Some authors have been concerned that mercury-based preservatives in certain vaccinations 
, mercury in maternal dental fillings 
, or childhood mercury exposure from a range of environmental sources 
may affect the brains of children, leading to autism in some individuals. This has arisen in the context of studies of neurological damage from environmental mercury or methylmercury poisoning 
, and speculation as to the effect of ethylmercury in thimerosal-based vaccines 
. Hypotheses such as these have generated much parental anxiety 
, have been implicated in reductions in childhood vaccination rates 
and have been subsequently associated with increases in cases of measles and mumps, with significant long term implications for individuals 
. As such, direct and rigorous testing of such hypotheses is vital not only for understanding autism, but for wider public health reasons.
Developmental problems associated with environmental mercury exposure are well documented. In a study of 63 infants in Japan with congenital mercury poisoning a range of reported problems were observed, including significant learning disabilities, limb deformities, cerebellar ataxia 
, hypersalivation, chorea and microcephaly 
. Cerebral pathological changes showed demyelination of the pyramidal tracts, hypoplasia of the corpus callosum, widespread disturbance of brain growth and neuronal migration, neuronal and generalised cortical atrophy and underdevelopment of the granula layer of the cerebellum 
. A further study in the Philippines where mercury is used in the gold mining industry found that prenatal exposure to mercury led to increased rates of global developmental delay 
It is well established that environmental mercury in high doses is very toxic 
. In Iraq in the 1970s, over 450 people died and over 5000 suffered poisoning following the use of methylmercury fungicide to treat grain 
and in Japan, industrial waste containing mercury, poisoned over 2000 people 
. There have been several reviews examining mercury poisoning from follow up studies in Japan, Iraq, Peru, the Philippines, the Faroe Islands and the Seychelles 
. but, none of these have to date presented an association specifically with autistic symptomatology.
Much lower exposure to mercury than seen in these studies occurs in most societies, with one route being the use of mercury in amalgam fillings. In a study in Portugal over 500 children aged 8–10 were randomised to receive either amalgam fillings or composite fillings 
. The amalgam group showed higher levels of creatinine-corrected urinary mercury levels at follow-up, but no differences in a range of neurobehavioural measures between the two groups over seven years follow-up. A similar study in Boston, USA followed children up for five years and came to similar conclusions 
, where children who were randomised to receive amalgam fillings were not statistically different on psychometric testing (including IQ and memory) to those receiving composite fillings.
The fear that mercury causes autism came from speculation that the use of thimerosal in certain vaccinations may have caused rates of autism diagnoses to rise 
. This was proposed despite the fact that the mercury compound it contains, ethylmercury cannot easily pass through the blood-brain barrier, as methlymercury can and is associated with few central nervous system problems in environmental health research 
. Although one research group has published several studies linking autism rates and mercury/thimerosal 
a number of high-quality cohort and ecological studies have found no evidence to support their claims 
. Most notably, increasing rates of autism have been observed in three countries even after thimerosal was removed from their vaccination programme 
Despite this, some authors have continued to posit mercury-related abnormalities in the development of autism. It has been hypothesised that children with autism may have a problem excreting mercury from the body 
following evidence of reported low concentrations of mercury in the hair of 90 children with autism compared to 45 healthy controls 
. This hypothesis exists despite the fact that other studies using hair mineral analysis have found no differences in mercury concentrations 
and one study found increased concentrations in hair, along with other potentially hazardous metals 
Another excretion route is urine; if mercury excretion were impaired in ASD children, this should also be evident in their urinary levels of mercury. Whilst urine studies exploring foetal exposure in mothers who eat large amounts of mercury in fish have found no neurocognitive risk to the children of mothers eating on average 12 fish meals per week 
, higher maternal mercury consumption (eating regular amounts of whale meat), has been associated with a range of subtle neurodevelopmental effects in language, attention and memory in their infants 
Studies that have looked specifically at the urine of children with autism have produced mixed results. Bradstreet and colleagues 
reported higher levels of mercury in the urine of 221 children with ASD compared to controls following oral chelation treatment (to bind mercury and force excretion), which they argued was consistent with Holmes and colleagues' 
suggestions of poor excretion and subsequent build-up of mercury levels in children with autism. Another study by the same group 
reported increased urinary porphyrin levels related to heavy metal body-burden in a sample of ASD children. In contrast, a study by Soden and colleagues 
found no evidence of increased levels of urinary mercury or any other heavy metals in ASD participants and controls following chelation.
None of the above studies directly measured urinary levels of mercury in children who had no form of chelation treatment. Furthermore, the Geier/Bradstreet group has only used very small control samples (n
18, 14 & 5 respectively), perhaps because of the use of chelation, which is potentially harmful for children 
. As such, there is a lack of high-quality evidence on ordinary urinary mercury levels in ASD children, at a time - with parental concerns about mercury persisting 
- when clear and unbiased data on the issue is needed.
We set out to do a blinded study to compare urine concentrations of mercury between groups of children with autism spectrum disorders and controls. Unlike other studies of urinary mercury in autism we examined ordinary, non-treatment levels of mercury and compared them to three different control groups; mainstream schoolchildren (n
115), children from special schools (n
28) and ASD siblings (n
40). To account for differing levels of mercury exposure across groups, the number of current amalgam fillings was recorded. Urine concentration was controlled for by correcting for creatinine. Given some authors views that heavy metals more broadly might be implicated or face excretion difficulties 
, we set out to do some pilot work in this area by doing preliminary analysis on other easily measurable heavy metals in the urine. We did this in part to check whether any hypothesised problems were specific or occurred across a group of heavy metals.