Objective: This study tested the hypothesis that maternal stress is associated with elevated maternal levels of corticotropin releasing hormone and activation of the placental-adrenal axis before preterm birth. Study Design: In a behavior in pregnancy study, 524 ethnically and socioeconomically diverse women were followed up prospectively and evaluated at 3 gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 36 weeks. Maternal variables included demographic data, medical conditions, perceived stress level, and state anxiety. Maternal plasma samples were collected at each gestational age. Eighteen case patients with spontaneous onset of preterm labor were matched against 18 control subjects who were delivered at term, and their samples were assayed for corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol by means of radioimmunoassay. Statistical tests were used to examine mean differences in these hormones. In addition, the relationship between stress level and each hormone was tested with a Pearson correlation coefficient and hierarchic multiple regressions in each group. Results: Patients who had preterm delivery had significantly higher plasma corticotropin-releasing hormone levels than did control subjects at all 3 gestational ages (P < .0001). Analyses did not find any differences in reported levels of stress between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation. A hierarchic multiple regression indicated that maternal stress level at 18 to 20 weeks' gestation and maternal age accounted for a significant amount of variance in corticotropin-releasing hormone at 28 to 30 weeks' gestation, after controlling for corticotropin-releasing hormone at 18 to 20 weeks' gestation (P < .001). In addition, patients who were delivered preterm had significantly elevated plasma levels of adrenocorticotropic hormone at all 3 gestational ages (P < .001) and significantly elevated cortisol levels at 18 to 20 weeks' gestation and 28 to 30 weeks' gestation (P < .001). Conclusion: Maternal plasma levels of corticotropin-releasing hormone are significantly elevated at as early as 18 to 20 weeks' gestation in women who are subsequently delivered preterm. Changes in corticotropin-releasing hormone between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation are associated with maternal age and stress level at 18 to 20 weeks' gestation. Maternal stress and corticotropin-releasing hormone levels may be potential markers for the patient at risk for preterm birth. Activation of the placental maternal pituitary-adrenal axis is consistent with the classic endocrine response to stress. (Am J Obstet Gynecol 1999;180:S257-63.)

Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks’ gestation in pregnancies ending in preterm delivery