Prenatal Inflammation May Increase Autism Risk

Deborah Brauser

January 31, 2013

Elevated levels of maternal C-reactive protein (CRP) may significantly increase the risk for autism in offspring, new research suggests.

The population-based cohort study of pregnant women in Finland showed that offspring of those with high levels CRP had a 43% elevated risk of having autism compared with children who had mothers with low levels of CRP during pregnancy.

Dr. Alan Brown

"This was in line with what we expected from other epidemiologic studies," lead author Alan S. Brown, MD, professor of clinical psychiatry and epidemiology at Columbia University College of Physicians and Surgeons in New York City and director of the Birth Cohort Studies unit in the Division of Epidemiology at New York State Psychiatric Institute, told Medscape Medical News.

Dr. Brown added that the study's take-away message is to be mindful of the effects of inflammation on a variety of outcomes.

"It's important for clinicians to be aware when a pregnant woman has an infection — not a mild infection such as a cold, but a more severe one. And to really follow her closely and make sure the infection gets treated," he said.

"I think it's also important for clinicians to advise these women to avoid certain sources of infection. For example, hand washing is very important, especially since we're now in the middle of flu season."

The study was published online January 22 in Molecular Psychiatry.

Potentially Plausible

CRP is "an acute-phase reactant" and an established biomarker for inflammation, according to the researchers. Dr. Brown added that elevated CRP levels signal a response to inflammation from, for example, a viral or bacterial infection.

As reported by Medscape Medical News, recent studies have shown that individuals with the highest levels of CRP were more than twice as likely to have depression and psychological distress than those with normal levels of the protein.

Dr. Brown said that past research has also shown that prenatal infections are associated with schizophrenia. The investigators note that these types of infections and immune dysfunction are also "biologically plausible potential causes of autism."

"There is substantial evidence that the immune response alters the development of the central nervous system during fetal life," they write.

They examined data from the Finnish Prenatal Study of Autism for all offspring born in Finland from 1987 to 2005. All of the mothers in the chosen cohort had serum drawn during their first and early second trimesters. And all children were followed until 2007.

Of the 1.2 million births occurring during this period, there were 1132 cases of childhood autism. A total of 677 of these children and 677 of their healthy peers were included in this analysis.

Be Aware, Not Alarmed

Results showed a significant association between increasing maternal CRP levels and risk for autism in the offspring (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.02 - 1.24; P = .02).

Compared with the women who had CRP levels in the lowest quintile (defined as 0.10 - 0.92 mg/dl), those with CRP levels in the highest quintile (defined as > 5.84 mg/dl, considered the top 20th percentile) showed a significantly higher risk for autism (OR, 1.43; 95% CI, 1.02 - 2.01; P = .039).

The women who had CRP levels in the top 10th percentile (defined as > 9.55 mg/dl) had an 80% increased risk for autism (95% CI, 1.09 - 2.97; P = .02).

"Inflammation during pregnancy may represent a common pathway by which infections...increase risk for the disorder," write the investigators, adding that the results will need to be replicated.

"I wouldn't say this is ready yet for clinical use in a pregnancy population, such as among obstetricians. But this might add more evidence or weight to the importance of identifying inflammation or inflammatory properties, as well as infection, in pregnancy as a potential risk factor for not only autism but other neurodevelopmental disorders," said Dr. Brown.

He added that the study should not scare patients but should remind them of the importance of telling their doctor about any potential concerns, especially because treating a problem such as an infection early can have huge effects.

"The vast majority of mothers who had the increased levels of CRP did not have children with autism. So it's important for mothers to be aware of these findings but not alarmed by it."

Important Implications

"This [study] has important implications for understanding how the environment and our genes interact to cause autism and other neurodevelopmental disorders," said Linda Birnbaum, PhD, director of the National Institute of Environmental Health Sciences (NIEHS), in a release. NIEHS was the primary funder for this study.

Dr. Birnbaum's colleague noted that this area of study often produces some unique difficulties.

"Studying autism can be challenging because symptoms may not be apparent in children until certain functions, such as language, come on line," said Cindy Lawler, PhD, head of the NIEHS Cellular, Organ, and Systems Pathobiology Branch and program lead for the Institute's extramural portfolio of autism research, in the same release.

"This study is remarkable because it uses biomarker data to give us a glimpse back to a critical time in early pregnancy," added Dr. Lawler.

The organization notes that they hope future studies will "help define how infections, other inflammatory insults, and the body's immune response interact with genes" to elevate the risk for various neurodevelopmental disorders.

The study was funded primarily by an American Recovery and Reinvestment Act grant from the NIEHS, with additional support from the National Institute of Mental Health. The study authors have disclosed no relevant financial relationships.

Mol Psychiatry. Published online January 22, 2013. Abstract