The relationship between dietary supplement use in late pregnancy and birth outcomes: A cohort study in British women. BJOG. 2010 Mar 29. [Epub ahead of print] DOI: 10.1111/j.1471-0528.2010.02549.x.

Objective: To examine the relationship between dietary supplement use during pregnancy and birth outcomes.

Design: A prospective birth cohort.

Setting: Leeds, UK.

Sample: One thousand two hundred and seventy-four pregnant women aged 18–45 years.

Methods: Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8–12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records.

Main outcome measures: Birthweight, birth centile and preterm birth.

Results: Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitamin-mineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, p = 0.02).

Conclusions: Regular multivitamin-mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study's findings need confirming by other cohorts and/or trials in developed countries.

Critical illness due to 2009 A/H1N1 influenza in pregnant and postpartum women: Population based cohort study. BMJ. 2010;340:c1279. doi: 10.1136/bmj.c1279.

Objective: To describe the epidemiology of 2009 A/H1N1 influenza in critically ill pregnant women.

Design: Population based cohort study.

Setting: All intensive care units in Australia and New Zealand.

Participants: All women with 2009 H1N1 influenza who were pregnant or recently post partum and admitted to an intensive care unit in Australia or New Zealand between 1 June and 31 August 2009.

Main Outcome Measures: Maternal and neonatal mortality and morbidity.

Results: 64 pregnant or postpartum women admitted to an intensive care unit had confirmed 2009 H1N1 influenza. Compared with non-pregnant women of childbearing age, pregnant or postpartum women with 2009 H1N1 influenza were at increased risk of admission to an intensive care unit (relative risk 7.4, 95% confidence interval 5.5 to 10.0). This risk was 13-fold greater (13.2, 9.6 to 18.3) for women at 20 or more weeks' gestation. At the time of admission to an intensive care unit, 22 women (34%) were post partum and two had miscarried. 14 women (22%) gave birth during their stay in intensive care and 26 (41%) were discharged from an intensive care unit with ongoing pregnancy. All subsequently delivered. 44 women (69%) were mechanically ventilated. Of these, nine (14%) were treated with extracorporeal membrane oxygenation. Seven women (11%) died. Of 60 births after 20 weeks' gestation, four were stillbirths and three were infant deaths. 22 (39%) of the liveborn babies were preterm and 32 (57%) were admitted to a neonatal intensive care unit. Of 20 babies tested, two were positive for the 2009 H1N1 virus.

Conclusions: Pregnancy is a risk factor for critical illness related to 2009 H1N1 influenza, which causes maternal and neonatal morbidity and mortality.

Vitamins C and E to prevent complications of pregnancy-associated hypertension. N Engl J Med. 2010;362:1282–1291.

Background: Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder. We assessed the effects of antioxidant supplementation with vitamins C and E, initiated early in pregnancy, on the risk of serious adverse maternal, fetal, and neonatal outcomes related to pregnancy-associated hypertension.

Methods: We conducted a multicenter, randomized, double-blind trial involving nulliparous women who were at low risk for preeclampsia. Women were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the 9th and 16th weeks of pregnancy. The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death.

Results: A total of 10,154 women underwent randomization. The two groups were similar with respect to baseline characteristics and adherence to the study drug. Outcome data were available for 9969 women. There was no significant difference between the vitamin and placebo groups in the rates of the primary outcome (6.1% and 5.7%, respectively; relative risk in the vitamin group, 1.07; 95% confidence interval [CI], 0.91 to 1.25) or in the rates of preeclampsia (7.2% and 6.7%, respectively; relative risk, 1.07; 95% CI, 0.93 to 1.24). Rates of adverse perinatal outcomes did not differ significantly between the groups.

Conclusions: Vitamin C and E supplementation initiated in the 9th to 16th week of pregnancy in an unselected cohort of low-risk, nulliparous women did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension (ClinicalTrials.gov number, NCT00135707). 2010 Massachusetts Medical Society.

Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010 Mar 24 [Epub ahead of print]

Background: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs.

Methods: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events.

Results: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, −2.6 percentage points; 95% confidence interval [CI], −15.0 to 9.9; aspirin only vs. placebo, −6.2 percentage points; 95% CI, −18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, −10.8 to 15.0; aspirin alone vs. placebo −5.4 percentage points; 95% CI, −18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups.

