Exposure to a mixture of toxic and essential metals during early in utero development and shortly after birth is associated with subsequent behavioral problems and physical changes in the brain. Researchers used naturally shed baby teeth to track weekly exposure to metals, revealing specific time windows when the developing brain is most vulnerable to these elements. The study was published in the journal Science Advances.
Mental health conditions such as depression, anxiety, and attention disorders affect many adolescents around the world. These conditions are caused by genetic risk factors, but are also shaped by the environment during early development. Medical experts believe that contact with neuroactive metals during fetal development and early infancy may increase a child’s chances of developing mental health conditions later in life.
Accurately tracing past chemical exposures is difficult. Traditional medical tests such as blood and urine tests only provide a snapshot of a person’s current chemical balance. Detailed historical records of what fetuses and newborns absorbed each week are not provided.
The research team was led by Elsa Rechtman, an environmental medicine researcher at the Icahn School of Medicine at Mount Sinai, New York. Rechtman and his colleagues wanted to understand exactly when the brain is most exposed to and most sensitive to different metals. Determining the precise period of vulnerability may help public health authorities design better prevention strategies.
To overcome the limitations of standard medical tests, the research team focused on primary teeth. Human teeth begin to form in the womb during the second trimester. As they grow, they form microscopic daily layers, similar to the growth rings inside the trunk of a tree.
These tooth layers trap trace amounts of chemicals circulating in the child’s body at that very moment. By examining fallen baby teeth taken during infancy, researchers can reconstruct the weekly timeline of a child’s chemical exposure before and after birth.
The study followed 489 children living in Mexico City who were part of an ongoing longitudinal birth cohort. The research team collected naturally fallen baby teeth from the participants. They analyzed each tooth using a special laser and mass spectrometer. Mass spectrometry is a laboratory technique used to measure trace amounts of elements embedded in solid samples.
The research team examined the boundary between the dentin on the inside of the tooth and the enamel on the outside. They used specific growth marks formed at birth to adjust the timeline. This biological timekeeping allowed us to measure weekly levels of nine metals.
The metals analyzed included manganese, zinc, lead, magnesium, lithium, copper, strontium, barium, and tin. The timeline covered the period from 20 weeks prenatal to approximately 40 weeks postnatal.
When children were between 8 and 12 years old, parents completed standardized behavioral questionnaires. This form measured internalizing problems such as anxiety, externalizing behaviors such as hyperactivity, and an overall behavioral symptom index.
Researchers conducted brain scans using magnetic resonance imaging on a small group of 215 children. They looked at three broad measures of overall brain health that typically peak in late childhood.
The first measurement was total brain volume. The second is global network efficiency, a measure of how well different regions of the brain communicate and share information to function as an integrated network. The third is fractional anisotropy, which checks the structural integrity of white matter fibers that connect different brain regions.
The researchers used statistical models to see whether increased exposure to metals during specific weeks in childhood corresponded to later behavioral and brain changes. They constrained the model to look for negative outcomes associated with metal mixtures. The model took into account the child’s age and gender.
Regarding child behavior, the analysis showed two sensitive postnatal periods in which exposure to metal mixtures was associated with higher overall behavioral problem scores. The first period occurred between 4 and 8 weeks of age. The second period occurred between 32 and 42 weeks of age.
These behavioral associations were primarily driven by early exposure to manganese. In the later stages, manganese, magnesium, and tin were the main factors. When the researchers tested internalizing and externalizing behaviors separately, the results were not statistically significant, raising questions about whether unmeasured gender differences were obscuring the pattern.
Magnetic resonance imaging results also showed a specific fragile timeline. Decreases in total brain volume were associated with metal exposure from 15 to 43 weeks of age. Zinc, tin, and manganese primarily caused this physical change.
Decreased functional transmission through brain networks was linked to metal mixtures present between 19 and 8 weeks prenatally and between 17 and 43 weeks postnatally. Reduced white matter integrity was associated with absorbed metals from late pregnancy until 43 weeks after birth.
Across all these results, 6 to 9 months of age consistently appears to be a sensitive period. During this stage of infancy, babies experience extreme biological and environmental changes. They often transition from an exclusively milk-based diet to solid foods, which changes the way nutrients and cytotoxins are absorbed in the intestine.
Infants at this age begin to crawl, which brings them into close contact with dust and trace elements on the floor. At the same time, their brains are growing rapidly and undergoing a process in which unnecessary neural connections are pruned. The blood-brain barrier is also maturing at this age, meaning that certain neurotoxic substances may still enter the central nervous system more easily than in older children.
The researchers noted that manganese plays a role in nearly all negative brain-behavior associations. Manganese is a necessary nutrient for biological functions, but high exposure from industrial emissions, contaminated water, or dietary sources can affect the nervous system. Similar exposure profiles were seen for zinc and magnesium. Zinc and magnesium are necessary for human health, but imbalanced levels can cause cell damage.
The study is observational, meaning it can only show a link, rather than proving that the metal directly damaged the brain. The sample size of the brain imaging group was not large enough to directly match changes in brain anatomy to behavioral scores in exactly the same children.
Although the statistical methods used were able to account for the varying timing of mixtures, they were not able to test whether certain metals multiplied the negative effects of other metals. Additionally, participants were primarily from low-income neighborhoods in Mexico City. This estimate may apply differently in communities with different socio-economic resources and different baseline chemical exposures.
Future studies will need more participants to elucidate the differences in how these metals affect the biology of men and women. The research team aims to more comprehensively map these developmental windows so that medical professionals can take protective measures during the most sensitive period of human development.
The study, “Changes in brain function related to fetal and postnatal metal metabolism are associated with behavioral disorders in childhood,” was authored by Elsa Rechtman, Abraham Reichenberg, Azula Invernizzi, Lazar Fleischer, Vida Rebello, Christy Oluyemi, Michelle A. Rodriguez, Anna Sather, Livni A. Torres-Olascoaga, and Luis F. Kennedy. Bautista-Arredondo, Sandra Martinez-Medina, Rafael Lara-Estrada, Chris Jennings, Martha M. Telles-Rojo, Robert O. Wright, Manish Arora, Megan K. Horton.
