Objectives: To describe this first experience with prenatal treatment for SMA-0 and the early postnatal course.
Background: Following maternal high-risk carrier screening for SMA, genetic testing revealed a fetus had 1 copy of the SMN2 gene, predicting SMA type 0. 27-week ultrasound showed normal fetal movements and intracardiac atrial septal defect, predicted to not require immediate surgical repair. After counseling, fetal therapy ethics board approval, and informed consent, prenatal risdiplam treatment was started (5 mg/day) at 28 weeks gestation hypothesizing that this increases SMN protein expression and might improve postnatal outcomes. The pregnancy was followed with weekly ultrasound and biophysical profiles (BPP). After birth, weight-based oral treatment with risdiplam continued and outcomes measured.
Results: Treatment was well tolerated with normal maternal labs, initially good fetal movements (FM) and BPPs, but FM decreased ~1 wk before delivery. Labor was induced at 38 weeks 3 days for oligohydramnios and BPP 4/8, followed by cesarean delivery for non-reassuring fetal heart rate. The infant had Apgar scores of 6 at 1 and 8 at 5 minutes, birthweight of 3640 gram and needed CPAP support. The newborn exam showed hypotonia, limited movement in distal extremities, and joint contractures. Gastrostomy and tracheostomy were performed at 2 months of life. At 4 months, strength and contractures improved. Comparative assessments performed at week of life 1 and at 4 months showed CHOP-Intend scores increased from 13/64 to 20/64; ulnar CMAP increased from 0.2 to 0.4 mV; and serum neurofilament light chain decreased from 423 pg/mL to 48 pg/mL.
Conclusions: Prenatal treatment of SMA-0 was well tolerated by mother and fetus, and the clinical impact of the genotype was lessened with continued postnatal improvement. Further follow-up is needed to determine how significantly prenatal treatment improves outcomes.