Maternal weight gain in excess of pregnancy guidelines is related to daughters being overweight 40 years later.

BACKGROUND: Exceeding the Institute of Medicine guidelines for pregnancy weight gain increases childhood and adolescent obesity. However, it is unknown if these effects extend to midlife. OBJECTIVE: We sought to determine if exceeding the Institute of Medicine guidelines for pregnancy weight gain increases risk of overweight/obesity in daughters 40 years later. STUDY DESIGN: This cohort study is based on adult offspring in the Child Health and Development Studies and the Collaborative Perinatal Project pregnancy cohorts originally enrolled in the 1960s. In 2005 through 2008, 1035 daughters in their 40s were recruited to the Early Determinants of Mammographic Density study. We classified maternal pregnancy weight gain as greater than vs less than or equal to the 2009 clinical guidelines. We used logistic regression to compare the odds ratios of daughters being overweight/obese (body mass index [BMI] ≥25) at a mean age of 44 years between mothers who did not gain or gained more than pregnancy weight gain guidelines, accounting for maternal prepregnant BMI, and daughter body size at birth and childhood. We also examined potential family related confounding through a comparison of sisters using generalized estimating equations, clustered on sibling units and adjusted for maternal age and race. RESULTS: Mothers who exceeded guidelines for weight gain in pregnancy were more likely to have daughters who were overweight/obese in their 40s (odds ratio [OR], 3.4; 95% confidence interval {CI}, 2.0-5.7). This magnitude of association translates to a relative risk (RR) increase of 50% (RR = 1.5; 95% CI, 1.3-1.6). The association was of the same magnitude when examining only the siblings whose mother exceeded guidelines in 1 pregnancy and did not exceed the guidelines in the other pregnancy. The association was stronger with increasing maternal prepregnancy BMI (P trend < .001). Compared to mothers with BMI <25 who did not exceed guidelines, the relative risks (RR) for having an overweight/obese adult daughter were 1.3 (95% CI, 1.1-1.7), 1.7 (95% CI, 1.4-2.1) and 1.8 (95% CI, 1.5-2.1), respectively, if mothers exceeded guidelines and their prepregnancy BMI was <25, overweight (BMI 25-<30), or obese (BMI >30). This pattern held irrespective of daughters' weight status at birth, at age 4 years, or at age 20 years. CONCLUSION: Our findings support that obesity prevention before pregnancy and strategies to maintain weight gain during pregnancy within the IOM guidelines might reduce the risk of being overweight in midlife for the offspring.

Is grand-parental smoking associated with adolescent obesity? A three-generational study.

BACKGROUND/OBJECTIVES: Data from previous studies consistently suggest that maternal smoking is positively associated with obesity later in life. Whether this association persists across generations is unknown. We examined whether grand-parental smoking was positively associated with overweight status in adolescence. SUBJECT/METHODS: Participants were grandmother-mother-child triads in the Nurses' Health Study II (NHS II), the Nurses Mothers' Cohort Study and the Growing up Today Study (GUTS). Grandmothers provided information on their and their partner's smoking during pregnancy with the child's mother. Information on child's weight and height at ages 12 (N=3094) and 17 (N=3433) was obtained from annual or biennial GUTS questionnaires. We used logistic regression to estimate the odds ratios (ORs) of being overweight or obese, relative to normal weight. RESULTS: Grand-maternal smoking during pregnancy was not associated with overweight status in adolescence. After adjusting for covariates, the OR of being overweight or obese relative to normal weight at age 12 years in girls whose grandmothers smoked 15+ cigarettes daily during pregnancy was 1.21 (95% confidence interval (CI) 0.74-1.98; P(trend)=0.31) and 1.07 (0.65-1.77; P(trend)=0.41) in boys. Grand-paternal smoking during pregnancy was associated with being overweight or obese at age 12 in girls only, but not at age 17 for either sex: the OR for being overweight or obese at age 12 was 1.38 (95% CI 1.01-1.89; P(trend)=0.03) in girls and 1.31 (95% CI 0.97-1.76; P(trend)=0.07) in boys. Among children of non-smoking mothers, the OR for granddaughter obesity for grand-paternal smoking was attenuated and no longer significant (OR 1.28 (95% CI 0.87-1.89; P(trend)=0.18)). CONCLUSIONS: Our findings suggest that the association between maternal smoking and offspring obesity may not persist beyond the first generation. However, grand-paternal smoking may affect the overweight status of the granddaughter, likely through the association between grand-paternal smoking and maternal smoking.

Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls.

STUDY QUESTION: Is sugar-sweetened beverage (SSB) consumption associated with age at menarche? SUMMARY ANSWER: More frequent SSB consumption was associated with earlier menarche in a population of US girls. WHAT IS KNOWN ALREADY: SSB consumption is associated with metabolic changes that could potentially impact menarcheal timing, but direct associations with age at menarche have yet to be investigated. STUDY DESIGN, SIZE, DURATION: The Growing up Today Study, a prospective cohort study of 16 875 children of Nurses' Health Study II participants residing in all 50 US states. This analysis followed 5583 girls, aged 9-14 years and premenarcheal at baseline, between 1996 and 2001. During 10 555 person-years of follow-up, 94% (n = 5227) of girls reported their age at menarche, and 3% (n = 159) remained premenarcheal in 2001; 4% (n = 197) of eligible girls were censored, primarily for missing age at menarche. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cumulative updated SSB consumption (composed of non-carbonated fruit drinks, sugar-sweetened soda and iced tea) was calculated using annual Youth/Adolescent Food Frequency Questionnaires from 1996 to 1998. Age at menarche was self-reported annually. The association between SSB consumption and age at menarche was assessed using Cox proportional hazards regression. MAIN RESULTS AND THE ROLE OF CHANCE: More frequent SSB consumption predicted earlier menarche. At any given age between 9 and 18.5 years, premenarcheal girls who reported consuming >1.5 servings of SSBs per day were, on average, 24% more likely [95% confidence interval (CI): 13, 36%; P-trend: <0.001] to attain menarche in the next month relative to girls consuming ≤2 servings of SSBs weekly, adjusting for potential confounders including height, but not BMI (considered an intermediate). Correspondingly, girls consuming >1.5 SSBs daily had an estimated 2.7-month earlier menarche (95% CI: -4.1, -1.3 months) relative to those consuming ≤2 SSBs weekly. The frequency of non-carbonated fruit drink (P-trend: 0.03) and sugar-sweetened soda (P-trend: 0.001), but not iced tea (P-trend: 0.49), consumption also predicted earlier menarche. The effect of SSB consumption on age at menarche was observed in every tertile of baseline BMI. Diet soda and fruit juice consumption were not associated with age at menarche. LIMITATIONS, REASONS FOR CAUTION: Although we adjusted for a variety of suspected confounders, residual confounding is possible. We did not measure SSB consumption during early childhood, which may be an important window of exposure. WIDER IMPLICATIONS OF THE FINDINGS: More frequent SSB consumption may predict earlier menarche through mechanisms other than increased BMI. Our findings provide further support for public health efforts to reduce SSB consumption. STUDY FUNDING/COMPETING INTERESTS: The Growing up Today Study is supported by grant R03 CA 106238. J.L.C. was supported by the Breast Cancer Research Foundation; Training Grant T32ES007069 in Environmental Epidemiology from the National Institute of Environmental Health Sciences, National Institutes of Health; and Training Grant T32HD060454 in Reproductive, Perinatal and Pediatric Epidemiology from the National Institute of Child Health and Human Development, National Institutes of Health. A.L.F. is supported by the American Cancer Society, Research Scholar Grant in Cancer Control. K.B.M. was supported in part by the National Cancer Institute at the National Institutes of Health (Public Health Service grants R01CA158313 and R03CA170952). There are no conflicts of interest to declare.

Prenatal vitamin intake during pregnancy and offspring obesity.

