Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. 
Karen Pendergrass is a researcher specializing microbial metallomics and microbiome signatures, with a focus on bridging research and clinical practice. She is the co-founder of several initiatives, including Microbiome Signatures and the Heavy Metal Tested & Certified program, which translate complex science into actionable standards. What was studied?
This study investigated the effects of prenatal heavy metal exposure and infant neurodevelopment, considering the adverse effects of multiple heavy metals—cadmium (Cd), nickel (Ni), mercury (Hg), and lead (Pb). Heavy metal levels were measured in maternal urine samples collected at the 12th week of gestation, while infant neurodevelopment was assessed at 40 days using the Bayley Scales of Infant and Toddler Development. The study applied multiple statistical approaches, including Generalized Additive Models (GAM), Multivariable Linear Regression (MLR) with restricted cubic splines (RCS), Bayesian Kernel Machine Regression (BKMR), and Weighted Quantile Sum (WQS) regression, to evaluate both individual and joint effects of these metals on early neurodevelopment.
Who was studied?
The study examined 400 mother-infant pairs recruited from a community-based birth cohort in Tarragona, Spain, between 2013 and 2017. Mothers were recruited during their initial prenatal visits, and urine samples were analyzed for metal concentrations using ICP-MS/MS with creatinine adjustment. Infants were assessed at 40 days old by trained psychologists, focusing on cognitive, language, and motor domains. The mothers had a mean age of 30.9 years, with most belonging to a low- or middle-socioeconomic class, and nearly 70% reported never smoking. Infants were almost evenly split between male and female, with 74.5% breastfed.
Most important findings
Cadmium was consistently associated with adverse neurodevelopmental outcomes. GAM and MLR analyses confirmed a negative linear association between Cd exposure and both cognitive and expressive language scores (β = −1.47 and β = −0.32, respectively, both statistically significant). Pb demonstrated a non-linear, inverted U-shaped relationship with language development, indicating risk at both low and high exposure levels. WQS regression revealed that mixtures of heavy metals were significantly associated with impaired expressive language development (β = −0.26, 95% CI = −0.44, −0.07), with Cd and Ni identified as the main contributors. BKMR analyses supported an overall negative trend for metal mixtures, though not statistically significant. Mercury exposure showed no consistent associations.
Key implications
The study highlights that prenatal heavy metal exposure and infant neurodevelopment are particularly negatively impacted by cadmium and nickel exposure, with expressive language being the most vulnerable domain. The findings underscore the limitations of focusing on single-metal exposures, as real-world scenarios typically involve complex mixtures. Importantly for a certification program such as Heavy Metal Tested and Certified (HMTC), the evidence supports the inclusion of cadmium and nickel within the Infant and Child Foods Standards alongside lead and mercury as priority metals for regulatory thresholds, given their demonstrable neurodevelopmental risks even at low levels of prenatal exposure. These results emphasize the urgency of establishing stricter heavy metal limits in foods consumed by pregnant women, since dietary intake is a major source of exposure. For industry, compliance with reduced heavy metal thresholds is not only protective of infant health but also scientifically justified by evidence linking prenatal exposure to cognitive and language deficits in early life. For regulators, the study validates the need for mixture-based risk assessment approaches, moving beyond single-metal evaluations to capture the cumulative effects on vulnerable populations.
Citation
Kou X, Palleja-Millan M, Canals J, Rivera Moreno V, Renzetti S, Arija V. Effects of prenatal exposure to multiple heavy metals on infant neurodevelopment: A multi-statistical approach.Environmental Pollution. 2025;367:125647. doi:10.1016/j.envpol.2025.125647.
The Infant and Child Foods HMTC program sets science-driven standards to reduce toxic heavy metals in baby foods. By enforcing strict testing, preventive supply-chain controls, and continuous improvement, HMTC safeguards infants and toddlers from neurotoxic risks while driving industry accountability and consumer trust.
