Outcomes after internal versus external tocodynamometry for monitoring labor. N Engl J Med. 2010;362:306–313

Background: It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis.

Methods: We performed a randomized, controlled trial in six hospitals in The Netherlands to compare internal tocodynamometry with external monitoring of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours).

Results: We randomly assigned 1456 women to either internal tocodynamometry (734) or external monitoring (722). The operative-delivery rate was 31.3% in the internal-tocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported.

Conclusion: Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.) 2010 Massachusetts Medical Society.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: A double-blind, randomised, non-inferiority trial. Lancet. 2010;375:217–223. Epub 2010 Jan 6.

Background: Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin.

Methods: In this double-blind, non-inferiority trial, 31,055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 mug misoprostol (n = 407) or 40 IU intravenous oxytocin (n = 402). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350.

Findings: All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95-1.04; crude difference 0.4%, 95% CI−3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09-1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died.

Interpretation: Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour. Copyright 2010 Elsevier Ltd. All rights reserved.

Brainstem serotonergic deficiency in sudden infant death syndrome. JAMA. 2010;303:430–437.

Context: Sudden infant death syndrome (SIDS) is postulated to result from abnormalities in brainstem control of autonomic function and breathing during a critical developmental period. Abnormalities of serotonin (5-hydroxytryptamine [5-HT]) receptor binding in regions of the medulla oblongata involved in this control have been reported in infants dying from SIDS.

Objective: To test the hypothesis that 5-HT receptor abnormalities in infants dying from SIDS are associated with decreased tissue levels of 5-HT, its key biosynthetic enzyme (tryptophan hydroxylase [TPH2]), or both.

Design, Setting, and Participants: Autopsy study conducted to analyze levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); levels of TPH2; and 5-HT(1A) receptor binding. The data set was accrued between 2004 and 2008 and consisted of 41 infants dying from SIDS (cases), 7 infants with acute death from known causes (controls), and 5 hospitalized infants with chronic hypoxia-ischemia.

Main Outcome Measures: Serotonin and metabolite tissue levels in the raphé obscurus and paragigantocellularis lateralis (PGCL); TPH2 levels in the raphé obscurus; and 5-HT(1A) binding density in 5 medullary nuclei that contain 5-HT neurons and 5 medullary nuclei that receive 5-HT projections.

Results: Serotonin levels were 26% lower in SIDS cases (n = 35) compared with age-adjusted controls (n = 5) in the raphé obscurus (55.4 [95% confidence interval {CI}, 47.2-63.6] vs 75.5 [95% CI, 54.2-96.8] pmol/mg protein, p = .05) and the PGCL (31.4 [95% CI, 23.7-39.0] vs 40.0 [95% CI, 20.1-60.0] pmol/mg protein, p = .04). There was no evidence of excessive 5-HT degradation assessed by 5-HIAA levels, 5-HIAA:5-HT ratio, or both. In the raphé obscurus, TPH2 levels were 22% lower in the SIDS cases (n = 34) compared with controls (n = 5) (151.2% of standard [95% CI, 137.5%-165.0%] vs 193.9% [95% CI, 158.6%-229.2%], p = .03). 5-HT(1A) receptor binding was 29% to 55% lower in 3 medullary nuclei that receive 5-HT projections. In 4 nuclei, 3 of which contain 5-HT neurons, there was a decrease with age in 5-HT(1A) receptor binding in the SIDS cases but no change in the controls (age x diagnosis interaction). The profile of 5-HT and TPH2 abnormalities differed significantly between the SIDS and hospitalized groups (5-HT in the raphé obscurus: 55.4 [95% CI, 47.2-63.6] vs 85.6 [95% CI, 61.8-109.4] pmol/mg protein, p = .02; 5-HT in the PGCL: 31.4 [95% CI, 23.7-39.0] vs 71.1 [95% CI, 49.0-93.2] pmol/mg protein, p = .002; TPH2 in the raphé obscurus: 151.2% [95% CI, 137.5%-165.0%] vs 102.6% [95% CI, 58.7%-146.4%], p = .04).

Conclusion: Compared with controls, SIDS was associated with lower 5-HT and TPH2 levels, consistent with a disorder of medullary 5-HT deficiency.

Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010 Jan 12;340:b5463. doi: 10.1136/bmj.b5463.