Conclusions: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.) Copyright 2010 Massachusetts Medical Society.

In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus. Am J Epidemiol. 2010;171:868–875 Epub 2010 Mar 25.

In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996 and 2003. Maternal smoking was associated with a significantly elevated risk of strabismus in the child, increasing with number of cigarettes smoked per day (<5 cigarettes/day: relative risk (RR) = 0.95, 95% confidence interval (CI): 0.80, 1.14; 5-<10 cigarettes/day: RR = 1.38, 95% CI: 1.12, 1.70; > or = 10 cigarettes/day: RR = 1.90, 95% CI: 1.57, 2.30). Nicotine replacement therapy was not associated with strabismus risk (RR = 1.22, 95% CI: 0.92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light alcohol consumption is associated with decreased risk.

Parity and risk of hemorrhagic strokes. Neurology. 2010 Mar 24. [Epub ahead of print]

Objectives: The association between parity and risk of hemorrhagic stroke (HS) remains to be clarified. This study assessed the association of parity with the overall risk of HS and compared its contribution to intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH).

Methods: We used a database from a nationwide multicenter case-control study, in which 471 female cases with incident HS were matched at 1:2 with 942 community or hospital controls. A total of 459 HS cases and 918 controls with information on parity were included. Parity was categorized as 0–1, 2, 3, and >/=4. Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated by conditional logistic regression. As potential confounders, age, history of hypertension, history of diabetes, family history of stroke, smoking status, alcohol consumption, educational status, age at menarche, and use of oral contraceptives were included in the models.

Results: Compared with nullipara and unipara, women with parity of 2, 3, and >/=4 had significantly higher risk for total HS, ICH, and SAH, respectively. Each additional parity increased the ORs of HS (adjusted OR for total HS = 1.27 [95% CI 1.14-1.41]; adjusted OR for SAH = 1.34 [95% CI 1.13-1.58]; adjusted OR for ICH = 1.27 [95% CI 1.08-1.48]). Likelihood ratio test for trends showed a significantly increased risk with increasing parity for total HS and for both types of HS (p trend < 0.05 in all analyses).

Conclusions: Increased number of childbirths may be related to an increased risk of both intracerebral hemorrhage and subarachnoid hemorrhage.

A prospective study of dietary fat consumption and endometriosis risk. Hum Reprod. 2010 Mar 23. [Epub ahead of print]

Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies.

Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires.

Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62-0.99; p-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17-1.88; Pt = 0.001).

Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply.

Efficacy of human papillomavirus testing for the detection of invasive cervical cancers and cervical intraepithelial neoplasia: A randomised controlled trial. Lancet Oncol. 2010;11:249–257. Epub 2010 Jan 18.

Background: Human papillomavirus (HPV) testing is known to be more sensitive, but less specific than cytology for detecting cervical intraepithelial neoplasia (CIN). We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing.

Methods: Between March, 2004, and December, 2004, in two separate recruitment phases, women aged 25–60 years were randomly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology (first phase) or alone (second phase). Randomisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres. During phase one, women who were HPV-positive and aged 35–60 years were referred to colposcopy, whereas women aged 25–34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive. During phase two, women in the HPV group were referred for colposcopy if the HPV test was positive. Two rounds of screening occurred in each phase, and all women had cytology testing only at the second round. The primary endpoint was the detection of grade 2 and 3 CIN, and of invasive cervical cancers during the first and second screening rounds. Analysis was done by intention to screen. This trial is registered, number ISRCTN81678807.

Findings: In total for both phases, 47,001 women were randomly assigned to the cytology group and 47,369 to HPV testing. 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening. We also retrieved the histological diagnoses from screening done elsewhere. The detection of invasive cervical cancers was similar for the two groups in the first round of screening (nine in the cytology group vs seven in the HPV group, p = 0.62); no cases were detected in the HPV group during round two, compared with nine in the cytology group (p = 0.004). Overall, in the two rounds of screening, 18 invasive cancers were detected in the cytology group versus seven in the HPV group (p = 0.028). Among women aged 35–60 years, at round one the relative detection (HPV vs cytology) was 2.00 (95% CI 1.44-2.77) for CIN2, 2.08 (1.47-2.95) for CIN3, and 2.03 (1.60-2.57) for CIN2 and 3 together. At round two the relative detection was 0.54 (0.23-1.28) for CIN2, 0.48 (0.21-1.11) for CIN3, and 0.51 (0.28-0.93) for CIN2 and 3 together. Among women aged 25–34 years, there was significant heterogeneity between phases in the relative detection of CIN3. At round one the relative detection was 0.93 (0.52-1.64) in phase one and 3.91 (2.02-7.57) in phase two. At round two the relative detection was 1.34 (0.46-3.84) in phase one and 0.20 (0.04-0.93) in phase two. Pooling both phases, the detection ratio of CIN2 for women aged 25–34 years was 4.09 (2.24-7.48) at round one and 0.64 (0.23-1.27) at round two.

