Estrogen receptor–negative (ER−) breast cancer has few known
or modifiable risk factors. Because ER− tumors account for only 15% to
20% of breast cancers, large pooled analyses are necessary to evaluate precisely the
suspected inverse association between fruit and vegetable intake and risk of
ER− breast cancer.
Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19
869 estrogen receptor positive (ER+) and 4821 ER−
breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95%
confidence intervals (CIs) using Cox proportional hazards regression analyses and then
combined them using a random-effects model. All statistical tests were two-sided.
Total fruit and vegetable intake was statistically significantly inversely associated
with risk of ER− breast cancer but not with risk of breast cancer
overall or of ER+ tumors. The inverse association for
ER− tumors was observed primarily for vegetable consumption. The
pooled relative risks comparing the highest vs lowest quintile of total vegetable
consumption were 0.82 (95% CI = 0.74 to 0.90) for ER− breast
cancer and 1.04 (95% CI = 0.97 to 1.11) for ER+ breast cancer
common-effects by ER status < .001). Total fruit consumption was
non-statistically significantly associated with risk of ER− breast
cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94,
95% CI = 0.85 to 1.04).
We observed no association between total fruit and vegetable intake and risk of overall
breast cancer. However, vegetable consumption was inversely associated with risk of
ER− breast cancer in our large pooled analyses.
A growing body of research documents multiple health disparities by sexual orientation among women, yet little is known about the possible causes of these disparities. One underlying factor may be heightened risk for abuse victimization in childhood in lesbian and bisexual women. Using survey data from 63,028 women participating in the Nurses’ Health Study II, we investigated sexual orientation group differences in emotional, physical, and sexual abuse in childhood and adolescence. Multivariable log-binomial and linear regression models were used to examine orientation group differences in prevalence and severity of abuse, with heterosexual as the referent and controlling for sociodemographics. Results showed strong evidence of elevated frequency, severity, and persistence of abuse experienced by lesbian and bisexual women. Comparing physical abuse victimization occurring in both childhood and adolescence, lesbian (30%; prevalence ratio [PR] 1.61; 95% confidence interval [CI] 1.40, 1.84) and bisexual (24%; PR 1.26; 95% CI 1.00, 1.60) women were more likely to report victimization than were heterosexual women (19%). Similarly, comparing sexual abuse victimization occurring in both age periods, lesbian (19%; PR 2.16; 95% CI 1.80, 2.60) and bisexual (20%; PR 2.29; 95% CI 1.76, 2.98) women were more likely to report victimization than were heterosexual women (9%). This study documents prevalent and persistent abuse disproportionately experienced by lesbian and bisexual women.
bisexual; child abuse; lesbian; sexual orientation; victimization
To study consumer acceptance of unmilled brown and under milled rice among urban south Indians.
Overweight and normal weight adults living in slum and non-slum residences in Chennai participated (n=82). Bapatla (BPT) and Uma (red pigmented) rice varieties were chosen. These rice varieties were dehusked (unmilled, 0% polish) and further milled to 2.3% and 4.4% polishing (under milled). Thus nine rice samples in both raw and parboiled forms were provided for consumer tasting over a period of three days. A hedonic 7-point scale was used to rate the consumer preferences. A validated questionnaire was used to collect demographic, anthropometric, medical history, physical activity, dietary intake data and willingness of the consumers to switch over to brown rice.
Consumers reported that the color, appearance, texture, taste and overall quality of the 4.4% polished rice was strongly preferred in both varieties and forms. Ratings for 0% polished (brown rice) were substantially lower than those of 2.3% polished rice, which were intermediate in ratings between 0% and 4.4% polishing. However, most of the consumers (93%) expressed willingness to substitute brown or 2.3% polished rice if affordable after the taste tests and education on nutritional and health benefits of whole grains.
While most consumers’ preferred polished white rice, education regarding health benefits may help this population switch to brown or under milled rice. Cooking quality and appearance of the grains were perceived as the most important factors to consider when purchasing rice among Chennai urban adults.
white rice; red rice; raw rice; parboiled rice; diabetes; obese Asian Indians
Beyond known familial colorectal cancer (CRC) syndromes, the mechanisms underlying the elevated CRC risk associated with CRC family history remain largely unknown. A recent retrospective study suggests familial clustering of CRC with hypomethylation in long interspersed nucleotide element 1 (LINE-1). We tested the hypothesis that CRC family history might confer a higher risk of LINE-1 methylation-low CRC.
