Hormonal contraceptive use before and after conception in relation to preterm birth and small for gestational age: an observational cohort study.

OBJECTIVE: To evaluate whether hormonal contraceptives, used before or in early pregnancy, confer increased risk of preterm birth or reduced fetal growth. DESIGN: Population-based cohort study conducted by the Norwegian Institute of Public Health (Mother and Child Cohort Study, 1998-2008) with linkage to the Norwegian Prescription Registry and to the Medical Birth Registry of Norway. SETTING: Norway. POPULATION: Of the 48,615 pregnancies meeting study inclusion criteria, 44,734 pregnancies were included in the complete case analysis. METHODS: We characterised hormonal contraception by type (combination oral, progestin-only oral, vaginal ring, transdermal, and injectable) and specific progestin component. We used generalised estimating equations to estimate the odds of adverse outcome according to formulation used. Several sensitivity analyses were conducted. MAIN OUTCOME MEASURES: Preterm birth, small for gestational age. RESULTS: We observed a positive association between use of a combination oral contraceptive and preterm birth for all exposure periods (e.g. adjusted odds ratio 1.21, 95% confidence interval 1.04-1.41 for last use 12 to >4 months before conception); combination contraceptives containing the progestin norethisterone were consistently related to risk. Other types of hormonal contraception were generally not associated with preterm birth; none were related to small for gestational age. Observed associations were robust to sensitivity analyses. CONCLUSION: Hormonally active agents may exert dose-, agent-, and timing-specific effects on growth and development. We found that the particular progestin component is important when assessing the potential for adverse effects among former users of hormonal contraceptives.

Maternal hormonal contraceptive use and offspring overweight or obesity.

BACKGROUND/OBJECTIVES: Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. SUBJECTS/METHODS: Using data from a large, prospective pregnancy cohort study (n=19 652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. RESULTS: We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. CONCLUSIONS: Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.

Maternal smoking during pregnancy and daughters' risk of gestational diabetes and obesity.

AIMS/HYPOTHESIS: The primary aim of the study was to investigate the risk of developing gestational diabetes in women who were exposed to tobacco smoke in utero. Secondary aims were to assess the risk of obesity and non-gestational diabetes. METHODS: Data were retrieved from the Medical Birth Register of Sweden for women who were born in 1982 (when smoking data were first registered) or later and who had given birth to at least one child; 80,189 pregnancies were included. The associations between in utero smoking exposure (three categories: non-smokers, 1-9 cigarettes/day [moderately exposed] and >9 cigarettes/day [heavily exposed]) and subsequent gestational diabetes (n = 291), non-gestational diabetes (n = 280) and obesity (n = 7,300) were assessed. RESULTS: The adjusted ORs (aORs) of gestational diabetes were increased among women who were moderately (1.62, 95% CI 1.24, 2.13) and heavily (1.52, 95% CI 1.12, 2.06) exposed. The corresponding aORs of obesity were 1.36 (95% CI 1.28, 1.44) and 1.58 (95% CI 1.48, 1.68), respectively. A reduced OR for non-gestational diabetes was seen in the offspring of heavy smokers (aOR 0.66, 95% CI 0.45, 0.96). CONCLUSIONS/INTERPRETATION: Women exposed to smoking during fetal life were at higher risk of developing gestational diabetes and obesity.

Triclosan exposure and allergic sensitization in Norwegian children.

BACKGROUND: Exposure to the synthetic antimicrobial chemical, triclosan, used in personal care products, has been hypothesized to lead to allergic disease. We investigated whether triclosan exposure was associated with allergic sensitization and symptoms in 10-year-old Norwegian children. METHODS: Urinary concentrations of triclosan were measured in one first morning void from 623 children, collected during 2001-2004. Logistic regression models, controlling for urine specific gravity, parental allergic disease, maternal education, and household income, were fitted for allergic sensitization (either skin prick test positivity or serum-specific IgE ≥ 0.35 kU/l to at least one of 15 evaluated inhalant and food allergens), current rhinitis, and current asthma (questionnaire and exercise challenge test). RESULTS: The adjusted odds ratio (aOR) for allergic sensitization among those in the fourth quartile of triclosan concentration was 2.0 [95% confidence interval (CI): 1.1, 3.4] compared with the reference group (

The concentration of bisphenol A in urine is affected by specimen collection, a preservative, and handling.

