Baby teeth reveal how early metal exposures shape the adolescent brain

Exposure to a mixture of toxic and essential metals during early development in the womb and shortly after birth is associated with later behavioral issues and physical changes in the brain. Researchers used naturally shed baby teeth to track weekly metal exposures, 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 like depression, anxiety, and attention disorders affect many adolescents worldwide. The origins of these conditions involve genetic risk factors, but they are also shaped by the environment during early development. Medical professionals suspect that contact with neuroactive metals during fetal growth and early infancy might increase the chances of a child developing mental health conditions later on.

Tracking exact chemical exposures from the past is difficult. Traditional medical tests, such as blood screens or urine tests, only offer a snapshot of a person’s current chemical balance. They do not provide a detailed historical record of what a fetus or newborn absorbed on a weekly basis.

The research team was led by environmental medicine researcher Elza Rechtman from the Icahn School of Medicine at Mount Sinai in New York. Rechtman and her colleagues wanted to understand exactly when the brain is most exposed and most sensitive to a range of metals. Identifying precise periods of vulnerability could help public health officials design better prevention strategies.

To overcome the limitations of standard medical tests, the team turned to baby teeth. Human teeth start forming in the womb during the second trimester of pregnancy. As they grow, they form microscopic daily layers, similar to the growth rings inside a tree trunk.

These dental layers trap trace amounts of the chemicals circulating in the child’s body at that exact moment. By examining shed baby teeth collected during childhood, researchers can reconstruct a 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 shed baby teeth from the participants. They analyzed each tooth using specialized lasers and mass spectrometry, which are laboratory techniques used to measure tiny amounts of elements embedded in a solid sample.

The team examined the boundary between the inner dentine and outer enamel of the teeth. They used a specific growth mark that forms at birth to align their timeline. This biological timekeeping allowed them to measure weekly levels of nine different metals.

The metals analyzed included manganese, zinc, lead, magnesium, lithium, copper, strontium, barium, and tin. The timeline covered the period from twenty weeks before birth up to approximately forty weeks after birth.

When the children reached eight to twelve years old, their parents completed standardized behavioral questionnaires. The forms measured internalizing issues like anxiety, externalizing behaviors like hyperactivity, and an overall behavioral symptom index.

For a smaller group of 215 children, the researchers conducted brain scans using magnetic resonance imaging. They looked at three broad measures of overall brain health that typically peak in late childhood.

The first measure was total brain volume. The second was global network efficiency, a metric of how well different areas of the brain communicate and share information to function as a unified network. The third was fractional anisotropy, which checks the structural integrity of the white matter fibers that connect different brain regions.

The research team used statistical models to see if higher metal exposures during specific weeks of early life corresponded to later behavioral or brain changes. They constrained their models to look for negative outcomes related to the metal mixtures. The models accounted for the age and sex of the children.

For child behavior, the analysis showed two sensitive postnatal windows where exposure to the metal mixture was associated with a higher overall behavioral problems score. The first window occurred between four and eight weeks after birth. The second window happened between 32 and 42 weeks after birth.

These behavioral associations were largely driven by exposure to manganese in the earlier window. In the later period, manganese, magnesium, and tin were the primary drivers. When the researchers tested for internalizing and externalizing behaviors separately, the results were not statistically significant, prompting questions about whether unmeasured sex differences might be obscuring the pattern.

The magnetic resonance imaging results also indicated specific vulnerable timelines. Drops in total brain volume were associated with metal exposure from weeks 15 to 43 after birth. Zinc, tin, and manganese primarily drove this physical change.

Reduced functional communication across the brain networks was tied to metal mixtures present between 19 and 8 weeks before birth, and again from 17 to 43 weeks after birth. Reductions in white matter integrity were linked to metals absorbed during the second half of pregnancy and stretching to 43 weeks after birth.

Across all these results, the period of six to nine months after birth emerged as consistently sensitive. During this stage of infancy, babies experience extreme biological and environmental transitions. They often transition from an exclusively milk-based diet to solid foods, which alters how nutrients and cellular toxins are absorbed in the gut.

Infants of this age also start crawling, putting them in closer contact with dust and trace elements on the floor. At the same time, their brain is growing at a rapid pace and undergoing a process where unnecessary neural connections are pruned away. The blood-brain barrier is also maturing during this window, meaning certain neurotoxic substances might still penetrate the central nervous system more easily than they do in older children.

The researchers noted that manganese played a constant role in almost all the negative brain and behavioral associations. While manganese is a required nutrient for biological function, high exposures from industrial emissions, contaminated water, or dietary sources can act on the nervous system. Similar exposure profiles were seen for zinc and magnesium, which are necessary for human health but can cause cellular distress if levels fall out of balance.

The study is observational, meaning it can only show associations rather than prove that the metals directly disrupted the brain. The sample size of the brain imaging group was not large enough to directly match the brain anatomy changes with behavioral scores in the same exact children.

The statistical methods used could describe the varied timing of the mixture but could not test whether certain metals multiplied the negative effects of others. Additionally, the participants were mainly from lower-income communities in Mexico City. The estimates might apply differently to communities with varying socioeconomic resources or different baseline chemical exposures.

Future research requires larger pools of participants to parse out differences in how these metals might affect male and female biology distinctly. The research team aims to map these developmental windows more comprehensively so medical professionals can implement protective measures during the most sensitive periods of human growth.

The study, “Fetal and postnatal metal metabolism-related changes in brain function are associated with childhood behavioral deficits,” was authored by Elza Rechtman, Avraham Reichenberg, Azzurra Invernizzi, Lazar Fleysher, Vida Rebello, Kristie Oluyemi, Michelle A. Rodriguez, Anna Sather, Libni A. Torres-Olascoaga, Luis F. Bautista-Arredondo, Sandra Martínez-Medina, Rafael Lara-Estrada, Chris Gennings, Martha M Téllez-Rojo, Robert O. Wright, Manish Arora, and Megan K. Horton.