Interpretation: HPV-based screening is more effective than cytology in preventing invasive cervical cancer, by detecting persistent high-grade lesions earlier and providing a longer low-risk period. However, in younger women, HPV screening leads to over-diagnosis of regressive CIN2.

Funding: European Union, Italian Ministry of Health, Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia-Romagna, and Public Health Agency of Lazio. Copyright 2010 Elsevier Ltd. All rights reserved.

Physical activity and change in mammographic density: The study of women's health across the nation. Am J Epidemiol. 2010 Mar 30. [Epub ahead of print]

One potential mechanism by which physical activity may protect against breast cancer is by decreasing mammographic density. Percent mammographic density, the proportion of dense breast tissue area to total breast area, declines with age and is a strong risk factor for breast cancer. The authors hypothesized that women who were more physically active would have a greater decline in percent mammographic density with age, compared with less physically active women. The authors tested this hypothesis using longitudinal data (1996–2004) from 722 participants in the Study of Women's Health across the Nation (SWAN), a multiethnic cohort of women who were pre- and early perimenopausal at baseline, with multivariable, repeated-measures linear regression analyses. During an average of 5.6 years, the mean annual decline in percent mammographic density was 1.1% (standard deviation = 0.1). A 1-unit increase in total physical activity score was associated with a weaker annual decline in percent mammographic density by 0.09% (standard error = 0.03; p = 0.01). Physical activity was inversely associated with the change in nondense breast area (p < 0.01) and not associated with the change in dense breast area (p = 0.17). Study results do not support the hypothesis that physical activity reduces breast cancer through a mechanism that includes reduced mammographic density.

Systematic review: Surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med. 2010;152:444–455; W144–154.

Background: Women treated with therapeutic chest radiation may develop breast cancer.

Purpose: To summarize breast cancer risk and breast cancer surveillance in women after chest radiation for pediatric or young adult cancer.

Data Sources: Studies from MEDLINE, EMBASE, the Cochrane Library, and CINAHL (1966 to December 2008).

Study Selection: Articles were selected to answer any of 3 questions: What is the incidence and excess risk for breast cancer in women after chest radiation for pediatric or young adult cancer? For these women, are the clinical characteristics of breast cancer and the outcomes after therapy different from those of women with sporadic breast cancer in the general population? What are the potential benefits and harms associated with breast cancer surveillance among women exposed to chest radiation?

Data Extraction: Three investigators independently extracted data and assessed study quality.

Data Synthesis: Standardized incidence ratios ranged from 13.3 to 55.5; cumulative incidence of breast cancer by age 40 to 45 years ranged from 13% to 20%. Risk for breast cancer increased linearly with chest radiation dose. Available limited evidence suggests that the characteristics of breast cancer in these women and the outcomes after diagnosis are similar to those of women in the general population; mammography can detect breast cancer, although sensitivity is limited.

Limitation: The quality of evidence for key questions 2 and 3 is limited by substantial study heterogeneity, variation in study design, and small sample size.

Conclusion: Women treated with chest radiation have a substantially elevated risk for breast cancer at a young age, which does not seem to plateau. In this high-risk population, there seems to be a benefit associated with early detection. Further research is required to better define the harms and benefits of lifelong surveillance.

Recovery of bone mineral density in adolescents following the use of depot medroxyprogesterone acetate contraceptive injections. Contraception. 2010;81:281–291. Epub 2009 Dec 14.

Background: Depot medroxyprogesterone acetate (DMPA) is a highly effective progestin-only contraceptive that is widely used by adolescents. We investigated bone mineral density (BMD) changes in female adolescents during and following use of this method.

