Placental and maternal serum activin A in spontaneous and induced labor in late-term pregnancy.

PURPOSE: Feto-placental unit represents an important source of activin A, a member of transforming growth factors-ß involved in the mechanisms of labor. No evidences are available on activin A in pregnancies beyond 41 weeks of gestation, where induction of labor is often required. The present study aimed to evaluate activin A maternal serum levels and placental mRNA expression in term and late-term pregnancy, with spontaneous or induced labor, and its possible role to predict the response to labor induction. METHODS: Maternal serum samples and placental specimens were collected from women with singleton pregnancy admitted for either term spontaneous labor (n = 23) or induction of labor for late-term pregnancy (n = 41), to evaluate activin A serum levels and placental mRNA expression. Univariate and multivariate analyses on activin A serum levels, maternal clinical parameters, and cervical length were conducted in women undergoing induction of labor. RESULTS: Maternal serum activin A levels and placental activin A mRNA expression in late-term pregnancies were significantly higher than at term. Late-term pregnancies who did not respond to induction of labor showed significantly lower levels of activin A compared to responders. The combination of serum activin A and cervical length achieved a sensitivity of 100% and a specificity of 93.55% for the prediction of successful induction. CONCLUSION: Late-term pregnancy is characterized by hyperexpression of placental activin A and increased maternal activin A secretion. By combining maternal serum activin A levels with cervical length, a good predictive model for the response to induction of labor was elaborated.

Thickness of fetal membranes: a possible ultrasound marker for preterm delivery.

OBJECTIVE: To evaluate whether measurement of the thickness of the fetal membranes by high-resolution ultrasound is a useful marker to predict preterm delivery. METHODS: One hundred and fifty-eight women with singleton pregnancies at 18-35 gestational weeks were enrolled consecutively at our referral center for obstetric care and the thickness of their fetal membranes was measured using high-resolution ultrasound equipment. Data were analyzed to determine whether there were significant differences between those delivering at term and those delivering preterm. Receiver-operating characteristics (ROC) curves were used to determine the best cut-off point of membrane thickness for predicting preterm birth. RESULTS: Women who delivered preterm had greater fetal membrane thickness than did those who delivered at term (1.67 +/- 0.27 mm vs. 1.14 +/- 0.30 mm, P < 0.0001). For the best cut-off indicated by ROC curve analysis (1.2 mm), the sensitivity and specificity for predicting preterm birth were 100% (95% CI, 80.3-100) and 69.5% (95% CI, 61.2-77.0), respectively, and positive and negative likelihood ratios were 3.3 and 0.0, respectively. CONCLUSION: Sonographic measurement of fetal membrane thickness could be helpful in the prediction of preterm delivery.

An informative probability model enhancing real time echobiometry to improve fetal weight estimation accuracy.

A multinormal probability model is proposed to correct human errors in fetal echobiometry and improve the estimation of fetal weight (EFW). Model parameters were designed to depend on major pregnancy data and were estimated through feed-forward artificial neural networks (ANNs). Data from 4075 women in labour were used for training and testing ANNs. The model was implemented numerically to provide EFW together with probabilities of congruence among measured echobiometric parameters. It enabled ultrasound measurement errors to be real-time checked and corrected interactively. The software was useful for training medical staff and standardizing measurement procedures. It provided multiple statistical data on fetal morphometry and aid for clinical decisions. A clinical protocol for testing the system ability to detect measurement errors was conducted with 61 women in the last week of pregnancy. It led to decisive improvements in EFW accuracy.

Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation.

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.

Virtual fetal touch through a haptic interface decreases maternal anxiety and salivary cortisol.

