Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: A Meta-Analysis of Individual Participant Data

Levie et al., 2018 | J Clin Endocrinol Metab | Meta Analysis

Citation

Levie Deborah, Korevaar Tim I M, ... Guxens Mònica. Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: A Meta-Analysis of Individual Participant Data. J Clin Endocrinol Metab. 2018-Aug-01;103(8):2967-2979. 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.

Key Findings

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.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range 5 to 8 years
Condition See abstract

MeSH Terms

  • Adult
  • Autistic Disorder
  • Child
  • Child Development
  • Child, Preschool
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Intelligence
  • Longitudinal Studies
  • Male
  • Mothers
  • Pregnancy
  • Pregnancy Complications
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects
  • Risk Factors
  • Thyroid Diseases
  • Thyroid Function Tests
  • Thyroid Gland
  • Thyrotropin
  • Thyroxine
  • Young Adult

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
  • Vertical: iodine

Provenance


Source extracted via PubMed E-utilities API on 2026-04-09