BACKGROUND/OBJECTIVES: In animal studies, exposure to multivitamins may be associated with obesity in the offspring; however, data in humans are sparse. We therefore examined the association between prenatal vitamin intake during pregnancy and offspring obesity. SUBJECTS/METHODS: We investigated the association between prenatal vitamin intake and obesity among 29,160 mother-daughter dyads in the Nurses' Health Study II. Mothers of participants provided information on prenatal vitamin use during pregnancy with the nurse daughter. Information on body fatness at ages 5 and 10, body mass index (BMI) at age 18, weight in 1989 and 2009, waist circumference, and height was obtained from the daughter. Polytomous logistic regression was used to predict BMI in early adulthood and adulthood, and body fatness in childhood. Linear regression was used to predict waist circumference in adulthood. RESULTS: In utero exposure to prenatal vitamins was not associated with body fatness, either in childhood or in adulthood. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted odds ratio (OR) of being obese in adulthood of 0.99 (95% confidence interval (CI) 0.92-1.05, P-value = 0.68) compared with women whose mothers did not take prenatal vitamins. Women whose mothers took prenatal vitamins during pregnancy had a covariate-adjusted OR of having the largest body shape at age 5 of 1.02 (95% CI 0.90-1.15, P-value = 0.78). In additional analyses, in utero exposure to prenatal vitamins was also unrelated to adult abdominal adiposity. CONCLUSIONS: Exposure to prenatal vitamins was not associated with body fatness either in childhood or in adulthood.

Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.

BACKGROUND/OBJECTIVES: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. SUBJECTS/METHODS: Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. RESULTS: In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. CONCLUSIONS: The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.

Parental smoking during pregnancy and risk of overweight and obesity in the daughter.

OBJECTIVE: Emerging evidence suggests that prenatal exposures may affect long-term health outcomes. In utero exposure to smoking is associated with an increased risk of overweight and obesity in children and adolescents. However, few studies have examined how prenatal exposure to parental smoking influences the risk of obesity during adulthood and whether these associations are independent of childhood and adolescent adiposity. The aim of the current study was to investigate whether prenatal exposure to parental smoking influences body size during adulthood and whether any association may be mediated by childhood and adolescent body size. METHODS: We investigated the association between parental smoking during pregnancy and the risk of being overweight and obese during adulthood and at age 18 and adiposity during childhood among 35 370 participants in the Nurses' Health Study II. Data on smoking during pregnancy and socioeconomic variables were provided by the mothers, and anthropometric data and adult risk factors were reported by participants. RESULTS: After adjustment for socioeconomic and behavioral variables, maternal smoking during pregnancy was associated with adiposity at ages 5-10, 18 and during adulthood. For age 18 overweight, the odd ratios, ORs (95% confidence intervals, CIs) for 1-14, 15-24 and 25+cigarettes per day were 1.13 (1.18-1.50), 1.40 (1.20-1.64) and 1.15 (0.79-1.69), and for obesity were 1.41 (1.14-1.75), 1.69 (1.31-2.18) and 2.36 (1.44-3.86). The corresponding ORs (95% CIs) for obesity during adulthood were 1.26 (1.16-1.37), 1.46 (1.30-1.63) and 1.43 (1.10-1.86). Risk of adiposity was not increased among daughters whose mothers stopped smoking during the first trimester (OR (95% CI) for overweight (1.03 (95% CI 0.90-1.17)) and for obesity (1.12 (95% CI 0.97-1.30)). Women whose fathers smoked during pregnancy were also at an increased risk of being overweight and obese during adulthood with covariate-adjusted ORs (95% CIs) for obesity of 1.19 (1.11-1.29) for 1-14 cigarettes per day, 1.27 (1.18-1.37) for 15-24 cigarettes per day and 1.40 (1.27-1.54) for 25+ cigarettes per day compared with fathers who did not smoke (Ptrend<0.0001). Paternal smoking during pregnancy was also associated with an increased risk of obesity at age 18 among those whose fathers smoked 15 or more cigarettes per day but was not associated with childhood body size. CONCLUSIONS: Maternal smoking during pregnancy was associated in a dose-response manner with overweight and obesity in the daughter across adolescence and adult life. Smoking cessation during the first trimester appears to mitigate this excess risk.Paternal smoking was also associated with the risk of being overweight and obese of the adult daughter and this association persisted after adjustment for maternal smoking.

