Elevated maternal plasma corticotropin releasing hormone levels in twin gestation

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Abstract
The placenta secretes large amounts of the hypothelamic hormone, corticotropin releasing hormone (CRH) into the maternal and fetal circulation during pregnancy. We and other investigators have shown that during normal pregnancy, maternal plasma CRH levels begin to rise in the second trimester with a dramatic increase in CRH levels during the 5-6 weeks preceding the onset of labor. This rise in maternal plasma CRH is parallel to the rise of placental CRH mRNA which has been reported to occur with gestational maturation. Mechanisms underlying the control of CRH secretion by the placenta have not yet been determined. In twin gestations, increased fetal-placental mass has been shown to be associated with elevated maternal levels of several placental hormones as compared to singleton gestation. We measured maternal plasma CRH in both twin and singleton gestation to investigate whether the larger size of the fetal-placental unit in twin gestation is associated with elevated maternal CRH levels. Seventy-six serial venous blood samples were collected from 20 women with twin gestation and 40 samples were obtained from 27 women with uncomplicated singleton gestation. Gestational age was determined by history of a known last menstrual period and first trimester clinical examination and confirmed by ultrasound examination. CRH was extracted from 1-2 ml plasma with SEP-Pak C18 cartridges and eluted with triethylamine-formic-acid propanolol. CRH was measured by radioimmunoassay (RIA) with human CRH standard and antiserum to human CRH raised in our laboratory. Mean CRH levels were calculated for four week intervals. In both singleton and twin gestation, the maternal plasma CRH levels increased with advancing gestational age. After 29 weeks of gestation, maternal plasma CRH levels in twin gestation were significantly higher than those in singleton gestation (p < 0.01). At 37 to 40 weeks of gestation, mean maternal CRH was 1167 .+-. 237 pg/ml in singleton gestation as compared to 6927 .+-. 1725 pg/ml in twin gestation (p < 0.05). In addition, the rapid rise in plasma CRH levels which occurs near term in singleton gestation, occurred earlier in twin gestation. This early rise in maternal CRH levels persisted when the data from twin pregnancies complicated by preterm labor were removed from the analysis. Maternal plasma CRH levels have been reported to rise precociously in singleton pregnancies complicated by preterm labor. Further investigation is needed to determine whether the early rise in maternal plasma CRH and the high levels seen in twin gestation are associated with the onset of pretern labor which frequently complicates twin gestation. We conclude that maternal plasma CRH levels are higher in twin gestation, findings most likely secondary to increased fetal-placental mass. The impact of these very high CRH levels on maternal pituitary-adrenal function and on mechanisms of parturition remains to be determined.