Lack of beneficiary effect of levothyroxine therapy of pregnant women with subclinical hypothyroidism in terms of neurodevelopment of their offspring

Abstract

Purpose: Despite the beneficial effects of levothyroxine (LT4) therapy on pregnancy outcomes of women with subclinical hypothyroidism (SCH), its impact on the developmental status of offspring remains unclear. We aimed to assess the effects of LT4 therapy on the neurodevelopment of infants of SCH women in the first 3 years of life.

Methods: A follow-up study was conducted on children born to SCH pregnant women who had participated in a single-blind randomized clinical trial (Tehran Thyroid and Pregnancy Study). In this follow-up study, 357 children of SCH mothers were randomly assigned to SCH + LT4 (treated with LT4 after the first prenatal visit and throughout pregnancy) and SCH-LT4 groups. Children born of euthyroid TPOAb-women served as the control group (n = 737). The neurodevelopment status of children was assessed in five domains (communication, gross motor, fine motor, problem-solving, and social-personal domains) using the Ages and Stages Questionnaires (ASQ) at the age of 3 years.

Results: Pairwise comparisons of ASQ domains between euthyroid, SCH + LT4, and SCH-LT4 groups show no statistically significant difference between groups in the total score [median 25-75 total score: 265 (240-280); 270 (245-285); and 265 (245-285); P-value = 0.2, respectively]. The reanalyzing data using the TSH cutoff value of 4.0 mIU/L indicated no significant difference between groups in the score of ASQ in each domain or total score with TSH levels < 4.0 mIU/L, however, a statistically significant difference in the median score of the gross motor was observed between those SCH + LT4 with baseline TSH values ≥ 4.0 mIU/L and SCH-LT4 [60 (55-60) vs. 57.5 (50-60); P = 0.01].

Conclusions: Our study does not support the beneficiary effect of LT4 therapy for SCH pregnant women in terms of the neurological development of their offspring in the first three years of life.

Keywords: Ages and stages questionnaire (ASQ); Neurodevelopment; Pregnancy; Subclinical hypothyroidism (SCH); Tehran thyroid and pregnancy study.