Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy of vaginal progesterone to prevent early preterm birth in women with sonographic evidence of a short cervical length in the midtrimester. METHODS: This was a planned, but modified, secondary analysis of our multinational, multicenter, randomized, placebo-controlled trial, in which women were randomized between 18 + 0 and 22 + 6 weeks of gestation to receive daily treatment with 90 mg of vaginal progesterone gel or placebo. Cervical length was measured with transvaginal ultrasound at enrollment and at 28 weeks of gestation. Treatment continued until either delivery, 37 weeks of gestation or development of preterm rupture of membranes. Maternal and neonatal outcomes were evaluated for the subset of all randomized women with cervical length < 28 mm at enrollment. The primary outcome was preterm birth at

Progesterone vaginal gel for the reduction of recurrent preterm birth: primary results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Preterm birth is the leading cause of perinatal morbidity and mortality worldwide. Treatment of preterm labor with tocolysis has not been successful in improving infant outcome. The administration of progesterone and related compounds has been proposed as a strategy to prevent preterm birth. The objective of this trial was to determine whether prophylactic administration of vaginal progesterone reduces the risk of preterm birth in women with a history of spontaneous preterm birth. METHODS: This randomized, double-blind, placebo- controlled, multinational trial enrolled and randomized 659 pregnant women with a history of spontaneous preterm birth. Between 18 + 0 and 22 + 6 weeks of gestation, patients were assigned randomly to once-daily treatment with either progesterone vaginal gel or placebo until either delivery, 37 weeks' gestation or development of preterm rupture of membranes. The primary outcome was preterm birth at

Mutations in the factor V, prothrombin and MTHFR genes are not risk factors for recurrent fetal loss.

OBJECTIVE: Recurrent fetal loss, defined as the occurrence of three or more consecutive spontaneous abortions regardless of previous live birth, is a condition that affects about 2% of all reproductive-aged women. The role of gene mutations in recurrent pregnancy loss is not fully understood. The present research examined the relationship between factor V Leiden, factor V HR2, prothrombin G20210A and MTHFR and recurrent fetal loss in a case-control study. METHODS: Women aged 22-45 with a history of three or more fetal losses, being seen at a perinatal medicine clinic in New Jersey or Georgia, were eligible as cases. Overall, the study consisted of 60 women with three or more fetal losses and 92 women with at least one successful pregnancy. RESULTS: Factor V HR2 and MTHFR were not related to recurrent fetal loss. The prothrombin G20210A mutation appeared to confer an elevation in risk but the association was based upon small numbers and was not statistically significant (OR 4.8, 95% CI 0.50-47.2). Cases were 90% less likely to have the factor V Leiden mutation than controls (OR 0.10, 95% CI 0.01-0.81). CONCLUSIONS: Our study did not demonstrate that women who are carriers of the factor V, prothrombin, or MTHFR mutations are at higher risk of recurrent fetal loss than women without these mutations. In regards to factor V Leiden, the prevalence in our cases (1.7%) was not statistically different from the known population prevalence of 5%. However, the high prevalence in our controls (14%) was unusual. Factor V Leiden may protect against bleeding in early pregnancy.

In utero intervention in a patient with prune-belly syndrome and severe urethral hypoplasia.

Prenatal ultrasound scanning of a 20-year-old woman at 17 weeks of gestation revealed findings suggestive of bladder outlet obstruction, including bladder distension, dilated bilateral ureters, urinary ascites, and oligohydramnios. Vesicoamniotic shunts were placed with decompression of the bladder and correction of the amniotic fluid levels. Labor was induced at 36 weeks' gestation. At birth, the infant was noted to have prune-belly syndrome with severe urethral hypoplasia, a variant usually associated with a poor prognosis, necessitating vesicostomy for bladder drainage. We present a case of a patient with prune-belly syndrome and bladder outlet obstruction in whom early intervention resulted in an excellent outcome with preservation of renal and pulmonary function.

Genetic factors associated with thrombosis in pregnancy in a United States population.

