Differences in inflammatory markers between nulliparous women admitted to hospitals in preactive vs active labor.

OBJECTIVE: To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. STUDY DESIGN: Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1ß, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. RESULTS: Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P < .001 and P = .003, respectively). CONCLUSION: Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission.

Baseline TNFα operational capacity in fetal and maternal circulation prior to the onset of labor: "tuned for different purposes".

OBJECTIVE: In this study, we sought to characterize the tumor necrosis factor α (TNFα) baseline operational capacity in mature fetuses and their mothers prior to the onset of labor. MATERIALS AND METHODS: We used an experimental pregnant nonhuman primate model to measure the plasma concentration of TNFα, TNF transmembrane receptor I (TNFRI), and TNFRII with validated enzyme-linked immunosorbent assays. Coefficients of correlations between the maternal and the fetal values and the soluble TNFα, TNFRI, or TNFRII concentrations and ratios were calculated. RESULTS: The TNFα/TNFRI ratio was 3 times lower in fetal circulation than in maternal circulation. No correlations were noted between the maternal and the fetal TNFα, TNFRI, or TNFRII plasma concentrations. CONCLUSIONS: These findings suggest that the fetal and maternal baseline circulatory operational capacities of TNFα are independent of each other and tuned differently. This differential regulation of TNFα in fetal and maternal circulation at the end of pregnancy may be guided to protect the fetus from the systemic inflammatory response that is essential for the mechanisms of labor to proceed in the mother.

IL-6 and TNFalpha across the umbilical circulation in term pregnancies: relationship with labour events.

OBJECTIVE: We have determined venous and arterial cord blood levels for IL-6 and TNFalpha at the time of delivery to assess gestational tissue versus fetal sources in labouring and non-labouring patients at term, and the relationship to labour events. METHODS: Fifty-five patients were studied (elective cesarean section n=24, and labouring n=31) with blood sampling from a clamped segment of cord after delivery of the fetus and from the cord at its insertion into the placenta after delivery of the placenta, with subsequent measurement of blood gases, pH, IL-6 and TNFalpha. RESULTS: Umbilical cord levels for IL-6 were increased by 4 fold in low risk labouring patients, and a further 6 fold when showing histologic chorioamnionitis, but with no evident effect of nuchal cord with 'variable' fetal heart rate decelerations, fetal acidemia, nor of labour duration. IL-6 levels from the cord at its insertion into the placenta were generally higher than those from the respective umbilical levels indicating that placental release of IL-6 into cord blood must be occurring. However, a consistent venoarterial difference for IL-6 and thereby a net flux from the placenta could not be demonstrated. TNFalpha levels for both patient groups were uniformly low for all of the cord measurements with no significant differences noted. CONCLUSION: Umbilical cord levels for IL-6 are increased in low risk labouring patients at term in the absence of evident infection which likely involves both gestational tissue and fetal contributions. Cord levels for IL-6 are further increased in low risk labouring patients showing histologic chorioamnionitis which might then contribute to newborn morbidity in these pregnancies.

Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor.

CONTEXT: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear. OBJECTIVES: Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P. DESIGN AND SETTING: A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital. PATIENTS: Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained. MAIN OUTCOME MEASURES: CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed. RESULTS: CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07). CONCLUSIONS: The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.

Follistatin serum concentrations during full-term labour in women--significant differences between spontaneous and induced labour.

Follistatin has been isolated from human placenta and has been identified in human foetal membranes and fluids. Serum follistatin levels in women rise during pregnancy particularly near term. In this study, we examined the effect of induction and stage of labour on maternal plasma concentrations of follistatin. Women who gave birth after a normal pregnancy were retrospectively divided into three groups: those who went in labour spontaneously (n = 33), needed induction by amniotomy and IV oxytocin (n = 18) or underwent planned caesarean section (n = 10). Serum was collected at 38-40 weeks of gestation, periodically through labour with a vaginal examination and once within 36 h postpartum and assayed for oestradiol, progesterone, prolactin and C-reactive protein. Follistatin was measured using a rabbit antiserum (#204) raised against purified 35 kDa bovine follistatin. Human recombinant follistatin was used as both standard and tracer. Concentrations of follistatin at 38-40 weeks of gestation were significantly different between groups. Those who had a spontaneous labour had concentrations higher than those who were induced. Similarly, those who were induced had concentrations higher than those who underwent a caesarean. In the spontaneous group, follistatin rose during labour, peaking at 57.9 +/- 5.48 ng/ml at > 3 cm of cervical dilation, and after delivery follistatin decreased to 26.16 +/- 3.4 ng/ml at 24 h post-delivery. In induced patients follistatin continued increasing to peak following delivery at 26.9 +/- 3.0 ng/ml and decreased at > 3 h post-delivery. Follistatin concentrations in caesarean section patients at 24 h post-surgery (18.53 +/- 3.74 ng/ml) were not different from that before the surgery and were comparable with the other two groups. Follistatin is clearly implicated in the onset of labour; however, further studies with a larger cohort of women are necessary to determine the nature of its role.

3alpha-reduced neuroactive steroids and their precursors during pregnancy and the postpartum period.