Using the Nurses’ Health Study and the Health Professionals Follow-up Study, we prospectively examined the association between CRC family history and the risk of rectal and colon cancer (N = 1224) according to tumor LINE-1 methylation level by duplication method Cox proportional hazards regression. We examined microsatellite instability (MSI) status to exclude the influence of Lynch syndrome. All statistical tests were two-sided.
The association between CRC family history and non-MSI CRC risk differed statistically significantly by LINE-1 methylation level (P
heterogeneity = .02). CRC family history was associated with a statistically significantly higher risk of LINE-1 methylation-low non-MSI cancer (multivariable hazard ratio [HR] = 1.68, 95% confidence interval [CI] = 1.19 to 2.38 for 1 vs 0 first-degree relatives with CRC; multivariable HR = 3.48, 95% CI = 1.59 to 7.6 for ≥2 vs 0 first-degree relatives with CRC; P
trend < .001). In contrast, CRC family history was not statistically significantly associated with LINE-1 methylation-high non-MSI cancer (P
trend = .35).
This molecular pathological epidemiology study shows that CRC family history is associated with a higher risk of LINE-1 methylation-low CRC, suggesting previously unrecognized heritable predisposition to epigenetic alterations. Additional studies are needed to evaluate tumor LINE-1 methylation as a molecular biomarker for familial cancer risk assessment.
Aspirin use reduces the risk of colorectal carcinoma. Experimental evidence implicates a role of RAF kinases in upregulation of PTGS2 (cyclooxygenase-2), suggesting that BRAF-mutant colonic cells might be less sensitive to the anti-tumor effects of aspirin than BRAF-wild-type neoplastic cells.
To examine if the association of aspirin intake with colorectal cancer risk differs according to status of tumor BRAF oncogene mutation.
Design and Setting
We collected biennial questionnaire data on aspirin use and followed participants from 1980 (in the Nurses’ Health Study) or 1986 (in the Health Professionals Follow-up Study) until July 1, 2006 for cancer incidence and until January 1, 2012 for cancer mortality. Duplication-method Cox proportional cause-specific hazards regression for competing risks data was used to compute hazard ratio (HR) for colorectal carcinoma incidence according to BRAF mutation status.
Among 127,865 individuals, with 3,165,985 person-years of follow-up, we identified 1,226 incident rectal and colon cancers with available molecular data. Compared with non-use, regular aspirin use was associated with lower BRAF-wild-type cancer risk (multivariable HR=0.73 [95% CI, 0.64–0.83]; age-adjusted incidence rate difference [IRD]=−9.7 [95% CI, −12.6 to −6.7] per 100,000 person-years). This association was observed irrespective of status of tumor PTGS2 expression or PIK3CA or KRAS mutation. In contrast, regular aspirin use was not associated with a lower risk of BRAF-mutated cancer (multivariable HR=1.03 [95% CI, 0.76–1.38]; age-adjusted IRD=0.7 [95% CI, −0.3 to 1.7] per 100,000 person-years) (Pheterogeneity=0.037, between BRAF-wild-type vs. BRAF-mutated cancer risks). Compared with no aspirin use, aspirin use of >14 tablets per week was associated with a lower risk of BRAF-wild-type cancer (multivariable HR=0.43 [95% CI, 0.25–0.75]; age-adjusted IRD=−19.8 [95% CI, −26.3 to −13.3] per 100,000 person-years). The relationship between the number of aspirin tablets per week and colorectal cancer risk differed significantly by BRAF mutation status (Pheterogeneity=0.005).
Conclusions and Relevance
Regular aspirin use was associated with lower risk of BRAF-wild-type colorectal cancer, but not with BRAF-mutated cancer risk. These findings suggest that BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin. Given the modest absolute risk difference, further investigations are necessary to determine clinical implications of our findings.
colon cancer; rectal cancer; adenocarcinoma; epigenomics; epigenetics
Lesbian and bisexual women may be at greater risk of breast cancer than heterosexual women during the premenopausal period due to disparities in risk factors.
