Antenatal Corticosteroids for Threatened Labour Facilitate Thyroid Maturation Among Preterm Neonates

Shintaro Hanaoka; Kogoro Iwanaga; Seiichi Tomotaki; Fusako Niwa; Junko Takita; Masahiko Kawai


Clin Endocrinol. 2020;93(5):613-619. 

In This Article

Abstract and Introduction


Objective: To examine the effect of antenatal corticosteroids (ANS) on the maturation of thyroid function in the preterm infants.

Context: ANS reduce mortality and morbidities in preterm neonates. Organ maturation by the glucocorticoids is the key, at least in part. However, the effect of ANS on thyroid is controversial.

Patients: A study group of 99 very low birthweight neonates (<34 weeks' gestational age) with the exception of those born more than 7 days after ANS administration were divided into a complete group (n = 49) whose mothers completed two doses of betamethasone and who were born more than 24 hours after the completion of ANS administration, and an incomplete group (n = 50) who were not exposed to any ANS or were born within 24 hours after the completion of ANS administration. Serum-free thyroxine and thyroid-stimulating hormone (TSH) levels were measured, and thyrotropin-releasing hormone (TRH) stimulation tests were performed at about 2 weeks of age.

Results: The incidence of hyperthyrotropinaemia (TSH > 15 mIU/L) in the complete group was significantly lower than in the incomplete group (6% vs 22%, P = .023). Exaggerated responses to TRH tests were more frequent in the incomplete group (17% vs 44%; P = .053). TSH30 was significantly lower in the complete group, (P = .046). Multivariate logistic regression analysis showed that the incidence of hyperthyrotropinaemia was associated with complete ANS administration (adjusted odds ratios 0.39).

Conclusions: ANS administration might facilitate thyroid maturation in preterm neonates.


Advances in perinatal care have improved the prognosis for preterm neonates.[1,2] Among them, the administration of antenatal corticosteroids (ANS) is one of the most effective. Since Liggins et al first reported that maternal ANS administration reduced the incidence of neonatal respiratory distress syndrome (RDS) in 1972,[3] its clinical efficacy has been verified in many studies.[4–6] The beneficial effects of ANS have been reported not only in reducing the incidence of RDS, but also in reducing the incidence of mortality, intraventricular haemorrhage, periventricular leucomalacia, and necrotizing enterocolitis.[7,8] As the mechanism of ANS in reducing the incidence of RDS is considered to involve organ maturation in the lungs by facilitating differentiation into type 2 pulmonary epithelial cells, this effect might contribute to a reduction in other morbidities in preterm neonates, at least in part. On the other hand, the suppression of somatic cell growth by ANS might result in unfavourable effects on the somatic and developmental outcome is of concern.[9,10] With increasing numbers of mothers receiving ANS, it is important to examine both the favourable and unfavourable effects of this intervention.

Endocrine function is one of the key factors that might influence psychomotor development in preterm neonates.[11–13] Thyroid function is considered a key issue among them.[14–16] Although preterm neonates do not often have primary hypothyroidism with elevated thyroid-stimulating hormone (TSH) levels,[17] preterm infants frequently show thyroidal dysfunctions. Many have transient hypothyroxinaemia of prematurity (THOP);[18] however, there is no consensus for the treatment with thyroid hormones. Delayed elevation of TSH is also common in preterm infants, but treatments for this condition remain controversial. Although the links between such thyroid status specific to preterm infants and subsequent neurological outcomes are tenuous at best,[19] thyroid maturation might be associated with a good outcome for preterm neonates. Maturation of thyroid function is accelerated in the third trimester of pregnancy, coinciding with a cortisol surge in the foetus.[20,21] Glucocorticoids are involved in the process.[22,23] Therefore, we hypothesized that ANS might promote the maturation of thyroid function, in addition to organs such as the lungs. In human studies, the effects of ANS on the maturation of thyroid function are controversial: one report claimed that administration of ANS reduced thyroid dysfunction in neonates,[24] but others found no such effect.[25,26] Therefore, we conducted a study to examine the effects of ANS on thyroid function in preterm neonates. We evaluated not only basal-free thyroxine (FT4) and TSH levels but also TRH stimulation tests, which are helpful in defining thyroid dysfunction in older children and full-term neonates.[27–29] In preterm neonates, we previously reported that the hypothalamic-pituitary--thyroid (HPT) axis could respond to TRH stimulation tests appropriately even in very low birthweight neonates born at < 30 weeks of gestation at about 2 weeks after birth.[30] Therefore, we consider that TRH stimulation tests are helpful for defining thyroid function.