Association of Gestational Maternal Hypothyroxinemia and Increased Autism Risk

GC Roman, Akhgar Ghassabian, JJ Bongers-Schokking, Vincent Jaddoe, Bert Hofman, Yolanda Rijke, Frank Verhulst, Henning Tiemeier

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ObjectiveTransient gestational hypothyroxinemia in rodents induces cortical neuronal migration brain lesions resembling those of autism. We investigated the association between maternal hypothyroxinemia (gestational weeks 6-18) and autistic symptoms in children. MethodsThe mother-and-child cohort of the Generation R Study (Rotterdam, the Netherlands) began prenatal enrollment between 2002 and 2006. At a mean gestational age of 13.4 weeks (standard deviation = 1.9, range = 5.9-17.9), maternal thyroid function tests (serum thyrotropin [TSH], free thyroxine [fT(4)], and thyroid peroxidase [TPO] antibodies) were assessed in 5,100 women. We defined severe maternal hypothyroxinemia as fT(4) < 5th percentile with normal TSH. Six years later, parents reported b ResultsSevere maternal hypothyroxinemia (n = 136) was associated with an almost 4-fold increase in the odds of having a probable autistic child (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 1.83-8.20, p < 0.001). Using PDP scores, children of mothers with severe hypothyroxinemia had higher scores of autistic symptoms by age 6 years (adjusted B = 0.23, 95% CI = 0.03-0.37); SRS results were similar. No risk was found for children of TPO-antibody-positive mothers (n = 308). InterpretationWe found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring. Findings are concordant with epidemiological, biological, and experimental data on autism. Although these findings cannot establish causality, they open the possibility of preventive interventions. Ann Neurol 2013;74:733-742
Original languageUndefined/Unknown
Pages (from-to)733-742
Number of pages10
JournalAnnals of Neurology
Issue number5
Publication statusPublished - 2013

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