Prediction of preterm delivery based on maternal plasma urocortin.

CONTEXT: Preterm birth still remains a significant management problem, and a large number of markers of the disease have been investigated. OBJECTIVE: We measured plasma levels of urocortin, a neuropeptide expressed by gestational tissues, in women with threatened preterm labor (TPTL) to evaluate whether the measurement may predict preterm delivery (PTD). DESIGN: We studied patients as part of an open observational study. SETTING: The study was conducted at a tertiary referral center for obstetric care. PATIENTS: Eighty-five women with singleton pregnancies between 28 and 34 completed gestational weeks with TPTL participated in the study. INTERVENTIONS: Interventions included clinical examination and urocortin measurement. MAIN OUTCOME MEASURES: Pregnancy outcome and evaluation of sensitivity, specificity, and predictive values of urocortin as diagnostic test for PTD were measured. RESULTS: Thirty of 85 patients (35.3%) had PTD: 23 of 30 delivered within 7 d from admission (delivery time interval: 2.91 +/- 1.62 d; gestational weeks at delivery: 32.12 +/- 1.7); the remaining delivered later (delivery time interval: 11.71 +/- 4.27 d; gestational weeks at delivery: 33.5 +/- 2.18). Urocortin was significantly higher in women who delivered preterm (median 131.2 pg/ml, interquartile interval 115.1-139.4 pg/ml) than in those who progressed to term delivery [95.4 (69.9-101.3) pg/ml, P < 0.0001] and still higher in those delivering within 7 d from admission [137.7 (124.8-141.2) pg/ml]. Receiver operating characteristic curve analysis revealed that urocortin at the cutoff of 113.9 pg/ml had sensitivity of 80%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 90% as a marker for PTD. CONCLUSIONS: Maternal plasma urocortin concentration is increased in patients with TPTL who have PTD, and its measurement may be a promising new biochemical marker of PTD.

Maternal plasma corticotrophin-releasing factor and urocortin levels in post-term pregnancies.

OBJECTIVE: Corticotrophin-releasing factor (CRF) and urocortin are two placental neuropeptides that are involved in the mechanisms of labour by modulating myometrial activity. Maternal plasma levels of both CRF and urocortin are increased at term and preterm labour, whilst those of CRF are reduced in women who are destined to experience post-term delivery. The present study evaluated maternal plasma levels in term and post-term pregnancies out of labour. DESIGN: A group of healthy pregnant women was enrolled and subdivided as follows: (i) at term out of labour (n = 19; 276 +/- 0.7 days of gestation; samples collected at the time of elective caesarean section due to previous uterine surgery); (ii) post-term (n = 19; 291 +/- 1.4 days of gestation), from whom samples were collected before induction of labour. METHODS: Urocortin and CRF measurements by radioimmunoassay; digital palpatory cervical examination and Bishop score computation; cervical length and funnelling presence assessment by transvaginal ultrasonography. RESULTS: Maternal plasma CRF concentrations were significantly (P < 0.05) lower whilst those of urocortin were unchanged in post-term compared with term pregnancy. However, CRF and urocortin levels were both significantly (P < 0.05 and P < 0.001 respectively) higher in pregnancies delivered within 12 h of labour induction than in those that remained undelivered, and were significantly correlated with the induction-delivery interval (CRF: r = -0.676, P = 0.0015; urocortin: r = -0.783, P < 0.0001). CONCLUSIONS: CRF and urocortin levels are decreased and unchanged, respectively, in post-term pregnancy when compared with term pregnancy. Both CRF and urocortin correlate with the time of labour onset after induction. Since CRF derives from the placenta, and urocortin from the fetus, the concerted expression of these neuropeptides appears to be relevant in determining the length of human gestation.

Reduced maternal plasma urocortin concentrations and impaired uterine artery blood flow at human mid pregnancy.

OBJECTIVE: Urocortin is a placental neuropeptide belonging to the family of corticotropin-releasing factors (CRFs), playing a role in the uteroplacental blood flow regulation through the binding to specific CRF receptors. Since CRF receptors are expressed in the uterine vascular bed of pregnant rats, and because urocortin has a relaxant effect on uterine vasculature, we evaluated mid-gestation plasma urocortin levels in women with impaired blood flow through uterine arteries. METHODS: Maternal plasma urocortin was assayed by specific radioimmunoassay and uterine artery resistance index (RI) by Doppler evaluation at 22-24 weeks' gestation in 57 healthy pregnant women, of which 29 showed a monolateral or bilateral uterine artery notch. Statistical analysis was performed by one-way analysis of variance (ANOVA), followed by post-hoc Tukey test for multiple comparison and Pearson correlation coefficient test. RESULTS: The mean uterine artery RI was significantly (P <.001) higher in women with a notch than healthy controls. Mean +/- SEM maternal plasma urocortin levels were significantly (P <.001) lower in women with unilateral (52.03 +/- 3.25 pg/mL) or bilateral (47.01 +/- 4.16 pg/mL) uterine artery notch than in healthy control pregnant women (84.01 +/- 3.5 pg/mL). While no difference was found in urocortin levels between patients with unilateral or bilateral uterine artery notch, urocortin concentrations inversely correlated with the mean RI (Pearson r = -0.7318; 95% confidence interval -0.8334 to -0.5822; P <.0001). CONCLUSIONS: The present findings suggest that reduced levels of circulating urocortin are associated with increased uterine artery resistances and support the hypothesis that urocortin may regulate uterine artery tone at mid gestation.

