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, 25.7 to 22.2) lower nonverbal IQ and a 2.1-point (95% CI, 24.0 to 20.1) 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.

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Journal Journal of Clinical Endocrinology and Metabolism
Levie, D, Korevaar, T.I.M, Bath, S.C. (Sarah C.), Dalmau-Bueno, A, Murcia, M, Espada, M, … Guxens, M. (Monica). (2018). Thyroid function in early pregnancy, child IQ, and autistic traits: A meta-analysis of individual participant data. Journal of Clinical Endocrinology and Metabolism, 103(8), 2967–2979. doi:10.1210/jc.2018-00224