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

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.