OBJECTIVE: Polymorphisms in the genes for factor V (factor V Leiden), prothrombin, methylenetetrahydrofolate reductase, and angiotensin-converting enzyme have been associated with the occurrence of venous thrombosis. The objective of this study was to determine the relationships of these polymorphisms to thrombosis during pregnancy. STUDY DESIGN: This case-control study included 41 case patients with venous thrombosis during pregnancy and 76 control subjects matched for hospital and for race (white vs black) who had a normal pregnancy. RESULTS: Among white subjects, mutations in the genes for factor V and prothrombin were associated with increased risks of venous thrombosis during pregnancy (factor V: odds ratio, 18.3; 95% confidence interval, 2.7-432; P =.001; prothrombin: odds ratio infinity; 95% lower confidence limit, 1.7; P =.01). No black subject had either of these two mutations. For both black and white subjects the D/D genotype of the gene for angiotensin-converting enzyme entailed increased risk compared with the other genotypes (odds ratio, 2.7; 95% confidence interval, 1.2-6.3; P =.02). The polymorphism in the gene for methylenetetrahydrofolate reductase was unrelated to thrombosis during pregnancy among both blacks and whites. CONCLUSION: Women who had thrombotic complications during pregnancy demonstrated an increased prevalence of genetic mutations related to coagulation. The additional risk of thrombosis during pregnancy associated with such genetic mutations can be substantial.

Daytime functional bladder capacity as a predictor of response to desmopressin in monosymptomatic nocturnal enuresis.

OBJECTIVE: The objective of this study was to identify a cost-effective method of predicting a therapeutic response to desmopressin (DDAVP) by correlating daytime functional bladder capacity, age and urine osmolalities in patients with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Thirty-five children out of 51 who initially presented to our institutions were included in the study. The remainder was excluded for lack of complete data. Constipation was actively addressed and was managed by administration of evening enemas for 3 consecutive days and dietary adjustment prior to initiating the study. Each micturition as measured throughout the day and the maximal daytime functional bladder capacity was determined as the largest void over a 2-day period. Urine samples were collected at home at 08:00, 16:00 and 22:00 (times that would best reflect the fluctuations in plasma vasopressin levels). Intranasal DDAVP was then administered, titrating the dose over a 2-week period. The initial dose was 10 micrograms and the dose was increased 10 micrograms every 3 days. RESULTS: The response to DDAVP was then evaluated and of the 35 children, 27 demonstrated a complete response to DDAVP (all at doses between 10 and 30 micrograms). These were then related to the possible predictive factors. There was a significant correlation between a high maximum daytime functional bladder capacity and response to DDAVP (p = 0.006). Similarly, age was also predictive of a good response to DDAVP treatment (p = 0.008). However, spot urine osmolalities were not predictive of a response to DDAVP (p > 0.1). CONCLUSIONS: Functional bladder capacity is a reliable predictor of response to desmopressin; children with larger capacities are more likely to exhibit a successful response. Older children have a better response rate than younger ones. Spot urine osmolality measured on specimens collected in the home setting is not predictive of response to desmopressin.

Anterior cruciate ligament injury: fast spin-echo MR imaging with arthroscopic correlation in 217 examinations.

OBJECTIVE: Our objective was to evaluate the accuracy of MR imaging strategy that uses primarily fast spin-echo sequences for the diagnosis of anterior cruciate ligament tears. MATERIALS AND METHODS: The original clinical interpretations of MR images of 217 examinations of the knee joint were correlated with subsequent arthroscopic results. Each MR examination included a double-echo fast spin-echo sequence as the only imaging sequence in the sagittal plane. Subsequent discordant MR and arthroscopic examinations were then subjected to reanalysis by two observers who were unaware of arthroscopic results to determine if misinterpretations were observer or image dependent. Two hundred sixteen patients who underwent MR imaging for suspected internal derangement of the knee subsequently underwent arthroscopic surgery. Two patients had both knees evaluated. One patient was excluded because he was referred for evaluation for osteomyelitis, not internal derangement. This yielded a total number of 217 MR examinations for suspected internal derangement of the knee. RESULTS: For 56 arthroscopically proven tears, the sensitivity of MR imaging was 96%. The specificity was 98%, yielding an overall accuracy rate of 98%. The positive and negative predictive values were 95% and 99%, respectively. These values are within the ranges of previously reported MR imaging strategies using conventional spin-echo sequences. CONCLUSION: Fast spin-echo MR imaging of the knee can be an alternative to conventional spin-echo imaging for the detection of anterior cruciate ligament tears.