With 16 years of prospective data from a large cohort of U.S. women ages 25–58 years, we conducted a breast cancer risk assessment for 87,392 premenopausal women by applying the Rosner-Colditz biomathematical risk-prediction model to estimate breast cancer risk based on known risk factors. Based on each woman’s comprehensive risk factor profile, we calculated the predicted one-year incidence rate (IR) per 100,000 person-years and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for lesbian and bisexual women compared to heterosexual women.
87,392 premenopausal women provided 1,091,871 person-years of data included in analyses. Mean predicted one-year breast cancer IRs per 100,000 person-years for each sexual orientation group were: heterosexual 122.55, lesbian 131.61, and bisexual 131.72. IRs were significantly elevated in both lesbian (IRR 1.06; 95 CI 1.06, 1.06) and bisexual (IRR 1.10; 95% CI 1.10, 1.10) women compared to heterosexual women.
Our findings suggest both lesbian and bisexual women have slightly elevated predicted breast cancer incidence compared to heterosexual women throughout the premenopausal period.
Health professionals must ensure that breast cancer prevention efforts are reaching these women. As more health systems around the country collect data on patient sexual orientation, the National Cancer Institute’s SEER cancer registry should add this information to its data system to monitor progress in reducing sexual orientation-related disparities in cancer incidence and mortality.
breast cancer; risk model; sexual orientation; bisexual; lesbian; premenopausal
Malnutrition is associated with morbidity and mortality in HIV infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression.
Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4 kg/m2 less than that of patients who did not use any drugs, after adjusting for other covariates (p= 0.02). The BMI of participants who were over the age of 55 years was 2.0 kg/m2 less than that of patients under the age of 35, and BMI increased by 0.3 kg/m2 with each 100 cells/mm3 increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model.
In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support.
drug users; cocaine users; BMI; HIV; CD4 count
Vitamin D may help prevent adverse pediatric outcomes, including infectious diseases and growth failure, based on its role in immune and metabolic functions. We examined the association of maternal vitamin D status and pediatric health outcomes in children born to HIV-infected women.
Vitamin D status was determined in 884 HIV-infected pregnant women at 12 to 27 weeks of gestation in a trial of vitamin supplementation (not including vitamin D) in Tanzania. Information on child morbidities, anemia and hypochromic microcytosis, and anthropometry was recorded through monthly clinic visits. Generalized estimated equations and Cox proportional hazards models were used to assess the relationships of outcomes with maternal vitamin D status.
A total of 39% of women had low vitamin D levels (<32 ng/mL). Children born to women with low vitamin D status were 1.11 times more likely to report cough during follow-up (RR: 1.11; 95% CI: 1.02-1.21). No significant associations were noted for other respiratory symptoms, diarrhea, or anemia outcomes. Low maternal vitamin D status was associated with significantly increased risk of stunting (height-for-age z-score <-2; RR: 1.29; 95% CI: 1.05-1.59) and underweight (weight-for-age z-score <-2; RR: 1.33; 95% CI: 1.03-1.71).
Maternal vitamin D status may be an important risk factor for respiratory infections, and ensuring optimal growth in HIV-exposed children.
Vitamin D; Morbidity; Anemia; Growth; Children; HIV/AIDS
Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART.
To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART.
Design, Setting, and Participants
A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania.
The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance.
Main Outcome Measure
The composite of HIV disease progression or death from any cause.
The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96–1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11–1.87) vs standard-dose supplementation.
In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels.
clinicaltrials.gov Identifier: NCT00383669
Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI.
Methods and Results
In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake.
Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation.
fatty acids; fish; magnetic resonance imaging; lacunar infarct; white matter disease
Existing study design formulas for longitudinal studies assume that the exposure is time invariant or that it varies in a manner that is controlled by design. However, in observational studies, the investigator does not control how exposure varies within subjects over time. Typically, a large number of exposure patterns are observed, with differences in the number of exposed periods per participant and with changes in the cross-sectional mean of exposure over time. This article provides formulas for study design calculations that incorporate these features for studies with a continuous outcome and a time-varying exposure, for cases where the effect of exposure on the response is assumed to be constant over time. We show that incorrectly using the formulas for time-invariant exposure can produce substantial overestimation of the required sample size. It is shown that the exposure mean, variance and intraclass correlation are the only additional parameters needed for exact solutions for the required sample size, if compound symmetry of residuals can be assumed, or to a good approximation if residuals follow a damped exponential correlation structure. The methods are applied to several examples. A publicly available programme to perform the calculations is provided.
