{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:56:34Z","timestamp":1788281794967,"version":"build-2803163510"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine if maternal plasma CRH and preterm birth history were associated with recurrent preterm birth risk in a high-risk cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>Secondary analysis of pregnant women with a prior preterm birth \u226435 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\u2019 gestation was measured using both enzyme-linked immunosorbent assay (ELISA) and extracted radioimmunoassay (RIA) technologies. The primary outcome was spontaneous preterm birth &lt;37 weeks. The association of CRH, prior preterm birth history, and the two combined was assessed in relation to recurrent preterm birth risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Recurrent preterm birth in this cohort of 169 women was 24.9%. Comparing women who subsequently delivered &lt;37 versus \u226537 weeks, mean levels of CRH measured by RIA were significantly different at 24 weeks (111.1\u00b187.5 vs. 66.1\u00b145.4 pg\/mL, P = .002) and 32 weeks (440.9\u00b1275.6 vs. 280.2\u00b1214.5 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\u20130.78) and 0.70 (95% CI 0.59\u20130.81), (2) prior preterm birth history was 0.75 (95% CI 0.67\u20130.83) and 0.78 (95% CI 0.69\u20130.87), and (3) combined was 0.81 (95% CI 0.73\u20130.88, P = .001) and 0.81 (95% CI 0.72\u20130.90, P = .01) respectively for delivery &lt;37 weeks. CRH measured by ELISA failed to correlate with gestational age or other clinical parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0257422","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T13:39:43Z","timestamp":1631799583000},"page":"e0257422","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Revisiting the placental clock: Early corticotrophin-releasing hormone rise in recurrent preterm birth"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-9850","authenticated-orcid":true,"given":"Christina L.","family":"Herrera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Bowman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald D.","family":"McIntire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"issue":"13","key":"pone.0257422.ref001","first-page":"1","article-title":"Births: Final Data for 2018.","volume":"68","author":"JA Martin","year":"2019","journal-title":"Natl Vital Stat Rep."},{"issue":"Suppl 2","key":"pone.0257422.ref002","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1046\/j.1365-3016.2001.00010.x","article-title":"Risk stratification and pathological mechanisms in preterm delivery.","volume":"15","author":"CJ Lockwood","year":"2001","journal-title":"Paediatric and perinatal epidemiology."},{"issue":"4","key":"pone.0257422.ref003","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/S0002-9378(98)70219-4","article-title":"Maternal corticotropin-releasing hormone levels in the early third trimester predict length of gestation in human pregnancy.","volume":"179","author":"PD Wadhwa","year":"1998","journal-title":"Am J Obstet Gynecol"},{"issue":"5","key":"pone.0257422.ref004","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1210\/jcem-63-5-1199","article-title":"High levels of corticotropin-releasing hormone immunoactivity in maternal and fetal plasma during pregnancy","volume":"63","author":"RS Goland","year":"1986","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"pone.0257422.ref005","doi-asserted-by":"crossref","first-page":"912","DOI":"10.2741\/2113","article-title":"Corticotrophin releasing hormone and the timing of birth","volume":"12","author":"R Smith","year":"2007","journal-title":"Frontiers in bioscience: a journal and virtual library"},{"issue":"5","key":"pone.0257422.ref006","first-page":"514","article-title":"Endocrine and paracrine regulation of birth at term and preterm","volume":"21","author":"JRG Challis","year":"2000","journal-title":"Endocrine reviews"},{"issue":"5","key":"pone.0257422.ref007","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nm0595-460","article-title":"A placental clock controlling the length of human pregnancy","volume":"1","author":"M McLean","year":"1995","journal-title":"Nature medicine"},{"issue":"1","key":"pone.0257422.ref008","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0002-9378(99)70461-8","article-title":"Predicting risk of preterm delivery by second-trimester measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations.","volume":"181","author":"M McLean","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"pone.0257422.ref009","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1749-6632.1999.tb07878.x","article-title":"Corticotrophin-releasing hormone and CRH-binding protein. 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