Maternal and fetal implications of anticonvulsive therapy during pregnancy.

A team approach with close communication among the obstetrician, neurologist, pediatrician, and patient will result in an uneventful pregnancy in most epileptic women. Women should be counseled regarding the greater than 90% likelihood of a favorable outcome. Maternal and neonatal outcome can be optimized by carefully evaluating the clinical necessity of anticonvulsant medications preconceptionally. One can then prescribe an appropriate choice based on seizure type and history of response, with a goal of achieving monotherapy at the lowest effective dose. Nonpharmacologic intervention, such as avoiding high levels of stress and sleep deprivation, will also help the patient to remain seizure-free during the pregnancy. In addition, folic acid and vitamin K can help optimize neonatal outcome. In short, most epileptic women will experience a normal pregnancy, labor, and delivery of a healthy baby and can breastfeed if desired. Although the incidence of congenital malformations with any anticonvulsant is increased, the actual incidence remains relatively low. Despite the shortcomings and risks of anticonvulsants, adequate therapy is clearly preferable to uncontrolled seizure activity. Women should be encouraged to optimize their anticonvulsive therapy prior to pregnancy, usually resulting in adequate therapy throughout the pregnancy and postpartum, with a happy and healthy outcome for mother and infant.

Spot urine osmolality, age and bladder capacity as predictors of response to desmopressin in nocturnal enuresis.

The objective of the current study was to find a cost-effective way of correlating spot urine osmolalities, bladder capacity and age in patients with monosymptomatic nocturnal enuresis with response to treatment with desmopressin (Minirin, DDAVP). A total of 35 children fulfilled the entry criteria and were included in the study. Constipation was eliminated in these children by appropriate enema treatment and diet adjustment prior to enrollment. Urine samples were collected at home at times that would best reflect fluctuations in plasma vasopressin levels (08:00, 16:00 and 22:00) over three consecutive 24-hour periods. Maximal functional bladder capacity was determined from the largest voided volume. A 2-week dose-titration treatment period with intranasal desmopressin was then conducted. With doses of desmopressin being increased by 10 micrograms every 3 days. Response to desmopressin treatment was then assessed and factors that were observed to be markers of a favourable response were noted. Of the 35 children, 27 demonstrated a complete response to desmopressin treatment, at doses of 10-30 micrograms. Spot urine osmolalities were not predictive of the response to desmopressin (P > 0.1). In contrast, there was a significant correlation between a high maximum functional bladder capacity and response to desmopressin (P = 0.006). Age was also predictive of a good response to desmopressin treatment (P = 0.008).

Comparison of gallium-67-citrate and thallium-201 scintigraphy in peripheral and intrathoracic lymphoma.

UNLABELLED: We performed this study in an attempt to reconcile the differences with respect to 67Ga uptake as a function of tumor grade and type in the literature, as well as to determine the sensitivity of 201Tl uptake in both Hodgkin's and non-Hodgkin's lymphoma. METHODS: Thirty-six (9 with low-grade lymphoma, 11 with intermediate-grade lymphoma, 4 with high-grade lymphoma and 12 with Hodgkin's lymphoma) patients underwent both 67Ga and 201Tl scintigraphy. Biopsies were done on all patients. A semiquantitative rating system was used to make statistical comparisons for thallium versus gallium in all lymphoma subgroups, as well as comparisons of thallium and gallium to themselves in all subgroups. RESULTS: Patient sensitivity was only 56% and site sensitivity was 32% in patients with low-grade lymphoma. Conversely, 201Tl sensitivity was 100%, respectively, for patients and sites. The difference between 201Tl and 67Ga sensitivity in patients with low-grade lymphoma on a site basis was statistically significant. When compared to itself in lymphoma subgroups, 201Tl was found to be statistically more avid for low-grade lymphoma than for intermediate, high or Hodgkin's lymphoma. Gallium-67 sensitivity for low-grade lymphoma was significantly less than for Hodgkin's and intermediate grade lymphomas. No significant differences were found when 201Tl and 67Ga were compared in the intermediate, high or Hodgkin's lymphoma groups. CONCLUSION: Thallium-201 demonstrates significantly greater tumor avidity in the low-grade lymphoma group compared to 67Ga citrate. Gallium-67-citrate appears relatively nonavid for low-grade lymphoma compared to 201Tl and is statistically inferior in detecting low-grade lymphoma in comparison to its ability to detect intermediate or high-grade lymphomas. Gallium-67-citrate should not be considered dependable in evaluating patients with low-grade lymphoma. Neither 201Tl or 67Ga is dependable in the evaluation of low-grade lymphoma within the abdomen, since gallium avidity for low-grade lymphoma is low and gastrointestinal excretion of 201Tl is poorly controlled.

