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Updated: Aug 15, 2026
An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Reference ranges for thyroid function tests in premature infants beyond the first week of life
S J Clark1, D D Deming, J R Emery
1Department of Pediatrics, Loma Linda University School of Medicine, Coleman Pavilion, Loma Linda, CA 92354, USA.
Insights
Establishing reference ranges for thyroid hormones in premature infants is crucial. This study provides new reference ranges for free thyroxine and thyrotropin in preterm neonates after the first week of life.
Area of Science:
- Neonatal endocrinology
- Pediatric thyroid function
- Premature infant health
Background:
- Thyroid hormone levels are critical for infant development.
- Accurate reference ranges for thyroid hormones in premature infants are essential for diagnosis and management.
- Existing data may not reflect current sensitive assay capabilities.
Purpose of the Study:
- To establish reference ranges for sensitive assays of thyrotropin (TSH) and free thyroxine (fT4) in premature infants.
- To determine if reference ranges vary by postconceptional age after the first week of life.
- To provide updated clinical guidelines for thyroid hormone assessment in preterm neonates.
Main Methods:
- Direct equilibrium dialysis for free thyroxine (fT4) and third-generation immunometric assay for thyrotropin (TSH) were used.
- 120 healthy premature infants (25-36 weeks' gestation) were studied.
- Infants were stratified by postconceptional age, and hormone levels were analyzed using ANOVA and linear regression.
Main Results:
- The reference range for fT4 was 10 to 33 pmol/l (0.8 to 2.6 ng/dl), showing no significant correlation with gestational or postnatal age.
- The reference range for TSH was 0.8 to 12 mU/l, with a minimal correlation to postnatal age.
- A single reference range for each hormone was deemed appropriate for premature infants up to 40 weeks postconceptional age.
Conclusions:
- Free thyroxine levels are tightly regulated in premature infants, similar to older children and adults, after the initial TSH surge.
- A single reference range for both fT4 and TSH is appropriate for premature infants after the first week of life until 40 weeks postconceptional age.
- These findings support standardized thyroid function testing in the neonatal intensive care unit.
Objectives:
To establish reference ranges for the more sensitive assays of thyrotropin and the best available assays of free thyroxine in premature infants after the first week of life.
Study Design:
Free thyroxine measurements by direct equilibrium dialysis and thyrotropin measurements by third generation immunometric assay were measured in 120 healthy premature infants 25 to 36 weeks' gestation at birth and every 3 weeks until hospital discharge. Infants were stratified by postconceptional age. Differences in free thyroxine and thyrotropin levels among groups were determined by ANOVA. Correlations between hormone measurements and gestational and postnatal ages were sought by linear regression analysis. Reference ranges were determined as arithmetic (free thyroxine) and geometric (thyrotropin) mean+/-2 SD ranges.
Results:
From 120 infants, 164 samples were obtained and grouped by postconceptional age at sampling. Free thyroxine was not different among postconceptional age groups and did not correlate with gestational or postnatal age. The free thyroxine reference range based on these data was 10 to 33 pmol/l (0.8 to 2.6 ng/dl). Thyrotropin did not correlate with gestational age. There was a clinically trivial but statistically significant (r(2)=0.03, p<0.05) correlation of thyrotropin with postnatal age. The thyrotropin reference based on these data was 0.8 to 12 mU/l.
Conclusions:
Free thyroxine was closely regulated in these premature infants and levels were similar to those in older children and adults, once the natal surge in thyrotropin has subsided. After the first week of life a single range for each hormone appeared appropriate for all premature infants until 40 weeks postconceptional age.
