(43) Congenital Hypothyroidism and the Missing Piece: Why Do Some Babies Have a Delayed TSH Rise on the Newborn Screen?

Background: Prior to the implementation of newborn screening, congenital hypothyroidism (CH) was the most common preventable cause of intellectual disability. While newborn screening programs for CH have been highly successful, some affected infants exhibit a delayed rise in thyroid-stimulating hormone (TSH) resulting in late diagnosis and treatment, thereby raising the risk of adverse neurodevelopmental outcomes. Data regarding the prevalence of these cases of CH are scarce and it is unknown whether there are factors aside from prematurity that confer an increased risk of having a delayed TSH rise.

Objectives: Our objective was to identify differences in clinical factors among infants with CH who have a delayed TSH rise on the newborn screen (NBS) compared to infants with CH who are detected early.

Design/Methods: NBS results were obtained from the Indiana State Department of Health for all cases of CH diagnosed between 2012-2022. A delayed TSH rise was defined as diagnosis > 14 days of life and serum TSH > 20 mU/mL following a normal NBS. Binary logistic regression was performed to identify factors associated with the delayed CH cohort using the following variables: gestational age, birth weight, maternal age, race, sex, and ethnicity.

Results: We identified 73 cases out of 524 infants with CH over a ten-year period that met the criteria of a delayed diagnosis of CH (prevalence rate 14%). Adjusted logistic regression demonstrated that only gestational age was significantly negatively associated with a delayed CH diagnosis (adjusted OR = 0.71, 95% CI 0.66-0.77, p< 0.001, Table 1). Infants in the delayed cohort underwent an average of 2.54 newborn screens (range 1-6) prior to detection of an elevated TSH (Figure 1), with mean time to diagnosis of 26.4 days (range 15-158 days). The mean serum TSH was 167.7 mU/mL (range 20.3-817.9 mU/mL).

Conclusion: Our results suggest that a lower gestational age confers an increased risk of having a delayed rise in TSH. The factors of race, sex, ethnicity, and maternal age do not appear to be associated with having an increased risk of a delayed diagnosis of CH. Next steps include matching delayed and timely cases by birth weight and gestational age to evaluate whether there are differences in other clinical factors associated with a delayed TSH rise. This information may be used to better identify populations at risk for a delayed diagnosis of CH with the goal of achieving expedient treatment and optimal outcomes in this vulnerable population.