Objective: Spontaneous labor at term involves the activation of placental corticotropin-releasing hormone and the fetal adrenal axis, but the basis for extreme preterm labor is unknown. Our objective was to determine whether placental corticotropin-releasing hormone is activated in extreme preterm labor.

Study design: One thousand five hundred six mothers delivering at less than 28 weeks' gestation were enrolled. Each mother/infant pair was assigned to the category that described the primary reason for hospitalization. Observers who had no knowledge of patient categorization assessed placenta microbiology, histology, and corticotropin-releasing hormone expression. These were correlated with the primary reason for hospitalization.

Results: Among infants delivered at less than 28 weeks' gestation, spontaneous (vs induced) delivery was associated with less placental corticotropin-releasing hormone expression and more frequent signs of placental inflammation and infection.

Conclusion: Inflammation and infection, rather than premature activation of the fetal adrenal axis, should be the major focus of research to prevent extremely preterm human birth.