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

Abstract

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.

Postnatal Serum Total Thyroxine Level Associated with Short- and Long-Term Anthropometric Outcomes in Very Preterm Infants

“…To the best of our knowledge, our study was the first to report that a lower risk of overweight status at 24 months old is associated with a higher thyroxine concentration at the neonatal stage. Although our study only used a single concentration, this time point may adequately represent the thyroxine level in early life [ 9 ].…”

“…Compared with full-term infants, very preterm infants display a unique and dynamic pattern in the thyroid-related hormone profile, as prematurity is associated with incomplete development of the hypothalamic–pituitary axis [ 6 , 7 ]. At first, compared to fetuses at an equivalent gestational age, very preterm infants are characterized by a temporary reduction in T4 that may last for 6–8 weeks, whereas their TSH remains low to normal [ 7 , 8 , 9 ]. Second, delayed TSH elevation is a common thyroid function anomaly in very preterm infants, which is not seen in term infants [ 10 , 11 , 12 ].…”

“…Second, delayed TSH elevation is a common thyroid function anomaly in very preterm infants, which is not seen in term infants [ 10 , 11 , 12 ]. Although a number of recent studies have proposed gestational age-specific references in TT4 or fT4 normal [ 9 , 13 ], there is still a knowledge gap regarding how to define thyroid insufficiency in very preterm infants, which is typically defined based on low T4 (<10 μg/dL) with normal TSH in term infants [ 14 ].…”

Postnatal Serum Total Thyroxine of Very Preterm Infants and Long-Term Neurodevelopmental Outcome

“…Importantly, Flores-Robles et al suggested that preterm infants may require lower TT4 cutoff values when undergoing newborn screenings [ 32 ]. Preterm infants with consistent thyroid dysfunction should be assessed using multipoint analyses [ 6 , 17 ].…”

“…Very preterm infants may experience a nadir duration of serum thyroxine without elevated TSH after birth [ 6 , 32 ]. The impact of the nadir duration on the rapidly growing brains of VPIs remains unclear, especially when solely using observational studies from term infants.…”