In-vivo stretch of term human fetal membranes.

INTRODUCTION: Fetal membranes (FM) usually fail prior to delivery during term labor, but occasionally fail at preterm gestation, precipitating preterm birth. To understand the FM biomechanical properties underlying these events, study of the baseline in-vivo stretch experienced by the FM is required. This study's objective was to utilize high resolution MRI imaging to determine in-vivo FM stretch. METHODS: Eight pregnant women (38.4 ± 0.4wks) underwent abdominal-pelvic MRI prior to (2.88 ± 0.83d) caesarean delivery. Software was utilized to determine the total FM in-vivo surface area (SA) and that of its components: placental disc and reflected FM. At delivery, the SA of the disc and FM in the relaxed state were measured. In-vivo (stretched) to delivered SA ratios were calculated. FM fragments were then biaxially stretched to determine the force required to re-stretch the FM back to in-vivo SA. RESULTS: Total FM SA, in-vivo vs delivered, was 2135.51 ± 108.47 cm(2) vs 842.59 ± 35.86 cm(2); reflected FM was 1778.42 ± 107.39 cm(2) vs 545.41 ± 22.90 cm(2), and disc was 357.10 ± 28.08 cm(2) vs 297.18 ± 22.14 cm(2). The ratio (in-vivo to in-vitro SA) of reflected FM was 3.26 ± 0.11 and disc was 1.22 ± 0.10. Reflected FM re-stretched to in-vivo SA generated a tension of 72.26 N/m, corresponding to approximate pressure of 15.4 mmHg. FM rupture occurred at 295.08 ± 31.73 N/m corresponding to approximate pressure of 34 mmHg. Physiological SA was 70% of that at rupture. DISCUSSION: FM are significantly distended in-vivo. FM collagen fibers were rapidly recruited once loaded and functioned near the failure state during in-vitro testing, suggesting that, in-vivo, minimal additional (beyond physiological) stretch may facilitate rapid, catastrophic failure.

Decreased adherence and spontaneous separation of fetal membrane layers--amnion and choriodecidua--a possible part of the normal weakening process.

INTRODUCTION: The fetal membrane (FM) layers, amnion and choriodecidua, are frequently noted to have varying degrees of separation following delivery. FM layers normally separate prior to rupture during in vitro biomechanical testing. We hypothesized that the adherence between amnion and choriodecidua decreases prior to delivery resulting in separation of the FM layers and facilitating FM rupture. METHODS: FM from 232 consecutively delivered patients were examined to determine the extent of spontaneous separation of the FM layers at delivery. Percent separation was determined by the weight of separated FM tissue divided by the total FM weight. Separately, the adherence between intact FM layers was determined. FM adherence was tested following term vaginal delivery (13), term unlabored cesarean section (10), and preterm delivery (6). RESULTS: Subjects enrolled in the two studies had similar demographic and clinical characteristics. FM separation was present in 92.1% of membranes. Only 4.3% of FM delivered following spontaneous rupture of the fetal membranes (SROM) had no detectable separation. 64.7% of FM had greater than 10% separation. FM from term vaginal deliveries had significantly more separation and were less adherent than FM of term unlabored, elective cesarean section (39.0+/-34.4% vs 22.5+/-30.9%, p=.046 and 0.041+/-0.018N/cm vs 0.048+/-0.019N/cm, p<.005). Preterm FM had less separation and were more adherent than term FM (9.95+/-17.7% vs 37.5+/-34.4% and 0.070+/-0.040N/cm vs 0.044+/-0.020N/cm; both p<.001). CONCLUSIONS: Separation of the amnion from choriodecidua at delivery is almost universal. Increased separation is associated with decreased adherence as measured in vitro. Increased separation and decreased adherence are seen both with increasing gestation and with labor suggesting both biochemical and mechanical etiologies. The data are consistent with the hypothesis that FM layer separation is part of the FM weakening process during normal parturition.

Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor.

The etiology of fetal membrane (FM) rupture is unknown. A hypothesis that the FM weakens by a process of collagen remodeling and apoptosis to facilitate rupture has been proposed. Human FMs reportedly exhibit a zone of altered histology, postulated to be the FM rupture site, but concomitant FM weakness has not been demonstrated. We hypothesized that a discrete zone of FM with marked weakness, histological change, and evidence of remodeling and apoptosis, develops in late gestation in the FM overlying the cervix. FM tissue from women undergoing prelabor cesarean delivery were perioperatively marked to identify the FM overlying the cervix, cut with a procedure that facilitates remapping the rupture strength of FM pieces to their former location and orientation on a three-dimensional model, and tested for strength. A 10-cm FM zone centered at the cervical mark was compared with the remaining FM. Mean rupture strength within the cervical zone was 55% of the remaining FM. The cervical zone also exhibited increased MMP-9 protein, decreased tissue inhibitor of metalloproteinases-3 (TIMP-3) protein, and increased PARP cleavage coincident with the previously reported zone of altered histology. A discrete zone of weakness is present in term prelabor FMs overlying the cervix and has biochemical characteristics consistent with tissue remodeling and apoptosis.

