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Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine
George M Ziegler1, Jonathan L Slaughter2,3,4, Monika Chaudhari5,6
1Department of Pediatrics, Division of Neonatology, Nationwide Children's Hospital, Columbus, OH, USA.
Insights
This study establishes new reference intervals for thyroid hormones in preterm infants, revealing that very premature babies (<31 weeks gestation) have higher thyroid-stimulating hormone and lower free thyroxine levels. These findings are crucial for accurate diagnosis and management of hypothyroidism in this vulnerable population.
Area of Science:
- Neonatal endocrinology
- Pediatric thyroid disorders
Background:
- Preterm infants possess an immature hypothalamic-pituitary-thyroid (HPT) axis.
- Various risk factors contribute to a hypothyroid state in preterm neonates.
- Current thyroid-stimulating hormone (TSH) cutoff values and free thyroxine (fT4) reference intervals lack sufficient data for clinical guidance in preterm infants.
Purpose of the Study:
- To establish reliable reference intervals for TSH and fT4 in preterm infants.
- To provide age-specific thyroid hormone reference ranges for clinical application.
- To improve the diagnosis and management of hypothyroidism in hospitalized preterm infants.
Main Methods:
- Retrospective evaluation of 1584 TSH and 1576 fT4 samples from 1087 preterm infants (25-43 weeks postmenstrual age).
- Utilized R and the mixtools package to determine median thyroid hormone values and reference intervals.
- Analyzed laboratory samples originally collected for screening delayed-onset hypothyroidism.
Main Results:
- TSH reference intervals showed minimal change across gestational ages (e.g., 0.340-9.681 µIU/mL in 25-27 weeks to 1.090-7.627 µIU/mL in 40-43 weeks).
- fT4 reference intervals increased with gestational age (e.g., 0.42-0.91 ng/dL in 25-27 weeks to 0.87-1.32 ng/dL in 40-43 weeks).
- Infants <31 weeks gestation exhibited higher baseline TSH and lower baseline fT4 than previously expected.
Conclusions:
- The identified reference intervals suggest distinct baseline thyroid hormone levels for infants <31 weeks gestation.
- Increasing fT4 values with advancing postmenstrual age reflect HPT axis maturation.
- Clinicians require postmenstrual age-specific reference intervals for accurate hypothyroidism screening and diagnosis in preterm infants.
Background:
Infants born preterm are affected by a hypothalamic-pituitary-thyroid axis that is immature and still developing as they progress closer to corrected term gestation. Multiple risk factors place preterm infants at risk for a hypothyroid state. However, there is variability in thyroid-stimulating hormone cutoff values and limited data on free thyroxine reference intervals to guide clinicians.
Methods:
1584 thyroid-stimulating hormone and 1576 free thyroxine laboratory samples that were originally collected to screen hospitalized infants for delayed-onset of hypothyroidism were retrospectively evaluated from a group of 1087 infants who ranged in postmenstrual age from 25 to 43 weeks gestation at the time of laboratory sample collection. Median thyroid hormone values and reference intervals were established using R and the mixtools package.
Results:
Thyroid-stimulating hormone reference intervals remained similar across gestational ages from 0.340-9.681 µIU/mL in 25-27 6/7-week infants to 1.090-7.627 µIU/mL in 40-43-weeks infants. For the same age groups, free thyroxine reference intervals increased from 0.42-0.91 ng/dL to 0.87-1.32 ng/dL.
Conclusion:
The reference intervals identified suggest that infants <31 weeks gestation have a higher thyroid-stimulating hormone and lower free thyroxine level at baseline than previously anticipated.
Impact:
The increasing free thyroxine values in preterm to term infants indicate a maturing hypothalamic-pituitary-thyroid axis. Clinicians need thyroid hormone reference intervals that also vary by postmenstrual age to aid the evaluation of sick preterm infants who are at risk of a delayed hypothyroidism diagnosis that can be missed on the initial newborn screen. This study provides one of the largest samples of thyroid-stimulating hormone and free thyroxine data to establish reference intervals in preterm infants. Clinicians may utilize the identified postmenstrual age-based reference intervals to inform follow-up thyroid testing in preterm infants at several weeks postnatal age.
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