Objectives: To identify participants' characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium.

Design: Individual patient data analysis using pooled data from randomised trials.

Data Sources: Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68,517 participants (mean age 69.9 years, range 47–107 years, 14.7% men).

Study Selection: Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants.

Data Synthesis: Logistic regression analysis was used to identify significant interaction terms, followed by Cox's proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use.

Results: Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, p = 0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, p = 0.07; studies using 10 microg of vitamin D given with calcium: 0.74, 0.60 to 0.91, p = 0.005). For vitamin D alone in daily doses of 10 microg or 20 microg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy.

Conclusion: This individual patient data analysis indicates that vitamin D given alone in doses of 10–20 microg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.

An integrated intervention to reduce intimate partner violence in pregnancy: A randomized controlled trial. Obstet Gynecol. 2010;115(2 Pt 1):273–283.

Objective: To estimate the efficacy of a psycho-behavioral intervention in reducing intimate partner violence recurrence during pregnancy and postpartum and in improving birth outcomes in African-American women.

Methods: We conducted a randomized controlled trial for which 1,044 women were recruited. Women were randomly assigned to receive either intervention (n = 521) or usual care (n = 523). Individually tailored counseling sessions were adapted from evidence-based interventions for intimate partner violence and other risks. Logistic regression was used to model intimate partner violence victimization recurrence and to predict minor, severe, physical, and sexual intimate partner violence.

Results: Women randomly assigned to the intervention group were less likely to have recurrent episodes of intimate partner violence victimization (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.29-0.80). Women with minor intimate partner violence were significantly less likely to experience further episodes during pregnancy (OR 0.48, 95% CI 0.26-0.86, OR 0.53, 95% CI 0.28-0.99) and postpartum (OR 0.56, 95% CI 0.34-0.93). Numbers needed to treat were 17, 12, and 22, respectively, as compared with the usual care group. Women with severe intimate partner violence showed significantly reduced episodes postpartum (OR 0.39, 95% CI 0.18–0.82); the number needed to treat was 27. Women who experienced physical intimate partner violence showed significant reduction at the first follow-up (OR 0.49, 95% CI 0.27–0.91) and postpartum (OR 0.47, 95% CI 0.27–0.82); the numbers needed to treat were 18 and 20, respectively. Women in the intervention group had significantly fewer very preterm neonates (1.5% intervention group, 6.6% usual care group; p = .03) and an increased mean gestational age (38.2+/−3.3 intervention group, 36.9+/−5.9 usual care group; p = .016).

Conclusion: A relatively brief intervention during pregnancy had discernible effects on intimate partner violence and pregnancy outcomes. Screening for intimate partner violence as well as other psychosocial and behavioral risks and incorporating similar interventions in prenatal care is strongly recommended.

Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00381823.

Level of Evidence: I.

Omega-3 fatty acid supplementation to prevent recurrent preterm birth: A randomized controlled trial. Obstet Gynecol. 2010 Feb;115(2 Pt 1):234–42.

Objective: To assess whether the addition of an omega-3 long-chain polyunsaturated fatty acid supplement would reduce preterm birth in women with at least one prior spontaneous preterm birth receiving 17alpha-hydroxyprogesterone caproate.

Methods: We conducted a randomized, double-masked, placebo-controlled trial in 13 centers. Women with a history of prior spontaneous singleton preterm birth and a current singleton gestation were assigned to either a daily omega-3 supplement (1,200 mg eicosapentaenoic acid and 800 mg docosahexaenoic acid) or matching placebo from 16–22 through 36 weeks of gestation. All participants received weekly intramuscular 17alpha-hydroxyprogesterone caproate (250 mg). The primary study outcome was delivery before 37 weeks of gestation. A sample size of 800 was necessary to have 80% power to detect a 30% reduction in the primary outcome from 30%, assuming a type I error two-sided of 5%.

Results: A total of 852 women were included, and none was lost to follow up. Delivery before 37 weeks of gestation occurred in 37.8% (164/434) of women in the omega-3 group and 41.6% (174/418) in the placebo group (relative risk 0.91, 95% confidence interval 0.77–1.07).

Conclusion: Omega-3 long-chain polyunsaturated fatty acid supplementation offered no benefit in reducing preterm birth among women receiving 17alpha-hydroxyprogesterone caproate who have a history of preterm delivery.

Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.

Level of Evidence: I.

Trends in birth weight and gestational length among singleton term births in the United States: 1990–2005. Obstet Gynecol. 2010;115(2 Pt 1):357–364.

Objective: To estimate changes over time in birth weight for gestational age and in gestational length among term singleton neonates born from 1990 to 2005.

Methods: We used data from the U.S. National Center for Health Statistics for 36,827,828 singleton neonates born at 37–41 weeks of gestation, 1990–2005. We examined trends in birth weight, birth weight for gestational age, large and small for gestational age, and gestational length in the overall population and in a low-risk subgroup defined by maternal age, race or ethnicity, education, marital status, smoking, gestational weight gain, delivery route, and obstetric care characteristics.

Results: In 2005, compared with 1990, we observed decreases in birth weight (−52 g in the overall population, −79 g in a homogenous low-risk subgroup) and large for gestational age birth (−1.4% overall, −2.2% in the homogenous subgroup) that were steeper after 1999 and persisted in regression analyses adjusted for maternal and neonate characteristics, gestational length, cesarean delivery, and induction of labor. Decreases in mean gestational length (−0.34 weeks overall) were similar regardless of route of delivery or induction of labor.

Conclusion: Recent decreases in fetal growth among U.S., term, singleton neonates were not explained by trends in maternal and neonatal characteristics, changes in obstetric practices, or concurrent decreases in gestational length.

Level of Evidence: III.

Menopausal hormone therapy use and risk of invasive colon cancer: The California Teachers Study. Am J Epidemiol. 2010;171:415–425. Epub 2010 Jan 11.

Results from epidemiologic studies of hormone therapy use and colon cancer risk are inconsistent. This question was investigated in the California Teachers Study (1995–2006) among 56,864 perimenopausal or postmenopausal participants under 80 years of age with no prior colorectal cancer by using Cox proportional hazards regression. Incident invasive colon cancer was diagnosed among 442 participants. Baseline-recent hormone therapy users were at 36% lower risk for colon cancer versus baseline-never users (baseline-recent users: relative risk (RR) = 0.64, 95% confidence interval (CI): 0.51, 0.80). Results did not differ by formulation. Estimated risk was lower among baseline-recent hormone therapy users with increasing duration between 5 and 15 years of use (RR = 0.49, 95% CI: 0.35, 0.68), but the trend did not persist in the longest duration group, more than 15 years of use (RR = 0.69, 95% CI: 0.52, 0.92; p(trend) = 0.60). Long-term recreational physical activity, obesity, regular use of nonsteroidal antiinflammatory medications, and daily alcohol intake did not modify these effects; baseline-recent use was more strongly associated with colon cancer risk among women with a family history of colorectal cancer [p(heterogeneity) = 0.04]. Baseline-recent hormone therapy use was inversely associated with invasive colon cancer risk among perimenopausal and postmenopausal women in the California Teachers Study.

Operative mortality in women and men undergoing coronary artery bypass grafting (from the California Coronary Artery Bypass Grafting Outcomes Reporting Program). Am J Cardiol. 2010;105:339–342. Epub 2009 Dec 21.

The comparative operative mortality (OM) in women and men undergoing isolated coronary artery bypass graft surgery (CABG) has not been clarified. Therefore, we evaluated factors related to OM in a large cohort of women and men undergoing isolated CABG. Results from 121 hospitals on patients undergoing isolated CABG in 2003 and 2004 were analyzed according to gender, including demographics, clinical characteristics, and surgical outcome. A total of 10,708 women and 29,669 men had isolated CABG in 2003 to 2004. Observed mortality in women was significantly higher than in men (4.60% vs 2.53%, p < 0.0001). Although men had a higher prevalence of >3 diseased coronary arteries and left ventricular dysfunction, women were more likely to be older, diabetic, have stage 3 to 5 chronic kidney disease, chronic lung disease, and nonelective CABG. Women were less likely to receive an internal mammary artery graft. Multivariate analysis indicated that women were at higher risk for OM than men (odds ratio 1.61, 95% confidence interval 1.40 to 1.84). In conclusion, data from the large state-mandated CCORP indicate that women are at increased risk of OM after isolated CABG compared to men, despite adjustment for preoperative risk factors. Copyright 2010 Elsevier Inc. All rights reserved.

