Assessment of arsenic, cadmium, lead, mercury, and per- and polyfluoroalkyl substances concentrations in human milk and infant formula in the United States: a systematic review

Abstract

Background: Foods, including human milk (HM) and infant formula (IF), can be sources of environmental contaminant exposure for infants, which can impact health and development.

Objectives: This systematic review describes arsenic, cadmium, lead, mercury, and per- and polyfluoroalkyl substances (PFAS) concentrations in HM and IF in the United States (PROSPERO #CRD42024528756).

Methods: We searched CAB Abstracts, CENTRAL, CINAHL, Embase, and MEDLINE for peer-reviewed articles published in English through 2 April, 2025 (no date restrictions). Studies that assessed contaminant concentrations in HM or IF from countries rated as "high" or "very high" on the Human Development Index were eligible. Screening, data extraction, and risk of bias assessments were performed by 2 independent reviewers. We narratively synthesized United States studies and assessed the certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We developed heat maps for studies from all countries that may help inform evidence gaps in future systematic reviews.

Results: From the United States, 14 HM and 16 IF studies were included. For HM, perfluorooctanoic acid (PFOA) concentrations ranged from undetected to 36.1 pg/mL, and perfluorooctane sulfonic acid (PFOS) ranged from undetected to 106 pg/mL (GRADE: moderate); evidence was lacking for perfluorononanoic acid and perfluorohexanesulfonic acid. For IF, all PFAS were largely undetected (GRADE: moderate). For HM and IF, studies for arsenic, cadmium, lead, and mercury had small and unrepresentative samples, and most were published before 2000. We identified 317 and 108 articles for HM and IF, respectively, from other countries.

Conclusions: In published, peer-reviewed United States studies, PFOA and PFOS were detected in HM; PFAS were largely undetected in IF. There was a paucity of contemporary evidence for arsenic, cadmium, lead, and mercury in HM or IF in the United States, but we identified evidence from other countries that could help inform these knowledge gaps. Public health agencies recommend feeding infants HM given the benefits outweigh potential risks of contaminant exposure. This trial was registered at PROSPERO as CRD42024528756 (https://www.crd.york.ac.uk/PROSPERO/view/CRD42024528756).

Keywords: PFAS; arsenic; breast milk; cadmium; heavy metal; human milk; infant feeding; infant formula; lead; mercury.