Gestational Age at Birth and Clinical Manifestations of Spinal Muscular Atrophy

Abstract

BACKGROUND AND OBJECTIVES: 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. METHODS: This is an Australian dual-center prospective cohort study of 42 consecutive mother-baby dyads with SMA (≤4 survival motor neuron 2 [SMN2] 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 SMN2 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). RESULTS: Forty-two mother-baby dyads participated (n = 1 with 1 SMN2; n = 21 with 2 SMN2, gestational age at birth 39.9 ± 1.8 weeks; n = 20 with 3 or 4 SMN2, gestational age at birth 39.4 ± 0.8 weeks). All neonates with 3 or 4 SMN2 copies were clinically silent at diagnostic assessment while 7 of 21 (33.3%) with 2 SMN2 copies had clinical manifestations of SMA (p = 0.009). In newborns with 2 SMN2 copies, higher gestational age at birth was associated with clinical manifestations of SMA (odds ratio 4.37, 95% CI 1.19-16.12, p = 0.001) and lower motor function (CHOP-INTEND: β = -4.52, 95% CI -7.018 to -2.019, p = 0.001) and strongly correlated with lower CMAP (R = -0.800, p < 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 SMN2 copies. DISCUSSION: 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.