In urine specimens that were collected from pregnant women in a large cohort, 24% contained more than 10 ng/ml of total bisphenol A (BPA), suggesting external contamination. Therefore, we conducted an investigation of the source(s) of extraneous BPA in the specimens. We found that under the conditions used to collect urine specimens in the epidemiologic study, contamination with BPA occurred, and by two separate mechanisms.

Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study.

AIMS/HYPOTHESIS: We assessed the effects of type 1 diabetes and type 2 diabetes on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large cohort of pregnant women. METHODS: This study is based on the Norwegian Mother and Child Cohort Study. Members of this large cohort were enrolled early in pregnancy and asked about TTP and other factors. Among the 58,004 women included in the analysis, we identified 221 cases of type 1 diabetes and 88 cases of type 2 diabetes using the Medical Birth Registry of Norway. A logistic analogue of the proportional probability model, a Cox-like discrete-time model, was used to compute fecundability odds ratios (FORs) and 95% CI for type 1 diabetes and type 2 diabetes, adjusted for maternal age and prepregnancy BMI. RESULTS: Compared with non-diabetic women, the adjusted FOR for women with type 1 diabetes was 0.76 (95% CI 0.64-0.89) and the adjusted FOR for women with type 2 diabetes was 0.64 (95% CI 0.48-0.84). These FORs did not change substantively and remained statistically significant after excluding women with irregular menstrual cycles and accounting for cycle length. CONCLUSIONS/INTERPRETATION: The results from the present study provide evidence of substantially decreased fecundability for women with type 1 and type 2 diabetes, even among those with a normal menstrual cycle.

In utero exposure to maternal smoking and women's risk of fetal loss in the Norwegian Mother and Child Cohort (MoBa).

BACKGROUND: Whether in utero exposure to tobacco smoke increases a woman's risk of fetal loss later in life is unknown, though data on childhood exposure suggest an association may exist. This study evaluated the association between in utero exposure to tobacco smoke and fetal loss in the Norwegian Mother and Child Cohort Study (MoBa), which enrolled ∼40% of the pregnant women in Norway from 1999 to 2008. METHODS: Information on exposure to tobacco smoke in utero, the woman's own smoking behavior during pregnancy and other factors was obtained by a questionnaire completed at ∼17 weeks of gestation. Subsequent late miscarriage (fetal death <20 weeks) and stillbirth (fetal death ≥ 20 weeks) were ascertained from the Norwegian Medical Birth Registry. This analysis included 76 357 pregnancies (MoBa data set version 4.301) delivered by the end of 2008; 59 late miscarriages and 270 stillbirths occurred. Cox proportional hazards models were fit for each outcome and for all fetal deaths combined. RESULTS: The adjusted hazard ratio (HR) of late miscarriage was 1.23 [95% confidence interval (CI), 0.72-2.12] in women with exposure to maternal tobacco smoke in utero when compared with non-exposed women. The corresponding adjusted HR for stillbirths was 1.11 (95% CI, 0.85-1.44) and for all fetal deaths combined, it was 1.12 (95% CI, 0.89-1.43). CONCLUSIONS: The relatively wide CI around the HR for miscarriage reflected the limited power to detect an association, due to enrollment around 17 weeks of gestation. However, for in utero exposure to tobacco smoke and risk of stillbirth later in life, where the study power was adequate, our data provided little support for an association.

Mother's age at menarche and offspring size.

