Gestational Age at Birth and Clinical Manifestations of Spinal Muscular Atrophy.

Abstract

Enhanced efficacy with spinal muscular atrophy (SMA) treatments is demonstrated with earlier initiation, ideally before the onset of symptoms. High-quality pregnancy and postnatal care for mother-baby dyads with SMA are important to ensure optimal outcomes. The aim of this study was to investigate obstetric and postnatal factors that could modify clinical outcomes of mother-baby dyads with SMA. This is an Australian dual-center prospective cohort study of 42 consecutive mother-baby dyads with SMA (≤4 survival motor neuron 2 [<i>SMN2</i>] copies) identified through a statewide newborn screening program or prenatal testing for SMA from 2018 to 2025. Sociodemographic, clinical, and genetic data were collated. For the group with 2 <i>SMN2</i> copies, regression models examined differences in gestational age at birth with study outcomes at diagnostic assessment, including clinical manifestations of SMA, motor function scores assessed with the CHOP-INTEND scale, and compound muscle action potential (CMAP). Forty-two mother-baby dyads participated (n = 1 with 1 <i>SMN2</i>; n = 21 with 2 <i>SMN2</i>, gestational age at birth 39.9 ± 1.8 weeks; n = 20 with 3 or 4 <i>SMN2</i>, gestational age at birth 39.4 ± 0.8 weeks). All neonates with 3 or 4 <i>SMN2</i> copies were clinically silent at diagnostic assessment while 7 of 21 (33.3%) with 2 <i>SMN2</i> copies had clinical manifestations of SMA (<i>p</i> = 0.009). In newborns with 2 <i>SMN2</i> copies, higher gestational age at birth was associated with clinical manifestations of SMA (odds ratio 4.37, 95% CI 1.19-16.12, <i>p</i> = 0.001) and lower motor function (CHOP-INTEND: β = -4.52, 95% CI -7.018 to -2.019, <i>p</i> = 0.001) and strongly correlated with lower CMAP (<i>R</i> = -0.800, <i>p</i> < 0.001). High medical acuity was common in the obstetric and postnatal care of mothers and babies with SMA, occurring in 12 of 42 (29.3%) and 8 of 41 (19.5%), respectively, and mostly in those with 1 or 2 <i>SMN2</i> copies. Early detection and timely administration of treatments are imperative in managing the rapid and severe loss of motor function that can occur in neonates with SMA. A personalized obstetric health care approach, prenatal testing, and planning the timing of delivery and initiation of treatment for newborns with genetically diagnosed SMA may improve outcomes.