OBJECTIVE: To evaluate whether a virtual reality workstation (Fetouch system) offering three-dimensional (3D) fetal visual and kinesthetic interaction may affect maternal stress. METHODS: Maternal-fetal visual and kinesthetic interaction was obtained through a haptic interface based on 3D reconstruction of sequencial bi-dimensional ultrasound images of the fetus. Maternal stress was assessed before and after visual/kinesthetic interaction with the fetus: 1) by using the State Trait Anxiety Inventory-Form Y (STAI) test, and 2) by measuring salivary cortisol levels. Statistical analysis was performed by paired t test and analysis of variance for repeated measures. RESULTS: After the fetal visual and kinesthetic experiences, a significant reduction was observed in anxiety (low state anxiety group, P < .0034; high state anxiety group, P < .0108), as well as in salivary cortisol concentration (P < .0004). CONCLUSION: Physical interaction with the fetus through a 3D model may reduce maternal stress.

Anterior placental location influences onset and progress of labor and postpartum outcome.

INTRODUCTION: The aim of the study is to evaluate whether placental location at term is associated with delivery outcome. METHODS: A prospective study including 2354 patients with singleton pregnancy at term admitted for vaginal delivery was conducted. Placental position was determined before delivery by ultrasonographic examination performed transabdominally with women in the supine position. Maternal characteristics and delivery outcome such as premature rupture of membranes, induction of labor, mode and gestational age at delivery, indication for cesarean section, duration of the third stage, postpartum hemorrhage (PPH) and manual removal of placenta were correlated with anterior, posterior or fundal placental locations. RESULTS: Among women enrolled: i) 1164 had an anterior placenta, ii) 1087 a posterior placenta, iii) 103 a fundal placenta. Women with anterior placenta showed: i) a higher incidence of induction of labor (p = 0.0001), especially for postdate pregnancies and prolonged prelabor rupture of membranes (p < 0.0001), ii) a higher rate of cesarean section rate for failure to progress in labor (p = 0.02), iii) a prolonged third stage (p = 0.01), iv) a higher incidence of manual removal of placenta (p = 0.003) and a higher rate of PPH in vaginal deliveries (p = 0.02). DISCUSSION: The present study showed the influence of anterior placental location on the course of labor, with a later onset of labor, a higher rate of induction and cesarean section and postpartum complications. The reason for this influence on labor and delivery complications remains to be elucidated.

Inhibins and activins in pregnancy.

Human placenta, decidua, and fetal membranes are the major sites of production and secretion of inhibin A and activin A in maternal serum, amniotic fluid, and umbilical cord blood. These tissues also express follistatin-related gene and betaglycan, the binding proteins of activin A and inhibin A, respectively, recently identified. They show a different expression throughout pregnancy, suggesting new functional roles into gestational tissues. The availability of suitable assays for measuring inhibin A and activin A lead us the possibility to investigate their secretion in healthy pregnancy. In addition, several evidences underline the potential role and the clinical usefulness of their measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as: threatened abortion, placental tumors, hypertensive disorders of pregnancy, intrauterine growth restriction, fetal hypoxia. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future further possibilities in early diagnosis, prediction, and monitoring pregnancy diseases.

Changes in inhibins and activin secretion in healthy and pathological pregnancies.

Inhibin-related proteins are involved in the control of the feto-maternal communication required to maintain pregnancy. Human placenta, decidua, and fetal membranes are the major sites of production and secretion of activin A, inhibin A and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability of suitable assays developed in the last years has enabled the measurement of inhibins and activin A in their dimeric forms, in order to investigate their role in physiological conditions of pregnancy. The studies conducted on inhibin-related proteins and human pregnancy suggested the possibility of an involvement of inhibin A and activin A in the pathogenesis of gestational diseases. In fact, several lines of evidence underline the potential role and the clinical usefulness of inhibin-related proteins measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as early pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy-induced hypertension, preterm delivery and intrauterine growth restriction. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future, further possibilities in the early diagnosis, prediction, and monitoring diseases of pregnancy.

Maternal serum inhibin A levels are a marker of a viable trophoblast in incomplete and complete miscarriage.