OBJECTIVE: An individual's growth trajectory is, at least in part, inherited. Mother's early age at menarche has been associated with taller offspring height and greater body mass index (BMI) at age 9 years, suggesting that mother's age at menarche may be an intergenerational marker of growth. We examined the association between mother's age at menarche and childhood size at birth, and at ages 1, 3, 4, 7 and 8 years in the Collaborative Perinatal Project. SUBJECTS: We examined 128,636 measurements obtained from 31,474 Black and White children. We transformed the original measurements into z-scores. Child size was examined in mixed models, adjusted for center, child sex, race, socioeconomic index, child's exact age at measurement (in months), mother's age at recruitment and, depending on which measure was the outcome in the specific model, mother's height, pre-pregnancy weight or BMI. RESULTS: Compared with children whose mother had menarche at age 15 years or later, children whose mothers had age at menarche before age 12 years were taller from 1 year of age and had higher BMI, particularly at ages 7 and 8 years (0.17 and 0.19 z-score units, respectively). CONCLUSIONS: Mothers' age at menarche is a modest predictor of their children's growth trajectory. The mechanism is likely to be heritable, although other explanations are possible.

Validation of self-reported recreational exercise in pregnant women in the Norwegian Mother and Child Cohort Study.

We compared the self-reported frequency of recreational exercise and corresponding metabolic equivalent (MET)-minutes with physical activity measured with a position and motion sensor in pregnant women. One hundred and twelve women in the Norwegian Mother and Child Cohort Study (MoBa) completed questions about weekly participation in recreational exercise by week 17 of pregnancy and participated in the validation study around week 20. Data from a validated motion sensor (ActiReg) that measures physical activity and total energy expenditure (TEE) served as the "gold standard." Self-reported recreational exercise was compared with the following ActiReg-based measures: physical activity energy expenditure (PAEE), minutes of vigorous physical activity (VPA), physical activity level (PAL) and TEE. Pearson's correlations between self-reported weekly exercise and the objectively assessed variables were: rPAEE=0.26, rVPA=0.32, rPAL=0.30 (all P<0.01) and rTEE=0.17 (P=0.07). The partial correlation coefficients between the questionnaire responses and the ActiReg measurements were similar after adjusting for parity, body mass index, education, age, height and smoking, but rTEE increased (r=0.27, P<0.01). We observed significant positive associations between self-reported exercise activities and motion sensor measurements of physical activity, indicating that the questions used for exercise assessment in MoBa may be useful for ranking pregnant women according to the recreational exercise level.

Maternal levels of perfluoroalkyl substances (PFASs) during pregnancy and childhood allergy and asthma related outcomes and infections in the Norwegian Mother and Child (MoBa) cohort.

INTRODUCTION: Prenatal exposure to perfluoroalkyl substances (PFASs) has been inconsistently associated with asthma and allergic diseases and increased number of infections in early childhood. We examined the association of PFASs measured in pregnancy with childhood asthma, allergies and common infectious diseases in a prospective pregnancy cohort followed to age 7 years. MATERIAL AND METHODS: Six PFASs (out of 19 measured) with at least 80% of measurements above the limit of quantification (LOQ) in maternal plasma during pregnancy in two subcohorts of the Norwegian Mother and Child Cohort Study (MoBa) were analyzed in relation to health outcomes: perfluorooctane sulfonic acid (PFOS), acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluoroheptane sulfonic acid (PFHpS). Follow-up questionnaires were completed at 3 years by 1270 women and at 7 years by 972 women among the 1943 with pregnancy questionnaire and PFAS measures. Health outcomes included parent reports of child's symptoms or doctor diagnosed asthma and allergic conditions at age 7 years and parent-reported frequency of various infections at 3 and 7 years of age. Logistic and Poisson regression were used. The false discovery rate was controlled at 5%. Sensitivity analyses on gender were performed. RESULTS: Among the allergy and asthma outcomes, a statistically significant inverse association was seen between PFUnDA concentrations and ever having atopic eczema in girls. PFUnDA also tended to be inversely associated with both wheeze and asthma. For infections from 0 to 3 and 6 to 7 years, 11 significant positive associations were seen between PFASs and airways infections (bronchitis/pneumonia, throat infection, pseudocroup), ear infection and gastric flu/diarrhea; whereas 6 inverse associations were seen for pseudocroup, ear infections and urinary tract infections. The majority of the findings with respect to infectious diseases were found in girls only. DISCUSSION: With the exception of an inverse association between PFUnDA and eczema, and a tendency of a similar association for wheeze and asthma, maternal PFAS levels during pregnancy showed little association with asthma or allergy related outcomes. Findings from the present study suggest immunosuppressive effects of PFASs on airways infections, such as bronchitis/pneumonia and throat infections, as well as diarrhea/gastric flu. Our results indicate a possible role of gender in the PFAS-health outcome associations.

