Impact of thyroxine treatment on myelination in premature neonates with intraventricular Hemorrhage: An MRI-based approach

Intraventricular hemorrhage (IVH) remains a major complication of prematurity. Survivors of IVH suffer from cerebral palsy, cognitive deficits, and neurobehavioral disorders. Thyroxine (T 4 ) treatment in preterm rabbits with IVH enhances the proliferation and maturation of oligodendrocytes, restoring myelination and neurological recovery. We hypothesized that T 4 treatment of neonates with grade III IVH or periventricular echo density (PVE) would promote white matter recovery, as evaluated by MRI-DTI metrics. We randomized preterm neonates with grade III IVH or PVE (Volpe’s IVH grading) of 23 0/7 -27 6/7 weeks of gestation into T 4 treatment and no treatment groups (n=7, each arm). Neonates in the T 4 group received thyroxine 8 μg/kg/d divided into two doses for 42 days. MRI with DTI was performed at 36 weeks postmenstrual age. The DTI analysis methods used for neonates with IVH were validated in 130 neonates previously diagnosed with IVH. It is feasible to recruit and retain preterm neonates with IVH in a T 4 treatment study. The semi-automated seed-based tractography analysis revealed that DTI metrics, including mean, radial, and axial diffusivity, were reduced in the splenium of T4-treated neonates compared with untreated controls. The data suggest that T 4 treatment enhances white matter recovery and myelination in neonates with moderate-to-severe IVH. This pilot study establishes a solid foundation for confirming this effect through a large multicenter clinical trial in preterm neonates with IVH.