flawed on several levels. Despite the increase in the number of vaccines over recent decades, improvements in vaccine design have reduced the immunologic load from vaccines; the total number of immunological components in the 14 vaccines administered to US children in 2009 is less than ten percent of what it was in the seven vaccines given in 1980. A study published in 2013 found no correlation between autism and the antigen number in the vaccines the children were administered up to the age of two. There were 1,008 children in the study, one quarter of whom were diagnosed with autism, and the whole cohort was born between 1994 and 1999, when the routine vaccine schedule could contain more than 3,000 antigens (in a single shot of DTP vaccine). The vaccine schedule in 2012 contains several more vaccines, but the number of antigens the child is exposed to by the age of two is 315. Vaccines pose a very small immunologic load compared to the pathogens naturally encountered by a child in a typical year; common childhood conditions such as fevers and middle-ear infections pose a much greater challenge to the immune system than vaccines, and studies have shown that vaccinations, even multiple concurrent vaccinations, do not weaken the immune system or compromise overall immunity. The lack of evidence supporting the vaccine overload hypothesis, combined with these findings directly contradicting it, has led to the conclusion that currently recommended vaccine programs do not "overload" or weaken the immune system. Any experiment based on withholding vaccines from children is considered unethical, and observational studies would likely be confounded by differences in the healthcare-seeking behaviors of under-vaccinated children. Thus, no study directly comparing rates of autism in vaccinated and unvaccinated children has been done. However, the concept of vaccine overload is biologically implausible, as vaccinated and unvaccinated children have the same immune response to non-vaccine-related infections, and autism is not an immune-mediated disease, so claims that vaccines could cause it by overloading the immune system go against current knowledge of the pathogenesis of autism. As such, the idea that vaccines cause autism has been effectively dismissed by the weight of current evidence. Prenatal infection There is evidence that schizophrenia is associated with prenatal exposure to rubella, influenza, and toxoplasmosis infection. For example, one study found a sevenfold increased risk of schizophrenia when mothers were exposed to influenza in the first trimester of gestation.