Methylation levels at imprinting control regions are not altered with ovulation induction or in vitro fertilization in a birth cohort.

STUDY QUESTION: Do fertility treatments, including ovulation induction (OI), alter epigenetic mechanisms such as DNA methylation at imprinted loci? SUMMARY ANSWER: We observed small but statistically significant differences in certain imprinting control regions (ICRs) based on the method of conception, however, these small changes in methylation did not correlate to the overall transcriptional levels of the genes adjacent to the ICRs (such as KCNQ1 and SNRPN). WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Assisted reproductive technology (ART) has been associated with an increase in the risk of rare childhood disorders caused by loss of imprinting (LOI). This study provides novel epigenetic analyses on infants conceived by OI and examines how methylation levels correlate with gene expression. DESIGN: Data and biospecimens used in this study were from 147 participants of the Epigenetic Birth Cohort comprising 1941 mother-child dyads recruited between June 2007 and June 2009 at the Department of Obstetrics, Gynecology and Reproductive Biology at Brigham and Women's Hospital (BWH) in Boston, MA, USA. Wilcoxon rank-sum tests were used to examine the differences in median percent methylation at each differentially methylated region (DMR) between the spontaneous conception control group and the fertility treatment groups (OI and IVF). PARTICIPANTS AND SETTING: For each woman who reported IVF we selected a woman who conceived spontaneously matched on age (± 2 years). To increase efficiency, we matched the same controls from the spontaneously conceived group to participants who reported OI. If an appropriate control was not identified that had been previously matched to an IVF participant, a new control was selected. The final analytic sample consisted of 61 spontaneous, 59 IVF and 27 OI conceptions. MAIN RESULTS AND THE ROLE OF CHANCE: No functionally relevant differences in methylation levels were observed across five (out of six) imprinted DMRs in either the placenta or cord blood of infants conceived with OI or IVF compared with infants conceived spontaneously. While KCNQ1, SNRPN and H19 DMRs demonstrated small but statistically significant differences in methylation based on the method of conception, expression levels of the genes related to these control regions only correlated with the methylation levels of H19. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION: Limitations of our study include the limited sample size, lack of information on OI medication used and culture medium for the IVF procedures and underlying reasons for infertility among OI and IVF patients. We did not perform allele-specific expression analyses and therefore cannot make any inferences about LOI. GENERALIZABILITY TO OTHER POPULATIONS: These results are likely to be generalizable to non-Hispanic white individuals in populations with similar ART and fertility treatments.

DNA methylation of stress-related genes and LINE-1 repetitive elements across the healthy human placenta.

OBJECTIVES: DNA methylation is known to play a critical role in regulating development of placental morphology and physiology. The methylation of genes mediated by glucocorticoid hormones may be particularly vulnerable to intrauterine stress in the placenta. However little is known about DNA methylation of stress-related genes within a healthy placenta, and particularly whether methylation occurs uniformly across different regions of the placenta, which is a critical question for researchers seeking to analyze methylation patterns. We examined DNA methylation across four regions of the placenta to evaluate methylation levels of stress-related genes within a healthy placenta, and to evaluate whether methylation patterns vary by sampling location. STUDY DESIGN: We evaluated levels of DNA methylation of three stress-related genes: NR3C1, BDNF, and 11B-HSD2 and of the repetitive element, LINE-1, in four different sample locations of 20 healthy placentas. MAIN OUTCOME MEASURES: Pyrosequencing was used to quantify levels of methylation at CpG sites within the promoter regions of each of the three stress-related genes, and global methylation of LINE-1. RESULTS: Very low levels of methylation were found across all three stress-related genes; no gene showed a median methylation level greater than 4.20% across placental regions. Variation in methylation between placental regions for stress-related genes and for LINE-1 was minimal. CONCLUSIONS: Our data suggest that these frequently studied stress-related genes have low levels of methylation in healthy placenta tissue. Minimal variation between sites suggests that sampling location does not affect DNA methylation analyses of these genes or of LINE-1 repetitive elements.