Universal Screening Versus Case Finding for Detection and Treatment of Thyroid Hormonal Dysfunction During Pregnancy. J Clin Endocrinol Metab. 2010 Feb 3. [Epub ahead of print]

Thyroid disease during pregnancy has been associated with multiple adverse outcomes. Whether all women should be screened for thyroid disease during pregnancy is controversial.

Objective: The objective of the study was to determine whether treatment of thyroid disease during pregnancy decreases the incidence of adverse outcomes and compare the ability of universal screening vs. case finding in detecting thyroid dysfunction.

Design: Women in the first trimester were randomly assigned to the universal screening group or case-finding group. Women in both groups were stratified as high risk or low risk based on risk factors for thyroid disease. All women in the universal screening group, and high-risk women in the case-finding group, were immediately tested for free T4, TSH, and thyroid peroxidase antibody. Low-risk women in the case-finding group had their sera tested postpartum.

Setting: The study was conducted at two ambulatory clinics of community hospitals in southern Italy.

Patients: A total of 4562 women were randomly assigned to the universal screening or case-finding group.

Intervention: Intervention included levothyroxine in women with a TSH above 2.5 mIU/liter in TPO antibody-positive women and antithyroid medication in women with a undetectable TSH and elevated free T4.

Main Outcome Measure: Total number of adverse obstetrical and neonatal outcomes was measured.

Results: No significant differences were seen in adverse outcomes between the case-finding and universal screening groups. Adverse outcomes were less likely to occur among low-risk women in the screening group than those in the case-finding group.

Conclusions: Universal screening compared with case finding did not result in a decrease in adverse outcomes. Treatment of hypothyroidism or hyperthyroidism identified by screening a low-risk group was associated with a lower rate of adverse outcomes.

Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women. J Clin Endocrinol Metab. 2010;95:740–747. Epub 2009 Nov 24.

Context: Few studies have examined whether endogenous testosterone is associated with the development of coronary heart disease (CHD) in women.

Objective: This study tested the association of total testosterone (total T) and bioavailable T (BioT) levels with risk of incident coronary events among older community-dwelling women.

Design, Setting, and Participants: This was a prospective, population-based study of 639 postmenopausal women, aged 50–91 (mean, 73.8) yr who had serum testosterone measurements at baseline (1984–87) and who were followed for incident CHD events through 2004.

Main Outcome Measures: A total of 134 incident CHD events occurred during follow-up [45 nonfatal myocardial infarctions, 79 fatal myocardial infarctions, and 10 coronary revascularizations].

Results: The median follow-up was 12.3 yr. Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest, suggesting a low threshold. In age-adjusted analyses, the lowest total T quintile (</= 80 pg/ml) was associated with a 1.62-fold increased risk of incident CHD [95% confidence interval (CI), 1.10–2.39] compared to higher levels. BioT showed a U-shaped association with incident CHD. Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 (95% CI, 1.03–3.16) and 1.96 (95% CI, 1.13–3.41), respectively. Additional adjustment for lifestyle, adiposity, estradiol, and ovarian status, or for CHD risk factor covariates, had minimal influence on results.

Conclusions: An optimal range of testosterone may exist for cardiovascular health in women, with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone.

Prevention of Bone Loss by Zoledronic Acid in Premenopausal Women Undergoing Adjuvant Chemotherapy Persist up to One Year following Discontinuing Treatment. J Clin Endocrinol Metab. 2010;95:559–566. Epub 2009 Dec 18.

Context: Adjuvant chemotherapy is associated with significant reductions in bone mineral density (BMD) in premenopausal women with breast cancer (BC) that is prevented with zoledronic acid (ZA) every 3 months for 1 yr.

Objective: The aim of the study was to examine the effect on BMD of discontinuing ZA during the subsequent year.

Design: We conducted a randomized, double-blind trial.

Patients: Premenopausal women (mean age, 42 yr) undergoing adjuvant chemotherapy for BC participated in the study.

Intervention: ZA (4 mg iv every 3 months) vs. placebo was administered for 12 months.

Outcome Measures: We measured percentage change in BMD and bone turnover markers at 12 and 24 months (1 yr after last infusion).