Quantitative bias analysis of the association of type 2 diabetes mellitus with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153).

An association between serum concentrations of persistent organic pollutants (POPs), such as 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and risk of type 2 diabetes mellitus (T2DM) has been reported. Conditional on body mass index (BMI) and waist circumference (WC), a higher serum PCB-153 concentration may be a marker of T2DM risk because it reflects other aspects of obesity that are related to T2DM risk and to PCB-153 clearance. To estimate the amount of residual confounding by other aspects of obesity, we performed a quantitative bias analysis on the results of a specific study. A physiologically-based pharmacokinetic (PBPK) model was developed to predict serum levels of PCB-153 for a simulated population. T2DM status was assigned to simulated subjects based on age, sex, BMI, WC, and visceral adipose tissue mass. The distributions of age, BMI, WC, and T2DM prevalence of the simulated population were tailored to closely match the target population. Analysis of the simulated data showed that a small part of the observed association appeared to be due to residual confounding. For example, the predicted odds ratio of T2DM that would have been obtained had the results been adjusted for visceral adipose tissue mass, for the ≥90th percentile of PCB-153 serum concentration, was 6.60 (95% CI 2.46-17.74), compared with an observed odds ratio of 7.13 (95% CI 2.65-19.13). Our results predict that the association between PCB-153 and risk of type 2 diabetes mellitus would not be substantially changed by additional adjustment for visceral adipose tissue mass in epidemiologic analyses. Confirmation of these predictions with longitudinal data would be reassuring.

Serum alpha-tocopherol concentration in relation to subsequent colorectal cancer: pooled data from five cohorts.

BACKGROUND: Vitamin E is an antioxidant that inhibits mutagenesis and cell transformation. Previous findings in five prospective epidemiologic studies suggested that the level of serum alpha-tocopherol, the predominant form of vitamin E in the blood, was lower in subjects who subsequently developed colorectal cancer than in control subjects. However, the difference was neither obvious nor statistically significant in any one of these five studies. PURPOSE: To evaluate in greater detail the association between serum alpha-tocopherol concentration and risk of colorectal cancer, we pooled and analyzed the original data from the five studies. Our analyses were designed to (a) test the hypothesis with greater statistical power, (b) examine the association after adjustment for serum cholesterol levels, and (c) evaluate the association after uniform exclusion of cases diagnosed shortly after blood specimens were drawn. METHODS: Data for individual subjects were analyzed. To make the design of the component investigations uniformly nested case-control studies with individual matching, we matched controls to cases in two of the cohorts. Subjects were categorized according to study-specific quartile of serum alpha-tocopherol level within the study. The pooled analysis included 289 cases of colorectal cancer and 1267 matched controls. RESULTS: For cancers of the colon and rectum combined, the matched odds ratio (OR) for the highest quartile of serum alpha-tocopherol concentration compared with the lowest was 0.6 (95% confidence interval [CI] = 0.4-1.0). Adjustment for serum cholesterol level attenuated the OR to 0.7 (95% CI = 0.4-1.1). CONCLUSION: The results suggest that serum alpha-tocopherol concentration may be inversely related to risk of colorectal cancer. It is unclear whether an association exists, however, because the association between serum alpha-tocopherol level and decreased risk of colorectal cancer was modest, the CIs were wide, and, overall, the tests for trend in effect were not significant. IMPLICATIONS: Larger observational studies with concurrent dietary data are needed to determine whether vitamin E has a modest but potentially important protective effect against colorectal cancer.

Risk of breast cancer in relation to lifetime alcohol consumption.

