Bioavailability of and US Infant Exposure to Arsenic, Cadmium, Lead, Mercury, and Per- and Polyfluoroalkyls from Human Milk and Infant Formula: Results from a Series of Systematic Reviews

Infants may be exposed to contaminants from environmental and food sources, including human milk (HM) or infant formula (IF). The objective of this series of systematic reviews (PROSPERO: CRD42024530332, CRD42024530336, CRD42024530339, and CRD42024530344) was to 1) assess infant exposure to contaminants from HM and/or IF in the United States and 2) assess the bioavailability of these contaminants from HM and IF when consumed by infants. The protocol was developed with a technical expert panel (TEP). Through 2 April, 2025, CAB Abstracts, CENTRAL, CINAHL, Embase, and MEDLINE databases were searched for peer-reviewed articles published in English. Another TEP critically appraised sample collection and contaminant assessment methods for included articles. Studies needed to report contaminant concentrations of biospecimens based on infant feeding (HM only, IF only, or HM and IF). Results were narratively described. Risk of bias was assessed using ROBINS-E. From 6799 unique records, 7 articles from 4 studies were identified. The New Hampshire birth cohort reported infant urinary concentrations of arsenic (n = 4 articles), cadmium (n = 2), lead (n = 1), and mercury (n = 1) between 2009 and 2019. Three other studies reported infant blood lead concentrations between 1975 and 1994. All articles had acceptable contaminant assessment methods, and most (n = 6 articles) had low risk or some concerns of bias. Collectively, most evidence was from 1 cohort or published 30+ y ago and lacked demographic and geographic diversity. Therefore, conclusions could not be made about exposure to arsenic, cadmium, lead, or mercury from HM and/or IF for infants in the United States. No evidence was found that reported on per- and polyfluoroalkyl substances in infant biospecimens or bioavailability of any of the contaminants from HM or IF. These findings highlight the need for research about infant exposure to and bioavailability of arsenic, cadmium, lead, mercury, and per- and polyfluoroalkyl substances from HM or IF in the United States.