In the JournalsPerspective

Gestational hypothyroxinemia associated with autism occurrence

Children born to mothers who had severe, early gestational hypothyroxinemia are nearly four times more likely to have autism, according to researchers. Although their results do not demonstrate causality, researchers said they lend support to the connection between low thyroid function and a child’s developing brain.

“It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics,” Gustavo C. Román, MD, neurologist at Houston Methodist Hospital, said in a press release. “That gives me hope that prevention is possible.”

Gustavo C. Román, MD 

Gustavo C. Román

The researchers used data from the Generation R Study to examine the relationship between thyroid function tests at 6 to 24 weeks of gestation in 5,100 women and parent-reported autistic symptoms in children aged 6 years. Autistic symptoms were measured by the Pervasive Development Problems (PDP) subscale (>98th percentile) and the Social Responsiveness Scale (SRS; the top 5%), according to researchers. Eighty children were defined as a “probable autistic child,” according to these scores.

Data indicate children born to mothers with early gestational hypothyroxinemia were four times more likely to have autism (adjusted OR=3.89; 95% CI, 1.83-8.20). However, no associations were made between maternal thyroid-stimulating hormone and free thyroxine during early pregnancy and children’s borderline and clinical PDP scores, the researchers wrote.

Children aged 6 years were twice as likely to demonstrate borderline PDP scores when their mothers had severe maternal hypothyroxinemia during early gestation (adjusted OR=2.02; 95% CI, 1.16-3.51), researchers added.

Furthermore, children of hypothyroxinemic mothers displayed higher odds for developing clinical PDP scores by age 6 years (adjusted OR=2.60; 95% CI, 1.30-5.18), according to data. No sex differences were observed.

“The next steps are interventional studies,” Román said. “We must look at a large nationwide population of women in early pregnancy to measure urine iodine and thyroid function. We must then correct thyroid deficiencies, if present, and provide prenatal vitamins with supplementary iodine. If autism cases fall precipitously compared with recent historical numbers, I think we will be able to conclude that thyroid function is critical.”

Disclosure: One of the researchers reports being remunerated contributing editor of the Achenbach System of Empirically Based Assessment.

Children born to mothers who had severe, early gestational hypothyroxinemia are nearly four times more likely to have autism, according to researchers. Although their results do not demonstrate causality, researchers said they lend support to the connection between low thyroid function and a child’s developing brain.

“It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics,” Gustavo C. Román, MD, neurologist at Houston Methodist Hospital, said in a press release. “That gives me hope that prevention is possible.”

Gustavo C. Román, MD 

Gustavo C. Román

The researchers used data from the Generation R Study to examine the relationship between thyroid function tests at 6 to 24 weeks of gestation in 5,100 women and parent-reported autistic symptoms in children aged 6 years. Autistic symptoms were measured by the Pervasive Development Problems (PDP) subscale (>98th percentile) and the Social Responsiveness Scale (SRS; the top 5%), according to researchers. Eighty children were defined as a “probable autistic child,” according to these scores.

Data indicate children born to mothers with early gestational hypothyroxinemia were four times more likely to have autism (adjusted OR=3.89; 95% CI, 1.83-8.20). However, no associations were made between maternal thyroid-stimulating hormone and free thyroxine during early pregnancy and children’s borderline and clinical PDP scores, the researchers wrote.

Children aged 6 years were twice as likely to demonstrate borderline PDP scores when their mothers had severe maternal hypothyroxinemia during early gestation (adjusted OR=2.02; 95% CI, 1.16-3.51), researchers added.

Furthermore, children of hypothyroxinemic mothers displayed higher odds for developing clinical PDP scores by age 6 years (adjusted OR=2.60; 95% CI, 1.30-5.18), according to data. No sex differences were observed.

“The next steps are interventional studies,” Román said. “We must look at a large nationwide population of women in early pregnancy to measure urine iodine and thyroid function. We must then correct thyroid deficiencies, if present, and provide prenatal vitamins with supplementary iodine. If autism cases fall precipitously compared with recent historical numbers, I think we will be able to conclude that thyroid function is critical.”

Disclosure: One of the researchers reports being remunerated contributing editor of the Achenbach System of Empirically Based Assessment.

    Perspective
    Elizabeth N. Pearce, MD, MSc

    Elizabeth N. Pearce

    This study’s findings, that severe hypothyroxinemia (maternal free T4 in the lowest 5th percentile with normal serum TSH) was associated with an almost fourfold increased risk for probable autism, add to the growing body of observational studies demonstrating that even mild maternal thyroid hypofunction in pregnancy is associated with adverse effects on child neurodevelopment. Dietary iodine deficiency is one potential cause of maternal hypothyroxinemia, but urinary iodine concentrations were not assessed in this study. The Controlled Antenatal Thyroid Screening (CATS) study is the only clinical trial to date to assess the effects of levothyroxine treatment for hypothyroxinemic pregnant women on child development; the CATS study found no effect of treatment on IQ at age 3 years. Prospective interventional studies are needed to better understand whether screening for and treatment of mild maternal thyroid hypofunction will improve IQ as well as risk for autism and attention deficit disorders.

    • Elizabeth N. Pearce, MD
    • Associate professor of medicine Boston University School of Medicine

    Disclosures: Pearce reports no relevant financial disclosures.