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

J Clin Endocrinol Metab. 2018 Aug 1;103(8):2967-2979. doi: 10.1210/jc.2018-00224.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autistic Disorder / epidemiology
  • Autistic Disorder / etiology*
  • Autistic Disorder / physiopathology
  • Child
  • Child Development / physiology*
  • Child, Preschool
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Intelligence / physiology*
  • Longitudinal Studies
  • Male
  • Mothers* / statistics & numerical data
  • Pregnancy
  • Pregnancy Complications / blood
  • Pregnancy Complications / epidemiology
  • Pregnancy Complications / physiopathology
  • Pregnancy Trimester, First* / blood
  • Prenatal Exposure Delayed Effects* / blood
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Risk Factors
  • Thyroid Diseases / blood
  • Thyroid Diseases / complications
  • Thyroid Diseases / epidemiology
  • Thyroid Diseases / physiopathology
  • Thyroid Function Tests
  • Thyroid Gland / physiology*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Young Adult


  • Thyrotropin
  • Thyroxine