Grandmaternal pre-pregnancy body mass index and infant birthweight: a mediation analysis of maternal pre-pregnancy body mass index.

The objectives of this study were to examine the total effect of grandmaternal [G0] pre-pregnancy body mass index (BMI) on infant [G2] birthweight z-score and to quantify the mediation role of maternal [G1] pre-pregnancy BMI. Data were extracted from the Nova Scotia 3G Multigenerational Cohort. The association between G0 pre-pregnancy BMI and G2 birthweight z-score and the mediated effect by G1 pre-pregnancy BMI were estimated using g-computation with adjustment for confounders identified using a directed acyclic graph and accounting for intermediate confounding. 20822 G1-G2 dyads from 18450 G0 were included. Relative to G0 normal weight, G0 underweight decreased mean G2 birthweight z-score (-0.11, 95% confidence interval (CI) -0.20, -0.030), while G0 overweight and obesity increased mean G2 birthweight z-score (0.091 [95% CI 0.034, 0.15] and 0.22 [95% CI 0.11, 0.33]). G1 pre-pregnancy BMI partly mediated the association, with the largest effect size observed for G0 obesity (0.11, 95% CI 0.080, 0.14). Estimates of the direct effect were close to the null. In conclusion, grandmaternal pre-pregnancy BMI was associated with infant birthweight z-score. Maternal pre-pregnancy BMI partly mediated the association, suggesting that factors related to BMI may play an important role in the transmission of weight across the maternal line.

A Postpartum Perineal Clinic in Nova Scotia: Characteristics Associated With Attendance and Its Association With Recurrent Obstetrical Anal Sphincter Tears.

OBJECTIVES: The Healthy Recovery after Childbirth Clinic (HRCC) in Nova Scotia provides postpartum care to patients who experience obstetric anal sphincter injuries (OASIS). The purpose of this study was to describe characteristics associated with HRCC attendance, characteristics associated with a trial of labour in a subsequent delivery, and OASIS recurrence by HRCC attendance status. METHODS: A retrospective cohort study using the Atlee Perinatal Database and clinical record review included primiparous individuals who sustained an OASIS at IWK Health in Halifax between 2013 and 2020. The χ2 and Fisher exact tests were performed to compare groups. RESULTS: Of the 1041 individuals included, 67% attended HRCC. Attendance increased from 58% in 2013-2015 to 77% in 2019-2020. Younger age (<25 years) and smoking were associated with lower HRCC attendance (P = 0.07 and <0.01, respectively). Other characteristics, including area-level income and driving distance to HRCC, were not associated with attendance (P > 0.05). Of the 439 individuals who had a subsequent delivery, 92% had a trial of labour. Individuals with fourth-degree injury were less likely to attempt a trial of labour than those with third-degree injury (73% vs. 94%, P < 0.01). Of those who delivered vaginally, OASIS recurrence was similar in those who did and did not attend the HRCC (7.5% vs. 6.5%, P = 0.84). CONCLUSIONS: HRCC attendance was high, but the disparity by age and smoking status suggests some barriers to access that should be explored. Although we found no difference in OASIS recurrence by HRCC attendance, more research with larger samples with adjustment for confounders is needed.

Health Care Utilization in the First 7 Years in Children with Fetal Growth Abnormalities: A Retrospective Cohort Study.

OBJECTIVE: To investigate the relationship between birth weight for gestational age and health care utilization of term offspring from birth to 7 years. STUDY DESIGN: We used a population-based retrospective cohort study of infants (≥37 weeks' gestational age) born between 2003 and 2007 in the Canadian province of Nova Scotia (n = 42 050). Perinatal records were linked to provincial administrative health data from birth to age 7 years. The primary outcome was health care utilization (physician visits and hospital admissions) and costs. Birth weight was categorized as small for gestational age (SGA, <10th percentile), appropriate for gestational age (AGA), or large for gestational age (LGA, >90th percentile). Regression models adjusted for potential confounders were used to investigate the associations. RESULTS: Children born SGA had a higher number of specialist visits and hospital admissions, a longer length of stay for the birth admission, and, as a result, higher physician and hospital costs amounting to a cost differential of Can $1222 during the first 7 years of life compared with children born AGA. By contrast, health care use and costs did not differ between children born LGA and AGA. CONCLUSION: Former SGA term infants have a moderate increase in health care use and costs in early childhood compared with former AGA infants, and LGA birth at term is not associated with higher health care utilization.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

