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Maternal hypothyroidism may influence risk for neurodevelopmental disorders in offspring
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Children born to women with subclinical hypothyroidism and hypothyroxinemia during pregnancy are more likely to have an intellectual disability than women without such conditions during pregnancy, according to findings from a meta-analysis.
“The fetal thyroid gland is not functional until the 12 to 14 weeks’ gestation, and during that period, the fetus is solely dependent on thyroxine from the mother,” William Thompson, a doctoral student at the University of Exeter Medical School in Exeter, United Kingdom, and colleagues wrote in the study background. “Therefore, it is plausible that maternal thyroid hormone insufficiency, particularly in early pregnancy, could impair fetal neurodevelopment.”
In a meta-analysis, Thompson and colleagues evaluated data from 27 articles published after 1994 that investigated the association between maternal thyroid hormone insufficiency (including overt hypothyroidism, subclinical hypothyroidism and maternal hypothyroxinemia) and neurodevelopmental outcomes in offspring (n = 909,176, including 857,014 from a single study). Studies were classified as indicating intellectual disability in which IQ, language delays or global development delays were measured, and were classified as attention-deficit/hyperactivity disorder or autism spectrum studies in which a diagnosis or a validated scale for measuring such conditions was reported as an outcome measure. Studies reporting on psychomotor development were excluded.
In 11 studies analyzing maternal subclinical hypothyroidism, researchers found that the condition was associated with the risk for intellectual impairment in children (OR = 2.14; 95% CI, 1.2-3.83).
In 11 studies analyzing maternal hypothyroxinemia and intellectual disability in children, researchers found that children born to mothers with hypothyroxinemia were more likely to show signs of intellectual impairment vs. children born to euthyroid mothers (OR = 1.63; 95% CI, 1.03-2.56).
Researchers did not observe an association between maternal subclinical hypothyroidism and hypothyroxinemia and ADHD, and any possible link between the conditions and autism spectrum disorders in children was unclear, they wrote.
In a meta-analysis of two randomized controlled trials reporting the effects of levothyroxine treatment on the incidence of low IQ in offspring, researchers found no evidence that levothyroxine therapy reduced the incidence of low IQ in offspring (OR = 0.95; 95% CI, 0.74-1.23).
“Considering that, at an observational level, both maternal hypothyroxinemia and subclinical hypothyroidism were associated with indicators of intellectual disability, this result is surprising,” the researchers wrote. “It could be that the intervention was delivered too late in gestation for it to have a meaningful effect. ... It is also possible that the studies measured the IQ of the children at too young an age.”
The researchers added that larger trials with levothyroxine intervention earlier in pregnancy, with longer follow-up of children, is needed to resolve the issue. – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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