Please visit our new web site www.autism.com
www.autism.com
 
printer friendly version

Fall DAN!TM 2003 Conference
*** Portland, Oregon *** October 3-5, 2003

Heavy Metal Exposures, Developmental Milestones, and Physical Symptoms in Children with Autism

1, C.E. Holloway1, M. Margolis2, F. George3

1 Arizona State University, Tempe, Arizona
2 My Dentist, Mesa, Arizona
3 Holistic Osteopathic Medical Care, Cave Creek, Arizona

Objectives: Examine possible sources of exposure to mercury and other heavy metals in children with autism vs. controls, to determine if any are possible risk factors for autism.   Also, investigate the physical symptoms and developmental milestones of children with autism vs. controls.  

Participant Selection: There were 53 children with ASD and 48 control children enrolled in the study.   The children with ASD included 49 with autism, 2 with PDD/NOS, and 2 with Asperger’s.    There were 12 girls and 11 girls in the ASD and control groups, respectively, comprising 23% of each of their groups.   There were two sets of twins in the ASD group, and one set of twins and one pair of siblings in the control group. Ages ranged from three to 15 years of age, with a mean age of 7.1 and 7.5 for the children with ASD and the controls, respectively, with standard deviations of 3.0 years for each.   Thus, there was overall a good match between the groups in terms of gender and age. A subset of this group and their mothers submitted current hair samples for elemental analysis, and those results are reported in the prior paper.

Methodology: For this study we created a heavy metal exposure and child development questionnaire (see Appendix 1).   It is divided into four areas:   Prenatal Exposure, Infantile Exposure, Physical Symptoms, and Developmental Milestones.  We also created a mother’s health questionnaire.   And, a board-certified dentist evaluated all the children and their mothers.

Results for Heavy Metal Exposure and Child Development Questionnaire

Prenatal Exposure: 

The two groups of mothers did not have a significant difference (p<0.05) in most of the investigated risk factors, including vaccinations during pregnancy, exposure to paint, smoking or second-hand smoke exposure, thimerosal in contact lens solution, tattoos, or pesticide use in the home.   They were equally likely to take prenatal supplements, which can help prevent absorption of heavy metals. The average age of the mothers at the birth of their child in the study was 32.0 years for the mothers of children with ASD, vs. 30.1 years for the mothers of the typical children.   The difference was not statistically significant, but warrants consideration in future studies.

The autism mothers reported slightly less injections with Rhogam, which is in marked contrast to the study by Holmes et al. that reported on a high use of Rhogam in mothers of children with ASD.3 The Rhogam issue needs further investigation.

Regarding maternal seafood consumption during pregnancy, it was found that 58% of the mothers of children with ASD reported consuming more than 2 servings of seafood per month, vs. only 33% of the mothers of typical children.   This is consistent with our finding of 57% more mercury in the hair of a subset of the ASD group vs. the control group.   This difference was not statistically significant when analyzed with a simple test, but a logistic regression model yielded a relative risk of 2.7, with a confidence interval of 1.1-6.2, p=0.02.   This relative risk is presumably due to the level of mercury in the fish.

Infantile Exposure:

Mothers of children with ASD nursed their children for approximately the same length of time as did the mothers of typical children.   Both groups of children ate similar amounts of seafood.The children with ASD were slightly more likely to eat/lick paint, (3 severe cases, 1 moderate case, 2 mild cases, vs. 1 moderate case in the controls), and the difference was marginally statistically significant (p=0.05).  

Pica:   A large fraction of the children with ASD (16 of 53, or 30%) were reported by their parents to have moderate to severe pica (eating non-food items), whereas only one of the typical children was reported to have moderate pica.   This result was extremely statistically significant (p=0.00002).    This is likely to result in a significantly higher intake of toxic metals, and indeed higher levels were found in their hair.