Cross-sectional studies and animal-experiments suggest that methylmercury exposure could increase risk of hypertension. This relationship has not been evaluated in large prospective studies. Using data from prior nested case-control studies in two separate prospective cohorts, we measured toenail mercury, a valid biomarker of long-term methylmercury exposure, among 6,045 US men and women free of hypertension at baseline. Median toenail mercury concentrations were 0.09 μg/g in the lowest quintile and 0.64 μg/g in the highest quintile, the latter corresponding to exposures about 1.7-fold higher than the EPA reference dose (RfD). Participants were followed prospectively (mean±SD=14.9±7.9 years) for a new self-report of physician-diagnosed hypertension (3,540 cases), shown to be >95% sensitive and specific for diagnosing hypertension in these cohorts as compared with review of medical records and direct blood pressure measurement, respectively. After adjustment for demographic, clinical, and lifestyle risk factors, the hazard ratio (95% CI) for incident hypertension in the highest vs. lowest quintile of mercury exposure was 0.96 (0.84–1.09) in women, 0.82 (0.62–1.08) in men, and 0.94 (0.84–1.06) in both cohorts combined. Findings were similar when more extreme categories of mercury were compared (across deciles, with median levels in highest decile about 2.5-fold higher than the RfD); and in analyses stratified by fish or omega-3 consumption, selenium levels, body mass index, and age. These findings from two separate large prospective cohort studies do not support any clinically apparent adverse effects of methylmercury exposure on risk of hypertension in men or women, including at levels up to 2.5-fold higher than the RfD.
Mercury; Hypertension; Prospective Studies; Selenium; Diet; Population Science; Environmental Medicine
Fruit and vegetable intake may protect against pancreatic cancer, since fruits and vegetables are rich in potentially cancer-preventive nutrients. Most case-control studies have found inverse associations between fruit and vegetable intake and pancreatic cancer risk, although bias due to reporting error cannot be ruled out. In most prospective studies, inverse associations have been weaker and imprecise because of small numbers of cases. The authors examined fruit and vegetable intake in relation to pancreatic cancer risk in a pooled analysis of 14 prospective studies from North America, Europe, and Australia (study periods between 1980 and 2005). Relative risks and 2-sided 95% confidence intervals were estimated separately for the 14 studies using the Cox proportional hazards model and were then pooled using a random-effects model. Of 862,584 men and women followed for 7−20 years, 2,212 developed pancreatic cancer. The pooled multivariate relative risks of pancreatic cancer per 100-g/day increase in intake were 1.01 (95% confidence interval (CI): 0.99, 1.03) for total fruits and vegetables, 1.01 (95% CI: 0.99, 1.03) for total fruits, and 1.02 (95% CI: 0.99, 1.06) for total vegetables. Associations were similar for men and women separately and across studies. These results suggest that fruit and vegetable intake during adulthood is not associated with a reduced pancreatic cancer risk.
diet; fruit; pancreatic neoplasms; prospective studies; vegetables
This study investigated the relationship between growing up in a violent home and developmental trajectories of body mass index (BMI) in a cohort of adolescents followed longitudinally from 1996 to 2003-4.
6,043 girls and 4,934 boys aged 9–14 years in 1996 who reported height and weight at least two times and whose mothers completed intimate partner violence (IPV) questions at the 2001 Nurses’ Health Study. Main exposure was experiencing the first family violence during early (0–5 years) or later (6–11 years) childhood, based on mother’s year-specific exposure of IPV and the birth year of each participant. Mother’s report of IPV was ascertained by the abuse assessment screen. Four distinct BMI trajectory groups were estimated from age-specific BMI (age 12–20 years), using general growth mixture modeling.
