High fetal urocortin levels at term and preterm labor.

CONTEXT: Placental urocortin has a role in the cascade of events leading to parturition by stimulating myometrial contractility and placental uterotonins secretion. OBJECTIVE: The objective of this study was to evaluate urocortin levels in maternal and fetal [umbilical cord artery (UCA) and vein (UCV)] plasma at term and preterm labor. DESIGN: The study design was a controlled cross-sectional study performed from November 2003 to June 2004. SETTING: This study was performed at the Division of Obstetrics and Gynecology, University of Siena (Siena, Italy). PATIENTS: Plasma samples were collected at term in the absence of labor (TNL; n = 27; 39.3 +/- 0.1 gestational weeks), at term spontaneous vaginal delivery (TL; n = 24; 40.1 +/- 0.2 gestational weeks), and at preterm labor (PTL; n = 19; 32.4 +/- 0.4 gestational weeks). Changes in urocortin mRNA expression were also evaluated in placentas collected from TNL (n = 11), TL (n = 11), and PTL (n = 10). INTERVENTION: Urocortin levels were measured by specific RIA. Changes in placental mRNA expression were determined by real-time quantitative RT-PCR analysis. RESULTS: Maternal and UCA plasma urocortin levels were significantly (P < 0.0001 for all) higher in TL and PTL than in TNL. Furthermore, UCA concentrations were significantly (P < 0.0001 for all) higher than and correlated with maternal concentrations (TNL: r = 0.45; P < 0.05; TL: r = 0.959; P < 0.0001; PTL: r = 0.7719; P < 0.0001). UCV levels were significantly (P < 0.001) higher in TL and PTL than in TNL and were significantly (P < 0.0001 for all) higher than and significantly (P < 0.0001 for all) correlated with maternal values, but were significantly (P < 0.0001 for all) lower than and correlated with UCA values (TNL: r = 0.9548; P < 0.0001; TL: r = 0.927; P < 0.0001; PTL: r = 0.838; P < 0.0001). Placental urocortin mRNA expression did not differ among TNL, TL, and PTL samples. CONCLUSIONS: Fetal urocortin secretion is increased in term and preterm labor. Whether these changes are a consequence rather than a cause of human parturition remains to be addressed.

Cervical ripening and induction of labor by prostaglandin E2: a comparison between intracervical gel and vaginal pessary.

OBJECTIVE: To compare the effectiveness and safety of two formulations of prostaglandin (PG) E2 (gel and pessary) for induction of labor. Primary outcomes were cervical ripening, initiation/duration of labor, and type of delivery. STUDY DESIGN: A total of 115 women with singleton gestations were consecutively enrolled and assigned to receive intracervical PGE2 (dinoprostone 0.5 mg) by gel (n = 66) or PGE2 (dinoprostone 10 mg) by intravaginal pessary (n = 49). RESULTS: Independently from parity, the vaginal pessary induced successful cervical ripening with a slightly higher but not statistically significant occurrence of vaginal delivery with respect to gel induction. The mean time interval from induction to vaginal delivery did not differ between groups, despite being shorter for the pessary group in inducation-delivery intervals > 12 h. No significant differences were found between the groups with respect to patients who required a second course of PGE2 (9% vs. 2%), as well as oxytocin (11% vs. 13%) induction. No significant difference was found in the incidence of uterine hyperstimulation and other adverse reactions in nulliparas, or in fetal and neonatal outcome. CONCLUSION: Independently from parity, both PGE2 administration routes appeared to be effective in achieving cervical ripening, initiation of labor and optimal type of delivery, and showed the same incidence of side-effects.

Plasma antiviral activity and interferon-gamma production by superantigen-stimulated lymphocytes during normal human pregnancy.

