Baby teeth from children with autism contain more toxic lead and less of the essential nutrients zinc and manganese than baby teeth from children without autism, according to an NIEHS-funded study. The findings, published June 1 in Nature Communications, suggest that differences in early-life exposure to metals, and more importantly, how a child’s body processes them, may affect the risk of autism.
“Autism is a condition in which both genes and environment play a role, but figuring out which environmental exposures may increase risk has been difficult,” said lead researcher Manish Arora, Ph.D., an environmental scientist and dentist at the Icahn School of Medicine at Mount Sinai. “Some scientists have proposed that events before we are born may increase our risk of autism, but what is needed is a window into our fetal life — which baby teeth provide,” he added.
Metal uptake and autism risk — important time periods
Analyzing baby teeth from children with and without autism allowed the researchers to compare patterns of metal uptake across time. In children with autism, they observed higher levels of lead uptake throughout childhood. The greatest difference occurred in the period right after birth.
Children with autism also showed lower uptake of the essential nutrient manganese both before and after birth. For zinc, the pattern was more complex — children with autism had lower zinc levels earlier in fetal development, but then higher levels after birth, compared to children without autism.
The researchers reconstructed the children’s metal uptake by using lasers to extract precise layers of dentine from naturally shed baby teeth. Dentine, the hard substance beneath tooth enamel, is added gradually during development, so the metals in each layer correspond to time periods before birth and during early childhood.
Studying twins sharpens focus on environmental factors
Additionally the researchers studied twins, which Arora said helped to control two things — genetics and the external environment. They observed larger differences between twins where only one sibling had autism than twins where neither or both had autism, but only during the specific time periods mentioned above.
According to the authors, 50 percent of autism risk can be attributed to genetic factors. Environmental factors, whether acting alone or interacting with genetics, make up the difference. The study included 32 pairs of twins and 12 individual twins, both fraternal and identical. Identical twins are ideal because they provide genetic and environmental consistency. Fraternal twins still have some genetic similarity and share the same environment before and after birth.
The authors noted that larger studies are needed to confirm the connection between metal uptake and autism. Arora said they plan to extend this work to other populations, including nontwin participants, and some families have already offered to participate.
Baby teeth record past metal exposures
The study addresses an important limitation of earlier research on autism and childhood exposure to metals. “A lot of studies have compared current lead levels in kids that are already diagnosed,” said Cindy Lawler, Ph.D., chief of the NIEHS Genes, Environment, and Health Branch. “Being able to measure something the children were exposed to long before diagnosis is a major strength of this work.”
Arora and his colleagues developed and validated this innovative use of baby teeth with NIEHS support. They previously showed that the amount of lead in dentine formed around the time of birth was strongly correlated with lead levels in umbilical cord blood.
Arora said NIEHS funding was invaluable for pursuing his novel and uncertain hypothesis, known as high risk research. “The New Innovator Award has allowed me to pursue higher risk projects, extend my collaborations internationally, and develop new technologies,” he said.
The method of using baby teeth to measure past exposures, which Arora shared at NIEHS in a 2014 talk, also holds promise for other disorders, such as attention deficit hyperactivity disorder.
“There is growing excitement about the potential of baby teeth as a rich record of a child’s early life exposure to both helpful and harmful factors in the environment,” said David Balshaw, Ph.D., chief of the NIEHS Exposure, Response, and Technology Branch. Balshaw’s branch supported the New Innovator Award.
Arora M, Reichenberg A, Willfors C, Austin C, Gennings C, Berggren S, Lichtenstein P, Anckarsater H, Tammimies K, Bolte S. 2017. Fetal and postnatal metal dysregulation in autism. Nat Commun 8:15493.
Arora M, Austin C, Sarrafpour B, Hernandez-Avila M, Hu H, Wright RO, Tellez-Rojo MM. 2014. Determining prenatal, early childhood, and cumulative long-term lead exposure using micro-spatial deciduous dentine levels. PLoS One 9(5):e97805.
(Virginia Guidry, Ph.D., is a technical writer and public information specialist in the NIEHS Office of Communications and Public Liaison and a regular contributor to the Environmental Factor.)