Reference Percentiles and Changes over Time for Total Thyroxine in Preterm Infants: A Retrospective Cohort Study

Hypothyroxinemia of prematurity increases the rate of false-positive results in total thyroxine (tT4)-based screening programs for congenital hypothyroidism. The use of specific cutoff values for preterm infants has been proposed, but data on tT4 reference ranges in this population are limited. The primary aim was to establish reference percentiles for tT4 in dried blood spots among Mexican preterm infants. Secondary aims included a comparison of the change of tT4 concentrations over time according to gestational age and to discuss its impact on tT4-based screening programs. This was a retrospective cohort study; 1561 preterm infants were included. Percentile 10th for tT4 concentration at 24-27, 28-30, 31-34, and 35-36 weeks of gestational age, measured in the first week of life was: 47.6, 56.6, 82.3, and 117.1 nmol/L, respectively. tT4 concentrations were compared in three different time points: first week of life, 2-3 weeks of life, and term-corrected gestational age (38 weeks of gestation), progressively increased in infants below 30 weeks, remained stable in infants from 31 to 34 weeks, and decreased in late preterm newborns (35-36 weeks). This study suggests that preterm infants may require the use of lower tT4 cutoff values in newborn screening.