Study Design: A multicenter, prospective, non-randomized observational study in 98 healthy female adolescents aged 12–18 years who initiated DMPA intramuscular injections for contraception and provided BMD data for up to 240 weeks while receiving DMPA and for up to 300 weeks after DMPA cessation. BMD at the lumbar spine (LS), total hip (TH) and femoral neck (FN) was assessed by dual-energy X-ray absorptiometry. A mixed model analysis of variance was used to examine BMD changes.

Results: At the time of their final DMPA injection, participants had mean BMD declines from baseline of 2.7% (LS), 4.1% (TH) and 3.9% (FN) (p < .001 at all three sites). Within 60 weeks of discontinuation of DMPA, mean LS BMD had returned to baseline levels, and 240 weeks after DMPA discontinuation, the mean LS BMD was 4.7% above baseline. Mean TH and FN BMD values recovered to baseline values more slowly: 240 weeks and 180 weeks, respectively, after the last DMPA injection.

Conclusions: BMD loss in female adolescents receiving DMPA for contraception is substantially or fully reversible in most girls following discontinuation of DMPA, with faster recovery at the LS than at the hip. Copyright 2010 Elsevier Inc. All rights reserved.

A comparison of prediction models for fractures in older women: Is more better? Arch Intern Med. 2009;169:2087–2094.

Background: A Web-based risk assessment tool (FRAX) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. However, it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models.

Methods: We conducted a prospective cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX models without BMD with simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models.

Results: The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip (AUC, 0.75 for the FRAX model and 0.76 for the simple model; p = .26), major osteoporotic (AUC, 0.68 for the FRAX model and 0.69 for the simple model; p = .51), and clinical fracture (AUC, 0.64 for the FRAX model and 0.63 for the simple model; p = .16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models (p > or = .16).

Conclusion: Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX models.

Effect of pregnancy on maternal asthma symptoms and medication use. Obstet Gynecol. 2010;115:559–567.

Objective: To examine whether factors related to the patient or her treatment influence asthma severity during pregnancy.

Methods: Symptom and medication data were collected by in-person and telephone interviews. Women were recruited before 24 weeks of gestation through private obstetricians and hospital clinics. Eight hundred seventy-two women had physician-diagnosed asthma, 686 were active asthmatics, and 641 with complete data were analyzed. The Global Initiative for Asthma measured severity. Cumulative logistic regression models for repeated measures assessed changes in asthma severity during each month of pregnancy.

Results: Two factors had significant and profound effects on the course of asthma: prepregnancy severity and use of medication according to Global Initiative for Asthma guidelines. Although several factors were analyzed (race, age, atopic status, body mass index, parity, fetal sex, and smoking), none were significant risk factors for changes in asthma severity, measured in a clinically important way as a one-step change in Global Initiative for Asthma category. Women with milder asthma received most benefit from appropriate treatment, 62% decreased risk for worsening asthma among those with intermittent asthma (0.38, 95% confidence interval 0.23-0.64) and 52% decreased risk among those with mild persistent asthma (odds ratio 0.48, 95% confidence interval 0.28-0.84). Month or trimester of gestation was not consistently associated with changes in asthma severity.

Conclusion: Asthma severity during pregnancy is similar to severity in the year before pregnancy, provided patients continue to use their prescribed medication. If women discontinue medication, even mild asthma is likely to become significantly more severe.

Trends in the diagnosis and treatment of ectopic pregnancy in the United States. Obstet Gynecol. 2010;115:495–502.

Objective: To estimate trends in the rates of diagnosis and treatment of ectopic pregnancy in the United States.

Methods: We analyzed data from a large administrative claims database of more than 200 U.S. commercial health plans, and estimated time trends in the rate and incidence of ectopic pregnancy among girls and women aged 15–44 years by 5-year age groups and by region from 2002 to 2007. We also estimated time trends in the proportion of cases that were treated surgically, either by laparoscopy or laparotomy, or medically with methotrexate.