Maternal position during non-stress test and fetal heart rate patterns.

OBJECTIVE: The aim of the study was to determinate whether maternal position during the non-stress test (NST) in different weeks of pregnancy influences fetal heart rate patterns. MATERIALS AND METHODS: A total of 1055 NST lasting 30 min were performed in 368 autochthonous mothers with low-risk pregnancies. On the basis of maternal position during the test we divided into three groups: reclining, sitting, and walking. The cardiotocographic parameters considered were: number of minutes of reactive NST with minimum length, number of fetal movements, fetal heart rate baseline, number of large accelerations, number of dubious NST, and number of variable decelerations. RESULTS: Fetal heart rate patterns in low-risk pregnancies were studied using NST in different gestational ages and in different maternal positions. Differences in heart rate were found in relationship to both gestational age and maternal position. The minimum length of NST necessary to record at least three large accelerations was significantly different in relationship to both gestational age and maternal position. The number of fetal movements perceived by the mother was greater in the reclining position than in sitting or walking. Together with the progression of pregnancy, the number of dubious NST decreased in all subgroups, especially in the sitting position. The greatest number of variable decelerations was observed in the reclining position and it was increased with pregnancy progression. The NST duration did not vary greatly in the reclining position, but in the sitting position or during walking, the time taken to record the three large accelerations required to define the trace as reactive, decreased significantly with the progression of pregnancy CONCLUSIONS: Non-stress test in sitting position or during walking should be encouraged because fetal reactivity is more quickly observed.

Listeriosis in pregnancy: a case report.

Listeria monocytogenes is an alimentary infection which can be extremely dangerous for pregnant women. A 34-year-old pregnant woman was hospitalized with fetal cardiac rate alterations and influenza-like symptoms. A caesarean section due to fetal distress was performed. A maternal-fetal listeriosis diagnosis was possible only after the birth through bacteriological and histological examination on both the placenta and the newborn.

Endometrial expression and secretion of activin A, but not follistatin, increase in the secretory phase of the menstrual cycle.

OBJECTIVE: Activin A is a growth factor expressed by human endometrium, and its biologic effects are counteracted by follistatin. We evaluate whether activin A and follistatin mRNA and peptide expression as well as protein secretion from human endometrium change throughout the menstrual cycle. METHODS: In 25 healthy fertile patients, uterine washing fluid was retrieved by hydrosonography. In a subgroup (n = 13), endometrial tissue samples were collected by hysteroscopy during the proliferative (n = 6) or secretory (n = 7) phase of the menstrual cycle. Activin and follistatin mRNA and peptide expression were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and by immunohistochemistry (IHC), respectively. Activin A and follistatin levels were assayed in uterine washing fluids by specific enzyme-linked immunosorbent assays and evaluated according to the endometrial thickness and menstrual cycle days. RESULTS: Both activin A and follistatin mRNAs were expressed by human endometrium, and their peptides immunolocalized both in proliferative and secretory endometrial epithelial and stromal cells. A significant increase in immunoreactive activin betaA but not in follistatin was observed in glandular epithelium during the secretory phase. Activin A but not follistatin was significantly (P <.0001) higher in the washing fluids collected during the secretory than proliferative phase of the menstrual cycle. In addition, a significant correlation was found between activin A, but not follistatin, and menstrual cycle days (P <.0001) or endometrial thickness (P <.0001). CONCLUSIONS: Both activin A and follistatin mRNAs are expressed by human endometrium; however, activin A but not follistatin peptide expression and secretion were increased in the secretory phase of the menstrual cycle, suggesting an important role in human endometrium.

Placental stress factors and maternal-fetal adaptive response: the corticotropin-releasing factor family.

The placenta and its accessory membranes amnion and chorion undertake the role of intermediary barriers and active messengers in the maternal-fetal dialog. They synthesize, metabolize, and serve as target to numerous hormones that regulate maternal and fetal physiology during pregnancy. Among these factors, corticotropin-releasing factor (CRF) has been one of the more investigated in the last decade. Increasing evidence indicates that in the event of acute or chronic metabolic, physical, or infectious stress, maternal or fetal physiologic and pathologic conditions may influence placental secretion of CRF. The current opinion is that the placenta actually takes part in a stress syndrome by releasing CRF, which may help to influence uterine perfusion, maternal metabolism, fluid balance, and possibly uterine contractility, thereby protecting the fetus from a hostile environment.

Identification of activin A and follistatin in human milk.

Activin A is a dimeric protein member of the transforming growth factor-beta (TGF-beta) family: it is synthesized by a variety of organs and follistatin is an activin-binding protein. A sensitive and specific assays for bioactive dimeric activin A and follistatin have recently allowed to measure these proteins in blood and other biological fluids, giving a new insights into their possible physiological role. Since human breast is able to produce activin A, the aim of the present study was to evaluate whether it and follistatin are measurable in breast milk of women during lactation. Concentrations of activin A and follistatin were measured in milk samples collected at 3, 5 and 30 days after delivery by using specific and sensitive two-site ELISAs. For the first time the presence of immunoreactive activin A and follistatin in human milk has been shown; no significant different concentration between the third and the fifth day after delivery was found. Furthermore, no difference of activin A and follistatin concentration between the whole and the skim milk or between spontaneous delivery and cesarean section was found. Milk activin A and follistatin concentrations after 1 month of lactation were significantly decreased (P < 0.01). Activin A and follistatin are present in human milk in high concentrations in the first week of lactation, while decrease after a month suggesting a possible role as growth factors in human milk.