disease due to mutations in the SMN1 gene and marked by muscle weakness and wasting.
NBS enables an SMA diagnosis in newborns via a small blood sample collected while they’re still at the hospital. The adoption of these programs has increased the number of children diagnosed early, sometimes capturing the disease and enabling therapy to start before symptoms do.
SMA treatment guidelines for babies born prematurely, however, are not well established. A preterm birth is described as birth at less than 38 weeks from the time of conception, also known as gestational age.
Approved SMA therapies currently are not authorized for use in preterm infants, as clinical trials did not include this population. In particular, the gene therapy Zolgensma (onasemnogene abeparvovec) is not recommended for preterm infants by health regulators in the U.S., because of the “potential adverse long-term effects” of its required steroid treatments on an newborn’s neurological development, the study noted.
“Given the progressive course of the disease and the potential risks of novel treatments, the optimal time to treat infants born preterm remains an open question and represents a complex therapeutic challenge,” the researchers wrote.
A team of researchers at centers across Germany conducted a retrospective analysis to look at disease course and treatment decisions for preterm infants diagnosed with SMA through newborn screening, which was added to NBS panels in Germany in 2021.
The analysis involved 12 preterm babies identified through NBS at eight German centers. These babies were born at a mean gestational age of 34 weeks (about 7.8 months after conception), and their diagnosis was confirmed a mean of 13 days after birth. Ten had two copies of the SMN2 gene, which also carries instructions to make the essential SMN protein, but does so less effectively than SMN1, while the two others had three SMN2 copies.
A range of health complications typical of premature birth were observed in the babies, and they required intensive care treatment.
Zolgensma was the most common DMT used, given to 10 of the 12 infants
Eleven of the 12 infants were presymptomatic for SMA at birth, and did not show obvious signs of the neuromuscular disease up until full-term gestational age. But low muscle tone became evident in one of these 11 babies at age 5 weeks, before starting treatment.
One newborn showed signs of SMA at birth, including low muscle tone, weak sucking, and a loss of reflexes.
With their parents’ consent, all the babies started on DMTs at mean of about 20 days after their SMA diagnosis was confirmed, and at a mean gestational age of 38.8 weeks. Most (83.3%) started treatment only after they were considered to be full term; two began with treatment earlier.
Zolgensma, a single-use gene therapy, was the most commonly used DMT, and the initial treatment for eight babies. Two others briefly were given oral Evrysdi (risdiplam) as a daily bridge therapy before receiving Zolgensma. The remaining two babies were treated with Spinraza (nusinersen), given via injection into the spinal canal (intrathecal injection) once every four months after a loading period.
“A recent parent survey demonstrated that treatment frequency and administration method are the most commonly reported factors impacting parental treatment choice,” the researchers wrote.
The scientists noted that four of the Zolgensma-treated infants showed elevations in liver enzymes over 12 weeks of follow-up, and three experienced vomiting or fever in the first week after treatment.
Plans to study how preterm babies with SMA, and their parents, progress
“In summary, our data confirms that SMA NBS enables early confirmation of diagnosis in preterm infants and early disease-modifying therapy, ideally in the presymptomatic stage of the disease, which is crucial for the future prognosis of the newborn,” the researchers wrote.
They noted plans to study longer term outcomes in preterm infants with SMA, as well as the psychosocial impact of the diagnosis on a child’s parents.
“Evidence from the literature is insufficient to evaluate the safety of [Spinraza, Evrysdi or Zolgensma] in preterm infants,” the scientists wrote. “Current data also do not permit a risk-benefit assessment of whether initiating therapy before 37 weeks of [gestational age] may improve the long-term prognosis of the patients compared to full-term [gestational age].”
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