Inflammatory and infectious risk factors are associated with the response to tocolysis in patients with preterm labor.

OBJECTIVE: Inflammation/infection is the most frequent conditions leading to preterm delivery (PTD). A few studies have assessed the clinical efficacy of long-term tocolysis with ritodrine hydrochloride. In this study, the relationship among inflammatory/infective risk factors of PTD, the response to long-term tocolysis, and timing of delivery were evaluated in women with preterm labor. METHODS: On the basis of different responses to long-term tocolysis, defined as ≥ 7 days tocolysis, the cohort were classified as: (i) patients delivering at term (Group A) and (ii) patients delivering preterm (group B). Group B was subclassified as: (i) delivery before 48 h (group B1); (ii) delivery between 48 h and 7 days (Group B2), and (iii) delivery after 7 days (Group B3). Group B is divided in early preterm (<32 weeks) (Group B early) and late PTD (32-36 weeks) (Group B late). RESULTS: Group A delivered at term and Group B preterm. Group B showed significantly higher (p < 0.0001) rate of CRP, bacterial vaginosis, and chorioamnionitis at placental histological examination than Group A. The same parameters were statistically higher (p < 0.0001) in group B1 than in B3. CRP, chorioamnionitis at placental histological examination was statistically higher (p < 0.0001) in Group B early than in Group B late. CONCLUSIONS: This retrospective study suggested that in women affected by preterm labor, the long-term tocolysis with intravenous ritodrine is able to prolong gestation beyond 7 days, in absence of inflammatory/infective risk factors of PTD.

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.

Low-molecular-weight heparin improves the performance of uterine artery Doppler velocimetry to predict preeclampsia and small-for-gestational age infant in women with gestational hypertension.

This study investigated whether a short course of subcutaneous low-molecular-weight heparin (LMWH) might modify the performance of uterine artery Doppler to predict preeclampsia and small-for-gestational age (SGA) newborns in a high-risk population. A controlled, open-labeled study included 94 women with gestational hypertension and 30 healthy women enrolled at 24 to 26 weeks gestation. Doppler evaluation of uterine arteries resistance index (RI) was performed before and after a two-week course of LMWH (enoxaparin, 4000 IU/d, n = 56 hypertensive patients) or no treatment (n = 38 hypertensive women and 30 healthy controls). There was a significant decrease of uterine artery RI after LMWH (p < 0.001, paired Student's t-test), whereas the untreated hypertensive patients and the healthy control group showed no change between the two Doppler evaluations. The change induced by LMWH was restricted to women with normal outcome, whose RI decreased from (mean +/- standard error) 0.62 +/- 0.01 to 0.56 +/- 0.01 (p < 0.0001). By consequence, the second RI measurement, performed after LMWH administration, had fewer false positive results and higher positive likelihood ratios (LR+) to predict both preeclampsia (LR + 5.91) and SGA (LR + 4.69) compared with the first Doppler examination (LR + 1.97 and 2.22, respectively). Thus, LMWH improved the performance of uterine artery RI to predict preeclampsia and SGA in women with gestational hypertension.

Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and fetal membranes.

OBJECTIVE: Urocortin 2 (UCN2) and urocortin 3 (UCN 3) are recently identified neuropeptides showing homology to corticotropin-releasing factor (CRF). In the present study, we evaluated their expression and localization in gestational tissues (placenta, decidua, fetal membranes), and their effect on placental adrenocorticotropic hormone secretion. STUDY DESIGN: The study was performed in a tertiary clinical care center. Tissues were obtained at first (n = 8; 8-11 weeks of pregnancy) and third (n = 8; 38-40 gestational weeks) trimester. The mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR); the cellular localization by immunohistochemistry; ACTH levels were measured in media collected from cultured placental villi. RESULTS: All tissues analyzed expressed UCN2 and UCN3 mRNA. UCN2 and UCN3 were localized in cytotrophoblast and syncytiotrophoblast cells; UCN2 was present in maternal and fetal vessels and in amniotic cells, while UCN3 was absent. Finally, UCN2 and UCN3 did not stimulate ACTH secretion. CONCLUSION: Gestational tissues differentially express UCN2 and UCN3 and, despite their homology to CRF, they did not stimulate placental ACTH secretion.

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.

Comparison of two-dimensional and three-dimensional ultrasound in the assessment of the cervix to predict preterm delivery.

This study sought to determine whether 3-D transvaginal ultrasound (3D-TVS), compared with the 2-D transvaginal approach (2D-TVS), offers a better identification of some specific features of the uterine cervix that could be useful in the prediction of spontaneous preterm delivery (PTD). A total of 103 women with singleton pregnancies were prospectively evaluated with 2D-TVS and 3D-TVS in the second or third trimester of pregnancy. Statistical analysis was performed with Wilcoxon matched-pairs test, chi2 and Pearson test (p<0.05 was considered significant) and receiver operating characteristic (ROC) curve analysis. Significant differences between these approaches were found for cervical length (p<0.001). A significant correlation was identified between 3D-TVS cervical length and the interval between ultrasound examination and delivery as well as the gestational age at delivery (both p<0.001). ROC curve identified a threshold for 3D-TVS cervical length of 35 mm as an optimal predictor of PTD in the second trimester (sensitivity 100%, specificity 88%). 3D-TVS evaluation of the cervix in pregnancy seems to be an effective, noninvasive method for predicting PTD risk.