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Autism linked to maternal thyroid dysfunction

Pregnant women with hypothyroxinemia in early gestation have nearly a 4-fold increased risk of having a child with autism, new research suggests.

“We found a consistent association between severe, early gestation maternal hypothyroxinemia and autistic symptoms in offspring,” investigators from Houston Methodist Neurological Institute in Texas write.

“It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics. That gives me hope that prevention is possible,” lead investigator Gustavo Román, MD, said in a statement.

The study was published online August 13 in Annals of Neurology.

Prevention Possible?

In a review published in 2007 in the Journal of the Neurological Sciences, Dr. Román made a case for why he believes the increase in autism diagnoses could be at least partly the result of an iodine-starved diet and/or exposure to toxins that interfere with normal thyroid function.

In the current study, an association between maternal thyroid dysfunction and autism in offspring emerged in the mother-child cohort of the Dutch Generation R Study, a multiethnic prospective birth cohort in Rotterdam, the Netherlands, that began prenatal enrollment between 2002 and 2006.

At a mean gestational age of 13.4 weeks, maternal thyroid function tests were assessed in 5100 women. A total of 136 mothers had severe maternal hypothyroxinemia, defined as free thyroxine (fT4) less than the 5th percentile with normal serum thyrotropin.

Six years later, parents reported behavioral and emotional symptoms in 4039 children using the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist and/or the Social Responsiveness Scale (SRS).

Eighty children (2.0%) had “probable” autism, defined by PDP score greater than the 98th percentile and SRS score in the top 5% of the sample. This rate is consistent with the Dutch rate of autism spectrum disorder, the researchers note.

After controlling for maternal factors and children’s characteristics, the researchers found that severe maternal hypothyroxinemia early in gestation increased the likelihood of having an autistic child by almost 4-fold (adjusted odds ratio [OR], 3.89; 95% confidence interval [CI], 1.83 – 8.20; P < .001).

Using the PDP scores, children of mothers with severe hypothyroxinemia had higher scores of autistic symptoms by age 6 years; SRS results were similar.

“Although these findings cannot establish causality, they suggest that maternal thyroid dysfunction could result in autistic symptoms in the child,” the investigators write.

A Hypothesis Worth Exploring- Autism

“This is an interesting study that shows an association that is worth exploring further,” Marie Lynn Miranda, PhD, dean of the University of Michigan School of Natural Resources and Environment, who was not involved in the study, told Medscape Medical News.

“Investing in further research designed to investigate causality, rather than association, is the next critical step,” she added.

Dr. Román and colleagues emphasize that the findings support epidemiologic, biological, and experimental data on autism.

“Thyroid hormones are critical during pregnancy,” they note, and maternal hypothyroidism causes pregnancy complications, including postpartum hemorrhage, placental abruption, and preterm labor; some of these have been shown to increase the risk for autism, as reported by Medscape Medical News.

An article published in 2011 in Autism Research found that infants born with very low fT4 had an increased risk for autism.

The study team also notes that thyroid deficiency in utero during critical periods of brain development causes mental retardation, psychomotor delay, and deafness and is also associated with other neurodevelopmental outcomes, such as cerebral palsy. It is possible that maternal hypothyroxinemia during gestation alters neuronal migration in the developing brain, they say.

“The next steps are interventional studies,” Dr. 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.”

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Ann Neurol. Published online August 13, 2013 Abstract

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