The role of human endogenous retroviruses in trophoblast differentiation and placental development.

A major portion of the human genome appears to be of retroviral origin. These endogenous retroviral elements are expressed in a variety of normal tissues and during disease states, such as autoimmune and malignant conditions. Recently, potential roles have been described for endogenous retroviral envelope proteins in normal differentiation of human villous cytotrophoblast into syncytiotrophoblast. This article provides a brief critical review of the current state of knowledge concerning the expression of the env regions of three endogenous retroviral elements: ERV-3, HERV-W, and HERV-FRD. A testable model of villous cytotrophoblast differentiation is constructed, in which a complementary expression of endogenous retroviral envelope proteins initiates hCG production, decreased cell proliferation, and intercellular fusion.

Antibiotics and preterm labor.

In summary, a definite association has been demonstrated between preterm labor and genital tract infection. Conclusions regarding the true benefits of antibiotics as adjunctive therapy in treatment of preterm labor are inconsistent. Whereas some of the studies were able to demonstrate significant prolongation of pregnancy, no consistent reduction in either maternal or neonatal morbidity has been demonstrated. However, because the actual incidental morbidity rate is low in the populations studied, the power of this finding is also low. The potential risks for using antimicrobials has yet to be adequately addressed. It has been shown that bacterial resistance can develop when antibiotics are used without specific aim or when a specific bacteria is undertreated. It has been recently shown that prenatal and intrapartum antibiotic use is associated with an increased risk for antibiotic resistant neonatal sepsis if infection occurs. Because of these reasons, we discourage the administration of antibiotic treatment to women in preterm labor for the purpose of pregnancy prolongations. Treatment should be directed towards those with specific indications for treatment (e.g., intrapartum, group B streptococci prophylaxis, urinary tract infection, etc). The primary flaw in these many evaluations of preterm labor is the true incidence of preterm birth. The clinical diagnosis of preterm labor is a difficult one. Approximately one-half of those individuals with preterm contractions will not deliver until term. So, the use of antibiotics for all women in idiopathic preterm labor is destined to treat many women who are unlikely to benefit. If we were able to truly identify those who were in "true" labor, perhaps we could be more selective in determining who may benefit from antibiotics. Biochemical markers such as onco-fetal fibronectin could well-be a helpful marker. Goldberg et al evaluated FFN in vaginal and cervical secretions while attempting to better-predict who would have upper genital tract infection. In this large, multicenter trial, patients were tested for FFN every 2 weeks from 23 to 30 weeks gestation. In those patients who proceeded to deliver before 32 weeks gestation, increased levels of cervical FFN (> 50 ng/ml) were identified in approximately one-quarter. Fetal fibronectin was positive in 4% of their samples and was found to be twice as likely in one with bacterial vaginosis. They showed that the presence of increased FFN was associated with upper genital tract infection (clinical and histologic chorioamnionitis) as a main reason for preterm labor and delivery (increased risk 16-20-fold). Those with increased FFN levels were also shown to have an increased incidence of neonatal sepsis as well. Peaceman et al used FFN to attempt to identify those at risk for preterm delivery among women with contractions between 24 and 34 6/7 weeks gestation. Those with negative FFN were less likely to deliver within 7 days of the test. The negative predictive value was 99.7%, suggesting that this test may be helpful in identifying women who would not benefit from antibiotic treatment. However, if in the absence of prospective clinical trials demonstrating the efficacy of this approach, we discourage the use of FFN screening for this indication.

Delivery of the marginally preterm infant: what are the minor morbidities?

OBJECTIVE: We sought to determine frequencies of minor morbidities associated with delivery between 32 and 36 weeks' gestation. STUDY DESIGN: The study population consisted of all infants delivered between 32 and 36 weeks' gestation at a tertiary care hospital during 1997. Maternal and neonatal charts were abstracted for maternal history, pregnancy complications, and neonatal demographics comparing complications present at each gestational week. The Student t test, chi(2) analysis, and stepwise regression analysis were used to assess statistical significance. Odds ratios were calculated. RESULTS: There were 553 patients eligible for study. There was increased risk of neonatal intensive care unit admission with delivery before 34 weeks' gestation (P <.04). An increased incidence of feeding difficulties was present before 35 weeks' gestation (P <.001). Hypothermia remained more frequent until 35 weeks' gestation (P <.05). Delivery at 35 weeks' gestation did not increase the mean number of neonatal hospital days. CONCLUSION: Although the incidences of major morbidities decline after 32 weeks' gestation, minor morbidities continue up to 35 to 36 weeks' gestation and may lengthen neonatal hospitalization.