Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data

Levie, Deborah; Korevaar, Tim I. M.; Bath, Sarah C.; Dalmau Bueno, Albert; Murcia, Mario; Espada Sáenz-Torre, Mercedes; Dineva, Mariana; Ibarluzea, Jesús; Sunyer Deu, Jordi; Tiemeier, Henning; Rebagliato, Marisa; Rayman, Margaret P.; Peeters, Robin P.; Guxens Junyent, Mònica

doi:http://dx.doi.org/10.1210/jc.2018-00224

Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data

Citation

Levie D, Korevaar TIM, Bath SC, Dalmau-Bueno A, Murcia M, Espada M et al. Thyroid function in early pregnancy, child IQ, and autistic traits: a meta-analysis of individual participant data. J Clin Endocrinol Metab. 2018;103(8):2967-79. DOI: 10.1210/jc.2018-00224

Abstract

Context: Low maternal free T4 (FT4) has been associated with poor child neurodevelopment in some single-center studies. Evidence remains scarce for the potential adverse effects of high FT4 and whether associations differ in countries with different iodine status. Objective: To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. Design, Setting, and Participants: Meta-analysis of individual participant data from 9036 mother–child pairs from three prospective population-based birth cohorts: INMA [Infancia y Medio Ambiente (Environment and Childhood project) (Spain)], Generation R (Netherlands), and ALSPAC (Avon Longitudinal Study of Parents and Children, United Kingdom). The exclusion criteria were multiple pregnancies, fertility treatments, thyroid-interfering medication usage, and known thyroid disease. Main Outcomes: Child nonverbal IQ at 5 to 8 years of age, verbal IQ at 1.5 to 8 years of age, and autistic traits within the clinical range at 5 to 8 years of age. Results: FT4 <2.5th percentile was associated with a 3.9-point (95% CI, −5.7 to −2.2) lower nonverbal IQ and a 2.1-point (95% CI, −4.0 to −0.1) lower verbal IQ. A suggestive association of hypothyroxinemia with a greater risk of autistic traits was observed. FT4 >97.5th percentile was associated with a 1.9-fold (95% CI, 1.0 to 3.4) greater risk of autistic traits. No independent associations were found with TSH. Conclusions: Low maternal FT4 was consistently associated with a lower IQ across the cohorts. Further studies are needed to replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.