ELEVATED LEVELS OF UMBILICAL-CORD PLASMA CORTICOTROPIN-RELEASING HORMONE IN GROWTH-RETARDED FETUSES

CRH is synthesized in the hypothalamus and released in response to str ess into the portal hypophyseal blood; an additional site of synthesis , the placenta, is present only during pregnancy. Placental CRH is rel eased into the maternal and fetal circulation during human pregnancy, and we hypothesized that the chronic fetal stress associated with feta l growth retardation may stimulate placental CRH release. We measured plasma CRH concentrations in the umbilical cord blood of 28 growth-ret arded fetuses and 28 normally grown fetuses matched for gestational ag e and mode of delivery. Plasma ACTH, dehydroepiandrosterone sulfate (D HEAS), and cortisol were also measured in the umbilical cord samples t o determine if CRH levels were correlated with levels of pituitary and adrenal hormones. The mean umbilical cord plasma CRH level in the gro wth-retarded fetuses was 206 +/- 25.8 pmol/L, which was significantly higher than that in the normally grown fetuses matched for gestational age, presence or absence of labor, and mode of delivery (49.4 +/- 16. 7 pmol/L; P < 0.01). The mean plasma ACTH level in the growth-retarded fetuses (5.7 +/- 1.2 pmol/L) was significantly higher than that in th e normally grown fetuses (3.3 +/- 0.7 pmol/L; P < 0.05). The mean cort isol concentration in the growth-retarded fetuses was 260 +/- 32.5 nmo l/L, and that in the normally grown fetuses was 220 +/- 40 nmol/L. The mean DHEAS level was significantly lower in the growth-retarded fetus es (4.8 +/- 0.6 mu mol/L) than that in the normally grown fetuses (7.7 +/- 0.6 mu mol/L; P < 0.001). There was a significant correlation bet ween umbilical cord plasma CRH and both ACTH and cortisol concentratio ns as well as a significant negative correlation between CRH and DHEAS levels in the growth-retarded fetuses. The umbilical cord plasma CRH level is extremely elevated in growth-retarded fetuses compared to tha t in normal fetuses. Placental CRH, like hypothalamic CRH, may be stim ulated in conditions of chronic stress and may modulate fetal pituitar y-adrenal function in high risk pregnancies.