Vaccinations:   Mothers of children with ASD reported significantly more adverse reactions, and of a more serious nature, than did the mothers of the typical children (29% for ASD vs. 6% for controls).   The difference was highly statistically significant (p=0.001).   Note that the criteria for these reactions were that it occurred within a few days of the vaccination, so that there was a close temporal association.   This data strongly suggests that further investigation into the adverse vaccine reactions in autism is warranted.

Physical Symptoms

Gastrointestinal Problems: 33 of the 53 children with ASD (62%) had moderate to severe gastrointestinal problems (chronic diarrhea and/or constipation) versus one of the typical children (2%) reported to have moderate gastrointestinal problems.   This result is extremely statistically significant (p<10-13).

Sleep Problems:   Similarly, 32 of the 53 children with ASD (60%) were reported to have moderate to severe sleep problems (falling asleep and/or night wakening), versus one of the typical children (2%) reporting moderate sleep problems. This result was highly statistically significant (p<10-11).  

Also, it should be noted that there was a significant correlation between sleep problems and gastrointestinal problems (correlation coefficient = 0.31).     In a previous small pilot study of a vitamin/mineral supplement, we found that the supplement resulted in statistically significant improvements in gastrointestinal and sleep problems.   Thus, it could be that some sleep problems are due to gastrointestinal problems, and that treatment of the gastrointestinal problems may reduce some sleep problems.

Low Muscle Tone :   16 of the children with ASD (30%) were reported to have moderate to severe loss of muscle tone, compared to one of the typical children (2%) reported to have moderate loss of muscle tone.   This result was highly statistically significant, with p=0.000000002.

Excessive Salivation/Drooling: The mothers reported that 3 children had severe salivation/drooling problems, 5 had moderate problems, and 9 had mild problems, compared to 2 of the typical children reporting mild problems.   The difference was highly statistically significant, with p=0.0003.   The salivation/drooling problem partially correlated with muscle tone problems (correlation coefficient=0.47), and parents often reported that they thought the drooling was due to poor muscle tone.

Ear Infections:   Children with ASD had an average of 10.9 ear infections during their first three years of life, versus 4.3 for the typical children, with medians of 10.0 and 2.5, respectively. This result is highly statistically significant, p=0.00006. According to the parents, virtually all of the ear infections were treated with oral antibiotics, often for months at a time.    This extended use of oral antibiotics is likely to have had two major effects:   1) Destroy most of the normal beneficial bacteria in the gastrointestinal tract, possibly resulting in overgrowth of yeast and possibly pathogenic bacteria.   2) Inhibit excretion of mercury, based on a study of rats, which found that oral antibiotics increase the half-life for mercury excretion 10x or more.

Regression and Developmental Milestones

62% of the children with ASD were reported by their mothers to have had a period of normal development, followed by a major regression at age 12-30 months (18 months on average, standard deviation of 4 months).   Two other children possibly had symptoms of regression, whereas the remaining 34% of the children seemed to have had developmental delays from birth.   We found that the children with regressive ASD reached their developmental milestones in sitting, crawling, walking and talking at almost exactly the same age as the typical children.   In contrast, the children with non-regressive ASD were on average 2 months late in learning to sit up and crawl, 4 months late learning to walk, and 17 months late learning to talk (not counting 4 children aged 5-6 years who had not learned to talk).   All of those delays are statistically significant, and most are highly statistically significant.  

Mother’s Health:

Since the child’s mother is their major source of environmental exposure and source of nutrients during pregnancy and breastfeeding, they were surveyed as to their current health status.   The mothers of children with ASD tended to have a higher incidence of certain physical symptoms (chronic fatigue, arthritis, muscle/joint pain, asthma, night vision problems, hair loss) and mental symptoms (anxiety, depression, memory problems, insomnia).   Some of those symptoms could have been due to dealing with a child with ASD.   However, the overall incidence of any one condition was low, and there was no statistically significant difference between the two groups for any of those categories.  

