Prenatal inflammation linked to autism risk
By Ed Kang
Maternal inflammation during early pregnancy may be related to an increased risk of autism in children, according to new findings supported by the National Institute of Environmental Health Sciences (NIEHS). Researchers found this in children of mothers with elevated C-reactive protein (CRP), a well-established marker of systemic inflammation.
The risk of autism among children in the study was increased by 43 percent among mothers with CRP levels in the top 20th percentile, and by 80 percent for maternal CRP in the top 10th percentile. The findings appear in the journal Molecular Psychiatry and add to mounting evidence that an overactive immune response can alter the development of the central nervous system in the fetus.
Fetal origin of brain development
“Elevated CRP is a signal that the body is undergoing a response to an inflammatory insult, for example, a viral or bacterial infection,” said lead scientist Alan Brown, M.D., professor of clinical psychiatry and epidemiology at Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, and Mailman School of Public Health. “The higher the level of CRP in the mother, the greater the risk of autism in the child.”
Brown cautioned that the results should be viewed in perspective since the prevalence of inflammation during pregnancy is substantially higher than the prevalence of autism.
“The vast majority of mothers with increased CRP levels will not give birth to children with autism,” Brown said. “We don’t know enough yet to suggest routine testing of pregnant mothers for CRP for this reason alone; however, exercising precautionary measures to prevent infections during pregnancy may be of considerable value.”
“The brain develops throughout pregnancy,” said Linda Birnbaum, Ph.D., director of NIEHS, which funds a broad portfolio of autism and neurodevelopmental-related research. “This has important implications for understanding how the environment and our genes interact to cause autism and other neurodevelopmental disorders.”
The study capitalized on a unique national birth cohort known as the Finnish Maternity Cohort (FMC), which contains an archive of samples collected from pregnant women in Finland, where a component of whole blood referred to as serum is systematically collected during the early part of pregnancy. The FMC consists of 1.6 million specimens from about 810,000 women, archived in a single, centralized biorepository. Finland also maintains diagnoses of virtually all childhood autism cases from national registries of both hospital admissions and outpatient treatment.
From this large, national sample, the researchers analyzed CRP in archived maternal serum corresponding to 677 childhood autism cases and an equal number of matched controls. According to the team, the findings were not explained by maternal age, paternal age, gender, previous births, socioeconomic status, preterm birth, or birth weight. The work was conducted in collaboration with investigators in Finland, including the University of Turku and the National Institute for Health and Welfare in Oulu and Helsinki.
“Studying autism can be challenging, because symptoms may not be apparent in children until certain brain functions, such as language, come online,” said Cindy Lawler, Ph.D., head of the NIEHS Cellular, Organ, and Systems Pathobiology Branch and program lead for the Institute’s extramural portfolio of autism research. “This study is remarkable, because it uses biomarker data to give us a glimpse back to a critical time in early pregnancy.”
A public health message about prevention
This work is expected to stimulate further research on autism, a complex disease that presents significant challenges to identifying causes. Future studies may help define how infections, other inflammatory insults, and the body’s immune response interact with genes to elevate the risk for autism and other neurodevelopmental disorders. Preventive approaches addressing the environmental causes of autism may also benefit from additional research.
The study was funded primarily by an American Recovery and Reinvestment Act grant from NIEHS, with additional support from the National Institute of Mental Health.
Citation: Brown AS, Sourander A, Hinkka-Yli-Salomäki S, McKeague IW, Sundvall J, Surcel HM. 2013. Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry; doi: 10.1038/mp.2012.197 [online 22 January 2013].
(Ed Kang is a public affairs specialist in the Office of Communications and Public Liaison, and a regular contributor to the Environmental Factor.)