Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: A prospective investigation
Open accessAbstract
Objectives Recent advances in the physiology of human pregnancy have implicated placental corticotropin-releasing hormone (CRH) as one of the primary endocrine mediators of parturition and possibly also of fetal development. The aim of this study was (1) to prospectively assess the relationship of maternal plasma concentrations of CRH in the early third trimester of gestation with two prematurity-related outcomes-spontaneous preterm birth (PTB), and small-for-gestational age birth (SGA), and (2) to determine whether the effects of CRH on each of these outcomes are independent from those of other established obstetric risk factors. Study design In a sample of 232 women with a singleton, intrauterine pregnancy, maternal plasma was collected at 33 weeks' gestation and CRH concentrations were determined by radioimmunoassay. Each pregnancy was dated on the basis of last menstrual period and early ultrasonography. Parity, obstetric risk conditions for prematurity, mode of delivery, and birth outcomes were abstracted from the medical record. Results After adjusting for the effects of established obstetric risk factors, elevated CRH levels at 33 weeks' gestation were significantly associated with a 3.3-fold increase in the adjusted relative risk (RR) for spontaneous preterm birth and with a 3.6-fold increase in the adjusted relative risk for fetal growth restriction. Women who delivered postterm had significantly lower CRH levels in the early third trimester than those who delivered at term. When outcomes were stratified by gestational length and birth weight, the lowest CRH levels at 33 weeks' gestation were associated with the term non-SGA births, intermediate and approximately equal CRH levels were associated with the preterm non-SGA and term SGA births, and the highest CRH levels were associated with the preterm SGA births. Conclusion For deliveries occurring after 33 weeks' gestation (the time of CRH sampling in this study), our findings support the notion that in humans placental CRH may play an impending, direct role in not only the physiology of parturition but also in processes related to fetal growth and maturation. Our results also support the notion that the timing of onset of parturition may be determined or influenced by events occurring earlier in gestation rather than those close to the time of actual onset of labor (ie, the notion of a "placental clock").
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Some studies have demonstrated elevated HPA activity in women with stress and preterm delivery, including elevated cortisol and CRH levels.
“Some studies have demonstrated elevated HPA activity in these women, including elevated cortisol and CRH levels [77,78,79].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [77]
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- Authors
- Wadhwa, P. D., Garite, T. J., Porto, M., Glynn, L., Chicz-DeMet, A., Dunkel-Schetter, C., & Sandman, C. A.
- Affiliations
- University of California, Irvine (US)
- Corresponding author
- Wadhwa, Pathik D.
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 191
- Issue
- 4
- Pages
- 1063-1069
- ISSN
- 0002-9378 (ISSN-L)
- OpenAlex
- W2105188889
- Cited by
- 402
- References
- 40
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 12 · 2023: 13 · 2022: 19 · 2021: 17 · 2020: 26 · 2019: 22 · 2018: 13 · 2017: 17 · 2016: 20 · 2015: 20 · 2014: 32 · 2013: 28 · 2012: 29
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD028413, R29HD033506, HD 041696, HD-28413, HD 33506, R01HD041696)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- spontaneous preterm birth, fetal growth restriction, small-for-gestational-age birth, childbirth, fetal growth, third trimester, prenatal risk factors
- MeSH terms
- Adolescent, Adult, Corticotropin-Releasing Hormone, Female, Humans, Infant, Newborn, Infant, Small for Gestational Age, Labor, Obstetric, Pregnancy, Pregnancy Trimester, Third, Prospective Studies, Risk Factors, Fetal Development, Premature Birth
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