The Sex Difference in the Pathophysiology of Preterm Birth

Preterm birth (PTB) refers to a labor before 37 gestational weeks. This is a major global contributor to neonatal morbidity and mortality. Although fetal sex is frequently treated as a confounding variable in PTB research, relatively few studies have conducted sex-stratified analyses to investigate how male and female fetuses may respond differently to various intrauterine exposures. This represents an underexplored area with important implications for understanding fetal sexual dimorphism-specific vulnerability to adverse pregnancy outcomes. Understanding the role of fetal sex differences in the pathophysiology of preterm birth (PTB) regarding processes such as inflammation, placental dysfunction, and oxidative stress is crucial. These delicate processes are tightly interrelated, but also independently contribute to pregnancy complications. Recognizing fetal sex as a biological variable for such processes is essential for improving mechanistic insight, providing refined predictive models.