Prenatal smoke exposure and mammographic density in mid-life.

Tobacco smoke has both carcinogenic effects and anti-estrogenic properties and its inconsistent association with breast cancer risk in observational studies may be because of these competing effects across the lifecourse. We conducted a prospective study of prenatal smoke exposure, childhood household smoke exposure, and adult active smoke exposure and mammographic density, a strong intermediate marker of breast cancer risk, in an adult follow-up of existing US birth cohorts. Specifically, we followed up women who were born between 1959 and 1967 and whose mothers participated in either the Collaborative Perinatal Project (Boston and Providence sites) or the Childhood Health and Development Study in California. Of the 1134 women interviewed in adulthood (ranging in age from 39 to 49 years at interview), 79% had a screening mammogram. Cigarette smoking was reported by mothers at the time of their pregnancy; 40% of mothers smoked while pregnant. Women whose mothers smoked during pregnancy had a 3.1% (95% confidence interval (CI) = -6.0%, -0.2%) lower mammographic density than women whose mothers did not smoke during pregnancy. When we further accounted for adult body mass index and adult smoking status, the association remained (ß = -2.7, 95% CI = -5.0, -0.3). When we examined patterns of smoking, prenatal smoke exposure without adult smoke exposure was associated with a 5.6% decrease in mammographic density (ß = -5.6, 95% CI = -9.6, -1.6). Given the strength of mammographic density as an intermediate marker for breast cancer, the inverse associations between mammographic density and smoking patterns across the lifecourse may help explain the complex association between cigarette smoking and breast cancer risk.

The Early Determinants of Adult Health Study.

This issue of the Journal features collaborative follow-up studies of two unique pregnancy cohorts recruited during 1959-1966 in the United States. Here we introduce the Early Determinants of Adult Health (EDAH) study. EDAH was designed to compare health outcomes in midlife (age 40s) for same-sex siblings discordant on birthweight for gestational age. A sufficient sample of discordant siblings could only be obtained by combining these two cohorts in a single follow-up study. All of the subsequent six papers are either based upon the EDAH sample or are related to it in various ways. For example, three papers report results from studies that significantly extended the 'core' EDAH sample to address specific questions. We first present the overall design of and rationale for the EDAH study. Then we offer a synopsis of past work with the two cohorts to provide a context for both EDAH and the related studies. Next, we describe the recruitment and assessment procedures for the core EDAH sample. This includes the process of sampling and recruitment of potential participants; a comparison of those who were assessed and not assessed based on archived data; the methods used in the adult follow-up assessment; and the characteristics at follow-up of those who were assessed. We provide online supplementary tables with much further detail. Finally, we note further work in progress on EDAH and related studies, and draw attention to the broader implications of this endeavor.

Age of mother and grandmother in relation to a subject's breast cancer risk.