BACKGROUND: The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. OBJECTIVES: This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. POPULATION: The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. DESIGN: Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. METHODS: The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. PRELIMINARY RESULTS: As of October 2018, the 3G cohort included 14 978 grandmothers (born 1939-1986), 16 766 mothers or cohort women (born 1981-2003), and 28 638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. CONCLUSIONS: The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38 years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.

Incidence, Intrapartum Risk Factors, and Prognosis of Neonatal Hypoxic-Ischemic Encephalopathy Among Infants Born at 35 Weeks Gestation or More.

INTRODUCTION: Neonatal hypoxic-ischemic encephalopathy (HIE) is associated with neonatal mortality, acute neurological injury, and long-term neurodevelopmental disabilities; however, the association between intrapartum factors and HIE remains unclear. METHODS: This population-based cohort study used linked obstetrical and newborn data derived from the Nova Scotia Atlee Perinatal Database (NSAPD, 1988-2015) and the AC Allen Perinatal Follow-Up Program Database (2006-2015) for all pregnancies with live, non-anomalous newborns ≥35 weeks gestation, not delivered by pre-labour cesarean section. Temporal trends in HIE incidence were described, and logistic regression estimated odds ratios (OR) with 95% confidence intervals (CI) for the association of intrapartum factors with HIE. RESULTS: The NSAPD identified 227 HIE cases in the population of 226 711 deliveries from 1988 to 2015. Women with clinical chorioamnionitis in labour (OR 8.0; 95% CI 3.9-16), emergency cesarean delivery (OR 10; 95% CI 7.6-14), shoulder dystocia (OR 3.5; 95% CI 2.1-5.7), placental abruption (OR 18; 95% CI 11-29), and cord prolapse (OR 30; 95% CI 15-61) were more likely to have newborns with HIE. Two-thirds of newborns with HIE had an abnormal intrapartum fetal heart rate tracing. The mortality rate among infants with HIE was 27% by 3 years of age. Neurodevelopmental outcomes in the surviving infants were normal in 43% and showed severe developmental delay in 40%. CONCLUSION: Overall, the rate of HIE was low in infants born at ≥35 weeks gestation. The identification of associated intrapartum factors should promote increased surveillance in these clinical situations and emphasize the importance of careful management to optimize newborn outcomes.

Maternal pre-pregnancy obesity and health care utilization and costs in the offspring.

BACKGROUND/OBJECTIVE: The association between maternal pre-pregnancy obesity and adverse child health outcomes is well described, but there are few data on the relationship with offspring health service use. We examined the influence of maternal pre-pregnancy obesity on offspring health care utilization and costs over the first 18 years of life. METHODS: This was a population-based retrospective cohort study of children (n = 35,090) born between 1989 and 1993 and their mothers, who were identified using the Nova Scotia Atlee Perinatal Database and linked to provincial administrative health data from birth through 2014. The primary outcome was health care utilization as determined by the number and cost of physician visits, hospital admissions and days, and high utilizer status (>95th percentile of physician visits). The secondary outcome was health care utilization by ICD chapter. Maternal pre-pregnancy weight was categorized as normal weight, overweight, or obese. Multivariable-adjusted regression models were used to examine the association between maternal weight status and offspring health care use. RESULTS: Children of mothers with pre-pregnancy obesity had more physician visits (10%), hospital admissions (16%), and hospital days (10%) than children from mothers of normal weight over the first 18 years of life. Offspring of mothers with obesity had C$356 higher physician costs and C$1415 hospital costs over 18 years than offspring of normal weight mothers. Children of mothers with obesity were 1.74 times more likely to be a high utilizer of health care and had higher rates of physician visits and hospital stays for nervous system and sense organ disorders, respiratory disorders, and gastrointestinal disorders compared to children of normal weight mothers. CONCLUSION: Our findings suggest that maternal pre-pregnancy overweight and obesity are associated with slightly higher offspring health care utilization and costs in the first 18 years of life.

