Inflammation in Pregnancy: Key Drivers, Signaling Pathways and Associated Complications

In the developmental origins of health and disease (DOHaD) paradigm, there is a clear link between an adverse prenatal environment and the development of non-hereditary diseases later in life. Exposure to intrauterine inflammation, for example, has been associated with several late-onset conditions, including neurological, cardiovascular, immune, and metabolic disorders. Moreover, maternal and fetal health are compromised under exacerbated inflammation, as it can result in spontaneous abortion, preterm delivery, or intrauterine growth restriction. Prominent gestational pathologies associated with inflammation include preeclampsia, gestational diabetes mellitus, obesity, and infections. The main causes of inflammation can be classified as either infectious or sterile in origin. Thus, triggers of inflammation include microorganisms, viruses, excess fat, placental dysfunction, tissue breakdown products, and unbalanced immunoendocrine factors. Other etiological agents of inflammation include environmental factors (e.g., pollutants), lifestyle factors (e.g., nutrient overload), and behavioral factors (e.g., chronic stress, smoking, alcohol, and drug abuse). The mediators that drive the response to these insults include biochemical effectors (e.g., cytokines), pattern recognition receptors (e.g., toll-like receptors), and immune cells. These trigger a cascade of events leading to the activation of specific nuclear factors such as NF-kB and STATs. Overactivation of these signaling networks can disrupt the homeostasis at the feto-maternal interface, which can jeopardize pregnancy maintenance and influence fetal programming mechanisms. This review examines the key triggers, signaling pathways, and complications associated with inflammation during pregnancy, emphasizing the importance of maternal well-being and adequate prenatal care in mitigating and preventing inflammation-related risks in the short and long term.