II.   Dental Data and Discussion

The mothers of children with ASD had slightly more mercury amalgam surfaces (10.0 vs. 8.3), but the difference was not statistically significant.    There was a trend that mothers of children with ASD were more likely to have had a mercury amalgam filling placed or removed during pregnancy (5 cases of placement and 2 of removal, vs. 1 placement and 0 removals for the controls, p=0.08).    We believe that the placement of a mercury filling during pregnancy could be a major risk factor for mercury exposure because our recent research found that a new mercury amalgam releases about 500x the amount of an old filling.  

Summary:

In summary, many different possible sources of exposure to heavy metals were considered.   The ones that were found to be statistically significant included:

  1. Seafood:   Maternal consumption of more than 2 servings per month was found to be a risk factor for ASD.   This was true of 57% of the mothers of children with ASD, vs. 33% of the controls.
  2. Oral Antibiotics:   Due to a high incidence of ear infections, the children with ASD received much higher levels of oral antibiotics.   This is important because 1) oral antibiotics destroy normal beneficial bacteria, can cause overgrowths of harmful bacteria and yeast, and 2) oral antibiotics greatly decrease the excretion of mercury, causing it to build up to higher levels.
  3. Vaccines:   Children with ASD were more likely to have an adverse reaction to vaccines, and those adverse reactions tended to be more severe.   This could be due to the thimerosal in the vaccines.
  4. Pica:   The children with ASD were reported to be much more likely to have moderate to severe pica (30%) than the typical children (2%).   Using a severity scale of 0-3, the difference was highly significant (0.9 vs. 0.04, p=0.00001).   This consumption of non-food items, including sand, dirt, paper, and other objects, probably resulted in a significant increase in their exposure to toxic metals.
  5. Dental Fillings: There was a trend (p=0.08) that the mothers of children with ASD were more likely to have had a mercury filling placed or removed during their pregnancy (7 cases vs. 1 case for the controls).   This is relevant because our recent study has found that fillings release much more mercury when initially placed.

Several physical symptoms were found to be very common in ASD, with an extremely high statistical significance:

  1. Gastrointestinal:   62% of the children with ASD had moderate or severe problems with chronic constipation and/or diarrhea, far more than the typical children (2%).  The difference was highly statistically significant, 1.9 vs. 0.1, p=1 x 10-12. This may be partly due to the high usage of oral antibiotics, which can disrupt normal GI flora, which are important in promoting normal motility.Sleep:   60% of the children with ASD were reported to have moderate or severe sleep problems, far more than the typical children (2%).   Using a severity scale of 0-3, the difference was highly statistically significant, 1.8 vs. 0.2, p=1x10-13).
  2. Sleep and gastrointestinal problems were moderately correlated, with a correlation coefficient of 0.31.
  3. Muscle Tone:   30% of the children with ASD had moderate or severe problems with low muscle tone, far more than the typical children (on a scale of 0-3, 1.0 vs. 0.06, p=0.000000002).
  4. Salivation/Drooling:   15% of the children with ASD had problems with salivation/drooling, much more than the typical children (p=0.0003).   Salivation/drooling problems were moderately correlated with muscle tone problems (correlation coefficient = 0.47).
  5. Ear infections:   Children with ASD were reported to have had many more ear infections than typical children during their first three years of life (10.9 vs. 4.3, p=0.00006).   Since almost all ear infections were treated with oral antibiotics, this resulted in much higher oral antibiotic use in children with ASD.  

Regressive ASD was found to occur in 62% of the children with ASD, at an average age of 18 months.   Those children met their developmental milestones (age of crawling, sitting, walking, and talking) at the normal time.  In contrast, the children with non-regressive ASD were two months late in crawling and sitting, four months late in walking, and 17 months late in talking.

Acknowledgements:

First and foremost, we thank the many autism families and their friends who volunteered as participants in this research study.   We thank the Greater Phoenix Chapter and the Pima County Chapter of the Autism Society of America for their financial support and for help with recruiting participants.< We also thank Arizona State University for financial support.   We thank Prof. Xianchen Liu for his assistance with statistical analysis.   We thank Amy Holmes, Mark Blaxill, and Boyd Haley for sharing their results with us.


© copyright 2005, 2006 Autism Research Institute