The Wakefield paper (Wakefield A et al., 1998), suggesting a link between the measles, mumps, rubella (MMR) vaccine and autism, was subsequently shown to be fraudulent and to have “killed children" (McBrien J et al., 2000; European Centre for Disease Prevention and Control (ECDC) - Surveillance and Communication Unit report, 2008; Godlee F et al., 2011; Poland & Jacobson, 2011). Furthermore, many high-quality independent studies have confirmed there is no link between autism spectrum disorder (ASD) the MMR vaccine (Taylor B et al., 1999, 2002; Dales L et al., 2001; Farrington CP et al., 2001; Fombonne & Chakrabarti S, 2001; Kaye JA et al., 2001; Demicheli V et al., 2005; Fombonne E et al., 2006; Cox & Kirkham, 2007; Hornig M et al., 2008; Gerber & Offit, 2009) or, indeed, any other vaccine (Price CS et al., 2010). The media has been criticized for its role in the MMR debacle (Roger D, 2003; Speers & Lewis, 2004; Hilton S et al., 2007; Katelaris A, 2007), but lay readers need to be aware that one ‘scientific’ journal is continuing to publish misleading studies on this topic (for example, see the discussion at http://photoninthedarkness.com/?p=222).
Multiple twin, family, and genetic-association studies have demonstrated that ASD is a classic complex genetic disorder. Most studies calculate heritability estimates of between 0.8-0.9 (80-90%) for ASD (reviewed by Ronald & Hoekstra, 2011). By contrast, non-inherited (referred to as de novo) mutations are calculated as contributing to between 5-20% of ASD cases, and contribute more to severe ASD than to milder ASD (Marshall et al., 2008; Sebat J et al., 2007; Zhao X et al., 2007; Pinto et al., 2010; Levy D et al., 2011). ASD risk factors may include increased parental age (see ARA Blog entry from Saturday, July 9, 2011), which is known to lead to increases in chromosomal abnormalities. Likewise, in utero infection has been suggested to increase the risk of ASD. The evidence for increased risk of ASD associated with foetal rubella syndrome (FRS) is the strongest (Chess S, 1971, 1977; Chess S et al., 1978). This evidence is limited to the output of a single research lab, but has been supported by animal studies and case studies. The link between other viral infections, such as CMV, and ASD remains weak.
On the basis of the increased link between FRS and ASD, a recent study has calculated how many ASD cases have been prevented by the use of rubella vaccination in the USA (Berger BE et al., 2011). Rubella virus infection is known to cause chromosomal anomalies (Plotkin SA et al., 1965; Nusbacher J et al., 1967; Konishi S et al., 1970; Ansari & Mason, 1977) and, while the vast majority children with FRS will not have ASD, there may be an increased risk of disruption of ASD-implicated genes in early infection in utero. Other mechanisms for increasing the risk of ASD are also possible. This recent study, therefore, indicates that rubella vaccination has prevented thousands of cases of ASD in the USA alone (Berger BE et al., 2011).
by Naomi Bishop
Key reference: Berger BE, Navar-Boggan AM, Omer SB. BMC Public Health 11: 340 (2011)
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