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Evidence suggests that maternal immune activation during pregnancy has a toxic effect on the developing fetal brain leading to neurodevelopmental problems like schizophrenia and autism in the child. Potential pathogenic mechanisms contributing/leading to immune activation in the mother include nutritional deficiencies, stress, infections, toxins and drugs especially antibiotics.
Although intuitive, role of infections in mom during pregnancy in causing autism has not been clearly established.
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A metaanalysis conducted by Dr. Gardener and colleagues (2011) from the Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, demonstrated that while there are numerous risk factors for autism, there is insufficient evidence to implicate any single prenatal factor in causing autism. The metaanalysis did suggest that pregnancy complications may increase the risk.
Animal data on maternal infections and autism
Shi et al in 2003 reported that immune activation of pregnant mice by inducing human influenza virus respiratory infection of leads to abnormal behavior as adults including deficits of acoustic startle response, exploratory behavior and social interaction. According to Drs. Smith and colleagues from the California Institute of Technology, Pasadena, California, these abnormal changes due to immune activation occur via increase of certain cytokines like interleukin-6 or IL6. Activation of the maternal immune system also results in hormonal changes in the placenta via IL-6.
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Human data on maternal infections and autism
Data has been conflicting and the differences may be attributed to differences in design of studies and subjects studies. While e meta-analysis of case control studies found that prenatal infection at any time during pregnancy causes a two-fold increase in risk of autism, a Swedish study using inpatient hospital register as well as a Danish hospital based register study failed to document any such linkage. The latter studies may however miss out many cases of maternal infection.
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Dr. Atladottir and colleagues from the University of Aarhus in Denmark and Center for Diseases Control and Prevention in Atlanta, GA wished to examine the effect of maternal infection on autism and antibiotic by using self-reported infections and antibiotic use with autism.
Study subjects
- Women: 101,033 pregnant subjects. This number represented 31% of all pregnant moms in Denmark during the study period. Recruitment was done through the subject’s primary care provider at prenatal visit.
- Children: 96,736 kids ranging from 8 to 14 years of age. 976 were diagnosed with autism by a psychiatrist.
- Period: 1996-2002
- Follow-up period: Average 10 years
Data studied
- Episodes of fever
- Maternal infections
- Antibiotic use
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Results of maternal infection, antibiotic use and autism study
- Maternal influenza results in a 2.3 fold increased risk of infantile autism. However, common specific infections like genital herpes, kidney infections or pyelonephritis, vaginal yeast infection had no effect on ASD.
- While most febrile episodes had no impact, fever episodes lasting 7 or more days were associated with 1.6-fold increased risk of autistic spectrum disorders and 3.2-fold increased risk of infantile autism.
- Use of antibiotics including penicillin, macrolides like erythromycin, and sulfonamides drugs was associated with a small but statistically significant increased risk of autism spectrum disorders.
Conclusions on maternal infection, antibiotic use and risk of autism
- Most common infections at any time during pregnancy do not increase risk of autism.
- Multiple studies including the above study have confirmed increased risk of autism due to viral infections like respiratory influenza infection.
- Of note, Drs Brown and colleagues from the College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY have based on serologic evidence demonstrated that influenza infection during early pregnancy is associated with schizophrenia in the unborn child.
Is It Leaky Gut or Leaky Gut Syndrome?
Potential role of Gut based on maternal infection and antibiotic use with autism
- Infection results not only just immune activation but also increased intestinal permeability or leaky gut along with alterations of intestinal bacteria or dysbiosis. Such intestinal changes can results in passage of potentially noxious substances/signals across the placenta to the developing fetus.
- These chemicals transferred to fetus and its developing brain may include maternal antibodies as a result of infection, abnormal neurochemical signals due to altered brain-gut-bacteria communications in mother, absorbed bacterial toxic products with their antibodies as well as potentially noxious semi-digested food products.
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