Four distinct BMI trajectories were identified separately for girls and boys: healthy growth; healthy to obese; steady overweight and consistently obese. Compared with boys not exposed to violence at home, boys raised in violent homes before 5 years were at increased risk of being in the consistently obese (OR =2.0; 95% CI 1.2 to 3.5) and steady overweight (OR 1.4; 95% CI 1.1 to 1.9) groups after adjusting for confounders. Girls raised in violent homes were more likely to be in the steady overweight group, but associations did not maintain statistical significance after adjusting for confounding.
These data link children’s exposure to domestic violence to a risk of unhealthy weight trajectories during adolescence in boys. Detrimental effects of exposure to a domestic violence environment may take root in the first few years of development for boys.
Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown.
To estimate the degree to which four conventional cardiovascular risk factors, smoking, hypertension, hypercholesterolemia and type 2 diabetes, are associated with the risk of PAD among men.
Design, settings and participants
We prospectively followed 44,985 men from the Health Professionals Follow-up Study without a history of cardiovascular disease at baseline for 25 years (1986-2011). The presence of risk factors was updated biennially during follow-up.
Main outcome measure
Clinically significant PAD (defined as limb amputation/revascularization, angiogram reporting vascular obstruction of ≥50%, ankle-brachial index<0.90 or physician-diagnosed PAD).
During a median follow-up of 24.2 years (interquartile range 20.8-24.7 years), 537 PAD cases occurred. Each risk factor was significantly and independently associated with a higher risk of PAD after adjustment for the other three risk factors and confounders. The age-adjusted incidence rates per 100,000 person years were 6 cases for 0 risk factors, 18 cases for 1 risk factor, 39 cases for 2 risk factors, 76 cases for 3 risk factors and 139 cases for 4 risk factors. The multivariable-adjusted hazard ratio (HR) for each additional risk factor compared was 2.06 (95% confidence interval [95% CI], 1.92-2.32). Men without any of the four risk factors had a HR of PAD of 0.23 (95% CI, 0.14-0.36) compared with all other men in the cohort. In 96% (95% CI, 94-98%) of PAD cases, at least one of the four risk factors was present at the time of PAD diagnosis. The population-attributable risk associated with these four risk factors was 75% (95% CI, 64-87%). The incidence of PAD among men with all four risk factors was 1.4/1,000.
Among men in this cohort, smoking, hypertension, hypercholesterolemia and type 2 diabetes account for most of the risk associated with development of clinically significant PAD.
This article presents semiparametric joint models to analyze longitudinal measurements and survival data with a cure fraction. We consider a broad class of transformations for the cure-survival model, which includes the popular proportional hazards structure and the proportional odds structure as special cases. We propose to estimate all the parameters using the nonparametric maximum likelihood estimators (NPMLE). We provide the simple and efficient EM algorithms to implement the proposed inference procedure. Asymptotic properties of the estimators are shown to be asymptotically normal and semiparametrically efficient. Finally, we demonstrate the good performance of the method through extensive simulation studies and a real-data application.
Cure-survival data; Joint models; Longitudinal data; Nonparametric maximum likelihood; Random effects; Transformation models
The etiology of autism is unknown, although prenatal exposures have been the focus of epidemiologic research for over 40 years.
To provide the first quantitative review and meta-analysis of the association between maternal pregnancy complications and pregnancy-related factors and risk of autism.
PubMed, Embase, and PsycInfo databases were searched for epidemiologic studies that examined the association between pregnancy-related factors and autism. Forty studies were eligible for inclusion in the meta-analysis. Summary effect estimates were calculated for factors examined in multiple studies.
Over 50 prenatal factors have been examined. The factors associated with autism risk in the meta-analysis were advanced parental age at birth, maternal prenatal medication use, bleeding, gestational diabetes, being first born vs. third or later, and having a mother born abroad. The factors with the strongest evidence against a role in autism risk included previous fetal loss and maternal hypertension, proteinuria, preeclampsia, and swelling.
There is insufficient evidence to implicate any one prenatal factor in autism aetiology, although there is some evidence to suggest that exposure to pregnancy complications may increase the risk.
