Norethindrone acetate enhances the antiatherogenic effect of 17beta-estradiol: a secondary prevention study of aortic atherosclerosis in ovariectomized cholesterol-fed rabbits

OBJECTIVE: Premature delivery is difficult to predict and causes considerable neonatal morbidity and mortality. Despite much research, little progress has been made in timely identification of the mothers at risk. We examined the uterine cervix with ultrasonography to discover whether such a procedure would be helpful in determining which women will deliver prematurely. METHODS: We performed transvaginal ultrasound examinations in addition to routine transabdominal ultrasonography at 18 to 22 weeks' gestation in 3694 consecutive pregnant women with live singleton fetuses. We measured the length of the uterine cervix and evaluated the dilatation, if any, of the internal os. The results of cervical ultrasonography were not available to the clinicians. RESULTS: Spontaneous delivery occurred before 37 completed weeks in 88 women (2.4%) and before 35 weeks in 31 (0.8%). The relative risk of delivery before 35 weeks was 8 (95% confidence interval 3, 19) when the cervical length was 29 mm or shorter. When dilatation of the internal cervical os of 5 mm or greater was present, the relative risk of delivery before 35 weeks was 28 (95% confidence interval 12, 67). Either short cervix (29 mm or less) or dilatation of internal cervical os (5 mm or greater) was present in 3.6% of the population; this combination had a sensitivity of 29% in predicting delivery at earlier than 35 weeks. After adjusting for cervical dilatation and length by using multiple logistic regression, nulliparity also remained a risk factor for delivery before 35 weeks (odds ratio 3.6, 95% confidence interval 1.7, 7.5). CONCLUSION: Transvaginal ultrasonography performed as an addition to routine transabdominal ultrasonography at 18 to 22 weeks helps to identify many patients at significant risk for prematurity; however, low sensitivity and low positive predictive value limit its usefulness in screening low-risk obstetric populations.     

Transvaginal ultrasonographic cervical assessment for the prediction of preterm delivery

To determine the usefulness of transvaginal ultrasonographic cervical assessment for the prediction of preterm delivery in an apparently normal population, 729 pregnant women (between 15 and 34 weeks' gestation) were randomly enrolled in the study in ten tertiary perinatal centers in Japan. Cervical parameters, including cervical length, internal os dilatation, and funneling depth, were measured by transvaginal ultrasound. The predictive values of these measurements for preterm delivery were investigated in a prospective fashion. Among various cervical parameters, cervical length showed the best correlation with pregnancy outcome. Cervical length (mm) was gradually decreased as the gestational age progressed, the regression line being y = 41.21-0.22x. When the mean cervical length minus 1 standard deviation at each gestational age was chosen as a cut-off value, the group with a shortened cervix showed a significantly high preterm delivery rate exclusively in the primigravidae (odds ratio: 4.86, 95% CI: 1.85-12.72). Internal os dilatation, in contrast, was a useful predictor in multiparous women (odds ratio: 6.00, 95% CI: 1.65-21.71). It was concluded that tranvaginal ultrasonographic cervical assessment, especially the measurement of cervical length, was effective for the prediction of preterm delivery in the primigravidae.     

From SA to UK: a profile of South African qualified dentists registered with the General Dental Council

Generally, it is preferable to tocolyze patients with idiopathic preterm labor (PTL). Little information is available about ultimate outcomes after successful tocolysis. Our objective is to evaluate the relationship between cervical change after the initiation of tocolysis and the delay in time to delivery in patients with preterm labor. A historical analysis of all patients with successful tocolysis after PTL between January 1992 and December 1993 was undertaken. The patients were then placed in one of three categories (regression, unchanged, or progression) based on cervical change after the initiation of tocolysis. Various demographic pregnancy characteristics and pregnancy outcome data were analyzed. One hundred and twenty-six patients had successful tocolysis and met the admission criteria. Patients who had cervical progression had shorter delay to delivery, delivered at an earlier gestational age (31.7 weeks compared to 34.0 and 34.1 weeks, respectively, p < 0.05), and were more likely to deliver before 35 weeks (88% compared to 50.0 and 55.0%, respectively, p < 0.05). Also, neonates remained in the hospital longer and were more likely to have respiratory distress syndrome when compared to the other two groups. Patients who had cervical progression after the initiation of tocolysis are more likely to deliver prematurely, had a shorter delay to delivery, and delivered lower birth weight infants than did patients whose cervix regressed or remained unchanged. In our population, patients who had successful tocolysis had a preterm delivery rate of 59.5% before the 35th week of gestation.     