Cesarean Delivery and Healthcare Utilization and Costs in the Offspring: A Retrospective Cohort Study.

OBJECTIVE: To examine the association between cesarean delivery and healthcare utilization and costs in offspring from birth until age 7 years. STUDY DESIGN: A retrospective cohort study of singleton term births in the Canadian province of Nova Scotia between 2003 and 2007 followed until age 7 years was conducted using data from the Nova Scotia Atlee Perinatal Database and administrative health data. The main exposure was mode of delivery (cesarean delivery vs vaginal birth); the outcome was healthcare utilization and costs during the first 7 years of life. Associations were modeled using multiple regression adjusting for maternal prepregnancy weight and sociodemographic factors. RESULTS: In total, 32 464 births were included in the analysis. Compared with children born by vaginal birth, children born by cesarean delivery had more physician visits (incidence rate ratio 1.06, 95% CI 1.05-1.08) and longer hospital stays (incidence rate ratio 1.12, 95% CI 1.03-1.21) and were more likely to be high utilizers of physician visits (OR 1.23, 95% CI 1.10-1.37). Physician and hospital costs were $775 higher for children born by cesarean delivery compared with vaginal birth. CONCLUSIONS: Cesarean delivery compared with vaginal birth is associated with small but statistically significant increases in healthcare utilization and costs during the first 7 years of life.

Factors Associated with Trial of Labour and Mode of Delivery in Robson Group 5: A Select Group of Women With Previous Caesarean Section.

OBJECTIVE: To determine the proportion of women in Robson group 5 (RG5) who were eligible for a trial of labour after Caesarean (TOLAC) and, among eligible candidates, identify determinants of having a TOLAC and subsequent vaginal delivery (VD). METHODS: This population-based cohort study used data derived from the Nova Scotia Atlee Perinatal Database. Deliveries from 1998-2014 to women in RG5 (≥1 previous CS with a singleton term cephalic fetus) were included. Eligibility for a TOLAC was based on SOGC criteria. Multivariable logistic regression was used to identify characteristics independently associated with TOLAC and VD. The characteristics associated with VD were used in a logistic model to predict the theoretical probability of VD in women who did not have a TOLAC. RESULTS: Of the 15 111 deliveries in RG5, 75.3% were by CS. Of the 14 763 eligible women, 5488 (37.2%) had a TOLAC, of which 3739 (68.1%) resulted in VD. Predictors of VD included high area-level income and either a CS without labour or a spontaneous VD in the preceding pregnancy. While mode of previous delivery also predicted TOLAC among eligible women, high area-level income was associated with reduced odds of TOLAC. The probability of VD in women who did not undergo TOLAC was estimated to be 47.1%, and the lowest CS rate attainable in RG5 was estimated at 46.3%. CONCLUSIONS: Sociodemographic factors such as income and previous mode of delivery were associated with the rates of TOLAC and subsequent VD in eligible women, and suggest that the Caesarean section rate in RG5 could be safely reduced.

Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy.

BACKGROUND: Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS: A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS: The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations ≥50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION: Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes.

Gestational Weight Gain and Perinatal Outcomes in Adolescent Mothers: A Retrospective Cohort Study.