Prenatal iron supplementation may improve pregnancy outcomes and decrease the risk of child mortality. However, little is known about the importance of postnatal maternal iron status for child health and survival, particularly in the context of HIV infection. We examined the association of maternal anemia and hypochromic microcytosis, an erythrocyte morphology consistent with iron deficiency, with child health and survival in the first two to five years of life. Repeated measures of maternal anemia and hypochromic microcytosis from 840 HIV-positive women enrolled in a clinical trial of vitamin supplementation were prospectively related to child mortality, HIV infection, and CD4 T-cell count. Median duration of follow-up for the endpoints of child mortality, HIV infection and CD4 cell count was 58, 17 and 23 months, respectively. Maternal anemia and hypochromic microcytosis were associated with greater risk of child mortality (HR for severe anemia=2.58, 95% CI: 1.66-4.01, P trend<0.0001; HR for severe hypochromic microcytosis=2.36, 95% CI: 1.27-4.38, P trend=0.001). Maternal anemia was not significantly associated with greater risk of child HIV infection (HR for severe anemia=1.46, 95% CI: 0.91, 2.33, P trend=0.08) but predicted lower CD4 T-cell counts among HIV-uninfected children (difference in CD4 T-cell count/μL for severe anemia:-93, 95% CI: -204-17, P trend=0.02). The potential child health risks associated with maternal anemia and iron deficiency may not be limited to the prenatal period. Efforts to reduce maternal anemia and iron deficiency during pregnancy may need to be expanded to include the postpartum period.
anemia; iron deficiency; postnatal; HIV; child
Compelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM.
RESEARCH DESIGN AND METHODS
We performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982–1983 and 1986–1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards.
During 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73–1.14), 0.78 (0.62–0.99), 0.72 (0.57–0.91), and 0.76 (0.60–0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear.
At dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk.
An increasing number of women are utilizing fertility treatments, but little is known about their relation to autism spectrum disorders (ASD).
To determine the association between maternal fertility therapy use and risk of having a child with ASD, we conducted a nested case-control study within the Nurses’ Health Study II (n = 116,430). Maternally reported diagnoses of ASD were confirmed through a supplementary questionnaire and, in a subgroup, the Autism Diagnostic Interview-Revised. Controls were randomly selected by frequency matching to case children’s year of birth. Associations were examined by self-reported infertility and type of therapy using conditional logistic regression.
In all, 9% of the 507 cases and 7% of 2,529 controls indicated fertility therapy use for the index pregnancy. No significant associations with self-reported fertility therapies or history of infertility were seen in primary analyses. In subgroup analyses of women with maternal age ≥35 years (n = 1,020), artificial insemination was significantly associated with ASD; ovulation inducing drug (OID) use was significantly associated in crude but not adjusted analyses (odds ratio 1.81, 95% CI 0.96–3.42). Results were similar by diagnostic subgroup, though within the advanced maternal age group, OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not-otherwise specified, but not autistic disorder.
Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study. However, the associations observed with OID and artificial insemination among older mothers, for whom these exposures are more common, warrant further investigation.
autism; infertility; fertility treatments; assisted reproductive technology (ART); ovulation-inducing drugs
Dietary changes characterized by a reduction in carbohydrate quality are occurring in developing countries and may be associated with a higher prevalence of obesity and chronic diseases such as type 2 diabetes mellitus. We assessed the preferences and acceptability of unrefined whole grain carbohydrate staples (i.e., brown rice, unrefined maize and unrefined sorghum ugali) as substitutes for commonly consumed refined carbohydrates in Tanzania.
A questionnaire was used to collect sociodemographic information and dietary habits, and pre-and post-tasting questionnaires were administered for test foods. A 10-point LIKERT scale was used to rate attributes of the three test foods.
White rice and refined maize ugali were the most commonly consumed carbohydrate staples in this population; 98% and 91%, respectively. Occasional consumption of unrefined maize and sorghum ugali was reported by 32% and 23% of the participants, respectively. All of the test foods were highly rated for smell, taste, color, appearance and texture. Taste was rated highest for unrefined maize ugali. Almost all of the participants were willing to participate in a future dietary intervention involving regular consumption of these unrefined carbohydrates for at least six months duration.
These findings suggest that whole grain carbohydrates are highly acceptable, and that there is a promising potential for their use in future dietary intervention studies in Tanzania.