The uterine cervix on in vitro and in vivo MR images: a study of zonal anatomy and vascularity using an enveloping cervical coil

OBJECTIVE: The purpose of this study was to characterize the normal zonal anatomy and vascularity of the cervix on in vivo and in vitro MR images obtained with a receiver coil surrounding the cervix. These appearances provide a normal data base from which to interpret subtle changes in early neoplasia. SUBJECTS AND METHODS: Thirteen women of reproductive age with clinically and cytologically normal cervices were imaged with a ring-design solenoid receiver coil that was placed intravaginally and enveloped the cervix. T1- and T2-weighted axial images were obtained. Seven uterine specimens resected for benign disease were similarly studied, and imaging appearances were correlated with histologic findings. RESULTS: In the in vivo studies, the endocervical mucosa and two stromal zones surrounding the high-signal central canal were identified. Unlike the uterine body, they could be differentiated on both T1- and T2-weighted images, on which the inner ring had a low signal and the outer ring had an intermediate signal intensity. The outer zone was highly vascularized, with inflow effects from large vessels visible on single-slice scans. On administration of gadopentetate dimeglumine, the endocervical mucosa enhanced rapidly, whereas the outer stroma showed more gradual enhancement. The inner zone enhanced slowly relative to the outer zone. The parametrium was visualized up to 6 cm from the center of the coil, and adjacent colon, fat, and blood vessels were identified. Up to four lymph nodes less than 1 cm in diameter were seen in the parametrium of three subjects. In the in vitro studies, the endocervical mucosa was of high signal intensity. In the fibromuscular cervix, an inner low-signal ring correlated with a region of tightly packed stroma (fibroblasts and smooth muscle cells; cell count, 5900 +/- 2376 nuclei/mm2) and the intermediate-signal-intensity outer zone corresponded to a region of more loosely packed stroma (cell count, 2199 +/- 558 nuclei/mm2). Retention cysts were present in two multiparous cervices. CONCLUSION: These detailed appearances and enhancement patterns of the normal cervix need to be recognized so that subtle changes in locally invasive cervical neoplasia can be identified.     

Histological study of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins

OBJECTIVE: To study the histological changes of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins (PG). METHODS: A total of 24 women who requested medical abortion was recruited. For each woman, 3 cervical biopsies were taken: before mifepristone treatment; 48 hours after mifepristone 150 mg single dose treatment (i.e. immediately before PG administration); and 1 hour after gestational sac expulsion. Specimens were studied by optical and electron microscopy. RESULTS: Significant collagenolysis as demonstrated by marked reduction and irregularity of collagen fibers, abundant accumulation of an amorphorous material of ground substance, and infiltration of neutrophilic polymorphonuclear leukocytes were shown in stroma as well as in the deep portion of cervix after mifepristone as compared to the samples of early pregnant cervix before treatment. These changes presented to a further extent after the expulsion of gestational sac. CONCLUSION: The changes observed were similar to previous reports during cervical dilatation in term delivery. The present study confirmed the histological cervical ripening effect by mifepristone and suggested it may be used as cervical ripening agent before induction of labor as well.     