BACKGROUND: On theoretical grounds, the age of the grandmother and the age of the mother at delivery of her daughter may affect the breast cancer risk of the granddaughter. METHODS: We used the data relating to the Diagnostic Research Mamma-carcinoma cohort (DOM (Diagnostisch Onderzoek Mammacarcinoom) 3), which comprises a population-based sample of 12 178 women aged 41-63 years at enrolment in 1982-85 and followed up until 2000. During follow-up 340 postmenopausal breast cancer cases were identified. To these we applied a case-cohort design together with a random sample from the baseline cohort (n=1826). Of these study participants, we were able to retrieve the birth dates of 998 mothers (309 cases, 689 controls), and for 547 of these we also retrieved the birth dates of the grandmothers (197 cases, 350 controls). A weighted Cox proportional hazards model was used to estimate the hazard ratios (HRs) for the effect of the age of the grandmother and the age of the mother on the breast cancer risk of the index women, while adjusting for potential confounders. RESULTS: Compared with the reference group aged 25-29.9 years, the group with the lowest maternal age (<25 years) had an age-adjusted HR of 0.77 (95% CI 0.19-3.12) and the group with the highest maternal age (> or = 40 years) had an age-adjusted HR of 1.58 (95% CI 0.01-267.81), P-value for trend=0.62. Compared with the same reference group, the group with the lowest grandmaternal age (<25 years) had an age-adjusted HR of 0.53 (95% CI 0.24-1.17) and the group with the highest grandmaternal age (> or = 40 years) had an age-adjusted HR of 7.29 (95% CI 1.20-44.46), P for trend=0.04. The associations did not change significantly after additional adjustment for various risk factors for breast cancer, neither for maternal age nor for grandmaternal age. CONCLUSION: This study does not suggest a major role of maternal age at delivery or grandmaternal age at delivery of the mother for the (grand)daughters' breast cancer risk.

Maternal-recalled gestational weight gain, pre-pregnancy body mass index, and obesity in the daughter.

OBJECTIVE: Emerging evidence suggests that exposures during fetal life affect adult metabolism. We assessed the relationship between recalled maternal pre-pregnancy body mass, gestational weight gain (GWG), and adiposity in the daughter. DESIGN: Retrospective cohort study among mother-nurse daughter dyads in the Nurses' Health Study II and the Nurses' Mothers' Cohort. Mothers of participants completed questionnaires regarding their nurse daughter in 2001. PARTICIPANTS: 26,506 mother-nurse daughter dyads born between 1946 and 1964. MAIN OUTCOME MEASURES: Body mass index (BMI) of the nurse daughter at age 18 and in 2001. RESULTS: At age 18, 561 (2.1%) daughters were obese (BMI>30), and in 2001, 5442 (22.0%) were obese. Adjusting for covariates, women whose mothers had a recalled pre-pregnancy BMI of 29 had a 6.1-fold increased risk of obesity at age 18 and a 3.4-fold risk of obesity in 2001, compared with women whose mothers had a pre-pregnancy BMI of 21. We found a U-shaped association between recalled GWG and offspring obesity. Compared with a maternal weight gain of 15-19 lb, GWG <10 lb was associated with a significant increase in obesity risk at age 18 (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.02-2.34) and in 2001 (OR 1.27, 95% CI 1.05-1.53). High weight gain (40+lb) was also associated with obesity risk at age 18 (OR 1.81, 95% CI 1.22-2.69) and in 2001 (OR 1.74, 95% CI 1.48-2.04). These associations were stronger among mothers who were overweight before pregnancy (P for interaction=0.03), and they persisted with adjustment for birth weight. CONCLUSION: A high recalled pre-pregnancy BMI and extremes of recalled GWG are associated with an increased risk of adolescent and adult obesity in offspring, particularly when the mother is overweight. Pre-pregnancy weight and GWG may be modifiable fetal origins of overweight and obesity in women.

Inverse association of farm milk consumption with asthma and allergy in rural and suburban populations across Europe.

BACKGROUND: Dietary interventions as a means for atopy prevention attract great interest. Some studies in rural environments claimed an inverse association between consumption of farm-produced dairy products and the prevalence of allergic diseases, but current evidence is controversial. OBJECTIVE: To investigate whether consumption of farm-produced products is associated with a lower prevalence of asthma and allergy when compared with shop-purchased products. METHODS: Cross sectional multi-centre study (PARSIFAL) including 14,893 children aged 5-13 years from five European countries (2823 from farm families and 4606 attending Steiner Schools as well as 5440 farm reference and 2024 Steiner reference children). A detailed questionnaire including a dietary component was completed and allergen-specific IgE was measured in serum. RESULTS: Farm milk consumption ever in life showed a statistically significant inverse association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and sensitization to pollen and the food mix fx5 (cut-off level of >or=3.5 kU/L): aOR 0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all four subpopulations and independent of farm-related co-exposures. Other farm-produced products were not independently related to any allergy-related health outcome. CONCLUSION: Our results indicate that consumption of farm milk may offer protection against asthma and allergy. A deepened understanding of the relevant protective components of farm milk and a better insight into the biological mechanisms underlying this association are warranted as a basis for the development of a safe product for prevention.

