A-082 Establishment of Infant Free T4 Reference Interval Through Indirect Methods

Background Children require reference intervals distinct from adults and, based on their unique developing physiology, several intervals are often required to accurately reflect the distribution of expected results in a healthy pediatric population. The establishment of pediatric reference intervals has proven challenging. While consenting adults volunteer to contribute their biological material towards the development of a reference interval, well children usually do not have the occasion to get blood drawn and the smaller the child, the more significant the impact of phlebotomy. For these reasons, scientists have sought out other methods for determining pediatric reference intervals. As an alternative, indirect statistical methods may be applied to large data sets of laboratory test results to ascertain a reference interval. The Multi-Modal Decomposition (MMD) is an iterative indirect method that decomposes a mixture of multiple normal distributions into separate components using the expectation-maximization (EM) algorithm The objective of the current study, was to apply MMD to ascertain reference intervals for free T4 in infants. Methods The study population included infants ranging in age from 1 day to 60 days who had specimens submitted for free T4 testing involving equilibrium dialysis followed by LC-MS/MS in a commercial reference laboratory (Quest Diagnostics Nichols Institute, San Juan Capistrano, CA). MMD was performed on 25,271 de-identified free T4 results to establish the reference intervals that were validated by comparison against free T4 values obtained on 238 de-identified specimens submitted for acylcarnitine testing, the specimen were analyzed for TSH and only the in-range specimens were include for Free T4 reference interval analysis. Results MMD analysis demonstrated distinct reference intervals for the following ages: 0 to 6 days (1.8 - 6.1 ng/dL), 7 days to <2 weeks (1 - 4.4 ng/dL), 2 to <3 weeks (0.8 - 3.5 ng/dL), 3 to <4 weeks (0.8 - 3 ng/dL), and 4 to <8 weeks (0.7 - 2.8 ng/dL). The data did not support the use of separate intervals for male and female children. Conclusions MMD analysis demonstrated distinct reference intervals for the following ages: 0 to 6 days (1.8 - 6.1 ng/dL), 7 days to <2 weeks (1 - 4.4 ng/dL), 2 to <3 weeks (0.8 - 3.5 ng/dL), 3 to <4 weeks (0.8 - 3 ng/dL), and 4 to <8 weeks (0.7 - 2.8 ng/dL). The data did not support the use of separate intervals for male and female children.