Randomized clinical trial of antibiotic therapy for antenatal pyelonephritis.

OBJECTIVE: The aim of this study was to prospectively evaluate the efficacy of a therapeutic course of intravenous antibiotics followed by oral antibiotics vs. intravenous antibiotics alone to prevent recurrent urinary tract infection. METHODS: Pyelonephritis was documented by strict criteria in 67 pregnant women who were then treated with appropriate intravenous antibiotics until afebrile and asymptomatic for 48 h. Women were then randomized to completion of a 10-day course of oral nitrofurantoin 100 mg qid or no further antibiotic therapy. Urine cultures (UC) were obtained 2 and 6 weeks after discharge, and at delivery. A positive UC or readmission for pyelonephritis was considered endpoints for participation in the study. Antibiotic suppression was not used. RESULTS: Readmission for pyelonephritis prior to the 2-week follow-up visit occurred in 2/36 (5.6%) women randomized to the oral therapy group compared to 4/31 (12.9%) in the no oral treatment group (P = 0.29). At the 2-week follow-up visit, 6/31 (19.4%) women had a positive UC in the oral therapy compared to 8/26 (30.1%) in the no oral treatment group but this difference was not statistically significant (P = 0.31). CONCLUSIONS: Completion of 10 days of antibiotic therapy with oral medication does not significantly reduce the risk of recurrent pyelonephritis immediately post-parenteral treatment. Women in the no oral treatment group had a non-significant increase in positive UC at the 2-week follow-up visit. The high rates of recurrent urinary tract infection during pregnancy in both groups underscore the need for regular UC and for the possible role of oral antibiotic suppression.

Route of delivery for the breech presentation: a conundrum.

OBJECTIVE: Our purpose was to determine the feasibility of resolving the controversy regarding route of delivery for breech presentation in a randomized, prospective fashion. STUDY DESIGN: The National Institute of Child Health and Human Development-sponsored Maternal-Fetal Medicine Units Network, which is composed of 11 perinatal centers, was surveyed to determine the feasibility of a randomized clinical trial of cesarean section versus trial of labor for breech presentation. A review of the literature was performed to determine the experience of other investigators with designing and conducting an adequate prospective, randomized trial. RESULTS: Principal investigators and faculty from seven of 11 centers within the Maternal-Fetal Medicine Units Network agreed to participate adn felt that they could adequately recruit patients for a trial in very-low-birth-weight infants. This would provide approximately 200 very-low-birth-weight fetuses in a breech presentation per year. Sample size calculations indicated that 1700 infants would be required. Investigators also had strong reservations about performing a trial of vaginal breech delivery for other gestational ages. A review of the literature indicates that other authors have encountered difficulty in attempting randomized clinical trials of this nature. CONCLUSIONS: The Maternal-Fetal Medicine Units Network with its pool of 60,000 deliveries per year agreed that a randomized, controlled delivery route of labor in the 24- to 28-week breech presentation was not feasible in a reasonable period of time. A randomized clinical trial of larger fetuses in a breech presentation was also considered extremely difficult. These findings are similar to those of other authors who have attempted or proposed randomized clinical trials to determine the safety of planned vaginal delivery of the breech presentation at various gestational ages.

Distance from an intrauterine hydrophone as a factor affecting intrauterine sound pressure levels produced by the vibroacoustic stimulation test.