OBJECTIVE: From early gestation the human trophoblast secretes large amounts of inhibin A and activin A, and their measurement provides a value for predicting the outcome in women who become pregnant after assisted reproductive techniques. The aim of the study was to investigate the putative role of maternal serum inhibin A and activin A levels as markers of a viable trophoblast in women who miscarry. DESIGN: Controlled cross-sectional study. METHODS: One group consisted of 65 healthy pregnant women (controls), progressing to deliver a healthy singleton baby and another group consisted of 54 miscarriages (38 incomplete (27 non-viable, 11 anembryonic pregnancies) and 16 complete). Maternal blood samples were collected between 5 and 12 weeks of gestation. RESULTS: Serum human chorionic gonadotrophin concentrations in women with incomplete or complete miscarriages were significantly (both P<0.001) lower than in controls; activin A levels being lowest only in women with a complete miscarriage (P<0.001). On the other hand, inhibin A levels were significantly lower in incomplete or complete miscarriage than in controls (both P<0.0001). CONCLUSIONS: Maternal serum inhibin A, but not activin A, determination reflects the lack of a viable trophoblast in complete miscarriage.

Ultrasound evaluation of the distal femoral epiphyseal ossification center as a screening test for intrauterine growth retardation.

In a heterogeneous group of 226 pregnant women, a retrospective study was done of the relation between the distal femoral epiphyseal ossification center detected by ultrasound and the birth weights of the infants. The ossification center of the femur was detectable in 202 of the 208 infants appropriate for gestational age; it was undetectable in 15 of the 18 infants small for gestational age. Because our results compared favorably with those reached by more complicated methods in the literature, we propose that the distal femoral epiphyseal ossification center be used as a screening test for intrauterine growth retardation.

Low estrogen oral contraceptives and the hypothalamo-pituitary axis.

The hypothalamo-pituitary axis in a group of 10 women (17-25 years of age) taking low-dose-estrogen oral contraceptives (20 micrograms ethinylestradiol (EE) + 150 micrograms desogestrel) for at least 6 months was investigated. The subjects underwent the GnRH (50 micrograms) and TRH (200 micrograms) stimulation tests for the evaluation of LH, FSH, Pr1, TSH and GH secretion. In the basal blood sample, E2, P, free T, A and SHBG levels were also determined. An elevation in LH response to GnRH was found, whereas FSH was inhibited. After TRH administration, the Pr1 response was the same in the oral contraceptive cycle as in the pretreatment cycle. Similar results were observed after TSH. Significantly, GH responded to TRH stimulation in the oral contraceptive cycles, but not in the pretreatment cycles. These results show that the new combination of 20 micrograms EE and desogestrel blocks hypothalamic production of GnRH. The different response to GnRH of LH and FSH reveals a differentiated sensitivity to the oral contraceptive which seems to inhibit the pituitary FSH-secreting gonadotrope cells in particular.

Prenatal ultrasonographic diagnosis of diastrophic dysplasia at 13 weeks of gestation.

Diastrophic dwarfism is a skeletal dysplasia that can be identified by ultrasound usually during the second trimester of pregnancy. This severe but non-lethal disorder of the cartilage can be diagnosed earlier using transvaginal sonography (TVS). We present a case of diastrophic dysplasia diagnosed at 13 weeks of gestation by TVS. The early TVS evaluation of the fetal biometric parameters and the accurate study of the morphological features of the fetal long bones and extremities allowed an early diagnosis of this rare pathology that leads to a progressive physical handicap, due mainly to severe kyphoscoliosis and arthropathies. Recently, the routine use of TVS at 11-14 weeks of gestation has permitted an earlier diagnosis to be reached of a great number of congenital anomalies. Patients at risk for skeletal dysplasia could benefit from the enhancements of ultrasound techniques. An early diagnosis of diastrophic dysplasia can be reached at the and of the first trimester of pregnancy, using TVS.

Voluminous perinatal pelvic mass: a case of congenital hydrometrocolpos.