A longitudinal study of infant feeding and obesity throughout life course.

BACKGROUND: The Centers for Disease Control and Prevention and the US Department of Health and Human Services promote breastfeeding as a strategy for reducing childhood overweight. We evaluated the relation between infant feeding and the development of overweight and obesity throughout life course. METHODS: We investigated the association between infant feeding and obesity among 35,526 participants in the Nurses' Health Study II who were followed prospectively from 1989 to 2001. Mothers of participants provided information by mailed questionnaires on the duration of breast- and bottle-feeding, as well as the type of milk or milk substitute in the bottle. Information on body shape at ages 5 and 10, weight at age 18, current weight between 1989 and 2001, and height was reported by the participants. RESULTS: The duration of breastfeeding, including exclusive breastfeeding, was not related to being overweight (25< or = body mass index (BMI) <30 kg/m(2)) or obese (BMI> or =30 kg/m(2)) during adult life. Women who were exclusively breastfed for more than 6 months had a risk of 0.94 (95% confidence interval (CI) 0.83-1.07) of becoming obese as adults compared with women who were not breastfed. Exclusive breastfeeding for more than 6 months was associated with leaner body shape at age 5 (odds ratio (OR)=0.81; 95% CI 0.65-1.01 for the highest vs the lowest category of body shape) compared to women who were not breastfed or breastfed for less than 1 week, but this association did not persist during adolescence or adulthood. CONCLUSIONS: We did not find that having been breastfed was associated with women's likelihood of becoming overweight or obese throughout life course. Although breastfeeding promotes the health of mother and child, it is unlikely to play an important role in controlling the obesity epidemic.

Allergic diseases and atopic sensitization in children related to farming and anthroposophic lifestyle--the PARSIFAL study.

BACKGROUND: The prevalence of allergic diseases has increased rapidly in recent decades, particularly in children. For adequate prevention it is important not only to identify risk factors, but also possible protective factors. The aim of this study was to compare the prevalence of allergic diseases and sensitization between farm children, children in anthroposophic families, and reference children, with the aim to identify factors that may protect against allergic disease. METHODS: The study was of cross-sectional design and included 14,893 children, aged 5-13 years, from farm families, anthroposophic families (recruited from Steiner schools) and reference children in Austria, Germany, The Netherlands, Sweden and Switzerland. A detailed questionnaire was completed and allergen-specific IgE was measured in blood. RESULTS: Growing up on a farm was found to have a protective effect against all outcomes studied, both self-reported, such as rhinoconjunctivitis, wheezing, atopic eczema and asthma and sensitization (allergen specific IgE > or = 0.35 kU/l). The adjusted odds ratio (OR) for current rhinoconjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and for atopic sensitization 0.53 (95% CI 0.42-0.67) for the farm children compared to their references. The prevalence of allergic symptoms and sensitization was also lower among Steiner school children compared to reference children, but the difference was less pronounced and not as consistent between countries, adjusted OR for current rhinoconjunctivitis symptoms was 0.69 (95% CI 0.56-0.86) and for atopic sensitization 0.73 (95% CI 0.58-0.92). CONCLUSIONS: This study indicates that growing up on a farm, and to a lesser extent leading an anthroposophic life style may confer protection from both sensitization and allergic diseases in childhood.

Correlated measurement error--implications for nutritional epidemiology.

