Oxidative stress - Related spontaneous preterm delivery challenges in causality determination, prevention and novel strategies in reduction of the sequelae

Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.