Elevated mid-trimester maternal corticotrophin-releasing hormone levels in pregnancies that delivered before 34 weeks

Objective To test whether maternal corticotrophin-releasing hormone levels are elevated in the midtrimester for those women who subsequently had spontaneous preterm delivery and to assess the clinical utility of the measurement in the prediction of preterm delivery. Design A prospective observational study. Setting Department of Obstetrics and Gynaecology, Prince of Wales hospital, Hong Kong. Population 1047 low risk pregnant women recruited at 15-20 weeks of gestation. Methods Venous samples were assayed for levels of corticotrophin-releasing hormone. The investigators responsible for the laboratory assay were blinded to the obstetric outcome. Main outcome measures Incidence of preterm, term and post-term pregnancies. Results Those who were delivered spontaneously at a preterm gestational age (before 34 weeks) had significantly higher corticotrophin-releasing hormone levels in the mid-trimester, compared with those who were delivered at term or post-term. There was a trend towards lower corticotrophin-releasing hormone levels with more advanced gestational age at delivery. When the measurement of corticotrophin-releasing hormone was used to predict delivery before 34 weeks, the best cut off was 1.9 MoM, which produced a sensitivity of 72.7% and specificity of 78.4%. This translated to a positive predictive value of 3.6%, negative predictive value of 99.6% and relative risk of 9.4 when the background prevalence of spontaneous preterm delivery before 34 weeks was 1.1%. The likelihood ratio was 3.4. Conclusions Mid-trimester maternal corticotrophin-releasing hormone levels are elevated in pregnancies destined to deliver preterm before 34 weeks. When used alone in a low risk population, the measurement has a low predictive power for preterm delivery. However, the likelihood ratio of 3.4 implies that in high risk populations the test may be considerably more valuable.