Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: A prospective investigation
Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: A prospective investigation
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DOI：
10.1016/j.ajog.2004.06.070
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发表时间：
2004-10-01
影响因子：
9.8
通讯作者：
Sandman, CA
中科院分区：
文献类型：
--
作者：
Wadhwa, PD;Garite, TJ;Sandman, CA
目的：人类妊娠生理学的最新进展表明，胎盘促肾上腺皮质激素释放激素（CRH）是分娩和胎儿发育的主要内分泌介质之一。本研究的目的是（1）前瞻性评估妊娠晚期早期母体血浆CRH浓度与两种早产相关结局的关系-自发性早产（PTB）和小孕龄出生（SGA），以及（2）确定CRH对这些结局的影响是否独立于其他已确定的产科风险因素。在232例单胎宫内妊娠妇女的样本中，在妊娠33周时收集母体血浆，用放射免疫法测定CRH浓度。根据末次月经和早期超声检查确定每次妊娠的日期。从病历中提取产次、早产的产科风险状况、分娩方式和出生结局。在调整了既定的产科风险因素的影响后，妊娠33周时CRH水平升高与自发性早产的校正相对危险度（RR）增加3.3倍显著相关，胎儿生长受限的校正相对风险增加一倍。过期分娩的妇女在孕晚期早期的CRH水平明显低于足月分娩的妇女。当结局按妊娠长度和出生体重分层时，妊娠33周时的最低CRH水平与足月非SGA出生相关，中间和近似相等的CRH水平与早产非SGA和足月SGA出生相关，最高CRH水平与早产SGA出生相关。妊娠33周后分娩（本研究中CRH采样时间），我们的发现支持了人类胎盘CRH可能在即将发生的，不仅在分娩生理学中，而且在与胎儿生长和成熟有关的过程中也有直接作用。我们的结果还支持这样的观点：分娩开始的时间可能由妊娠早期发生的事件而不是接近实际分娩开始时间的事件决定或影响（即“胎盘钟”的概念）。(C)2004爱思唯尔公司All rights reserved.
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-forgestational 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"). (C) 2004 Elsevier Inc. All rights reserved.