OBJECTIVE: Optimal gestational weight gain (GWG) may differ for adolescents since they themselves may continue to grow throughout pregnancy. We examined the associations between GWG and perinatal outcomes among adolescents aged < 20 years and determined whether they differed from the associations among adult women aged 20 to 35 years. METHODS: We conducted a retrospective cohort study of live born, singleton deliveries to 3725 adolescents and 50 400 adult women in Nova Scotia between 2003 and 2014. GWG was categorized as below, within, or above the 2009 Institute of Medicine recommendations. Primary outcomes were preterm birth (< 37 weeks), small for gestational age (SGA; < 10(th) percentile), large for gestational age (LGA; > 90th percentile), and delivery by Caesarean section. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated from logistic regression models. RESULTS: Adolescent mothers with GWG above the recommendations (relative to mothers who gained within the recommendations) had higher odds of having an LGA neonate (OR 2.20; 95% CI 1.62 to 2.99) and having a Caesarean section (OR 1.33; 95% CI 1.07 to 1.64), but lower odds of having an SGA neonate (OR 0.65; 95% CI 0.51 to 0.84). Adolescent mothers with low GWG had decreased odds of having an LGA neonate (OR 0.58; 95% CI 0.34 to 0.98) and increased odds of having an SGA neonate (OR 1.72; 95% CI 1.30 to 2.27). CONCLUSION: Among adolescents, GWG was significantly associated with several perinatal outcomes. More research considering other outcomes is needed to determine the optimal GWG for adolescent women.

Cord blood vitamin D status and neonatal outcomes in a birth cohort in Quebec, Canada.

PURPOSE: Some evidence suggests that low maternal vitamin D status adversely affects perinatal health but few studies have examined cord blood vitamin D status. This project aimed to determine the association between the cord blood concentration of 25-hydroxyvitamin D [25(OH)D] and neonatal outcomes. METHODS: A nested case-control study was conducted in Quebec City, Canada from 2005 to 2010. Included were 83 cases of low birthweight (LBW; <2500 g), 301 cases of small for gestational age (SGA; <10th percentile), 223 cases of preterm birth (PTB; <37 weeks' gestation), and 1027 controls. Levels of 25(OH)D were determined by chemiluminescence immunoassay. Adjusted odds ratios (OR) and 95 % confidence intervals (CI) were estimated with logistic regression. RESULTS: Cord blood [25(OH)D] <50 nmol/L was associated with a lower risk of LBW compared to [25(OH)D] ≥75 nmol/L (OR 0.47 95 % CI 0.23-0.97). For 25(OH)D levels 50-75 nmol/L, a significant association was not demonstrated (OR 0.58, 95 % CI 0.34-1.01). No significant associations were observed between [25(OH)D] and either SGA or PTB after adjustment. CONCLUSIONS: Although our findings suggest that [25(OH)D] <50 nmol/L is associated with reduced risk of having a LBW infant, prenatal vitamin D recommendations require an examination of the literature that considers the full spectrum of maternal and neonatal outcomes.

The impact of an educational intervention on knowledge about infant crying and abusive head trauma.

BACKGROUND: Infants follow a predictable trajectory of increased early crying. Frustration with crying is reported to be a trigger for abusive head trauma (AHT). OBJECTIVE: To evaluate the impact of postpartum delivery of the educational program, the Period of PURPLE Crying (PURPLE), in a group of first-time mothers. The primary objective was to determine whether there was a change in knowledge about infant crying and shaking after exposure to PURPLE. Factors associated with change in knowledge were also examined. METHOD: A total of 93 participants were recruited over a four-month period at a tertiary care hospital in Nova Scotia. Pre- and postintervention data were collected. RESULTS: Knowledge about infant crying increased significantly after program delivery (P=0.001). Low baseline crying knowledge was a significant predictor of increased knowledge about infant crying (P≤0.01). There was an insignificant decrease in shaking knowledge (P=0.5), which may have been the consequence of high baseline knowledge. CONCLUSION: An educational program for new parents appears to be warranted, especially with respect to improving knowledge about infant crying. This may have a positive benefit in AHT prevention. Additional studies are required to evaluate the impact of the program on other caregivers and on rates of AHT.

