Thyroid hormone and folinic acid in young children with Down syndrome: the phase 3 ACTHYF trial.

PURPOSE: To determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS). METHODS: The Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6-18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months. Randomization was done by age and sex. The primary endpoint was adjusted change from baseline in Griffiths Mental Development Scale global development quotient (GDQ) after 12 months. RESULTS: Of 175 patients randomized, 143 completed the study. The modified intention-to-treat (mITT) population included all randomized patients who did not prematurely discontinue due to elevated baseline thyroid stimulating hormone (TSH). Baseline characteristics in the mITT were well balanced between groups, with reliable developmental assessment outcomes. Adjusted mean change in GDQ in the mITT showed similar decreases in all groups (placebo: -5.10 [95% confidence interval (CI) -7.84 to -2.37]; FA: -4.69 [95% CI -7.73 to -1.64]; L-thyroxine: -3.89 [95% CI -6.94 to -0.83]; FA+L-thyroxine: -3.86 [95% CI -6.67 to -1.06]), with no significant difference for any active treatment group versus placebo. CONCLUSION: This trial does not support the hypotheses that thyroxine and/or folinic acid improve development of young children with DS or are synergistic. This trial is registered with ClinicalTrials.gov number, NCT01576705.

Non-verbal development of children with deafness with and without cochlear implants.

Deprivation of sensory input affects neurological development. Our objective was to explore clinically the role of hearing in development of sensorimotor integration and non-verbal cognition. The study involved 54 children (15 males, 839 females; 5 to 9 years old) with severe or profound bilateral prelocutive deafness but without neurological or cognitive impairment. Of these, 25 had received an early cochlear implant (CIm). Patients were compared with 40 children with normal hearing. All were given a battery of non-verbal neuropsychological tests and a balance test, and were timed for simple and complex movement of limbs. Deafness, whether treated by CIm or not, resulted in a delay in development of complex motor sequences and balance. Lack of auditory input was also associated with lower, but non-pathological, scores in visual gnoso-praxic tasks and sustained attention. Such differences were not observed in children with CIm. Hearing contributes to clinical development of spatial integration, motor control, and attention. An early CIm enables good verbal development and might also improve non-verbal capacities.