Incidence and risk factors of transient hypothyroxinemia of prematurity: a prospective cohort study

Abstract

Background: Transient hypothyroxinemia of prematurity (THOP) is characterized by low thyroxine (T4) levels with normal thyroid-stimulating hormone (TSH) levels. This study aimed to determine the incidence and factors associated with THOP.

Methods: This prospective cohort study included neonates who were born before 37 weeks of gestation in the neonatal intensive care unit (NICU) between April 2017 and December 2020. Serum TSH and free thyroxine (FT4) levels were routinely screened at 3-5 days and 2, 4, and 6-8 weeks postnatally. The criteria for diagnosis of THOP were a TSH level < 7 mU/L with a FT4 level < 0.8 ng/dL at any screening timepoint.

Results: The incidence of THOP in infants born before 28, 34, and 37 weeks of gestation was 39.5 (17/43), 8.4% (29/343), and 4.8% (35/722), respectively. A multivariate analysis revealed that a gestational age of < 28 weeks (adjusted odds ratio [aOR]: 5.35, 95% confidence interval [CI]: 1.89-15.13, p=0.002); 5-min Apgar score of ≤3 (aOR: 5.72, 95% CI: 2.2-14.89, p < 0.001); and treatment with aminophylline (aOR: 2.95, 95% CI: 1.08-8.11, p=0.037), dobutamine (aOR: 4.12, 95% CI: 1.55-10.98, p=0.004), or morphine (aOR: 4.91, 95% CI: 1.29-18.74, p=0.011) were associated with an increased risk of THOP. The TSH and FT4 levels in infants with THOP returned to normal ranges by 2 weeks of age.

Conclusions: THOP is frequently found in preterm infants. An extremely low gestational age, a low Apgar score, and the use of certain medications in the NICU are risk factors for the development of THOP. Therefore, a thyroid screening program should be implemented for evaluating congenital hypothyroidism (CH) and THOP in preterm neonates in all settings.

Keywords: neonatal screening; premature birth; risk factors; thyroid-stimulating hormone; thyroxine.