OBJECTIVE: The purpose of this study was to determine whether intrauterine sound pressure levels produced by vibroacoustic stimulation were associated with distance from an intrauterine hydrophone in human parturients and to evaluate the effects of distance on the spectrum of the stimulus. STUDY DESIGN: Measurements of intrauterine sound were taken in eight volunteer parturients in normal active-phase labor by use of an intrauterine hydrophone. Vibroacoustic stimulation was performed on the maternal abdomen directly overlying the hydrophone; at distance of 5, 10, 15, 20, and 25 cm from the hydrophone; and at the maternal sternum. Intrauterine sound pressure levels were tape-recorded for later analysis. Fetal heart rate and fetal movement were assessed with each vibroacoustic stimulation. Spectral analyses were performed by taking the fast Fourier transform of the tape-recorded stimulation at each position. RESULTS: Analysis of variance with repeated measures indicated a statistically significant decrease (F = 4.1, p = 0.004) in the sound pressure levels as distance increased. Spectral analysis indicated large variability between and within subjects. CONCLUSION: Sound exposure of the fetal ear is on average decreased as the distance between the ear and the vibroacoustic stimulation is increased. The spectrum of the stimulus produced with vibroacoustic stimulation is highly variable.

Evaluation of diagnostic tests in the differential diagnosis of primary aldosteronism: unilateral adenoma versus bilateral micronodular hyperplasia.

Effective management of primary aldosteronism is dependent upon correct localization of excessive aldosterone production. We report our results of localization studies in patients with biochemically and pathologically confirmed primary aldosteronism. Retrospective chart review identified 69 patients with unilateral adrenal adenoma and 11 with adrenal hyperplasia. Correct unilateral versus bilateral localization of excessive aldosterone production was predicted in 70% versus 71%, respectively, by adrenal venography, 100% versus 63% by adrenal vein hormone sampling, 46% versus 56% by adrenal nuclear scanning and 69% versus 13% by anomalous postural decline of aldosterone. Adrenal computerized tomography appeared to localize correctly 86% versus 80% of the lesions. Unilateral adrenalectomy normalized blood pressure in 79% of the patients with unilateral adenomas versus only 18% of those with adrenal hyperplasia. Once primary aldosteronism is confirmed, localization by adrenal vein sampling, adrenal venography and adrenal computerized tomography is most effective in directing antihypertensive therapy.

Breech presentation.

This review covers recent literature relevant to breech presentation. Some have advocated routine elective cesarean delivery of the breech fetus of any gestational age to reduce the alleged increase in perinatal morbidity and mortality associated with breech presentation. This indication for cesarean delivery accounts for approximately 15% of all cesarean deliveries and costs society approximately US$ 1.4 billion per year. As a result of concerns with vaginal breech delivery, external cephalic version in the term fetus has become well accepted. A new scoring system has been developed to predict the success of external cephalic version. Repeated external cephalic version has been shown to be successful. Careful ultrasound continues to be important before the procedure. It has been suggested that magnetic resonance pelvimetry may be a practical alternative in evaluating candidates for breech vaginal delivery. There is still no compelling prospective data supporting cesarean delivery for preterm breech presentation. Legal considerations have prevented many from attempting vaginal breech delivery, even in carefully selected patients.

Randomized trial of intraumbilical vein oxytocin in midtrimester pregnancy losses.

OBJECTIVE: The purpose of this double-blind prospective randomized trial was to determine whether high-dose intraumbilical vein oxytocin injection shortens the third stage of labor in midtrimester pregnancy losses. STUDY DESIGN: Patients (n = 50) with spontaneous or induced midtrimester pregnancy losses (14 to 26 weeks' gestation) were randomized to receive either 100 IU of oxytocin in 20 ml of normal saline solution or 20 ml of normal saline solution alone as a placebo. The umbilical vein was injected as soon as the cord was clamped. Outcome data were collected. RESULTS: Of the 50 patients randomized, 45 completed the study. Five were excluded after randomization because of either cesarean delivery (1 patient) or en caul delivery (4 patients). Twenty-one patients received oxytocin, and 14 received placebo. Ten patients who were not injected because of technical failure were evaluated separately. There were no differences between the three groups with regard to gestational age, fetal weight, length of the third stage, blood loss, or need for operative removal of the placenta. CONCLUSION: Injection of high-dose oxytocin into the umbilical vein in second-trimester pregnancy losses does not shorten the third stage of labor or decrease the need for surgical intervention because of retained placenta.