Results: Of 101 women randomized, 85 completed 12-month and 62 completed 24-month evaluations. In the placebo group, serum C-telopeptide (CTX) increased progressively over the first 12 months, returned toward baseline but remained significantly above baseline by 24 months. Lumbar spine BMD decreased from baseline by 5.5% at 12 and 6.3% at 24 months. Similarly, by 24 months, total hip and femoral neck BMD declined by 2.6 and 2.4%, respectively. In ZA patients, BMD remained stable (p < 0.0001 compared to placebo). Serum CTX declined significantly by 6 months, but returned to baseline by 12 months, remaining there at 24 months.

Conclusions: Premenopausal women receiving chemotherapy for BC sustained significant bone loss during the first year, without recovery during the second year. ZA effectively prevented bone loss during the first year of chemotherapy. BMD remained stable 1 yr after completion of ZA. Serum CTX increased significantly by 12 and 24 months. More frequent administration may be required to suppress bone resorption in this patient population.

Prepregnancy overweight and gestational diabetes as determinants of subsequent diabetes and hypertension after 20-year follow-up. J Clin Endocrinol Metab. 2010;95:772–778. Epub 2009 Dec 1.

Context: Overweight is a strong risk factor for gestational diabetes (GDM), and both states indicate increased risk for subsequent metabolic syndrome. Data separating effects of overweight and GDM on risk for metabolic diseases are limited.

Objective: The aim of the study was to evaluate prepregnancy overweight and GDM as determinants of risk for subsequent diabetes and hypertension.

Design: Population-based data from the Northern Finland Birth Cohort 1986 were compounded with register-based data on diagnosis of diabetes and hypertension.

Setting: The study was conducted in Northern Finland.

Participants: We studied: 1) normal-weight women with GDM (n = 70); 2) overweight women with GDM (n = 54); 3) normal-weight (n = 768); and 4) overweight (n = 250) women with risk factors for GDM but normal oral glucose tolerance test results; and 5) women with no risk factors for GDM (n = 5341).

Main Outcome Measures: We measured cumulative incidence of diabetes and hypertension, hazard ratio (HR), and population-attributable fraction (PAF) for determinants of risk.

Results: The cumulative incidence of diagnosed diabetes and hypertension in the whole study population was 1.3 and 7.5%, respectively. Concomitant overweight and GDM indicated high risks for diabetes (HR, 47.24; PAF, 15.8%) and hypertension (HR, 9.16; PAF, 4.4%). Even when the OGTT in pregnancy was normal, prepregnancy overweight associated with risks for diabetes (HR, 12.63; PAF, 22.2%) and hypertension (HR, 2.86; PAF, 6.0%). In normal-weight women, GDM indicated risk for diabetes (HR, 10.61; PAF, 5.2%) but not for hypertension.

Conclusions: Prepregnancy overweight is an essential risk factor for subsequent diabetes and hypertension, especially when combined with GDM.

Predictive Value of Symptoms for Early Detection of Ovarian Cancer. J Natl Cancer Inst. 2010 Jan 28. [Epub ahead of print]

Background: A recent consensus statement encouraged use of certain symptoms to diagnose ovarian cancer earlier. We assessed the sensitivity, specificity, and positive predictive value of a proposed symptom index and of symptoms included in the consensus recommendation.

Methods: In-person interviews were conducted with 812 case patients, aged 35–74 years, who had epithelial ovarian cancer that was diagnosed from January 1, 2002, through December 31, 2005, and with 1313 population-based control subjects. The symptom index was considered positive when pelvic or abdominal pain or bloating or feeling full was reported at least daily for at least 1 week, with an onset of less than 12 months before diagnosis or a reference date (for control subjects). The consensus criteria were considered fulfilled when any symptom above or urinary urgency or frequency was reported for at least 1 month, with an onset of less than 12 months before diagnosis or a reference date. Positive predictive value was calculated by use of external estimates of cancer prevalence.

Results: Most case patients who had a positive index or met consensus criteria did so only within 5 months before diagnosis. Symptoms (except nausea) were somewhat less likely to have occurred among women diagnosed with early-stage than late-stage ovarian cancer. The estimated positive predictive value of the symptom index or symptoms meeting the consensus criteria was 0.6%–1.1% overall and less than 0.5% for early-stage disease.

Conclusion: Use of symptoms to trigger medical evaluation for ovarian cancer is likely to result in diagnosis of the disease in only one of 100 women in the general population with such symptoms.