Allopregnanolone (ALLO) and pregnanolone (PREG), the 3alpha-reduced metabolites of progesterone (PROG), are potent modulators of gamma-aminobutyric acid type A receptors that may function as endogenous anxiolytics. They are purported to be involved in the etiology or expression of clinical depression. In the present study we quantified ALLO and PREG, as well as PROG, 5alpha-dihydroprogesterone (5alpha-DHP), 5beta-dihydroprogesterone (5beta-DHP), epiallopregnanolone and pregnenolone (PREGNEN), in plasma from healthy women at five time points during pregnancy and the postpartum period. Analysis was by gas chromatography/electron capture - negative chemical ionization - mass spectrometry. Neuroactive steroids increased significantly from 10 to 36 weeks of pregnancy, except for 5beta-DHP and PREGNEN which did not change significantly. PROG was the most abundant steroid throughout pregnancy, followed by 5alpha-DHP and ALLO. Metabolite to precursor ratios differed depending on the enzyme and substrate: the turnover of PROG to 5alpha-DHP (catalyzed by 5alpha-reductase) was stable while the conversion of PROG to 5beta-DHP (catalyzed by 5beta-reductase) decreased later in pregnancy. 3alpha-Hydroxysteroid oxidoreductase-mediated turnover of 5alpha- and 5beta-DHP to their metabolites ALLO and PREG, respectively, rose during pregnancy, but the turnover of 5alpha-DHP to ALLO dropped at the late prenatal visit. At 6 weeks postpartum all steroids were significantly reduced compared with late prenatal values, with 5alpha-DHP being the most abundant postpartum steroid. These results provide the basis for further study of neuroactive steroids in psychiatric conditions of pregnancy and the postpartum period.

[The change in placental estradiol-progesterone ratio and its relationship with the fetal membrane's response to IL-1 beta in labor].

This study was designed to investigate the local changes in the levels of placental estradiol and progesterone and their ratio during term labor and to determine whether the PGE2-generating ability of the fetal membrane in response to IL-1 beta at term labor is greater than that at term not-in-labor. Forty pregnant women were divided into two groups: term labor and term not-in-labor. Placental estradiol and progesterone were measured by radioimmunoassay. The levels of fetal membrane PGE2 were measured by enzymoimmunoassay. The results showed that the placental concentration of estradiol and progesterone remained unchanged at the onset of labor, but the ratio of estradiol to progesterone increased significantly (P < 0.05). IL-1 beta stimulated fetal membrane to produce more PGE2 at term labor, and at term not-in-labor, too. But the increment of PGE2 generated by fetal membrane at term labor was greater than that at term not-in-labor. It is concluded that the change in placental estradiol to progesterone ratio may play an important role in the initiation of labor by altering the PGE2-generating ability of fetal membrane in response to cytokines.

Tumor necrosis factor during pregnancy and at the onset of labor and spontaneous abortion.

OBJECTIVE: The aim of this study was to evaluate the production of tumor necrosis factor (TNF) by peripheral blood cells during pregnancy, at the onset of labor and of spontaneous abortion (SA), as well as in non-pregnant women with and without a history of recurrent spontaneous abortions (RSA). STUDY DESIGN: The peripheral blood cells TNF production was evaluated in 28 women in the 1st trimester of pregnancy, 21 in the 2nd, and 30 in the 3rd, 47 at term labor; 43, at the onset of SA; 19 healthy and 19 RSA non-pregnant women. The statistical method used was the Mann-Whitney test. RESULTS: We observed (1) lack of TNF detection in the 1st gestational trimester; (2) increase of TNF production with gestational age, with the highest values being observed at labor (P<0.05); (3) high TNF production at the onset of SA; (4) no difference in the TNF production by healthy and RSA non-pregnant women. CONCLUSIONS: The suppression of TNF production during the 1st trimester of pregnancy seems to favor the normal development of pregnancy. It remains to be investigated whether the assessment of TNF production is a valuable prognostic parameter for the occurrence of abortion.

[Blood gas and acid-base equilibrium in normal pregnancy and pregnancy with fetal distress by vaginal delivery or cesarean section].

Blood gas and acid-base assessment of maternal dorsalis pedis artery and umbilical artery and vein was carried out immediately after delivery in 46 cases of normal term pregnancy and 41 cases of pregnancy with fetal distress (FD). Blood gas and acid-base equilibrium differences between vaginal delivery and cesarean section were studied. The results showed a low BE value (< -3mmol/L) in maternal artery of both groups, and that the other parameters were all within normal range, not being different between the normal pregnancy and FD group. Blood gas assaying of umbilical veins of the 2 groups also showed no difference. In comparison with the normal pregnant group, the FD group yielded significantly decreased values of pH, PO2 and O2Sat in umbilical artery but significantly increased PCO2 (P < 0.05). Women of both groups delivered vaginally had milder metabolic acidosis and slighter hypoxia than those delivered by cesarean section. Marked fetal acidosis and low Apgar score were more commonly seen in the FD group. These indicated that to delay labor to near term and to perform cesarean section for relieving fetal distress is advisable.

[Ripening effect of mylis and tiluoan on the uterine cervix in pregnant rats].

Effect of Mylis and Tiluoan on cervical ripening and blood levels of estradiol and progesterone of pregnant rats were studied. Dehydroepiandrosterone (DHA) is the main component in both of the drugs. Pregnant rats groups were given the drugs on the 19th day of gestation at dosage of 10, 20 and 40 mg/kg respectively. The results indicated that both drugs at different dose were able to significantly decrease the cervical extensibility, to dilate the cervical OS, increase the cervical wet weight, and elevate the blood estradiol level, lower the progesterone concentration. It indicated that DHA enhances estradiol synthesis and suppresses progesterone secretion.