Placental corticotropin-releasing hormone (CRH), spontaneous preterm birth, and fetal growth restriction: A prospective investigation

• Published in: American journal of obstetrics and gynecology Vol. 191; no. 4; pp. 1063 - 1069
• Main Authors: Wadhwa, Pathik D., Garite, Thomas J., Porto, Manuel, Glynn, Laura, Chicz-DeMet, Aleksandra, Dunkel-Schetter, Christine, Sandman, Curt A.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Mosby, Inc 01.10.2004; Elsevier
• Subjects: Adolescent; Adult; Biological and medical sciences; Birth weight; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - blood; Diseases of mother, fetus and pregnancy; Female; Fetal Development - physiology; Fetal growth restriction; Gynecology. Andrology. Obstetrics; Humans; Infant, Newborn; Infant, Small for Gestational Age - physiology; Labor; Labor, Obstetric - physiology; Medical sciences; Obstetric risk; Parturition; Pregnancy; Pregnancy Trimester, Third; Pregnancy. Fetus. Placenta; Premature Birth - diagnosis; Prematurity; Prenatal stress; Preterm birth; Prospective Studies; Risk Factors; Small-for-gestational age; Parturition; Preterm birth; Prematurity; Fetal growth restriction; Obstetric risk; Birth weight; Labor; Corticotropin-releasing hormone; Small-for-gestational age; Prenatal stress; Intrauterine growth retardation; Pregnancy disorders; Gynecology; Corticotropin releasing factor; Premature delivery; Obstetrics; Placental hormone; Stress; Hypothalamic hormone; Prenatal; Fetal diseases; Risk factor; Hormone releasing factor; Corticotropin- releasing hormone Labor Parturition Birth weight Prematurity Preterm birth Fetal growth restriction Small-for-gestational age Obstetric risk Prenatal stress
• DOI: 10.1016/j.ajog.2004.06.070
• ISSN: 0002-9378

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. 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. 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. 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”).