Amniotic fluid index in the uncomplicated term pregnancy. Prediction of outcome.

OBJECTIVE: To establish whether an association between oligohydramnios and pregnancy outcome is present in the uncomplicated term pregnancy. STUDY DESIGN: Pregnancies with a singleton fetus in cephalic presentation at term (> or = 37 weeks), a reactive non-stress test and an antepartum amniotic fluid index performed within four days of delivery between January 1994 and September 1998 were identified. Excluded were those with any maternal or fetal complication or unavailable outcome information. The primary outcome measure was rate of operative vaginal or abdominal delivery for a nonreassuring fetal heart rate tracing. Statistical analysis included Fisher's exact test and one-way analysis of variance, with a two-tailed P < .05 considered significant. RESULTS: Two hundred thirty-two women met the inclusion criteria; of them, 44 (19%) had an amniotic fluid index < or = 5 cm. There was no difference in the operative delivery rate for a nonreassuring fetal heart tracing between those with a normal amniotic fluid index > 5 cm vs. < or = 5 cm (39 [21%] vs. 5 [11%], P > .05). In addition, there were no differences between the two groups in rates of neonatal intensive care unit admissions or five-minute Apgar scores < 7. Patients with a normal amniotic fluid index had a significantly lower labor induction rate (96 [51%] vs. 42 [98%], P < .001) and higher rate of meconium-stained amniotic fluid (65 [35%] vs. 7 [16%], P = .01) than those with a low amniotic fluid index. CONCLUSION: In the uncomplicated pregnancy at term, an amniotic fluid index < or = 5 cm increases the incidence of labor induction but does not appear to affect the rate of operative delivery for abnormal fetal heart rate tracings.

Tampons, dioxins, and endometriosis.

Concern has been expressed that rayon tampons contain dioxins as a result of chlorine bleaching and, further, that the dioxins in tampons may increase the risk of endometriosis. Rayon tampons do not contain 2,3,7,8-tetrachlorodibenzo-p-dioxin, the chemical commonly meant when the generic term "dioxin" is used. In addition, rayon tampons contain only trivial amounts of dioxin-like environmental contaminants, similar to the amounts contained in unbleached cotton tampons. The amount of dioxin-like material that is theoretically available from tampons is at least six orders of magnitude lower than estimated daily food exposure levels to these contaminants. The evidence for a causal relationship between environmental exposure to dioxins and endometriosis is inconsistent. Prediction of the effective dioxin dose based on the most suggestive of the primate studies on endometriosis does not raise concerns about typical human food exposures to these compounds, let alone the considerably lower levels that could be present in tampons.

Medical and surgical therapies for pain associated with endometriosis.

Endometriosis is a common condition for which a number of treatments have been proposed. Medical treatments are based on the hormonal responsiveness of endometriosis implants. These therapies include progestins (with or without estrogens), androgens, and gonadotropin-releasing hormone (GnRH) analogs. Surgical treatments may include hysterectomy with oophorectomy or organ-sparing surgery involving ablation or resection of visible lesions of endometriosis and restoration of pelvic anatomy. There are no studies that directly compare the effectiveness or adverse effects of medical therapy and surgical therapy. Studies on medical therapy compare different treatments with placebo or with other active treatments. Hormone-based therapies for endometriosis show 80%-100% effectiveness in relief of pelvic pain over a 6-month course of therapy. Serious adverse outcomes after medical therapy are unusual. Studies on surgical therapy are largely anecdotal, with noncomparative reports on a variety of surgical methods. A few comparative surgical studies have been reported. Because of the noncomparative nature of many of the surgical studies, the use of combinations of surgical procedures and techniques in the reported studies, and the reporting of results from surgeons with an unusually high level of technical skill, the gynecological practitioner has little basis in the literature for assessing the optimum surgical approach. Surgical complications are believed to be underreported and may be related to how aggressive a surgical procedure is undertaken.

Hydroxylamine moiety of developmental toxicants is associated with early cell death: a structure-activity analysis.