Role of the cervix uteri at labor onset from ultrasound studies

The cervix uteri is of greatest importance for the environment of the fetus. The sonographic imaging of the cervix uteri can be done by transabdominal, perineal and transvaginal route. Each of these methods are associated with specific advantages and disadvantages. During the time of gestation the cervix uteri can be measured sonographically concerning the length, the thickness, the width of the cervical canal and in addition the diameter of the internal and the external os. At the beginning of labour the cervix shows a transformation: a shortening with an increase of thickness. The phase of contraction is followed by a phase of reformation. Individual formations of the cervix regarding the a premature opening of the internal os or the external os could be demonstrable without clinical symptoms. By W. Eppel a score-like formula "Incompetence-Factor" was described for a quantification of these measurements.     

Management of pregnancies beyond forty-one weeks' gestation with an unfavorable cervix

OBJECTIVE: Our purpose was to determine the optimal management of pregnancies beyond 41 weeks' gestation with a cervix unfavorable for induction. STUDY DESIGN: All uncomplicated pregnancies that reached 41 weeks' gestation with a Bishop score of < or = 4 were randomly assigned to one of three groups: (1) daily cervical examinations, (2) daily membrane stripping, or (3) daily placement of prostaglandin gel until 42 weeks. RESULTS: In 105 pregnancies the Bishop score on admission to labor and delivery was significantly greater in the groups receiving prostaglandin or stripping of the membranes versus the control group, whereas the converse was time of gestational age at delivery (p = 0.0001). Fewer patients required induction in the two treatment groups (20%, 17%) versus the control (69%) patients (p < 0.0001). CONCLUSIONS: Daily membrane stripping or daily placement of prostaglandin gel is successful in reducing the number of inductions at 42 weeks for postdatism.     

Comparative study of AgNOR and PCNA in experimental carcinogenesis of salivary glands of rats

The findings of MRI and pathologic investigation were correlated in curatively irradiated uterine cervical carcinoma. Four patients having residual carcinoma diagnosed by biopsy underwent hysterectomy. MRI demonstrated the mass lesion in one patient with pathologic confirmation of massive viable cancer cells (case I). Of the other three patients, MRI demonstrated normal configuration of the uterine cervix. Cervical signal intensity, however, varied. Hyperintensity was noted in an area of the posterior wall on T2WI in case 2. The anterior wall of the case 2 and the other two cases showed hypointensity. Cervical specimens with normal intensity showed only a small number of degenerated cancer cells. On the other hand, pathologic examination of the posterior wall of the case 2 revealed both cancer cells with varying degrees of degeneration and necrotic tissues. Degeneration of cancer cells was stronger in the superficial layer than the deeper layer. Fibrosis, hemorrhage, granulation and hyalinization were hypointense on T2WI. T2 elongation reflected not only the residual tumor but the post-irradiation changes. Post-irradiated cervix with normal intensity indicated that only a small number of degenerated cancer cells may persist even if the biopsy was positive. We conclude that MRI is useful in evaluating tumor response to radiotherapy.     

Induction of labor with use of a Foley catheter and extraamniotic corticosteroids

OBJECTIVE: Our purpose was to examine the hypothesis that corticosteroids, when administered extraamniotically, can enhance the labor process and reduce the induction-to-delivery interval. STUDY DESIGN: A double-blind, randomized study was conducted on 98 women with a gestational age of 36 to 42 weeks, an unfavorable cervix, and medical indications for delivery, who were assigned to receive either 20 mg of dexamethasone in saline solution (study group, n = 50) or saline solution only (control group, n = 48) administered extraamniotically through an intracervical inflated Foley balloon catheter. The net effect of steroids was assessed with use of multivariant logistic regression analysis. RESULTS: The mean time intervals between induction of labor to the active phase and between induction of labor to delivery were significantly shorter in the study group compared with those of the control group (7.8 +/- 3.1 hours vs 9.9 +/- 3.9 hours, p < 0.03, 11.9 +/- 3.0 hours vs 14.5 +/- 4.8 hours, p < 0.01, respectively). Those not receiving steroids were at a 3.2 higher risk of having a longer time interval of induction to delivery (95% confidence interval 1.1 to 9.5). The general success rate in achieving vaginal delivery was, however, similar between the groups. CONCLUSIONS: Induction of labor with use of an intracervical Foley balloon catheter and extraamniotic corticosteroids reduces the time interval from induction of labor to delivery. This may indicate a possible role for corticosteroids in the parturition process.     

Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial

OBJECTIVE: To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester. DESIGN: Prospective, randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Forty-eight primigravid women undergoing surgical termination of pregnancy before 12 weeks of gestation. METHODS: The women were randomised to receive per vaginam before surgery either the nitric oxide donor isosorbide mononitrate, the nitric oxide donor glyceryl trinitrate, the prostaglandin analogue gemeprost, or no treatment. MAIN OUTCOME MEASURES: The cumulative force required to dilate the cervix to 8 mm was measured objectively and the cervical diameter before surgical dilatation was recorded. RESULTS: Following isosorbide mononitrate or gemeprost, a lower cumulative force was required to dilate the cervix to 8 mm and a higher cervical diameter before dilatation was recorded. Pretreatment with glyceryl trinitrate reduced the cumulative force required to dilate the cervix but had no effect on cervical diameter. CONCLUSIONS: Like the prostaglandin analogue gemeprost, the nitric oxide donors isosorbide mononitrate and glyceryl trinitrate can effect cervical ripening. Nitric oxide donors may provide an alternative to prostaglandins for cervical ripening before surgical procedures in the first trimester.     

Vaginal lever pessary in patients with multiple gestation, preterm labor and low fetal station. A report of three cases

BACKGROUND: The vaginal pessary has been utilized previously in patients with cervical incompetence, resulting in improvement in pregnancy outcome. The mechanical advantages generated by the vaginal lever pessary could theoretically be applied to patients in preterm labor with low station of the presenting part to prevent cervical dilatation. CASES: One patient with twins and two with triplet pregnancies presented in preterm labor with advanced cervical dilatation and low fetal station. They were treated with tocolytic drugs, and a vaginal lever pessary was placed. The gestational age at delivery was delayed with the addition of the vaginal pessary. Based on previous experience with these difficult cases, it was judged that the use of the pessary achieved a delay in delivery that would not have occurred without the device. CONCLUSION: Vaginal pessaries can be used as mechanical adjuvants in the treatment of preterm labor. These devices work by altering the pressure dynamics on the cervix and lower uterine segment. They may also help limit cervical change by preventing engagement of the presenting part into the maternal pelvis. In these cases, a vaginal pessary appears to be beneficial in delaying delivery in multiple gestations presenting with advanced cervical dilatation and low station of the presenting part.     

Elective cesarean section is preferred after the completion of a minimum of 38 weeks of pregnancy

OBJECTIVE: To determine the frequency of neonatal respiratory morbidity following elective caesarean delivery at term and to identify prognostic factors for this morbidity. DESIGN: Retrospective. SETTING: Academic Hospital Utrecht/Wilhelmina Children's Hospital Neonatal Intensive Care Unit, Utrecht, the Netherlands. METHOD: All elective caesarean deliveries in the Academic Hospital Utrecht from the period 1990-1995 were studied. Also, neonates were included who were admitted for intensive neonatal care because of respiratory insufficiency following elective caesarean delivery in the region surrounding Utrecht. An elective caesarean delivery was defined as a delivery performed after 37 weeks of gestation without any complicating factor that might influence the timing of delivery. Prognostic factors for neonatal morbidity after caesarean delivery were identified by multivariate logistic regression analysis. RESULTS: During 1990-1995, 272 elective caesarean deliveries after 37 weeks of gestation were performed that fulfilled the inclusion criteria; 5.1% of the neonates were admitted to the medium care unit because of respiratory problems. The relative risk of respiratory morbidity after delivery by caesarean section with a gestational age of 39-42 weeks compared with a gestational age of 37-38 weeks, was 0.14 (95% confidence interval: 0.03-0.64; p < 0.001). Male sex was a cofactor. Nine neonates of whom 8 (90%) had a gestational age of less than 39 weeks were admitted to the intensive care unit. CONCLUSION: Most of neonatal respiratory morbidity could have been avoided by postponement of the at-term elective caesarean section until a certain gestational age of at least 38 complete weeks. An elective caesarean section should not be performed before that period.     