HISTORIQUE: Les nourrissons suivent une trajectoire prévisible d'augmentation des pleurs peu après la naissance. La frustration à l'égard de ces pleurs est considérée comme un déclencheur des traumatismes crâniens non accidentels (TCNA). OBJECTIF: Évaluer l'effet de la transmission d'un programme d'éducation postnatale, la Period of PURPLE Crying (PURPLE), à un groupe de mères d'un premier enfant. L'objectif primaire consistait à déterminer si les connaissances relatives aux pleurs et aux secousses des nourrissons changeaient après l'exposition à PURPLE. Les facteurs liés aux changements de connaissances ont également été examinés. MÉTHODOLOGIE: Les chercheurs ont recruté 93 participantes sur une période de quatre mois dans un hôpital de soins tertiaires de la Nouvelle-Écosse. Ils ont colligé les données avant et après l'intervention. RÉSULTATS: Les connaissances sur les pleurs des nourrissons augmentaient de manière significative après la prestation du programme (P=0,001). Le peu de connaissances sur les pleurs en début d'étude était un prédicteur important d'augmentation des connaissances sur les pleurs des nourrissons (P≤0,01). Il y avait une diminution non significative des connaissances sur les secousses (P=0,5), qui peut découler des connaissances importantes avant l'intervention. CONCLUSION: Un programme d'éducation pour les nouveaux parents semble justifié, particulièrement pour accroître les connaissances sur les pleurs des nourrissons. Il pourrait contribuer à prévenir les TCNA. Il faudra réaliser d'autres études pour évaluer l'effet du programme auprès d'autres personnes qui s'occupent de nourrissons et sur le taux de TCNA.

Mammographic density and breast cancer risk by family history in women of white and Asian ancestry.

PURPOSE: Mammographic density, i.e., the radiographic appearance of the breast, is a strong predictor of breast cancer risk. To determine whether the association of breast density with breast cancer is modified by a first-degree family history of breast cancer (FHBC) in women of white and Asian ancestry, we analyzed data from four case-control studies conducted in the USA and Japan. METHODS: The study population included 1,699 breast cancer cases and 2,422 controls, of whom 45% reported white (N = 1,849) and 40% Asian (N = 1,633) ancestry. To standardize mammographic density assessment, a single observer re-read all mammograms using one type of interactive thresholding software. Logistic regression was applied to estimate odds ratios (OR) while adjusting for confounders. RESULTS: Overall, 496 (12%) of participants reported a FHBC, which was significantly associated with breast cancer risk in the adjusted model (OR 1.51; 95% CI 1.23-1.84). There was a statistically significant interaction on a multiplicative scale between FHBC and continuous percent density (per 10 % density: p = 0.03). The OR per 10% increase in percent density was higher among women with a FHBC (OR 1.30; 95% CI 1.13-1.49) than among those without a FHBC (OR 1.14; 1.09-1.20). This pattern was apparent in whites and Asians. The respective ORs were 1.45 (95% CI 1.17-1.80) versus 1.22 (95% CI 1.14-1.32) in whites, whereas the values in Asians were only 1.24 (95% CI 0.97-1.58) versus 1.09 (95% CI 1.00-1.19). CONCLUSIONS: These findings support the hypothesis that women with a FHBC appear to have a higher risk of breast cancer associated with percent mammographic density than women without a FHBC.

Methods for assessing and representing mammographic density: an analysis of 4 case-control studies.