BACKGROUND: Although an association between alcohol consumption and risk of breast cancer has been observed in many studies, questions of major importance remain, including the nature of the dose-response relationship and the effects of drinking at various periods in life. PURPOSE: Our goal was to address the issues listed above with a large case-control study. METHODS: We conducted a population-based case-control study in Maine, Massachusetts (excluding the four counties that include metropolitan Boston), New Hampshire, and Wisconsin. Case patients were eligible if their diagnosis of invasive breast cancer was first reported to one of the four statewide cancer registries during the period of 1988 through 1991. During the accrual period, 11,879 potentially eligible case patients and 16,217 control subjects were identified. After excluding ineligible women from the study, telephone interviews were obtained from 6888 case patients and 9424 control subjects. Complete data for recent alcohol consumption, and thus final eligibility for study participation, were determined for 6662 case patients and 9163 control subjects. The average age at time of interview was 58.7 years. The questions on alcohol use addressed average consumption during five periods of the subjects' lives: ages 16-19, 20-29, 30-39, 40-59, and 60-74 years. Similar responses from 211 control subjects upon reinterview 6-12 months later were taken to be indicative of the reliability of the questionnaire used in this study. RESULTS: Lifetime average alcohol consumption (measured as the average grams per day consumed from age 16 to the recent past) and recent alcohol consumption (average grams per day consumed in the previous age interval) were associated with risk of developing breast cancer. The multivariate relative risk of breast cancer, in those who drink compared with abstainers, associated with average lifetime consumption of 12-18 g/day of alcohol (about one drink) was 1.39 (95% confidence interval [CI] = 1.16-1.67), of 19-32 g/day (about two drinks) was 1.69 (95% CI = 1.36-2.10), of 33-45 g/day (about three drinks) was 2.30 (95% CI = 1.51-3.51), and of greater than or equal to 46 g/day (four or more drinks) was 1.75 (95% CI = 1.16-2.64) (P for trend < .0001). The multivariate relative risk per 13 g/day (about one drink) of alcohol consumed before 30 years of age was 1.09 (95% CI = 0.95-1.24), whereas the relative risk associated with recent consumption of 13 g/day was 1.21 (95% CI = 1.09-1.34). CONCLUSIONS: In these data, alcohol consumption was clearly related to breast cancer risk. Risk appeared to increase even at moderate levels of consumption. For women of all ages combined, consumption before 30 years of age was not an important determinant of risk.

Glutathione transferase (GSTM1) null genotype, smoking, and prevalence of colorectal adenomas.

Colorectal cancer is caused by environmental exposures and genetic predisposition. However, little is known of hereditary factors that influence development of common, non-Mendelian forms of this cancer. Interactions among carcinogen exposure, hereditary variants of enzymes involved in carcinogen metabolism, and other host factors may play a role. Genetic polymorphisms of carcinogen metabolism, such as the glutathione transferase M1 (GSTM1) null genotype, are thus possibly related to cancer risk. The GSTM1 enzyme detoxifies mutagens formed from polycyclic aromatic hydrocarbons which are found in tobacco smoke. We analyzed GSTM1 genotypes and smoking among 488 controls and 446 individuals with a first time diagnosis of colorectal adenomas which are precursors to cancer. Subjects were from two Kaiser Permanente sigmoidoscopy clinics in southern California. We observed no overall effect of the GSTM1 null genotype on the risk for colorectal adenomas (odds ratio, 0.85; 95% confidence interval = 0.65-1.10). The odds ratio for smokers with the null genotype was 2.07 (95% confidence interval = 1.14-3.77) when compared to "never smokers" without the null genotype. Using this same reference group, the odds ratio for smokers without the null genotype was 1.73 (95% confidence interval = 1.03-2.90). These two odds ratios were not significantly different (P = 0.30).

Acetylation polymorphism and prevalence of colorectal adenomas.

Polymorphic N-acetyltransferase (NAT2), an enzyme present in the colon, may effect incidence of colon cancer. Individuals with NAT2 fast acetylator genotypes may have higher colon cancer risks due to faster conversion of certain carcinogens to mutagens. We determined NAT2 genotypes in 447 subjects with distal colon adenomas and in 487 controls. No significant increase in adenoma prevalence among fast acetylators was observed. However, there was a suggestion of ethnic differences in NAT2 effects. For example, white fast acetylators potentially had slightly increased risks for adenomas (odds ratio, 1.29; 95% confidence interval, 0.90-1.84), whereas fast acetylation was potentially protective among blacks (odds ratio, 0.64; 95% confidence interval, 0.32-1.28). The apparent difference between blacks and whites may simply reflect random variation around an overall null effect, or it could represent a real difference. There was preliminary evidence for a possible interaction between NAT2 and the glutathione transferase M1 null genotype. Smokers' adenoma prevalence was 10-fold higher for fast acetylators with the null genotype compared to slow acetylators without the null genotype. Large, multiethnic populations and analysis of combinations of genes for carcinogen metabolism may be needed to further assess the role of NAT2 in colorectal tumorigenesis.