Magnetic resonance imaging of the fetus: a study of 20 cases performed without curarization

Twenty patients underwent magnetic resonance imaging (MRI) at a mean gestational age of 32 weeks. There were 12 patients with suspected fetal brain abnormality and four with intrauterine growth retardation (IUGR), while the remaining four cases were studied for other reasons. The MRI examinations were performed on a 0.5 Tesla machine, with surface coils. One minute acquisition time T1 sequences were used. All the studies were performed without fetal curarization, and only under maternal sedation using flunitrazepam given per os 1 h before MRI examination. Three examinations were incomplete because of fetal movement artefacts. In the remaining cases, MRI allowed the examination of fetal brain anatomy. In five cases, it helped to differentiate isolated hydrocephalus and corpus callosum agenesis. Sub-ependymal nodules were depicted in a case of fetal tuberous sclerosis. One suspected arachnoid cyst was proved to be an ultrasound artefact. Decreased fetal fat on MR images was correlated with low birth weight in cases of IUGR. Due to its better spatial resolution, ultrasonography was more accurate for the diagnosis of facial and lumbar anomalies. Fetal MRI may be performed without curarization. Surface coils allow the detailed analysis of brain parenchyma, and thus MRI is especially useful in the difficult prenatal diagnosis of fetal brain abnormalities.     

Static magnetic resonance imaging of the pelvic floor muscle morphology in women with stress urinary incontinence and pelvic prolapse

In a study, the magnetic resonance imaging (MRI) findings of 69 women were analyzed to define the typical MRI appearance of the pelvic floor musculature in healthy subjects (n = 20) and women with urinary incontinence (UI) and/or genitourinary prolapse (GP) (n = 49). The following parameters were determined: thickness and signal intensity of the levator muscles on each side, distance between the urethra and symphysis, diameter of the proximal urethra, and thickness and configuration of the anterior vaginal wall. These parameters were correlated with the patients' age and parity, urodynamic parameters, and the clinical assessment of the pelvic floor. In contrast to healthy subjects, the frequent findings in women with UI and/or GP are higher signal intensity of the levator muscles (p < 0.05) and loss of the hammock-like configuration of the vagina (p < 0.01). On static MRI, the morphometry of the levator musculature identified no findings typical of either UI or GP. Analysis of MRI combined with patients' parity suggests that the severity of damage to the pelvic floor at delivery is determined by the traumatic event as such and not by the number of deliveries. Urethral diameter, distance of the symphysis to the urethra, and vaginal wall thickness cannot distinguish between controls and women with UI and/or GP. Urodynamic and functional clinical parameters do not correlate with the changes in the pelvic floor musculature demonstrated by static MRI. Although morphological changes in UI and/or GP can be demonstrated by MRI, they can be assigned a pathogenic role only if clinical symptoms are present.     

Ultrasonographic and Biochemical Markers of Preterm Labor

> At present preterm delivery is the leading cause of perinatal morbidity and mortality and its incidence is remained stable during the past 10 years. Conventional methods of identifying patients at risk of preterm delivery such as obstetrics history, demographic factors or evaluation of uterine contractions and cervix by digital examination show disappointintly low sensitivity and positive predictive value. In this review we describe new ultrasonographic and biochemical approaches that have been recently proposed to screen for preterm labor both in patients with intact and with premature rupture of the membranes. The ultrasonographic detection of a short uterine cervix and/or of a dilation of the internal os, expression of weakening of the lower uterine segment or cervical ripening, seems to efficiently predict patients at risk of preterm delivery. The efficiency of this marker may be improved by the association with the assay of fetal fibronectin or pro inflammatory cytokines (interleukin-6 and interleukin-8) in cervical secretions. Further by the concentrations of interleukin-6 and interleukin-8 in cervical secretions seems to be possible to predict among patients in preterm labor those secondary to subclinical endoamniotic infection or chorioamnionitis. The use of these new markers in the future may allow a better identification of patients at risk of preterm labor and a proper selection of the treatment (medical or surgical) required for such patients.     

