Exposure to environmental toxicants during pregnancy and placental angiogenic biomarkers: An integrative review.

Placental angiogenic biomarkers, including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio, are indicators of placental vascular health and are implicated in adverse pregnancy outcomes such as preeclampsia and preterm birth. Exposure to environmental toxicants, including air pollutants, metals and trace elements, per- and polyfluoroalkyl substances (PFAS), and endocrine-disrupting chemicals (EDCs), are increasingly recognized as contributors to placental dysfunction; however, their effects on angiogenic biomarkers remain unclear. This integrative review synthesized evidence on these relationships using Whittemore and Knafl's framework. Literature searches in PubMed, CINAHL, and EMBASE (October-November 2025; Search B updated May 2026) identified 129 articles from Search A and 452 from Search B. After duplicate removal and title/abstract screening, 35 and 37 articles, respectively, underwent full-text review. Following full-text screening and removal of overlap, 19 human studies were included. Exposure to air pollutants (PM₂.₅, NO₂, O₃, PM₁₀) predominantly demonstrated anti-angiogenic patterns, including elevated sFlt-1 or sFlt-1/PlGF ratios and reduced PlGF. Metal and trace element findings were heterogeneous, though cadmium and copper were associated with increased sFlt-1 and decreased PlGF, while lead showed no consistent association. Exposure to PFAS was associated with elevated sFlt-1 and reduced PlGF, and EDCs demonstrated anti-angiogenic trends. Overall, 14 of 19 studies reported at least one association between environmental toxicants and angiogenic biomarkers consistent with an anti-angiogenic pattern, although several studies also reported null or opposing associations. Exposure to environmental toxicants may disrupt placental angiogenic balance, highlighting potential pathways for early risk identification and prevention of adverse pregnancy outcomes.