BACKGROUND: In nutritional epidemiology, it is common to fit models in which several dietary variables are included. However, with standard instruments for dietary assessment, not only are the intakes of many nutrients often highly correlated, but the errors in the estimation of the intake of different nutrients are also correlated. The effect of this error correlation on the results of observational studies has been little investigated. This paper describes the effect on multivariate regression coefficients of different levels of correlation, both between the variables themselves and between the errors of estimation of these variables. METHODS: Using a simple model for the multivariate error structure, we examine the effect on the estimates of bivariate linear regression coefficients of (1) differential precision of measurement of the two independent variables, (2) differing levels of correlation between the true values of the two variables, and (3) differing levels of correlation between the errors of measurement of the two variables. As an example, the prediction of plasma vitamin C levels by dietary intake variables is considered, using data from the European Prospective Investigation of Cancer (EPIC) Norfolk study in which dietary intake was estimated using both a food frequency questionnaire (FFQ) and a 7-day diary (7DD). The dietary variables considered are vitamin C, fat, and energy, with different approaches taken to energy adjustment. RESULTS: When the error correlation is zero, the estimates of the bivariate regression coefficients reflect the precision of measurement of the two variables and mutual confounding. The sum of the observed regression coefficients is biased towards the null as in univariate regression. When the error correlation is non-zero but below about 0.7, the effect is minor. However, as the error correlation increases beyond 0.8 the effect becomes large and highly dependent on the relative precision with which the two variables are measured. At the extreme, the bivariate estimates can become indefinitely large. In the example, the error correlation between fat and energy using the FFQ appears to be over 0.9, the corresponding value for the 7DD being approximately 0.85. The error correlation between vitamin C and fat, and vitamin C and energy, appears to be below 0.5 and smaller for the 7DD than for the FFQ. The impact of these error correlations on bivariate regression coefficients is large. The effect of energy adjustment differs widely between vitamin C and fat. CONCLUSION: High levels of error correlation can have a large effect on bivariate regression estimates, varying widely depending on which two variables are considered. In particular, the effect of energy adjustment will vary widely. For vitamin C, the effect of energy adjustment appears negligible, whereas for fat the effect is large indicating that error correlation close to one can partially remove regression dilution due to measurement error. If, for fat intake, energy adjustment is performed by using energy density, the partial removal of regression dilution is achieved at the expense of substantial reduction in the true variance.

Fruit, vegetables, dietary fiber, and risk of colorectal cancer.

BACKGROUND: Several recent large prospective cohort studies have failed to demonstrate the presumed protective effect of fruit, vegetable, and dietary fiber consumption on colorectal cancer risk. To further explore this issue, we have examined these associations in a population that consumes relatively low amounts of fruit and vegetables and high amounts of cereals. METHODS: We examined data obtained from a food-frequency questionnaire used in a population-based prospective mammography screening study of women in central Sweden. Women with colorectal cancer diagnosed through December 31, 1998, were identified by linkage to regional cancer registries. Cox proportional hazards models were used to estimate relative risks. All statistical tests were two-sided. RESULTS: During an average 9.6 years of follow-up of 61 463 women, we observed 460 incident cases of colorectal cancer (291 colon cancers, 159 rectal cancers, and 10 cancers at both sites). In the entire study population, total fruit and vegetable consumption was inversely associated with colorectal cancer risk. Subanalyses showed that this association was due largely to fruit consumption. The association was stronger, however, and the dose-response effect was more evident among individuals who consumed the lowest amounts of fruit and vegetables. Individuals who consumed less than 1.5 servings of fruit and vegetables per day had a relative risk for developing colorectal cancer of 1.65 (95% confidence interval = 1.23 to 2.20; P(trend) =.001) compared with individuals who consumed more than 2.5 servings. We observed no association between colorectal cancer risk and the consumption of cereal fiber, even at amounts substantially greater than previously examined, or of non-cereal fiber. CONCLUSIONS: Individuals who consume very low amounts of fruit and vegetables have the greatest risk of colorectal cancer. Relatively high consumption of cereal fiber does not appear to lower the risk of colorectal cancer.