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

https://doi.org/10.1016/j.ajog.2004.06.070Get rights and content

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-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.

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”).

Section snippets

Material and methods

We conducted a prospective, longitudinal investigation in a sample of women recruited during pregnancy and monitored through delivery. Our sample included low-risk as well as high-risk pregnancies, and deliveries were differentiated on the basis of presence/absence of labor preceding delivery.

Statistical analysis

Associations among continuous variables were computed with Pearson product-moment correlation coefficients, whereas those involving categorical variables were computed with an exact test of significance (Student t tests for independent samples with unequal Ns), χ2 or odds ratios. When necessary, the t test was modified to allow for unequal variances. The joint contributions of 2 or more predictors on categorical outcomes were computed by using multivariate logistic regression procedures to

Results

The mean plasma concentration of CRH (at 33 weeks' gestation) was 140.81 ± 10.35 pg/mL (±SEM). These values were approximately normally distributed (ie, skewness <2).

Delivery was preceded by labor in all subjects. The mean gestational age at birth was 39.3 ± 0.09 weeks (±SEM), and ranged between 34.5 and 43.1 weeks; 22 of these deliveries (9.5%) were preterm (<37 completed weeks' gestation) and 18 (7.8%) were postterm (>41 completed weeks' gestation). The mean infant birth weight was 3384 ±

Comment

These results demonstrate that in humans, placental CRH plays an impending role in not only the physiology of parturition but also in processes related to fetal growth and maturation. Moreover, our findings are also among the first to suggest that placental CRH directly participates in these physiologic processes, as evidenced by the prospective relationship between elevated CRH levels and relative risk for preterm birth and fetal growth restriction after adjusting for the effects of other

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    Supported in part by US PHS (NIH) grants HD-28413, HD-33506, and HD-041696.

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