Prenatal lead exposure was associated with a significantly increased risk for major depressive disorder (MDD) in adulthood, an analysis of baby teeth showed.

Investigators found adults with higher prenatal lead exposure, especially in the third trimester, were nearly twice as likely to have MDD later in life, an association most pronounced among women.

“Our findings suggest that early lead exposure may have lasting implications on mental health well beyond childhood and adolescence. These results, considered alongside findings from other follow-up studies, suggest that public health interventions to reduce lead exposures, even before birth, could deliver mental health benefits that last well into adulthood,” lead author Joyce Lin, PhD, postdoctoral research fellow at the Harvard T.H. Chan School of Public Health in Boston, told Medscape Medical News.

The study was published online on October 22 in JAMA Psychiatry.

Exposure to Lead Persists

Across the US, an estimated 9 million lead service lines may contaminate household drinking water. Lead exposure can cause brain damage, behavioral problems, and delayed development.

Previous research has shown that children living in areas of high lead exposure scored worse on cognitive tests and had decreased brain volume than those who weren’t as highly exposed.

Although it’s well-established that lead is toxic, particularly during pregnancy and early childhood, very few studies show long-term associations with health outcomes, Lin said.

Baby teeth were collected during the 1950s-1970s as part of the Baby Tooth Survey. The investigators analyzed a single tooth from each of 718 participants (mean age, 62 years; 53% female) for lead using laser ablation inductively coupled plasma mass spectrometry.

Participants were asked to fill out the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Screener-7 (GAD-7), which measure symptoms of depression and anxiety over the past 2 weeks, respectively.

Exposure periods were measured as prenatal (second trimester to birth) and early postnatal (birth to 6 months old).

The researchers used logistic regression models to estimate the odds of mental health outcomes. Models were adjusted for covariates including age, sex at birth, parental education, family income level, and family structure.

To pinpoint the relevant lead exposure windows, they coadjusted for exposure periods to avoid confounding.

In a secondary analysis, they continuously analyzed symptoms to capture potential comorbidity between anxiety and depression.

Risk Peaks in Third Trimester

Combined lead exposure was associated with nearly twice the odds of MDD later in life (odds ratio [OR] per IQR, 1.90; 95% CI, 1.20-2.99).

The analysis showed the late prenatal period, particularly the third trimester, as the most sensitive period (OR, 1.55; 95% CI, 1.23-1.97).

Lead exposure during the third trimester was linked to nearly a threefold higher likelihood of MDD when comparing those in the highest with those in the lowest exposure groups (90th vs 10th percentile). This is “an estimate comparable with that observed for well-established risk factors, such as being overweight and developing type 2 diabetes,” they wrote.

The odds of depression were higher in the third trimester among women (OR, 1.79; 95% CI, 1.39-2.32) than among men (OR, 0.97; 95% CI, 0.38-2.50).

The researchers found no association between early lead exposure and the risk for subsequent generalized anxiety disorder. The continuous analysis showed an association between lead exposure in the prenatal period and later-life depression.

Public Health Implications

Commenting on the research for Medscape Medical News, Eric Rafla-Yuan, MD, chair of the APA Caucus on the Social Determinants of Mental Health and chief financial officer for the Social Determinants of Health Network, said baby teeth provide window-specific measurements of prenatal and postnatal lead exposure and offer stable, retrospective information that typical venous blood levels cannot provide.

“The correlation of such a reliable marker of early-life exposure with clinical phenotype multiple decades later is a valuable addition to the field,” he said.

Limitations of the study were possible selection bias and the long gap between lead exposure and outcome.

Another limitation, Rafla-Yuan noted, was the study’s reliance on the PHQ-9 and GAD-7, which only assess symptoms over the past 2 weeks and may not fully capture other facets of mood or anxiety disorders.

Early life lead exposure, including dose-dependent effects and sensitive developmental windows, poses substantial public health implications, with risks present in every state, Rafla-Yuan said.

“The premise for action mirrors other successful population-level measures that protect prenatal development, such as folate fortification of cereal grains,” he added.

While Rafla-Yuan did not find the study results particularly surprising, he said the more unexpected aspect of the study was the fact “that efforts to remove these known exposures from the national water-supply infrastructure have progressed so slowly.”

Lin and Rafla-Yuan reported having no relevant disclosures. This study was supported by the National Institute of Environmental Health Sciences (R01ES031943, P42ES030990, P30ES000002, and T32ES007069) and the National Institute of General Medical Sciences (R24GM141194).