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Low maternal thyroxine levels associated with lower nonverbal child IQ
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Children born to mothers with a low level of free thyroxine during pregnancy are more likely to have a lower nonverbal IQ score at age 5 to 8 years vs. children born to mothers with a normal level of the thyroid hormone, according to an analysis of three mother-child birth cohorts.
“The consistent association of low maternal [free] T4 with adverse child neurocognitive outcomes, specifically lower nonverbal IQ in three independent cohorts, is particularly relevant given the fact that all three cohorts used a different immunoassay to measure [free] T4,” Monica Guxens, MD, MPH, PhD, assistant research professor at the Barcelona Institute for Global Health (ISGlobal), Spain, and colleagues wrote. “The value of a [free] T4 measurement during pregnancy has been under debate because absolute values of [free] T4 may be under- or overestimated when measured by immunoassays in pregnancy, particularly in the third trimester. However, these results suggest that [free] T4 is a reliable clinical marker of fetal thyroid state in early pregnancy.”
Guxens and colleagues analyzed data from 9,036 mother-child pairs without known thyroid disease from three prospective population-based birth cohorts: INMA (Spain; mean maternal age, 32 years), Generation R (the Netherlands; mean maternal age, 31 years) and ALSPAC (United Kingdom; mean maternal age, 28 years). Across the three cohorts, researchers assessed child nonverbal IQ at age 5 to 8 years, verbal IQ at age 1.5 to 8 years and autistic traits within the clinical range at age 5 to 8 years. Researchers used linear regression models to study the association between maternal free T4, thyroid-stimulating hormone and thyroid disease entities — specifically hypothyroxinemia and subclinical hypothyroidism — with child nonverbal and verbal IQ and child autistic traits within the clinical range.
Across the three cohorts, autistic traits within the clinical range occurred in 1.4% of children in INMA, 3.1% of children in Generation R and 7.5% of children in ALSPAC. Hypothyroxinemia prevalence was between 2% and 2.5% across cohorts and subclinical hypothyroidism prevalence was between 2.4% and 3.6% across cohorts.
The researchers observed a nonlinear association between maternal free T4 and mean nonverbal IQ, with maternal free T4 level below the 2.5th percentile associated with a 3.9-point lower nonverbal IQ (95% CI, –5.7 to –2.3), with similar results observed when using the 5th percentile cutoff. A high free T4 level was not associated with nonverbal IQ, according to researchers.
Researchers did not observe a continuous association between maternal free T4 levels and child autistic traits, although there was an association between maternal free T4 levels at the 97.5th percentile or greater and a 1.9-fold higher risk for autistic traits (95% CI, 1-3.4), with risk persisting after adjustment for nonverbal IQ.
When examining specific thyroid diseases, maternal hypothyroxinemia, based on the 2.5th and 97.5th population-based percentiles, was associated with a 3.8-point lower nonverbal IQ and a 2.8-point lower verbal IQ in children, but was not associated with autistic traits, according to researchers. However, hypothyroxinemia, based on the 5th and 95th population-based percentiles, was associated with similar nonverbal and verbal IQ scores in children as well as a 1.8-fold higher risk for autistic traits (95% CI, 1.1-2.8).
Subclinical hypothyroidism was not associated with nonverbal IQ, verbal IQ or autistic traits when defined by the 5th and 95th population-based percentiles, according to the researchers. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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