Preterm Birth and Corticotrophin-Releasing Hormone as a Placental Clock

Abstract

Preterm birth worldwide remains a significant cause of neonatal morbidity and mortality. Yet the exact mechanisms of preterm parturition remain unclear. Preterm birth is not a single condition, but rather a syndrome with a multifactorial etiology. This multifactorial nature explains why individual predictive measures for preterm birth have had limited sensitivity and specificity. One proposed pathway for preterm birth is via placentally synthesized corticotrophin-releasing hormone (CRH). CRH is a peptide hormone that increases exponentially in pregnancy and has been implicated in preterm birth due to its endocrine, autocrine, and paracrine roles. CRH has actions that increase placental production of estriol and of the transcription factor NF-kB that likely play a key role in activating the myometrium. CRH has been proposed as part of a placental clock, with early activation of placental production resulting in preterm birth. This article will review the current understanding of preterm birth, CRH as an initiator of human parturition, and the evidence regarding the use of CRH in the prediction of preterm birth.

The Impact of Stress, Microbial Dysbiosis, and Inflammation on Necrotizing Enterocolitis

“…By activating the embryonic HPA axis, placental CRH may initiate labor. Elevated placental CRH concentrations have been linked to preterm labor [ 17 , 18 ]. Furthermore, preterm fetuses have higher plasma EPI concentrations than term fetuses [ 19 ].…”

Ambient temperature and preterm birth: A case‐crossover study

“…10,11 In addition, cold-stress may trigger the release of placental corticotropin-releasing hormone, a key factor in initiating human parturition. 12 Conversely, high temperatures can cause dehydration, leading to reduced uterine blood flow and increased secretion of antidiuretic hormone and oxytocin, which could induce labour. 13 While recent systematic reviews have indicated possible associations between low-and high-temperature exposures and increased PTB risks, they have also reported inconsistencies in the findings across studies.…”

“…Low temperatures may induce increased blood viscosity and vascular constriction, 9 ultimately impairing uteroplacental blood flow and potentially resulting in PTB 10,11 . In addition, cold‐stress may trigger the release of placental corticotropin‐releasing hormone, a key factor in initiating human parturition 12 . Conversely, high temperatures can cause dehydration, leading to reduced uterine blood flow and increased secretion of antidiuretic hormone and oxytocin, which could induce labour 13 …”