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Summary of Advances Cover 2015

Summary of Advances

In Autism Spectrum Disorder Research


Question 3: What Caused This to Happen and Can It Be Prevented?

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autismlike behavior or neuropathology
Gadad BS, Li W, Yazdani U, Grady S, Johnson T, Hammond J, Gunn H, Curtis B, English C, Yutuc V, Ferrier C, Sackett GP, Marti CN, Young K, Hewitson L, German DC. Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12498-503. [PMID: 26417083]

This study examined whether exposure to vaccines containing ethyl mercury (found in the vaccine preservative thimerosal) or the measles, mumps, and rubella (MMR) vaccine could be demonstrated to be linked to development of autism-like symptoms in an animal model. The researchers carried out their study in infant monkeys (rhesus macaques) by exposing six groups of animals to thimerosal-containing vaccines (TCVs) and/or MMR or placebos according to one of six schedules, which included a historical and recent recommended vaccine schedule. The research team then looked for behavioral changes in the monkeys and for any unusual patterns in three brain regions corresponding to those known to exhibit changes in the postmortem brains of humans diagnosed with ASD. The six groups of animals used in the study had 12 or more monkeys per group. The control group received only saline (a salt solution), while the other groups received either a combination of vaccines from a historical (1990s) vaccine schedule, an accelerated historical vaccine schedule, a more recent (2008) vaccine schedule, or a single vaccine and saline combination. An analysis of social behavior in the juvenile monkeys showed no significant differences in “negative” social behaviors between animals (such as fear, withdrawal, or repetitive behaviors) in the control and experimental groups. In addition, when comparing postmortem tissue from animals in the control group with tissue from animals in the two groups having the highest exposure to vaccines, no neuropathological changes (e.g., changes in organ volume, cell number, or cell size) were found in three areas of the brain known to show changes in humans with ASD: the cerebellum, hippocampus, and amygdala. The researchers concluded that their study does not support the hypothesis of a role for certain vaccines in the development of autism; they state that “our data strongly support the conclusion that childhood TCVs do not produce ASD-like neuropathology or behavioral changes in the nonhuman primate.”

Autism occurrence by MMR vaccine status among US children with older siblings with and without autism
Jain A, Marshall J, Buikema A, Bancroft T, Kelly JP, Newschaffer CJ. JAMA. 2015 Apr 21;313(15):1534-40. [PMID: 25898051]

Although numerous research studies over the past 15 years have suggested that vaccines, and in particular, the MMR (measles, mumps, and rubella) vaccine is not associated with development of ASD, this issue continues to be a concern among some members of the autism community as well as the general public. The goal of this study was to compare autism rates in MMR-vaccinated and MMR-non-vaccinated siblings of children with autism (a high-risk population) to determine whether vaccination increases autism risk in this population. This study examined the occurrence of ASD by vaccine status in a sample of 95,727 children in the United States between birth and 5 years of age and who have an older sibling with or without ASD. This study used a large administrative commercial health plan claims database (the Optum Research Database) to identify the study participants. Children were determined to have received the MMR vaccine if they received a medical code indicating that they received each component (zero, one, or two doses) after 1 year of age. Children and their older siblings were determined to have ASD through a review of insurance claims, with the requirement that two or more claims had been made on separate dates with the appropriate medical codes for autistic disorder, other specified pervasive development disorder (PDD), including Asperger syndrome, or an unspecified PDD.

The study found that receiving the MMR vaccine was not associated with an increased risk of ASD at any age. Specifically, the study found that for children, age 2, with an older sibling with ASD the relative risk of ASD for one dose of MMR vaccine compared to no vaccine was 0.76, and for children age 5, the relative risk of ASD for two doses compared to no vaccine was 0.56. For children, age 2, who did not have an older sibling with ASD, the relative risk of ASD for one dose of MMR vaccine compared to no vaccine was 0.91, and at age 5, the risk of ASD for two doses was 1.09. The finding that no link was observed between MMR vaccination (either one or two doses) and increased ASD risk among children with older siblings that have ASD is consistent with studies done in other groups, and supports the conclusion that MMR vaccination is not associated with ASD. These findings indicate that there is no harmful association between receiving the MMR vaccine and ASD, even among children already at a higher risk for ASD.

Association of maternal diabetes with autism in offspring
Xiang AH, Wang X, Martinez MP, Walthall JC, Curry ES, Page K, Buchanan TA, Coleman KJ, Getahun D. JAMA. 2015 Apr 14;313(14):1425-34. [PMID: 25871668]

There is some evidence children who are exposed to maternal diabetes (a mother’s diabetes diagnosed prior to pregnancy) are at increased risk for ASD although there is less evidence about prenatal exposure to gestational diabetes mellitus (GDM, diabetes diagnosed during pregnancy). Importantly, no studies have collected data on the importance of timing of exposure to hyperglycemia (high blood sugar, or too much glucose in the bloodstream) through maternal diabetes or GDM on the risk of ASD. To help fill this knowledge gap, this study analyzed already existing data from a single health care system to try to determine if there is a connection between maternal diabetes and the risk of ASD in children. The study also investigated using the timing of the GDM diagnosis as a surrogate, or substitute, for the timing of fetal exposure to hyperglycemia.

The study included a group of 322,323 children from diverse backgrounds who were born at 28 to 44 weeks of pregnancy in Kaiser Permanente Southern California (KPSC) hospitals between January 1, 1995 and December 31, 2009. The children were followed for an average of 5.5 years after their birth, and during this time, 3,388 children (2,963 unexposed to either type 2 diabetes or GDM, 115 exposed to type 2 diabetes, and 310 exposed to GDM) were diagnosed with ASD. The main study finding was that in these 3,388 children, having a mother who had GDM diagnosed by 26 weeks of pregnancy was associated with the risk of ASD, but children whose mothers had diabetes before they became pregnant did not have this increased risk. The authors speculate that this difference may be due to the fact that mothers who are known to have type 2 diabetes may already be receiving treatment to control hyperglycemia, which could reduce the exposure of the fetus to high blood sugar and thus maternal diabetes may have less of an impact on fetal brain development than GDM diagnosed early in pregnancy. Although this kind of study cannot determine whether the mother having GDM caused autism in the child, the results do suggest that the children of women with GDM who are diagnosed by 26 weeks of pregnancy are at higher risk, and therefore should receive early screening for ASD. In addition, until further research is conducted on GDM and autism risk, it is important to screen pregnant women for GDM and control maternal blood sugar levels to potentially reduce the risk of autism for the child.

Question 3

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