Acceptability; Brown rice; Unrefined carbohydrates; Obesity; Tanzania
Cervical cancer is the third most common cancer among women worldwide, and in Nigeria it is the second most common female cancer. Cervical cancer is an AIDS-defining cancer; however, HIV only marginally increases the risk of cervical pre-cancer and cancer. In this study, we examine the risk factors for cervical pre-cancer and cancer among HIV-positive women screened for cervical cancer at two medical institutions in Abuja, Nigeria.
A total of 2,501 HIV-positive women participating in the cervical cancer screen-and-treat program in Abuja, Nigeria consented to this study and provided socio-demographic and clinical information. Log-binomial models were used to calculate relative risk (RR) and 95% confidence intervals (95%CI) for the risk factors of cervical pre-cancer and cancer.
There was a 6% prevalence of cervical pre-cancer and cancer in the study population of HIV-positive women. The risk of screening positivity or invasive cancer diagnosis reduced with increasing age, with women aged 40 years and older having the lowest risk (RR=0.4; 95%CI=0.2–0.7). Women with a CD4 count of 650 per mm3 or more also had lower risk of screening positivity or invasive cancer diagnosis (RR=0.3, 95%CI=0.2–0.6). Other factors such as having had 5 or more abortions (RR=1.8, 95%CI=1.0–3.6) and the presence of other vaginal wall abnormalities (RR=1.9, 95%CI=1.3–2.8) were associated with screening positivity or invasive cancer diagnosis.
The prevalence of screening positive lesions or cervical cancer was lower than most previous reports from Africa. HIV-positive Nigerian women were at a marginally increased risk of cervical pre-cancer and cancer. These findings highlight the need for more epidemiological studies of cervical cancer and pre-cancerous lesions among HIV-positive women in Africa and an improved understanding of incidence and risk factors.
Cervical cancer; Screen and treat; HIV; VIA/VILI
To determine whether human immunodeficiency virus (HIV) infection is associated with increased risk of malaria incidence and recurrence in children.
Newborn infants of HIV-infected mothers were enrolled at 6 weeks and followed for 2 years. HIV status was assessed by enzyme-linked immunosorbant assay and confirmed by HIV DNA polymerase chain reaction. Malaria was defined as (1) physician-diagnosed clinical malaria; (2) probable malaria, in which laboratory testing is requested for parasitemia; and (3) blood smear–confirmed malaria. Cox proportional hazards models estimated hazard ratios (HRs) for development of first and second malaria episodes, and generalized estimating equation models estimated malaria rate differences per 100-child-years in relation to time-updated HIV status.
Child HIV infection was associated with clinical (HR, 1.34; 95% confidence interval [CI], 1.12–1.61), probable (HR, 1.47; 95% CI, 1.19–1.81), and confirmed (HR, 1.67; 95% CI, 1.18–2.36) malaria episodes. Per 100 child-years, HIV-infected children experienced 88 (95% CI, 65–113), 36 (95% CI, 19–53), and 20 (95% CI, 9–31) more episodes of clinical, probable, and confirmed malaria episodes, respectively, than HIV-uninfected children. Among children with ≥1 malaria episodes, those with HIV infection developed second clinical (HR, 1.28; 95% CI, 1.04–1.57), probable (HR, 1.60; 95% CI, 1.26–2.14), and confirmed (HR, 2.27; 95% CI, 1.06–3.89) malaria sooner than HIV-uninfected children.
HIV infection is a risk factor for the development of malaria. Proactive malaria disease prevention and treatment is warranted for all children, particularly those with HIV infection in settings of coendemicity.
Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania.
Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period.
Antenatal clinics in Dar es Salaam, Tanzania.
Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995–1997).
Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1·4 and 2·3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period.
Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings – particularly during the pre- and postpartum periods.
Anaemia; Iron; HIV/AIDS; Pregnancy; Africa
Children born to HIV-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized.
To identify maternal, socioeconomic, and child characteristics that are associated with stunting, wasting, and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks for 24 months.
Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant’s birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting, and underweight.
2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birthweight (<2500g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting, and underweight was 8.7, 7.2, and 7.0 months, respectively. Low maternal education, few household possessions, low infant birthweight, child HIV infection and male sex were all independent predictors of stunting, wasting, and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted.
Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women.
Child undernutrition; child growth; HIV