A two-screen approach to diagnostic testing for congenital hypothyroidism, performed in newborns during the first 48 hours after birth and again at age 7 to 28 days, better identified missed cases of the disease vs. lowering the diagnostic threshold for a single test, according to an analysis published this week in the CDC’s Morbidity and Mortality Weekly Report.
Untreated congenital hypothyroidism can result in cognitive impairment and growth complications, and newborn screening for primary congenital hypothyroidism is part of the U.S. Recommended Uniform Screening Panel, David E. Jones, PhD, of the Utah Public Health Laboratory in Salt Lake City, and colleagues wrote in the study background. Initial screenings for congenital hypothyroidism are typically performed 24 to 48 hours after birth; however, 14 states, including Utah, perform a routine second screen at approximately age 2 weeks, the researchers wrote, and an analysis of Utah data suggests a second screening identifies missed cases of the condition.
“The goal of screening is not to miss cases, while avoiding overwhelming the health care system with false-positive screens requiring unnecessary follow-up and diagnostic testing,” Jones and colleagues wrote. “In Utah, a two-screen program supports this goal.”
In Utah, all infants receive two screenings for primary congenital hypothyroidism — completed by measuring thyroid stimulating hormone (TSH) from dried whole blood spots collected by heel stick —even if the first screen is positive for the disease. In Utah, any TSH value of at least 40 µIU/mL is considered abnormal for either a first or second screen, and elevated screening results are followed by diagnostic testing. Between 2010 and 2016, 359,432 infants in Utah were screened for congenital hypothyroidism.
Jones and colleagues analyzed data from 123 infants with confirmed cases of congenital hypothyroidism, identified in Utah between 2010 and 2016, who underwent two screenings for the disease. Within the cohort ,98 cases were identified by the first screen and 25 cases were identified in the second screening. Researchers stratified infants by two groups: those with an abnormal first screen (group 1) and those with a normal first screen but abnormal second screen (group 2), calculating mean TSH concentrations for both groups. Researchers performed a retrospective cutoff analysis to determine whether all group 2 cases could be identified by a single screen, analyzing the number of false positives and false negatives as a function of adjusting the first screening cutoff value to a range between 5 and 40 µIU/mL.
Researchers found that, among group 2 infants, TSH concentrations were lower on the first screen, with all infants having concentrations below the 40 µIU/mL cutoff value, but with TSH values above the cutoff value on the second screen. Compared with all infants with and without congenital hypothyroidism, TSH levels for group 1 and group 2 infants were elevated for the first and second screenings, according to researchers.
The researchers determined that a moderate cutoff adjustment from 40 µIU/mL to 20 µIU/mL would have resulted in approximately 27,600 false-positives cases and 11 missed cases.
“To ensure that all group 2 cases were detected through a single screen, a TSH cutoff values of 5 µIU/mL would have been necessary, which would have resulted in 282,850 false-positive cases or approximately 79% of the screened population, the researchers wrote.
The researchers concluded that the study underscores the utility and power of a two-screen approach in identifying congenital hypothyroidism cases with a normal TSH concentration on the first screen but an elevated TSH concentration on the second screen. – by Regina Schaffer
Disclosure: The authors report no relevant financial disclosures.