Pre- and postnatal brain development in neonates with congenital hypothyroidism

Patients with early treated congenital hypothyroidism (CH) often develop subnormally and display subtle neurological defects. Can optimal treatment fully prevent these abnormalities, especially in patients with severe CH? This question was addressed by examining 61 patients (27 severe, 34 mild CH) aged 10-30 months using the Bayley Scales of Infant Development, a developmental test appropriate for this age. According to age at start of treatment (Early <13 days, Late > or = 13 days) and levothyroxine dose at the onset of treatment (High > or = 9.5 microg/kg/day, Low <9.5 microg/kg/day), four treatment groups were formed: Early/High, Early/Low, Late/High and Late/Low. Within the severe group, only the Early/High-treated patients reached normal developmental scores. Within the mild group, the Late/Low-treated infants had lower scores than the other patients with mild CH. The results suggest that if patients are treated early with a relatively high dosage of levothyroxine, normal psychomotor development can be expected, irrespective of the type of CH. When treated later on with a lower dose, suboptimal development is likely in infants exhibiting both types of CH. These cerebral abnormalities can originate during the pre- or postnatal period. The most important argument for a prenatal origin of the abnormalities is the relationship between bone age at diagnosis and subsequent developmental scores. We found, however, that this relationship can also be the result of late and inadequate treatment. In a series of 21 infants with CH (10 severe, 11 mild), somatosensory evoked potentials (SEP) were used to assess neurological maturation at diagnosis and after 12 months of treatment. At diagnosis, which was late (21 days after birth), SEP values were significantly less retarded than bone age (3.1 versus 6.5 weeks of delay, p < 0.001), measured using Sénécal's method. At 21 days, SEP and bone age values did not correlate, but they did correlate at 12 months (r = 0.47, p = 0.012). Therapy was inadequate in the whole group (mean initial dosage of levothyroxine 6.2 microg/kg/day), and in the severe group hypothyroidism persisted longer than in the mild group. The results suggest that the relationship between bone age and SEP values at 12 months was caused by late and inadequate hormone substitution more than intrauterine thyroid hormone deficiency.