Assessment of Neurodevelopment and Growth in Congenital Hypothyroidism: Serial 6-Year Follow-up Study of 408 Patients

Abstract Context The link between congenital hypothyroidism (CH) and neurodevelopment is suggested, yet studies applying quantifiable measures are lacking. Moreover, socioeconomic disparities and subtle variation in timing of approach make the relationship difficult to detect. Objective To evaluate associations between CH and abnormalities in neurodevelopment and growth and determine the critical period for intervention. Methods We utilized a nationwide database to conduct a longitudinal analysis of 919 707 children. Exposure to CH was identified using claims-based data. The primary outcome of interest was suspected neurodevelopmental disorder, as measured using the Korean Ages & Stages Questionnaires (K-ASQ) administered annually from 9 to 72 months of age. Secondary outcomes were height and BMI z-scores. After randomly matching cases and controls at a 1:10 ratio, we employed inverse probability of treatment weighting and generalized estimating equation models for our analyses. We conducted subgroup analysis based on the age of treatment initiation. Results The prevalence of CH in our population was 0.05% (n = 408). Relative to the control group, the CH group had higher risk of suspected neurodevelopmental disorders (propensity score–weighted odds ratio: 4.52; 95% CI: 2.91, 7.02), and significantly increased risk in each of the 5 K-ASQ domains. No time interactions were noted at any rounds for the outcomes according to when the neurodevelopmental assessment was conducted (all P for interaction >.05). The CH group also had higher risk for low height-for-age z-score, but not for elevated BMI-for-age z-score. In subgroup analysis, delayed medication for CH correlated with worse neurodevelopmental outcomes. Conclusion The CH group had worse neurodevelopmental outcomes and reduced height-for-age z-score. Outcomes were worse when onset of treatment was increasingly delayed.