Neurodevelopmental Outcomes From the PREVeNT Trial.

This study followed 84 babies with Tuberous Sclerosis Complex (TSC) to see if a medication called vigabatrin could prevent intellectual disability and autism. At 3 years old, children's development was mostly in the low-average range. About 31% were diagnosed with autism, with no difference between those who got the medication and those who didn't. Importantly, none of the children without seizures developed autism, suggesting seizures may increase autism risk in TSC.

The PREVeNT trial was a Phase IIb randomized controlled trial evaluating vigabatrin's effectiveness in preventing intellectual disability and autism in 84 infants with Tuberous Sclerosis Complex (TSC). At 36 months, 65 participants completed assessments showing cognitive scores in the low average range at 12 months with slight decline over time. Adaptive functioning was also in the low average range for seizure groups. The watchful waiting group demonstrated higher neurocognitive scores compared to treatment groups.

Language development improved to match cognitive abilities by 36 months. Thirty-one percent received an ASD diagnosis with no significant differences between treatment groups. Notably, no participants without epilepsy were diagnosed with ASD, suggesting a potential link between seizures and autism risk in TSC.

Results suggest vigabatrin may not prevent autism in TSC. The finding that no children without seizures developed autism highlights the importance of seizure management. Early developmental monitoring remains crucial for TSC management.

Sample size limitations with only 65 participants completing through 36 months. COVID-19 pandemic impacts on study participation. Potential baseline differences between groups not fully described. Early seizure detection and intensive monitoring may have influenced outcomes.

Tuberous Sclerosis Complex (TSC) is associated with high prevalence of epilepsy, intellectual and developmental disability, and autism spectrum disorder (ASD). PREVeNT, a Phase IIb, multicenter, double-blind placebo-controlled trial, evaluated the efficacy of vigabatrin in preventing intellectual and developmental disability and ASD in infants with TSC. Phenotypic, developmental, and ASD-specific outcomes at 36 months are presented. Eighty-four infants with TSC were enrolled in PREVeNT across 13 TSC clinics in the United States.

Participants underwent neurodevelopmental assessments at ages 6 months through 36 months. Clinical best estimate diagnosis of ASD or non-ASD along with a rating of clinical certainty was determined at 36 months. Sixty-five participants completed assessments through 36 months of age. Mean cognitive scores on the Bayley-III were in the low average range at 12 months.

Cognitive scores declined slightly in all groups over time. Adaptive scores were in the low average range for the seizure groups. For all neurocognitive measures, those in the watchful waiting group exhibited higher scores compared to the other cohorts. Language scores became more commensurate with cognitive scores by 36 months.

The Clinical Certainty Rating was available for 58 patients, with 31% rated as having ASD; this did not differ by treatment assignment. No significant differences in developmental or autism-specific outcomes were seen between treatment groups, and no participants without epilepsy were diagnosed with ASD. This may be due to early detection of seizures, closer developmental monitoring and follow-up in the trial, and impacts of the pandemic on study participation.