PROBLEM: Plasma interferon (IFN)-beta levels, lymphocyte responsiveness, and evaluation of the relationship between circulating antiviral activity (AA) and IFN-gamma production were studied in pregnant women and nonpregnant age-matched controls with the objective of elucidating the downregulation of IFN-gamma production in successful pregnancy. METHOD OF STUDY: In plasma and supernatants of peripheral blood mononuclear cell (PBMC) cultures, stimulated with staphylococcal enterotoxin A (SEA) superantigen, from 43 pregnant women with a history of normal pregnancy and 30 healthy nonpregnant age-matched controls, levels of AA were measured in a micromethod by inhibition of the cytopathic effect (CPE) caused by vesicular stomatitis virus (VSV) in the human amnionic cell line (WISH). RESULTS: Significantly higher plasma AA (60% was IFN-gamma and residual activity was acid-labile IFN-like) was present in pregnant women than controls. On the other hand, SEA-activated PBMCs from pregnant women produced significantly lower IFN-gamma levels than those of nonpregnant women. Furthermore, maternal plasma AA levels correlated negatively with IFN-gamma production by SEA-stimulated PBMCs. CONCLUSION: The hypothesis that successful pregnancy requires downregulation of IFN-gamma is only partially sustained, suggesting that the immunology of pregnancy is more complex and that murine and human pregnancy have different cytokine profiles.

Human placenta as a source of neuroendocrine factors.

Progress in the understanding of the physiological and pathological functions of the placenta introduced the concept that the placenta is a neuroendocrine organ, since it shows local production and release of substances analog to neurohormones. These products act as endocrine, paracrine and autocrine factors to control the secretion of other regulatory molecules, including the pituitary hormones of both mother and fetus and their placental counterparts. Furthermore, they may play a role in the regulation of maternal and fetal physiology during pregnancy, ranging from the control of placental anchoring to fetal growth and maturation, fine regulation of uterine blood flow and/or initiation of labor. All this evidence underlines the decisive contribution of the placenta to all phases of gestation, through a range of substances largely exceeding the classically known sex steroids and chorionic gonadotropin, throughout normal pregnancy as well as in the presence of gestational diseases.

Early neonatal brain injury in histologic chorioamnionitis.

The relation between clinical or histologic chorioamnionitis and early neonatal adverse neurologic outcome was investigated (n = 483). Histologic, but not clinical, evidence of chorioamnionitis was found to be a significant predictor of periventricular echodensity (odds ratio, 2.4; 95% CI, 1.8-3.2), echolucency (3.3; 1.9-5.6), ventriculomegaly (2.7; 1.8-4.2), intraventricular hemorrhage > or =3 (3.5; 2.4-5.2), and seizures (2.3; 1.4-3.7).

Effects of estrogens and androgens on erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase activities during the menstrual cycle.

The effects of physiological changes in estrogens and androgens on the erythrocyte antioxidant superoxide dismutase, catalase and glutathione peroxidase enzyme activities during the menstrual cycle were investigated in healthy eumenorrheic women. Blood samples were taken on alternate days from twelve normally cyclic women (age range: 20 to 27 years; mean age: 24.1 years) from the first day of one menstrual cycle until the first day of the subsequent one. Plasma was analyzed for FSH, LH, estradiol, progesterone, testosterone, free testosterone and androstenedione concentrations. Erythrocyte superoxide dismutase, catalase and glutathione peroxidase activities were evaluated on the same days and cycle length was standardized on the basis of the preovulatory estradiol peak. Significant cyclic phase-related changes were observed in glutathione peroxidase (P<0.05), with higher glutathione peroxidase activity levels from the late follicular to the early luteal phase compared with those found in the early follicular phase (P<0.001 and P<0.002 respectively). A significant positive correlation was observed between mean estradiol and glutathione peroxidase cycle-related variations (r=0.80, P<0.001), whereas no significant cycle phase-dependent changes were seen in superoxide dismutase and catalase. No effect of progesterone and androgens on the erythrocyte antioxidant enzyme system was documented. The findings indicate that physiological ovarian estradiol production during the menstrual cycle may have an important role in regulating erythrocyte glutathione peroxidase activity.

