Abstract
ObjectiveTo determine if maternal plasma CRH and preterm birth history were associated with recurrent preterm birth risk in a high-risk cohort.Study designSecondary analysis of pregnant women with a prior preterm birth ≤35 weeks receiving 17-alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm birth. All women with a 24-week blood sample were included. Maternal plasma CRH level at 24- and 32-weeks’ gestation was measured using both enzyme-linked immunosorbent assay (ELISA) and extracted radioimmunoassay (RIA) technologies. The primary outcome was spontaneous preterm birth <37 weeks. The association of CRH, prior preterm birth history, and the two combined was assessed in relation to recurrent preterm birth risk.ResultsRecurrent preterm birth in this cohort of 169 women was 24.9%. Comparing women who subsequently delivered <37 versus ≥37 weeks, mean levels of CRH measured by RIA were significantly different at 24 weeks (111.1±87.5 vs. 66.1±45.4 pg/mL, P = .002) and 32 weeks (440.9±275.6 vs. 280.2±214.5 pg/mL, P = .003). The area under the receiver operating curve (AUC) at 24 and 32 weeks for (1) CRH level was 0.68 (95% CI 0.59–0.78) and 0.70 (95% CI 0.59–0.81), (2) prior preterm birth history was 0.75 (95% CI 0.67–0.83) and 0.78 (95% CI 0.69–0.87), and (3) combined was 0.81 (95% CI 0.73–0.88, P = .001) and 0.81 (95% CI 0.72–0.90, P = .01) respectively for delivery <37 weeks. CRH measured by ELISA failed to correlate with gestational age or other clinical parameters.ConclusionIn women with a prior preterm birth, CRH levels were higher and had an earlier rise in women who experienced recurrent preterm birth. Second trimester CRH may be useful in identifying a sub-group of women with preterm birth due to early activation of the placenta-fetal adrenal axis. Assay methodology is a variable that contributes to difficulties in reproducibility of CRH levels in the obstetric literature.
Highlights
Preterm birth occurred in 10.02% all of births in 2018 in the United States and remains a substantial cause of neonatal morbidity and mortality [1]
The area under the receiver operating curve (AUC) at 24 and 32 weeks for (1) Corticotropin-releasing hormone (CRH) level was 0.68 and 0.70, (2) prior preterm birth history was 0.75 and 0.78, and (3) combined was 0.81 and 0.81 respectively for delivery
CRH measured by enzyme-linked immunosorbent assay (ELISA) failed to correlate with gestational age or other clinical parameters
Summary
Preterm birth occurred in 10.02% all of births in 2018 in the United States and remains a substantial cause of neonatal morbidity and mortality [1]. The etiology of preterm birth is multifactorial, resulting from inflammation from systemic disease or infection, abruption, uterine overdistention, abnormalities of the cervix and early activation of the maternal-fetal hypothalamic-pituitary adrenal systems [2]. Given the multifactorial pathogenesis and significant morbidity, there is a need to identify early markers of preterm birth to enable prediction and possible prevention strategies. Corticotropin-releasing hormone (CRH) has been investigated as a marker for preterm birth due to its endocrine, autocrine, and paracrine roles (Fig 1) [3]. Corticotropin-releasing hormone binding protein (CRH-BP) binds to CRH in the circulation reducing its activity until the binding protein becomes saturated late in pregnancy as CRH levels continue to rise [5]. CRH is suspected to contribute to preterm birth by increasing prostaglandins and estriol, which create an environment in favor of labor [6]
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