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This version published online on June 17, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2843
A more recent version of this article appeared on September 1, 2008
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Submitted on December 26, 2007
Accepted on June 9, 2008

Amniotic fluid and umbilical cord plasma corticotropin-releasing factor (CRF), CRF-binding protein, ACTH and cortisol concentrations in intra-amniotic infection and inflammation at term

Pasquale Florio*, Roberto Romero, Tinnakorn Chaiworapongsa, Juan Pedro Kusanovic, Michela Torricelli, Phil J. Lowry, and Felice Petraglia

Chair of Obstetrics and Gynecology, Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Siena, Italy; Perinatology Research Branch, NICHD/NIH/DHHS, Bethesda, Maryland and Detroit, Michigan, and Wayne State University/Hutzel Hospital, Department of Obstetrics and Gynecology, Detroit, MI, USA; and School of Animal and Microbial Sciences, University of Reading, Whiteknights, Reading, UK

* To whom correspondence should be addressed. E-mail: florio{at}unisi.it.

Context: Pregnant tissues express corticotropin-releasing factor (CRF), a peptide modulating fetal and placental ACTH and cortisol secretion. These actions are modulated by the locally expressed CRF-binding protein (CRF-BP).

Objective: to determine if CRF, CRF-BP, ACTH, and cortisol concentrations change in amniotic fluid and umbilical cord plasma in the presence of intra-amniotic infection/inflammation (IAI) in women with spontaneous labor at term.

Design: cross-sectional study

Setting: Tertiary referral center for obstetric care

Patients: women in active labor at term with (n=39) and without (controls; n=78) IAI.

Main outcome measures: Amniotic fluid and umbilical cord plasma concentrations of CRF, CRF-BP, ACTH, and cortisol measured by radioimmuno (RIA) and immunoradiometric (IRMA) assays.

Results: In patients with IAI, amniotic fluid CRF (0.97 ± 0.18 ng/mL) and CRF-BP (33.06 ± 5.54 nmol/L) concentrations were significantly (p<0.001) higher than in controls (CRF: 0.32 ± 0.04 ng/mL; CRF-BP: 14.69 ± 2.79). The umbilical cord plasma CRF and CRF-BP concentrations were significantly (p<0.001, for all) higher in women with IAI than in controls (CRF: 2.96 ± 0.35 ng/mL vs. 0.38 ± 0.18 ng/mL; CRF-BP: 152.12 ± 5.94 nmol/L vs. 106.9 ± 5.97). In contrast, amniotic fluid and umbilical cord plasma ACTH and cortisol concentrations did not differ between groups.

Conclusions: amniotic fluid and umbilical cord plasma CRF and CRF-BP concentrations are increased in women with spontaneous labor at term and IAI. CRF-BP may modulate CRF actions on ACTH and cortisol secretion, playing a pivotal role in limiting the inflammatory process and, thus, avoiding an over activation of the fetal/placental HPA axis at birth.


Key words: placenta • hypothalamic-pituitary-adrenal axis • chorioamnionitis • labor • fetus • inflammation • microbial invasion of the amniotic cavity (MIAC)







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