Prenatal and early postnatal lead exposure was associated with poorer cognitive function more than 60 years later, with the strongest effects observed among women who were exposed in utero during the second trimester.

In a unique analysis, researchers conducted cognitive tests in adults who had participated in the prospective St. Louis Baby Tooth cohort study, which collected deciduous teeth from children born in the 1950s primarily in St. Louis.

A comparison of participants’ test results with lead levels found in their baby teeth revealed that those who were exposed to higher lead levels in the second trimester performed worse on tests of processing speed, attention, and working memory. However, the findings were only significant in women.

Each 1 part per million (ppm) increase in second-trimester tooth lead in female participants was associated with cognitive performance equivalent to approximately 3 additional years of aging.

“This study was the first to look at the association between lead exposure specifically in the prenatal and early postnatal period with later cognitive function,” study investigator Ruby Hickman, PhD, MPH, postdoctoral fellow, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, told Medscape Medical News.

The findings, she added, underline “the importance of preventing lead exposure among pregnant individuals and in early life, as the consequences on cognitive health may be longer-lasting than previously understood.”

The study was published online on February 19 in Neurology.

Exploring the Long-term Consequences

Early life exposure to lead is known to impair neurodevelopment and result in lower IQ, behavioral issues, and deficits in fine motor skills in children. However, the long-term consequences of prenatal and early postnatal lead exposure on cognitive function in older adulthood are not as well understood.

While previous studies have linked childhood lead exposure to lower cognitive performance in adulthood, most were limited by small sample sizes or short follow-up windows.

To examine the potential lifelong cognitive effects of early lead exposure, the researchers analyzed data from the St. Louis Baby Tooth – Later Life Health Study.

The cohort includes individuals who donated baby teeth between 1958 and 1972 as part of the original Baby Tooth Survey. Baby teeth form over specific prenatal and early infancy periods, and any exposure during this time to circulating metals — including lead — is preserved in tooth dentin.

Using the original tooth donation records, investigators traced participants through LexisNexis and invited them to complete follow-up surveys and at-home cognitive testing between 2021 and 2023.

Of the initial cohort, 5131 responded to follow-up invitations, and 4236 completed cognitive testing. Cognitive assessments included six computerized tests administered remotely that measured processing speed, working memory, attention, and visual and verbal memory.

Tooth-lead analysis was completed for 715 participants (mean age at cognitive testing, 62.4 years; 52% female; 94.8% White; 72% college degree). Laser ablation and mass spectrometry were used to precisely measure lead levels in teeth corresponding to specific prenatal (second and third trimesters) and early postnatal periods.

Analyses accounted for maternal smoking, socioeconomic status, and other environmental exposures.

Higher second-trimester tooth lead levels in women were associated with lower cognitive performance, equivalent to 3 years of additional aging. For each 1 ppm increase in second-trimester tooth lead, cognitive performance declined by 0.16 SD (95% CI, -0.28 to -0.04; P = .01).

Women in the highest quartile of combined tooth lead concentration (> 1.82 ppm) performed worse on measures of processing speed, attention, and working memory than those in the lower exposure groups.

A Potential Underestimate?

The findings may underestimate the true association of lead exposure and later cognition, Hickman noted, citing epidemiologic factors such as selection bias that could have disproportionately excluded individuals more vulnerable to the metal’s effects.

In the highest exposure quartile, 51% of participants were male and 49% were female. Investigators cautioned that the absence of statistically significant findings in men does not mean they were unaffected, noting that methodological limitations may have reduced the ability to detect associations.

“Although we found generally stronger effects in females, it is possible that an adverse association between early lead and later adulthood cognitive function also exists among males but was masked in our study by selection bias,” the investigators noted.

Participants in the highest lead quartile were more likely to have grown up in areas with older housing, with about 35% of homes in these areas built before 1940 compared with 25% of homes in the lowest quartile (P = .05). Given the widespread use of lead-based paint and leaded gasoline during that era, the finding is consistent with known environmental sources of childhood lead exposure.

“Our findings suggest that a known history of lead exposure in pregnancy or early life could be a contributor to current cognitive function in older adults,” Hickman said.

“Future research should investigate whether even earlier periods of lead exposure may be important, as we could only examine as early as the second trimester due to the nature of tooth formation,” she added.

The study’s limitations include potential selection bias, a largely White and college-educated sample, and reliance on at-home cognitive testing rather than standardized in-person assessments, which may affect the generalizability and accuracy of the findings.

Lasting Impact

Previous research and the current study suggest that childhood lead exposure can have lasting effects on cognitive function well into adulthood, wrote Aaron Reuben, PhD, from the Lab of Environmental Neuropsychology, Department of Psychology, University of Virginia in Charlottesville, Virginia, in an accompanying editorial.

However, it remains uncertain whether these deficits reflect lower peak cognitive development in childhood or a gradual, age-related decline.

“Either would mean that millions exposed to lead as children during the era of leaded gasoline now face increased dementia risk as they age, but the latter (enhanced decline) would signal a risk warranting immediate, proactive intervention,” Reuben wrote, emphasizing that these consequences are likely to persist for decades to come.

The findings offer an even broader clinical implication, said Bruce Lanphear, MD, MPH, professor in the Faculty of Health Sciences, Simon Fraser University in Burnaby, British Columbia, Canada.

“Certainly, for children, or people that had recognized lead poisoning in their childhood, this could help neurologists even today to understand why some people are really struggling [cognitively],” Lanphear told Medscape Medical News. Lanphear was not part of the current study.

The findings may help explain why some individuals reach the threshold for dementia earlier and could eventually assist in identifying those at higher risk, he added.

There also may be broader public health implications in the study, such as the importance of including long-term environmental exposures along with genetics and other risk factors when studying certain medical conditions, such as dementia, heart disease, and diabetes.

“We have been missing out on major risk factors because we haven’t been looking at long-term exposures to environmental triggers like lead,” Lanphear said.

Hickman, Reuben, and Lanphear reported having no relevant financial relationships.