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Cited by 411Preterm Birth and ChorioamnionitisStress Responses and CortisolMaternal Mental Health During Pregnancy and Postpartum

Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): Priming the placental clock

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Sandman, Curt A., Glynn, Laura, Schetter, Christine Dunkel, Wadhwa, Pathik, Garite, Thomas, Chicz-DeMet, Aleksandra, Hobel, Calvin·2006·Peptides
DOI 10.1016/j.peptides.2005.10.002
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Abstract

The purposes of this study were to determine the intervals when placental corticotrophic-releasing hormone (CRH) was most responsive to maternal cortisol. A sample of 203 women each were evaluated at 15, 19, 25 and 31 weeks gestation and followed to term. Placental CRH and maternal adrenocorticotropin hormone (ACTH), B-endorphin and cortisol were determined from plasma. CRH levels increased faster and were higher in women who delivered preterm compared with women who delivered at term (F3,603 = 5.73, p < .001). Simple effects indicated that CRH levels only at 31 weeks predicted preterm birth (F1,201 = 5.53, p = .02). Levels of cortisol were higher in women who delivered preterm at 15 weeks gestation (F1,201 = 4.45, p = .03) with a similar trend at 19 weeks gestation. Hierarchical regression suggested that the influence on birth outcome of maternal cortisol early in pregnancy was mediated by its influence on placental CRH at 31 weeks. Elevated cortisol at 15 weeks predicted the surge in placental CRH at 31 weeks (R = .49, d.f. = 1,199, Fchange = 61.78, p < .0001). Every unit of change in cortisol (microg/dl) at 15 weeks was associated with a 34 unit change of CRH (pg/ml) at 31 weeks. These findings suggested that early detection of stress signals by the placenta stimulated the subsequent release of CRH and resulted in increased risk for preterm delivery.

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  • The accelerated placental clock theory proposes that stress-induced HPA activation speeds the normal pregnancy rise in maternal cortisol, which increases placental CRH production through feed-forward mechanisms.

    “In pregnancy, a popular theory proposed to explain stress-related PTB is that of the accelerated “placental clock,” which posits that stress-induced hypothalamic-pituitary-adrenal (HPA) activation hastens the expected pregnancy-associated rise in maternal cortisol, upregulating placental corticotropin-releasing hormone (CRH) production via feed-forward mechanisms (Sandman et al., 2006).”

    From Childhood stress and birth timing among African American women: cortisol as biological mediator (2017) · cites this paper as Sandman et al., 2006

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Authors
Sandman, C. A., Glynn, L., Schetter, C. D., Wadhwa, P., Garite, T., Chicz-DeMet, A., & Hobel, C.
Affiliations
  • University of California, Irvine (US)
  • University of California, Los Angeles (US)
  • University of California, Irvine Medical Center (US)
  • Cedars-Sinai Medical Center (US)
Corresponding author
Sandman, Curt A.
ORCID
Venue
Peptides
Publisher
Elsevier BV
Published
2006-06
Volume
27
Issue
6
Pages
1457-1463
ISSN
0196-9781 (ISSN-L)
DOI
10.1016/j.peptides.2005.10.002
OpenAlex
W2122548940
Cited by
411
References
52
Citations by year
2026: 9 · 2025: 16 · 2024: 23 · 2023: 16 · 2022: 19 · 2021: 15 · 2020: 25 · 2019: 26 · 2018: 32 · 2017: 18 · 2016: 27 · 2015: 26 · 2014: 26 · 2013: 21 · 2012: 19
FWCI
7.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Peptides (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institute of Neurological Disorders and Stroke (NS-41298;, R01NS041298)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD028413, HD-28413)
Topics
  • Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords
maternal cortisol, preterm birth, maternal stress, ACTH, beta-endorphin, third trimester, early pregnancy
MeSH terms
Adrenocorticotropic Hormone, Adult, beta-Endorphin, Corticotropin-Releasing Hormone, Female, Humans, Hydrocortisone, Mothers, Placenta, Pregnancy, Pregnancy Trimester, Third, Regression Analysis, Risk, Premature Birth

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