BACKGROUND: Cellular debris, an indicator of cell death, appears in limb buds of gestational day 12 rabbit embryos 4 hr after either a subcutaneous injection of hydroxyurea to pregnant rabbits or an injection of hydroxyurea into the exocoelomic cavities of the embryos. This episode of early cell death appears to be central to the teratogenic action of hydroxyurea. Several chemicals that are structurally related to hydroxyurea, and that possess a terminal hydroxylamine moiety (-NHOH), also produce limb abnormalities. METHODS: To investigate whether the hydroxylamine moiety is responsible for early cell death and, therefore, is likely to be associated with teratogenesis, five structurally related hydroxylamine-bearing chemicals (hydroxylamine hydrochloride, N-methylhydroxylamine hydrochloride, hydroxyurea, acetohydroxamic acid, and hydroxyurethane) were administered at equimolar doses to rabbits either by subcutaneous (8.55 mmol/kg) or intracoelomic (2.66 micromol/embryo) injection on gestational day 12. Five additional chemicals, structurally similar to the hydroxylamine-bearing compounds, but possessing a terminal amino group (-NH(2)) (ammonium hydroxide, methylamine, urea, acetamide, and urethane), were tested at equimolar or higher doses by an identical protocol. In a subsequent experiment, the antioxidant propyl gallate (3.0 mmol/kg or 1.30 micromol/embryo) was co-administered with the hydroxylamine-bearing compounds to determine its effect on early cell death. Embryos were harvested 4 or 8 hr after treatment and analyzed by light microscopy. RESULTS: Cellular debris was obvious in forelimb buds from embryos treated with the hydroxylamine-bearing compounds; however, none of the amino compounds produced an early episode of embryonic cell death. In all cases, the antioxidant propyl gallate prevented or delayed the early episode of cell death observed after treatment with the hydroxylamine-bearing compounds. CONCLUSIONS: These results are consistent with the concept that the rapidly occurring embryonic cytotoxicity induced by hydroxylamine-bearing compounds involves a free radical mechanism that requires the presence of a terminal hydroxylamine group for initiation.

Magnesium sulfate therapy affects attention and working memory in patients undergoing preterm labor.

OBJECTIVE: Patients commonly consent to undergoing invasive procedures while receiving magnesium sulfate therapy. This study evaluated the effects of magnesium sulfate on attention, comprehension, and memory in patients undergoing preterm labor. STUDY DESIGN: Consenting patients were studied while receiving(study) and not receiving (control) intravenous magnesium sulfate tocolysis for preterm labor. Excluded were patients with possible preeclampsia, imminent delivery, sedative administration, or prior mental illness. Patient comprehension was assessed with the Boston Diagnostic Aphasia Examination. Level of attention and working memory were evaluated with the Paced Auditory Serial Addition Test. Verbal learning, short-term memory, and recognition were determined with the Hopkins Verbal Learning Test. Gross mental-neurologic deficits were evaluated with the Mini-Mental Status Examination. The tests were administered by the same examiner. Control testing was performed >24 hours after intravenous magnesium sulfate was discontinued. Magnesium levels were obtained at the time of testing. The primary outcome measure was the Paced Auditory Serial Addition Test score because of its ability to elicit subtle differences in attention capacity. Statistical analysis included the paired t test and the McNemar test. RESULTS: Fifteen patients completed the study. Paced Auditory Serial Addition Test scores were significantly higher (ie, more errors were made) during magnesium sulfate therapy than periods without therapy (14 +/- 8 vs 7 +/- 7; P <.05). Comprehension (Boston Diagnostic Aphasia Examination score) was not different between the groups (P =.7). There was no difference in short-term memory (Hopkins Verbal Learning Test) or gross mental-neurologic deficits between the 2 groups (all P >.1). CONCLUSIONS: Magnesium sulfate therapy appears to have an effect on attention and working memory but not on long-term memory or comprehension. The significant differences in Paced Auditory Serial Addition Test scores reveal deficits in information-processing ability in patients on a regimen of magnesium sulfate therapy.

Intermittent leuprolide acetate for the nonsurgical management of women with leiomyomata uteri.

OBJECTIVE: To evaluate the feasibility of intermittent 6-month courses of leuprolide acetate for the long-term control of symptoms attributed to leiomyomata uteri. DESIGN: Prospective open-label feasibility study. SETTING: University department of obstetrics and gynecology. PATIENT(S): Thirty women with abnormal bleeding or discomfort (pain or pressure) due to leiomyomata uteri. INTERVENTION(S): Patients received an initial 6-month course of the GnRH agonist leuprolide acetate, after which they were observed for symptom recurrence. Symptom recurrence was managed by repeated 6-month courses of leuprolide acetate. MAIN OUTCOME MEASURE(S): Relief of symptoms, responses on a quality-of-life questionnaire, serum lipid levels, blood count, and ferritin level. The number of doses of leuprolide acetate required to maintain symptom control was recorded. Serial bone mineral density measurements were made in selected patients. RESULT(S): Twenty of the 30 women who began therapy with leuprolide acetate continued in the protocol. Each individual 6-month course of leuprolide acetate therapy was followed by a median of 9 additional months of symptom control (range, 2 to >25 months). Women remaining in the protocol experienced a mean decrease of 2.4% in bone mineral density of the lumbar spine; bone mineral density of the hip did not change. CONCLUSION(S): Intermittent courses of leuprolide acetate can be used in the nonsurgical management of women with symptomatic leiomyomata uteri. Use of antiresorptive add-back therapy and monitoring of bone mineral density can be considered when repeated courses of leuprolide acetate are given.

Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women.

Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.

Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms.

OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.

Evaluating chronic pelvic pain. A consensus recommendation. Pelvic Pain Expert Working Group.

OBJECTIVE: To identify a comprehensive approach to evaluating women with chronic pelvic pain based on findings in the literature. STUDY DESIGN: A working group of gynecologist pelvic pain specialists was convened to consider principles on which consensus could be reached and to identify areas in which consensus is not yet possible. RESULTS: Chronic pelvic pain affects 15% of American women. The diagnostic and therapeutic approach to the complaint may be influenced inordinately by the specialty of the practitioner to whom the woman presents. A comprehensive approach to the complaint requires recognition of the multiple organ systems that may be involved. Evaluation of the woman with chronic pelvic pain begins with a comprehensive history and physical examination, followed by selected laboratory and imaging studies. For those women in whom the evaluation does not yield a likely cause of the complaint, the empiric use of nonsteroidal antiinflammatory agents, oral contraceptives, and perhaps antibiotics or antispasmodics is indicated. Women who fail to respond to empiric therapy should be considered highly likely to have endometriosis or adenomyosis. Further diagnostic (laparoscopy) or therapeutic (gonadotropin-releasing hormone agonist) interventions should be directed toward the high likelihood of endometriosis or adenomyosis. CONCLUSION: A comprehensive approach to chronic pelvic pain includes consideration of multiple organ systems, with empiric therapy appropriate after a thorough history and physical examination, to further delineate the pain problem.

Initial results from uterine fibroid embolization for symptomatic leiomyomata.

PURPOSE: To evaluate the safety and short-term efficacy of uterine fibroid embolization (UFE) in patients with symptomatic uterine fibroids. MATERIALS AND METHODS: Bilateral UFE was performed in 61 patients with symptomatic uterine leiomyomata during a 16-month period. Imaging was performed before the procedure and at 3 months and 1 year after the procedure. Questionnaires were obtained at regular intervals after the procedure to assess patient outcome. RESULTS: All procedures but one were technically successful. Mean clinical follow-up was 8.7 months. Minor complications occurred in five patients during the follow-up period. All were treated without permanent sequelae. Menstrual bleeding was improved in 89%, with 81% of patients moderately to markedly improved. Pelvic pain and pressure was improved in 96% of patients, with moderate to marked improvement in 79%. At initial imaging follow-up (mean, 4.4 months postprocedure), median uterine volume decreased 34% (P = .0001) and the median dominant fibroid volume decreased 50% (P = .0001). Imaging at 1 year (mean, 12.3 months) after the procedure showed continued reduction with a median uterine volume reduction of 48% (P = .0002) and median dominant fibroid volume decrease of 78% (P = .0002). CONCLUSION: In the authors' initial clinical experience, UFE appears effective in controlling symptoms and substantially reducing fibroid volume with few complications.

Apparent lability of neural tube closure in laboratory animals and humans.

Neural tube defects (NTDs), a set of structural abnormalities affecting the brain, spinal cord, and the skeletal and connective tissues that protect them, are common malformations among humans and laboratory animals. The embryogenesis of the neural tube is presented to convey the complexity of the phenomenon, the multiplicity of requisite cellular and subcellular processes, and the precise timing of events that must occur for successful neural tube development. Interruption, even transitory, of any of these intricate processes or disruption of an embryo's developmental schedule can lead to an NTD. The population distribution of human NTDs demonstrates that genetic predisposition functions in susceptibility to NTDs. Data from animal studies support these concepts. NTDs are common outcomes in developmental toxicity safety assessments, occurring among control and treated groups. Numerous agents have caused increased levels of NTDs in laboratory animals, and species with shorter gestational periods appear more prone to toxicant-induced NTDs than those with longer gestations. Data from post-implantation whole embryo culture, although not predictive of human risk, are useful in studying neurulation mechanisms and in demonstrating the importance of maintaining embryonic schedules of development. We conclude that the concept that NTDs are produced by only a few toxicants that selectively target the developing nervous system is untenable. Rather, the combination of the time in gestation that an agent is applied, its dose, and its ability to disrupt critical processes in neurulation leads to NTDs. We further conclude that, because of both the relatively high prevalence and the multifactorial nature of NTDs, the mere occurrence of an NTD is insufficient for inferring that the defect was caused by an exogenous agent.

