A child’s early exposure can leave a lasting biological mark. This study shows how tiny layers in baby teeth can identify when metals can affect brain development and behavior years later.
Research: Changes in brain function related to fetal and postnatal metal metabolism are associated with behavioral disorders in childhood. Image credit: Onjira Leibe/Shutterstock.com
A new study using deciduous dental biomarkers to track metal exposure throughout fetal and early infancy has identified a critical period in early neurodevelopment where such exposure is associated with long-term differences in behavior and brain measures observed in late childhood and adolescence. The study was published in the journal Science progresses.
Baby teeth reveal hidden timeline of prenatal exposure
Environmental factors, such as exposure to metals, interact with genetic factors to contribute to the risk of mental health disorders, which currently affect approximately 1 in 7 children and adolescents worldwide. However, it is difficult to accurately track the factors at play during early pregnancy.
To retrospectively and accurately quantify fetal exposure, the authors of this study developed the use of deciduous teeth as a previously validated novel biomarker. These teeth begin to develop during the second trimester of pregnancy, which provides a very detailed level of exposure. Metal that changes time from week to week.
This is confirmed by previous studies that demonstrated strong agreement between metal levels in tooth dentin and maternal, umbilical cord, and infant biomarkers.
Researchers examined the primary teeth of a cohort of 489 children aged 8 to 14 enrolled in the ongoing Programming Study of Obesity, Growth, Environmental, and Social Stressors (PROGRESS) study. Primary teeth were first sampled at one sampling site every 7–10 days, at sites corresponding to metal deposition from 4 months of gestation to 10 months of age.
This allowed us to reproduce the weekly concentrations of nine metals from approximately 20 weeks prenatally to approximately 40–44 weeks postnatally. These include manganese (Mn), zinc (Zn), lead (Pb), magnesium (Mg), lithium (Li), copper (Cu), strontium (Sr), barium (Ba), and tin (Sn).
In addition, they assessed children’s behavior using questionnaires (a subset of participants) and magnetic resonance imaging (MRI) of brain structure and function (a smaller subset). They used three MRI findings: total brain volume, global network efficiency (a measure of functional connectivity), and white matter integrity. These develop early in life, with the highest growth rate occurring during the perinatal period (around childbirth).
These phenotypic differences have been reported to correlate with poor development in adolescence. For example, adolescents with reduced brain volume are more likely to exhibit cognitive impairment and mental illness.
Poor white matter integrity slows down brain processing, limiting your attention span and ability to learn. Reduced global functional connectivity is associated with impairments in executive function and emotion regulation, as well as neuropsychiatric disorders.
The researchers found that manganese concentrations in dentin peaked during the second trimester, declined rapidly before birth, and declined more slowly after birth. Other metals except Ba and Sr remained stable and increased slightly after birth.
Relevance to behavioral change
Researchers identified postnatal periods between 4 and 8 weeks and between 32 and 42 weeks in which increased exposure to metal mixtures was associated with a risk of behavioral changes later in life.
At 5 and 38 weeks of age, Behavioral Symptom Index (BSI) scores increased by 0.1 standard deviation (SD) vs. 0.13 SD for each quartile increase in exposure, respectively. These were initially driven by Mn and in subsequent windows by Mn, Mg, and Sn. However, these windows disappeared once internalizing and externalizing factors were separated.
Association with MRI phenotype
Significant susceptibility windows were identified for all three MRI phenotypes.
total brain volume
Between 15 and 43 weeks of age, total brain volume decreased with increasing exposure to metal mixtures. Thus, at 8 months of age, at 32 weeks, we found that a one-quartile increase in exposure resulted in a 0.45 SD decrease in total brain volume, primarily due to changes in Zn, Sn, and Mn levels.
Improving the efficiency of global network functions
Overall network efficiency (indicating the efficiency of communication within the brain) decreased by 0.18 SD per quartile of increased exposure at 17 weeks of gestation and by 0.21 SD at 33 weeks of age. These points fall within two important periods: prenatal (8 to 19 weeks before delivery) and postnatal (17 to 43 weeks). These associations were mainly due to variations in prenatal Mn levels and postnatal Mg and Pb levels.
white matter integrity
White matter makes up the connecting nerve fiber pathways. The researchers identified two periods when exposure to metal mixtures was correlated with decreased white matter integrity: prenatal and postnatal. At 15 prenatal weeks and 33 weeks postnatally, white matter integrity decreased by 0.19 SD and 0.32 SD per quartile increase, respectively. These were associated with prenatal changes in Mn, Zn, Cu, and Mg and postnatal changes in Mn, Ba, and Li.
Putative relevant mechanisms
The authors point out that 6 to 9 months of age is a critical developmental period. During this period, infants begin to crawl and are weaned. This coincides with increased opportunities for exposure and changes in the absorption and metabolism of nutrients and toxins, which may influence sensitivity to metals.
Additionally, this period is a time of greater neurodevelopmental plasticity, with ongoing but incomplete maturation of the blood-brain barrier, and rapid brain growth and synaptic pruning.
The authors point to a prominent role for manganese and agree with earlier studies that showed manganese’s ability to disrupt normal neurodevelopment at high levels during critical periods. They also highlight the link that exists between zinc and magnesium, which affect neural signaling, and neurodevelopmental disorders such as autism spectrum disorder, attention-deficit hyperactivity disorder, and behavioral problems in children.
The current study builds on these findings by adjusting the effects of exposure to metals, particularly manganese, magnesium, and zinc, with the timing of exposure and simultaneous exposure to other metals that act on neural tissue.
Research limitations
Brain changes and behavioral changes were not examined in the same individuals, and gender-specific effects were not examined due to insufficient sample size. Most participants were from poor neighborhoods, limiting generalizability. Exposure to metals before the second trimester of pregnancy could not be investigated. Metal-metal interactions also could not be evaluated. Additionally, several studied metals, such as Zn, Mn, and Mg, are essential nutrients, and both deficiencies and excesses can be harmful.
Exposure during critical windows may shape the risk of adverse neurological outcomes
The developing brain is especially vulnerable to metals during childhood, and the effects continue into adolescence.
For each metal mixture, different periods of vulnerability were identified and associated with specific outcomes. Behavioral problems and brain volume reduction were associated with the postpartum period. Conversely, other MRI phenotypes were associated with exposure during the prenatal and postnatal periods.
Future research is needed to validate these findings and address the limitations of this study. We also need to identify sensitive periods when environmental factors impede development and form preventive public health strategies.
Click here to download your PDF copy.
Reference magazines:
- Rechtman, E., Reichenberg, A., Invernizz, A., et al. (2026). Changes in brain function related to fetal and postnatal metal metabolism are associated with behavioral disorders in childhood. Science progresses. doi: https://doi.org/10.1126/sciadv.adz1340. https://www.science.org/doi/10.1126/sciadv.adz1340