Results: We identified 11,989 ectopic pregnancies during the period from 2002 to 2007. The overall rate of ectopic pregnancy among pregnant girls and women aged 15–44 years during the 6-year study period was 0.64%. We did not observe a trend in the rate of ectopic pregnancy by 5-year age group or by geographic region. The ectopic pregnancy rate increased with age; it was 0.3% among girls and women aged 15–19 years and 1.0% among women aged 35–44 years. Methotrexate treatment increased from 11.1% in 2002 to 35.1% in 2007 (p < .001); the methotrexate failure rate was 14.7% over the 6-year study period. Surgical management with laparotomy decreased over the study period from 40.0% to 33.1% (p < .001).

Conclusion: We did not find an increasing or decreasing trend in the rate of ectopic pregnancy among U.S. commercially insured women from 2002 to 2007. The use of administrative claims data are likely the most feasible method for estimating the rate and monitoring trends of ectopic pregnancy in the United States.

Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: The EVA trial. J Clin Oncol. 2010;28:1450–1457. Epub 2010 Feb 22.

Purpose: We investigated the respective contribution (in terms of cancer yield and stage at diagnosis) of clinical breast examination (CBE), mammography, ultrasound, and quality-assured breast magnetic resonance imaging (MRI), used alone or in different combination, for screening women at elevated risk for breast cancer.

Methods: Prospective multicenter observational cohort study. Six hundred eighty-seven asymptomatic women at elevated familial risk (>or = 20% lifetime) underwent 1,679 annual screening rounds consisting of CBE, mammography, ultrasound, and MRI, read independently and in different combinations. In a subgroup of 371 women, additional half-yearly ultrasound and CBE was performed more than 869 screening rounds. Mean and median follow-up was 29.18 and 29.09 months.

Results: Twenty-seven women were diagnosed with breast cancer: 11 ductal carcinoma in situ (41%) and 16 invasive cancers (59%). Three (11%) of 27 were node positive. All cancers were detected during annual screening; no interval cancer occurred; no cancer was identified during half-yearly ultrasound. The cancer yield of ultrasound (6.0 of 1,000) and mammography (5.4 of 1,000) was equivalent; it increased nonsignificantly (7.7 of 1,000) if both methods were combined. Cancer yield achieved by MRI alone (14.9 of 1,000) was significantly higher; it was not significantly improved by adding mammography (MRI plus mammography: 16.0 of 1,000) and did not change by adding ultrasound (MRI plus ultrasound: 14.9 of 1,000). Positive predictive value was 39% for mammography, 36% for ultrasound, and 48% for MRI.

Conclusion: In women at elevated familial risk, quality-assured MRI screening shifts the distribution of screen-detected breast cancers toward the preinvasive stage. In women undergoing quality-assured MRI annually, neither mammography, nor annual or half-yearly ultrasound or CBE will add to the cancer yield achieved by MRI alone.

Aspirin intake and survival after breast cancer. J Clin Oncol. 2010;28:1467–1472. Epub 2010 Feb 16

Purpose: Animal and in vitro studies suggest that aspirin may inhibit breast cancer metastasis. We studied whether aspirin use among women with breast cancer decreased their risk of death from breast cancer.

Methods: This was a prospective observational study based on responses from 4,164 female registered nurses in the Nurses' Health Study who were diagnosed with stages I, II, or III breast cancer between 1976 and 2002 and were observed until death or June 2006, whichever came first. The main outcome was breast cancer mortality risk according to number of days per week of aspirin use (0, 1, 2 to 5, or 6 to 7 days) first assessed at least 12 months after diagnosis and updated.

Results: There were 341 breast cancer deaths. Aspirin use was associated with a decreased risk of breast cancer death. The adjusted relative risks (RRs) for 1, 2 to 5, and 6 to 7 days of aspirin use per week compared with no use were 1.07 (95% CI, 0.70 to 1.63), 0.29 (95% CI, 0.16 to 0.52), and 0.36 (95% CI, 0.24 to 0.54), respectively (test for linear trend, p < .001). This association did not differ appreciably by stage, menopausal status, body mass index, or estrogen receptor status. Results were similar for distant recurrence. The adjusted RRs were 0.91 (95% CI, 0.62 to 1.33), 0.40 (95% CI, 0.24 to 0.65), and 0.57 (95% CI, 0.39 to 0.82; test for trend, p = .03) for 1, 2 to 5, and 6 to 7 days of aspirin use, respectively.

Conclusion: Among women living at least 1 year after a breast cancer diagnosis, aspirin use was associated with a decreased risk of distant recurrence and breast cancer death.