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Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine

Abstract

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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Fig. 1: Flowchart of Study Participants.
Fig. 2: TSH Values According to Postmenstrual Age.
Fig. 3: TSH median laboratory values with reference intervals organized by postmenstrual age groupings.
Fig. 4: FT4 Values According to Postmenstrual Age.
Fig. 5: Median FT4 According to Postmenstrual Age Subgroups.

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All authors made substantial contributions to the conception and design, acquisition of data, or analysis and interpretation of data. All authors contributed towards drafting the article or revising it critically for important intellectual content. All authors gave final approval of the version to be published.

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Correspondence to Jonathan L. Slaughter.

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The authors declare no competing interests.

Consent statement

For this cohort study using laboratory values that were previously collected in a neonatal intensive care unit per local standard of care, the Nationwide Children’s Hospital Institutional Review Board deemed this research to be no more than minimal risk and granted a waiver of informed consent.

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Ziegler, G.M., Slaughter, J.L., Chaudhari, M. et al. Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine. Pediatr Res 91, 1130–1135 (2022). https://doi.org/10.1038/s41390-021-01838-3

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