Maternal and neonatal plasma cytokine levels in relation to mode of delivery.

After birth, host defences must be recruited to manage the transition from an almost sterile to a normal environment. The present study was undertaken to evaluate the relationship between cytokine plasma levels and phagocyte burst in mothers and neonates during the peripartal period. Plasma levels of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and whole blood superoxide anion (.O2-) generation were evaluated in 27 healthy mothers, 16 undergoing vaginal delivery (VD) and 11 elective caesarean section (ECS) and in their babies. Blood specimens were taken from the mothers at the beginning of labour, during labour, immediately after delivery and 4 days later in the VD group, and before anaesthesia, immediately after delivery and 4 days later in the ECS group; neonatal samples were taken at birth (cord blood) and 4 days later. After delivery by VD, these mothers had higher plasma levels of IL-1 beta, IL-6, IFN-gamma and higher .O2- generation than those delivered by ECS. IL-6 plasma levels and .O2- generation were higher in babies born by VD than in those born by ECS. A statistically significant correlation between IL-6 plasma levels and .O2- release was observed in cord blood of babies born by VD (r = 0.69; p < 0.006). The study demonstrates that labour plays an important role in modulating host defences in the newborn.

Superoxide anion release by polymorphonuclear leukocytes in whole blood of newborns and mothers during the peripartal period.

Superoxide anion (.O2-) production was investigated in whole blood of mothers in the peripartal period and in neonates. Blood samples from 14 mothers undergoing vaginal delivery (VD) were tested at the beginning of labor, during labor, after delivery, and 4 d after delivery. Nine mothers undergoing elective cesarean section (ECS) were tested before anesthesia, after extraction of the fetus, and 4 d later. Seventy-two healthy, full-term newborn infants were examined at birth and on the fourth day of life. Red cell glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase activities were also measured at birth and on the fourth day of life in 26 of the 72 neonates. Higher .O2- levels were detected in mothers undergoing VD compared with ECS (p < 0.05). A significant decrease was detected in zymosan-stimulated .O2- production between cord and fourth-day blood samples in both VD- and ECS-delivered infants (p < 0.01). Zymosan-stimulated samples showed higher values after VD than ECS, both in cord blood (p < 0.004) and on the fourth day of life (p < 0.006). A positive correlation was found between .O2- release in zymosan-stimulated cord blood and that found in the mothers at the beginning of labor (r = 0.654; p < 0.01), during labor (r = 0.721; p = 0.008), and after delivery (r = 0.832; p = 0.0008). A positive correlation was also found between .O2- release and glutathione peroxidase on the fourth day (r = 0.709, p = 0.014).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of epimestrol on gonadotropin and prolactin plasma levels and response to luteinizing hormone-releasing hormone/thyrotropin-releasing hormone in secondary amenorrhea and oligomenorrhea.

The effects of epimestrol (5 mg every 6 hours for 5 days) on basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (Prl), estradiol, progesterone, and dehydroepiandrosterone sulfate, and on the response to LH-releasing hormone (LH-RH) and thyrotropin-releasing hormone (TRH) stimulation, were studied in 18 cases of secondary amenorrhea and oligomenorrhea of hypothalamic-pituitary origin, in three cases of anorexia nervosa, in two cases of long-lasting progestin-induced amenorrhea, and in one case of precocious menopause. The results in the first 18 patients indicate that epimestrol treatment induces a significant increase in LH and Prl levels after 24 hours, while the FSH increase becomes significant only after 4 days of therapy. Twelve hours after discontinuation of treatment, all three hormone levels decreased significantly to values similar to the basal levels, while the pituitary response to LH-RH indicated a much more marked LH secretion than before treatment. A second test, performed 36 hours after the last drug administration, again showed a significantly higher LH response than that found under basal conditions. No significant variations were observed in the FSH response to LH-RH, nor in the Prl response to TRH. These data suggest that epimestrol interferes at the level of the centers responsible for Prl and gonadotropin secretion in the manner of a weak estrogen.