Failure to detect intrauterine growth restriction following in utero exposure to MRI

Echo planar imaging is a form of MRI with short image acquisition times, which permits in utero fetal imaging without motion artefacts. Echo planar imaging has been used to measure accurately fetal organ volume and to assess placental function. Two small animal studies have suggested the possibility of intrauterine growth restriction consequent upon MRI. We thus performed a prospective study of pregnancies in which fetuses were exposed to echo planar imaging, compared with a control group in which there was no in utero echo planar imaging exposure. There were no significant differences between the groups when maternal age, parity, proportion of smokers and proportion of Caucasian women were compared. Although the gestational age of delivery was lower in the echo planar imaging group, the proportion of women delivering prematurely was not significantly different. Although infant birthweights were significantly lower in the MRI group, the corrected birthweight for gestational age centiles (individualized birthweight ratio) was not significantly different between the two groups. In utero exposure to echo planar imaging thus did not have a marked effect on intrauterine fetal growth. A 10 year follow-up study of all infants imaged in utero is being performed.     

Prevention of neonatal respiratory distress syndrome through the administration of prednisolone in the fetal period

The clinical effectiveness of antenatal prednisolone medication (prednisolone hemisuccinate) for the prophylaxis of idiopathic respiratory distress syndrome (IRDS) was studied in 114 premature infants with a gestational age between 28 and 36 weeks. There was a statistically significant difference (chi2 - test, p less than 0,01) between the frequency of IRDS in this group and in another one consisting of 137 premature babies with a nearly identical distribution of gestational age, whose mothers did not get prednisolone before delivery. It could be shown that the time interval between medical induction and delivery should not exceed 2 weeks, since the effect decreases with time. At present prednisolone medication during the fetal period may serve as useful prophylactic measure for IRDS in cases of premature birth. As there are a lot of contraindication against prednisolone and as we do know very much about side effects, it seems necessary to seek for other, less dangerous inductors.     

Cervical ultrasonography compared with manual examination as a predictor of preterm delivery

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery. STUDY DESIGN: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (< 35 weeks) delivery. RESULTS: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately (p < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively. CONCLUSION: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation.     

Selective termination and elective reduction in twin pregnancies: 10 years experience at a single centre

Selective termination is employed in multifetal pregnancies, in the presence of an abnormal fetus, in order to improve the prognosis of the normal fetuses. The term elective reduction is used to describe reduction in twin pregnancies for maternal medical conditions, psychological, or socioeconomic reasons. The purpose of this study was to evaluate the factors that influence outcome in such pregnancies. Eighty-two twin pregnancies underwent selective termination (n = 59) or elective reduction (n = 23) over a 10-year period. Early procedures, performed < or = 14 weeks (n = 31), had a pregnancy loss of 9.7% and a mean procedure-to-loss interval of 4.1 +/- 2.8 weeks; mean birthweight was 3299 +/- 395 g in survivors, with a mean gestational age at delivery of 38.4 +/- 2.3 weeks. In comparison, procedures performed > 14 weeks (n = 51) had a pregnancy loss of 7.8%, with a procedure-to-loss interval of 1.2 +/- 0.6 weeks. Mean birthweight was 2577 +/- 999 g, with a mean gestational age at delivery of 35.7 +/- 5 weeks. In conclusion, outcomes were more favourable among patients who underwent a first trimester procedure. The slight increase in pregnancy loss may be attributed to a higher than expected rate of spontaneous abortions in the first trimester, as manifested by the higher procedure-to-loss interval after a first trimester procedure. These facts underscore the importance of early detection of fetal abnormalities in twin pregnancies by ultrasonography and chorionic villus sampling.