Children with high blood lead levels throughout childhood and by age 8 were significantly more likely to report symptoms of depression at age 12, based on a new study published in JAMA Network Open.

Lead exposure remains a persistent public health problem, with no known safe level. However, the reference value that should prompt intervention in children is 3.5 μg/L, representing the 97.5th percentile of blood lead concentrations among the pediatric population in the US between 2015 and 2018, according to the US CDC.

Although lead exposure in relation to cognition, defiance, hyperactivity, and conduct disorder has been well studied, far less is known about its association with depression and anxiety in late childhood and early adolescence, said Christian Hoover, MPH, PhD student in epidemiology at Brown University in Providence, Rhode Island, who led the study.

“We hope that clinicians take away the message that lead exposure remains a contemporary problem, even at levels that are often considered low,” Hoover told Medscape Medical News.

The findings underscore the importance of screening for environmental risk factors and mental health symptoms in pediatric care, he said.

Hoover and colleagues examined low-level, repeated lead exposure across childhood in relation to later mental health symptoms. They conducted a prospective study of 121 children (55% girls; 64% White) recruited via caregivers between 2003 and 2006 in Cincinnati and were followed from the second trimester to age 12. Their serum blood lead concentrations were measured at regular intervals. Self-reported and caregiver-reported depressive and anxiety symptoms were assessed using various scales.

By blood lead concentration, the adjusted mean differences in self-reported depression scores increased from a nonsignificant 1.82 at age 1 to a significant 3.22 at age 8.

Hoover and his team also found a significantly increased risk for elevated child-reported depressive symptoms with each doubling in mean childhood blood lead concentrations (relative risk, 1.90; 95% CI, 1.00-3.66; P = .05). Every SD change in lead exposure was associated with a 2.7-point higher score (95% CI, -0.27 to 5.61; P = .08).

The study findings are consistent with results of a 2021 study that suggested children aged 8 years were especially susceptible to the negative effects of exposure.

Overall median concentrations decreased from age 1 to age 8, with the highest concentrations in subgroups of boys and Black children and among those with caregivers who had less education.

No significant associations appeared between blood lead concentrations and anxiety.

In the Clinic

Although childhood lead poisoning has been greatly reduced in the US through public policy interventions and improved surveillance, the current study broadens clinicians’ understanding of lead toxicity, said Noah Buncher, DO, pediatrician at Children’s Hospital of Philadelphia, Philadelphia, and former director of the Boston Medical Center Lead Clinic, which treats children with possible lead poisoning.

The study shows a critical window of vulnerability in later childhood and early adolescence in which lead exposure has a stronger association with depressive symptoms, he said.

Pediatric clinicians should consider the risk for lead exposure throughout childhood, not just in infancy and early childhood, Buncher said.

“Children with autism, developmental delay, or those exhibiting pica behaviors are all at higher risk for lead exposure due to increased hand-to-mouth behaviors,” he said.

Hoover said he and his colleagues plan to follow the study cohort over a longer period to examine whether these associations persist into young adulthood, as well as to evaluate additional and emerging sources of lead exposure.

The study was funded by the National Institute of Environmental Health Sciences. Hoover and Buncher disclosed having no financial conflicts of interest.