To maximize statistical power in studies of mammographic density and breast cancer, it is advantageous to combine data from several studies, but standardization of the density assessment is desirable. Using data from 4 case-control studies, we describe the process of reassessment and the resulting correlation between values, identify predictors of differences in density readings, and evaluate the strength of the association between mammographic density and breast cancer risk using different representations of density values. The pooled analysis included 1,699 cases and 2,422 controls from California (1990-1998), Hawaii (1996-2003), Minnesota (1992-2001), and Japan (1999-2003). In 2010, a single reader reassessed all images for mammographic density using Cumulus software (Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada). The mean difference between original and reassessed percent density values was -0.7% (95% confidence interval: -1.1, -0.3), with a correlation of 0.82 that varied by location (r = 0.80-0.89). Case status, weight status, age, parity, density assessment method, mammogram view, and race/ethnicity were significant determinants of the difference between original and reassessed values; in combination, these factors explained 9.2% of the variation. The associations of mammographic density with breast cancer and the model fits were similar using the original values and the reassessed values but were slightly strengthened when a calibrated value based on 100 reassessed radiographs was used.

The association between physical activity and maternal and neonatal outcomes: a prospective cohort.

Some evidence, but not enough to be conclusive, suggests that physical activity in pregnancy reduces the risk of perinatal complications. Our objective was to examine if physical activity in the year before pregnancy and in the first half of pregnancy is associated with maternal and neonatal outcomes. Associations between physical activity and maternal and neonatal outcomes were examined in a prospective cohort (n = 1,749) in Halifax, Canada. The Kaiser Physical Activity Survey, completed at approximately 20 weeks' gestation, requested information regarding physical activity during the year before the pregnancy and the first 20 weeks of pregnancy. Outcomes were assessed by medical chart review. Multiple logistic regression was used to estimate odds ratios (OR) with 95 % confidence intervals (CI). Women with prepregnancy physical activity levels in the middle and highest tertiles were more likely to have high gestational weight gain relative to women in the lowest tertile [OR (CI): 1.40 (1.06-1.85) and 1.57 (1.18-2.09), respectively]. Higher physical activity in the first half of pregnancy decreased the odds of delivering a macrosomic infant (p trend = 0.005). Associations were not observed between total physical activity and gestational diabetes, gestational hypertension, pre-eclampsia, preterm birth, and low birth weight. Physical activity before, but not in the first half of pregnancy, is associated with high gestational weight gain. Physical activity in the first half of pregnancy may reduce the occurrence of macrosomia without affecting preterm birth or low birth weight.

Association between sex hormones, glucose homeostasis, adipokines, and inflammatory markers and mammographic density among postmenopausal women.

The biological mechanisms underlying the relationship between mammographic density and breast cancer risk are unknown. Our objective was to examine the association between mammographic density and circulating factors that are putative breast cancer intermediate endpoints. Biologic data from a year-long aerobic exercise intervention trial conducted in 302 postmenopausal women aged 50-74 years were analyzed. Sex hormones, markers of glucose homeostasis, inflammatory markers, and adipokines were assayed in fasting blood drawn at baseline and after 1 year. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Multiple linear regression was used to examine the association between the circulating factors and mammographic measures and partial correlations were estimated. Mammographic nondense volume was positively correlated with concentrations of estradiol (r = 0.28), estrone (r = 0.13), insulin (r = 0.41), glucose (r = 0.15), leptin (r = 0.49), and C-reactive protein (r = 0.22), and negatively correlated with sex hormone binding globulin (r = -0.30) and adiponectin (r = -0.12) but correlations became null after adjustment for overall body adiposity as represented by body mass index and waist circumference. With adjustment for overall adiposity, mammographic dense volume, a measure that represents fibroglandular tissue, was negatively correlated with leptin (r = -0.19) and C-reactive protein (r = -0.19). As expected, circulating factors originating from or correlated with adipose tissue were also correlated with mammographic measures of breast adipose tissue, but not after adjustment for overall body adiposity. Interpreting correlations between adiposity-derived factors and mammographic measures whose validity may be affected by adiposity is problematic. To rectify this problem, future studies with very good measures of the volume of fibroglandular tissue in the breast will be necessary.

Fruit and vegetable intakes are associated with lower risk of bladder cancer among women in the Multiethnic Cohort Study.

Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients, phytochemicals, and antioxidants with potentially anticarcinogenic properties. In a prospective analysis of 185,885 older adults participating in the Multiethnic Cohort Study, we examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk. Cox proportional hazards models were used to calculate HRs and 95% CIs for bladder cancer in relation to dietary intakes. A total of 581 invasive bladder cancer cases (429 men and 152 women) were diagnosed over a mean follow-up period of 12.5 y. In women, total fruits and vegetables [HR = 0.35 (95% CI: 0.22, 0.56); highest vs. lowest quartile], total vegetables [HR = 0.49 (95% CI: 0.29, 0.83)], yellow-orange vegetables [HR = 0.48 (95% CI: 0.30, 0.77)], total fruits [HR = 0.54 (95% CI: 0.34, 0.85)], and citrus fruits [HR = 0.56 (95% CI: 0.34, 0.90)] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids α-carotene, ß-carotene, and ß-cryptoxanthin; and folate had a lower risk of bladder cancer. For men, no associations for fruits, vegetables, or nutrients were found overall, although inverse associations were observed for vegetable intake among current smokers, and in ethnic-specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies.

Mammographic density and risk of breast cancer by adiposity: an analysis of four case-control studies.

The association of mammographic breast density with breast cancer risk may vary by adiposity. To examine effect modification by body mass index (BMI), the authors standardized mammographic density data from four case-control studies (1994-2002) conducted in California, Hawaii and Minnesota and Gifu, Japan. The 1,699 cases and 2,422 controls included 45% Caucasians, 40% Asians and 9% African-Americans. Using ethnic-specific BMI cut points, 34% were classified as overweight and 19% as obese. A single reader assessed density from mammographic images using a computer-assisted method. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. Modest heterogeneity in the relation between percent density and breast cancer risk across studies was observed (p(heterogeneity) = 0.08). Cases had a greater age-adjusted mean percent density than controls: 31.7% versus 28.5%, respectively (p <0.001). Relative to <20 percent density, the ORs for >35 were similar across BMI groups whereas the OR for 20-35 was slightly higher in overweight (OR = 1.69, 95% CI: 1.28, 2.24) and obese (OR = 1.62, 95% CI: 1.12, 2.33) than in normal weight women (OR = 1.49, 95% CI: 1.11, 2.01). Furthermore, limited evidence of effect modification by BMI of the OR per 10% increase in percent density (p(interaction) = 0.06) was observed, including subgroup analyses by menopausal status and in analyses that excluded women at the extremes of the BMI scale. Our findings indicate little, if any, modification by BMI of the effects of breast density on breast cancer risk.

Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case-control studies.

Mammographic density is strongly and consistently associated with breast cancer risk. To determine if this association was modified by reproductive factors (parity and age at first birth), data were combined from four case-control studies conducted in the United States and Japan. To overcome the issue of variation in mammographic density assessment among the studies, a single observer re-read all the mammograms using one type of interactive thresholding software. Logistic regression was used to estimate odds ratios (OR) while adjusting for other known breast cancer risk factors. Included were 1,699 breast cancer cases and 2,422 controls, 74% of whom were postmenopausal. A positive association between mammographic density and breast cancer risk was evident in every group defined by parity and age at first birth (OR per doubling of percent mammographic density ranged between 1.20 and 1.39). Nonetheless, the association appeared to be stronger among nulliparous than parous women (OR per doubling of percent mammographic density = 1.39 vs. 1.24; P interaction = 0.054). However, when examined by study location, the effect modification by parity was apparent only in women from Hawaii and when examined by menopausal status, it was apparent in postmenopausal, but not premenopausal, women. Effect modification by parity was not significant in subgroups defined by body mass index or ethnicity. Adjusting for mammographic density did not attenuate the OR for the association between parity and breast cancer risk by more than 16.4%, suggesting that mammographic density explains only a small proportion of the reduction in breast cancer risk associated with parity. In conclusion, this study did not support the hypothesis that parity modifies the breast cancer risk attributed to mammographic density. Even though an effect modification was found in Hawaiian women, no such thing was found in women from the other three locations.