Imperforate hymen is the most frequent congenital malformation of the female genital tract; it usually does not show symptoms until puberty. Only rarely, imperforate hymen manifests itself as an abdominal mass detectable in the prenatal period. We describe a rare case of voluminous hydrometrocolpos, antenatally diagnosed and successfully treated immediately after birth.

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.

Postdate pregnancy: changes of placental/membranes 11ß-hydroxysteroid dehydrogenase mRNA and activity.

11ß-Hydroxysteroid dehydrogenase 1 and 2 (11ß-HSD1 and 11ß-HSD2) are involved in the complex mechanism of human parturition. The present study examined mRNA expression and activity of membrane 11ß-HSD1 and placental 11ß-HSD2 in postdate pregnancies according to response of labor induction. In comparison to postdate women who had spontaneous delivery or after induction the non-responders showed significantly low c and high 11ß-HSD2 expression and activity These data suggest that disrupted expression and activity of 11ß-HSDs may occur in some postdate pregnancies.

Effects of urocortin 2 and urocortin 3 on IL-10 and TNF-α expression and secretion from human trophoblast explants.

OBJECTIVES: The aim of the present study was to evaluate the effect of Ucn2 and Ucn3 on cytokine expression and secretion from placental explants. STUDY DESIGN: Placentas were collected from healthy pregnancies at term elective caesarean delivery and trophoblast explants were prepared and treated with Ucn2 or Ucn3 in presence/absence of the selective CRH-R2 antagonist, astressin 2b. The mRNA expression and secretion of IL-10 and TNF-α were evaluated by Real Time RT-PCR and ELISA, respectively. MAIN OUTCOME MEASURES: To evaluate the possible role of Ucn2 and Ucn3 in inflammatory pathways. RESULTS: Ucn2 increased the mRNA expression and secretion of IL-10 and TNF-α, and Ucn3 increased the mRNA expression and secretion of IL-10, but did not modify the secretion of TNF-α. Ucn3 treatment reversed the LPS-induce increase of TNF-α expression and release, an effect blocked by astressin 2b. Ucn2 potentiated the LPS-induced increase of TNF-α expression and release, an effect reversed by astressin 2b. CONCLUSIONS: The present study showed that Ucn2 and Ucn3 differentially regulate the LPS-induced TNF-α and IL-10 expression and secretion in trophoblast explants acting through CRH-R2. A pro inflammatory effect of Ucn2 and an anti-inflammatory effect of Ucn3 in placental immunomodulatory mechanisms is suggested.

Effects of raloxifene therapy on plasma renin and aldosterone levels and blood pressure in postmenopausal women.

OBJECTIVE: Blood pressure, which generally increases after menopause, is one of the best tools to characterize cardiovascular disease. The renin-aldosterone system plays a role in determining cardiovascular risk and the role of estrogen in the regulation of angiotensinogen gene expression and serum levels is well known. Raloxifene can induce endothelium-dependent vasodilation without affecting endothelium-independent vasorelaxation. The aim of the study was to investigate the effects of raloxifene on the renin-aldosterone system and blood pressure in postmenopausal women. DESIGNS: Forty women, 54-59 years of age, in physiological menopause for 6 months to 4 years, were enrolled in the study and treated with raloxifene 60 mg/day for 6 months. All had blood pressure less than 130/85 mm Hg at the start of the study. The women were divided into two groups: the first (group A; 20 women) with normal blood pressure and the second (group B; 20 women) with previous high blood pressure treated with antihypertensive drugs, not angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. RESULTS: No significant changes in plasma renin activity (PRA) or plasma concentrations of aldosterone were observed between the two groups after 6 months of raloxifene use. There was a slight reduction in PRA (11+/-4% for group A and 13+/-5% for group B) and in plasma levels of aldosterone (3.6+/-0.5% and 4.6+/-0.5%, respectively) with respect to basal values, but neither change was statistically significant. CONCLUSIONS: The results of the present study show that raloxifene at 60 mg/day dose is well tolerated and has no clinical impact on blood pressure, PRA or aldosterone in postmenopausal women.