Human placental impact from exposure to non-smoked tobacco and nicotine products: A scoping review.

Globally, non-smoked tobacco and nicotine containing products (NST&N) including nicotine replacement therapy are now widely used during pregnancy, yet evidence on human placental development and function which isolates the effects of nicotine from those of tobacco combustion is not readily available. This is a particularly important gap in the literature given nicotine replacement therapy is advocated in pregnancy for mothers who are unable to cease smoking. The intent of this scoping review is to critique the magnitude and quality of evidence on the impact of NST&N containing products on human placental health to inform clinical practice and direct future research. PubMed and Web of Science and their reference lists were searched to the end of November 2024 identifying 949 papers; screening by two independent reviewers eliminated 813 papers. Full text review eliminated a further 118 papers with 18 remaining for full extraction. The synthesis was challenged by widely different populations, dissimilar NST&N products and disparate reporting. Nevertheless, the findings indicate that the use of NST&N products results in placental hypoxia-related changes, as evidenced by increased resistance in the maternal-placental-foetal unit and significant upregulation of 8-OHdG. In addition, cytoplasmic HIF-1α expression and several ABC/SLC transporters are impacted. The pathological response to these hypoxia-induced changes is evidenced as placental morphology changes with increased subtrophoblastic membrane, decreased syncytial cytoplasm, necrotic areas in syncytium of placental villi, increased syncytial knots and apoptotic cells, and excessive collagen-factors which altered placenta size, weight, and haemodynamic parameters. These findings indicate maternal use of NST&N is not safe for the placenta.