The Organization of Teratology Information Services (OTIS) Registry Study.

Some population-based studies of the risks of gestational medication use are limited by differential recall or enrollment of mothers of children with abnormalities. Prospective acquisition of exposure information, before knowledge of pregnancy outcome, is the most unbiased manner in which to obtain denominator-based outcome information. The Organization of Teratology Information Services (OTIS) Registry Study will prospectively evaluate pregnancy outcomes in relation to exposures to asthma medications. Patients will be enrolled by participating Teratology Information Services. Information regarding medication exposure, asthma severity, and other important medical events will be assessed during pregnancy by means of standardized interviews, supplemented by medical records. Outcome information will be obtained from copies of the pediatric records. Data analysis will evaluate relative risks of adverse outcomes in exposed compared with unexposed asthmatic and nonasthmatic subjects.

Alternatives to hysterectomy for benign conditions.

Hysterectomy is the second most commonly performed major operation in the United States. Approximately one in three women will have this operation, resulting in 590,000 procedures per year. The most common indications for hysterectomy are leiomyomata uteri, abnormal uterine bleeding, endometriosis, pelvic pain, and pelvic organ prolapse. Although hysterectomy is an appropriate therapeutic option for some women with these conditions, in many instances less radical alternatives may be offered. Leiomyomata may be managed expectantly if symptoms are not bothersome; for women with troubling leiomyomata symptoms, alternatives to hysterectomy include: endoscopic removal or destruction of myomas, arterial embolization, or hormonal therapy to inhibit or modify bleeding. Endometriosis and abnormal uterine bleeding of leiomyomata are both amenable to hormonal therapy. Pelvic pain is most effectively approached with a thorough evaluation (particularly for nongynecologic illness), with specific therapy directed at the cause of the pain. Pelvic organ prolapse may respond symptomatically to pelvic floor exercises, or to the use of a pessary. After alternatives to removal of the uterus are discussed, the informed woman may decide that hysterectomy is the option best suited to her. It is unusual for hysterectomy to be her only option.

An assessment of the developmental toxicity of inorganic arsenic.

A critical analysis of the literature base regarding the reproductive and developmental toxicity of arsenic compounds, with emphasis on inorganic arsenicals, was conducted. The analysis was stimulated by the great number of papers that have purported to have shown an association between exposure of pregnant laboratory animals to arsenic compounds and the occurrence of offspring with cranial neural tube defects, particularly exencephaly. For the most part, the literature reports of arsenic developmental toxicity in experimental animals are inadequate for human risk assessment purposes. Despite the shortcomings of the experimental database, several conclusions are readily apparent when the animal studies are viewed collectively. First, cranial neural tube defects are induced in rodents only when arsenic exposure has occurred early in gestation (on Days 7 [hamster, mouse], 8 [mouse], or 9 [rat]). Second, arsenic exposures that cause cranial neural tube defects are single doses that are so high as to be lethal (or nearly so) to the pregnant animal. Third, the effective routes of exposure are by injection directly into the venous system or the peritoneal cavity; even massive oral exposures do not cause increases in the incidence of total gross malformations. Fourth, repetition of similar study designs employing exaggerated parenteral doses is the source of the large number of papers reporting neural tube defects associated with prenatal arsenic exposure. Fifth, in five repeated dose studies carried out following EPA Guidelines for assessing developmental toxicity, arsenic was not teratogenic in rats (AsIII, 101 micromol/kg/d, oral gavage; 101 micromol/m3, inhalation), mice (AsV, 338 micromol/kg/d, oral gavage; est. 402 micromol/kg/d, diet), or rabbits (AsV, 21 micromol/kg/d, oral gavage). Data regarding arsenic exposure and adverse outcomes of pregnancy in humans are limited to several ecologic epidemiology studies of drinking water, airborne dusts, and smelter environs. These studies failed to (1) obtain accurate measurements of maternal exposure during the critical period of organogenesis and (2) control for recognized confounders. The lone study that examined maternal arsenic exposure during pregnancy and the presence of neural tube defects in progeny failed to confirm a relationship between the two. It is concluded that under environmentally relevant exposure scenarios (e.g., 100 ppm in soil), inorganic arsenic is unlikely to pose a risk to pregnant women and their offspring.