Antibiotics, Inflammation, and Preterm Labor: A Missed Conclusion

Regarding the risk of antibiotic therapy during pregnancy, any medication given to the mother should be according to the indications due to the risk of possible side effects. Antibiotics are one of the most important groups of these medications to be considered. Along with direct antibiotic-induced side effects, indirect pathways also affect the fetus through the maternal changes. According to the data, different cytokines including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) are involved in both term and preterm parturition. These cytokines could trigger expression of different substances such as prostaglandins (PGs), their receptors, and PGs synthetizing molecules with already proven roles in parturition. Moreover, IL-1, IL-6, and TNF-α knocked-out mice have delayed parturition and lower levels of PGs compared to the wild types. The earlier-mentioned cytokines are able to induce matrix metalloproteinases and are also involved in parturition. Certain antibiotics have been shown capable of inducing inflammation cascade directly. Both in-vivo and in-vitro studies in human have also demonstrated this inflammation as elevated levels of inflammatory cytokines especially IL-1, IL-6, and TNF-α. This increase has been observed both in the presence and the absence of lipopolysaccharide (LPS). Moreover, antibiotics can induce endotoxemia in healthy cases which finally leads to the pro-inflammatory cytokine release. Regarding the role of mentioned pro-inflammatory cytokines in both term and preterm parturition, it seems that non-indicated use of antibiotics during pregnancy may increase the risk of preterm labor.