Insulin and a sulfonylurea agent in non-insulin-dependent diabetes mellitus.

Using a double-blind crossover design, we studied the effect of tolazamide, an orally administered sulfonylurea, in 11 patients with non-insulin-dependent diabetes mellitus, poorly controlled on 40 units/day or more of insulin; all had previously failed to respond adequately to oral hypoglycemic agents and diet. In addition, six nondiabetic sex-, age-, and weight-matched controls were studied. Tolazamide significantly lowered fasting plasma glucose level from 272 +/- 21 to 222 +/- 31 mg/dL, increased fasting C peptide concentration from 0.09 +/- 0.03 to 0.28 +/- 0.10 pmole/mL (controls, 0.23 +/- 0.2 pmole/mL), and increased integrated C peptide concentration during a test meal (area under the curve) from 42 +/- 18 to 95 +/- 22 pmole/mL X min (controls, 94 +/- 8 pmole/mL X min). These data show that addition of tolazamide markedly increased fasting and meal-stimulated insulin secretion and modestly lowered fasting plasma glucose concentrations. We conclude that some patients who cannot achieve satisfactory control with oral hypoglycemic agents and diet may benefit from combined therapy with oral sulfonylurea agents plus insulin.

Polychlorinated biphenyl serum levels in pregnant subjects with diabetes.

OBJECTIVE: Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain; detectable amounts are in the blood of nearly everyone. Their effect on humans at background levels of exposure is an area of active investigation. Increased blood levels of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), a PCB-like compound, have recently been reported among subjects with diabetes, suggesting that PCB levels could be similarly elevated. To test this hypothesis, we examined a group of pregnant women whose serum PCB levels had been measured and whose diabetes status had been previously recorded. RESEARCH DESIGN AND METHODS: Using stored serum from a large birth cohort study, we conducted a cross-sectional study of 2,245 pregnant women, of whom 44 had diabetes (primarily type 1) and 2,201 were control subjects. RESULTS: The adjusted mean serum level of PCBs among the subjects with diabetes was 30% higher than in the control subjects (P = 0.0002), and the relationship of PCB level to adjusted odds of diabetes was linear. CONCLUSIONS: The possibility exists that PCBs and diabetes are causality related; alternatively, the pharmacokinetics of PCBs could be altered among patients with diabetes. At any event, if the association is replicated in other studies, increased serum levels of PCBs in subjects with diabetes or their offspring may put them at increased risk of PCB-induced changes in thyroid metabolism or neurodevelopment.

A 1-y trial of the effect of high-selenium bread on selenium concentrations in blood and toenails.

The concentration of selenium in toenail clippings and blood reflects dietary intake better than does intake calculated from dietary data because of the highly variable selenium concentration in different samples of the same food. However, the time course of selenium intake in relation to subsequent concentrations in toenail clippings is unclear. Therefore, 12 males were fed high-dose (4.91 mumol Se/d), medium-dose (2.61 mumol Se/d), or control (0.41 mumol Se/d) whole-wheat-bread for 1 y and the concentration of selenium was measured in toenail clippings collected every 12 wk for 2 y. Toenail selenium concentration was unaffected by dietary intake in the previous 3 mo and appeared to provide a time-integrated measure of intake over a period of 26-52 wk. Use of selenium concentration in toenail clippings may be an alternative to blood when a measure of long-term average intake is desired. The absence of a short-term effect of diet on toenail selenium concentration also makes this a useful marker of intake in retrospective studies.

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area.

To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes greater than 2.54 mumol/d (200 micrograms/d) (range 0.86-9.20 mumol/d, or 68-724 micrograms/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20 mumol/d (724 micrograms/d).

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area.

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.