Safety of nanoparticle therapies during pregnancy: A systematic review and meta-analysis

The exclusion of pregnant women from clinical trials has led to insufficient safety data for many treatments, making it necessary to evaluate their potential benefits and risks during preclinical stages. Nanomedicines show potential for reduced toxicity but there is limited evidence about their safety for pregnant women and their fetuses. We conducted the first systematic review and meta-analysis of the effect of nanoparticles (NPs) on a key outcome of fetal toxicity (low birth weight) in murine models. In the meta-analysis of mouse models, negatively charged NPs tended to decrease birth weight (-69.8 mg, 95 % CI: -196 to 56.5), as did small (-191 mg, 95 % CI: -369 to -13.3) and plain inorganic nanosystems (-249 mg, 95 % CI: -535 to 37.4). In contrast, positively charged NPs resulted in increased birth weight (+29.3 mg, 95 % CI: 23.4 to 35.2). All findings were validated in studies with low heterogeneity and low risk of publication bias. Neither large NPs (+4.37 mg; 95 % CI: -45.3 to 54.0) nor polymer-coated NPs (+16.5 mg; 95 % CI: -44.7 to 77.6) had any clear association with birth weight. Similar results were observed in other models and experimental designs from articles not included in the meta-analysis, although no conclusions were drawn for other parameters due to high variability. Our findings pave the way for future research and the rational development of safer nanomedicines for use during pregnancy.