Lynn L. Moore

Teratogenicity of High Vitamin A Intake

Background Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest. Methods Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the womens diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. Results For defects associated with cranial-neural-crest tis...

Does early physical activity predict body fat change throughout childhood

BACKGROUND Declining levels of physical activity in the population at large may be responsible in part for the rising rates of childhood obesity. Studies to date, however, have not consistently demonstrated such a protective effect. We used longitudinal data from the Framingham Childrens Study (FCS) to address this important question. METHODS We used 8 years of activity monitoring (Caltrac electronic motion sensors) and repeated anthropometry measures for 103 children to examine the effect of activity on body fat change from preschool to early adolescence. Longitudinal data analysis methods were employed to account for the use of repeated measures on these children. RESULTS Children in the highest tertile of average daily activity from ages 4 to 11 years had consistently smaller gains in BMI, triceps, and sum of five skinfolds throughout childhood. By early adolescence (age 11), the sum of five skinfolds was 95.1, 94.5, and 74.1 for the low, middle, and high tertiles of activity, respectively (P for trend = 0.045). This protective effect of activity was evident for both girls and boys. CONCLUSION This longitudinal study adds strong support for the hypothesis that higher levels of physical activity during childhood lead to the acquisition of less body fat by the time of early adolescence.

BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham Study adults

BACKGROUND: It is unclear whether the increased risk of colon cancer associated with obesity differs for men and women, by distribution of body fat, or by location of the tumor. The primary goal of this study was to address these questions.METHODS: Eligible subjects from the Framingham Study cohort were classified according to body mass index (BMI) and waist size during two age periods: 30–54 y (n=3764) and 55–79 y (n=3802). All eligible men and women were cancer-free at baseline and had complete information on the following potential confounders: age, sex, education, height, activity, smoking, and alcohol. There were 157 incident lifetime cases of colon cancer among those followed beginning at 30–54 y of age and 149 lifetime cases among those whose follow up began at 55–79 y. Subjects were stratified further by gender, activity, and tumor location. The Cox Proportional Hazards Models were used to adjust for possible confounding by the above-described factors.RESULTS: A BMI ≥30 led to a 50% increased risk (95% CI: 0.92–2.5) of colon cancer among middle-aged (30–54 y) and a 2.4-fold increased risk (95% CI: 1.5–3.9) among older (55–79 y) adults. The BMI effect was stronger for men than for women and for cases occurring in the proximal colon. These adverse effects generally diminished when waist was added to the multivariable models. A larger waist size (≥99.1 cm (39 in) and 101.6 cm (40 in) for women and men, respectively) was associated with a two-fold increased risk of colon cancer; this risk increased linearly with increasing waist size and was evident for both proximal and distal colon cancer. There was no attenuation of these effects when BMI was added to the multivariable models. A larger waist had a particularly adverse effect among sedentary subjects (relative risk (RR)=4.4 for middle-aged adults; RR=3.0 for older adults).CONCLUSION: These findings suggest that waist circumference is a stronger predictor of colon cancer risk than is BMI, and that central obesity is responsible for an increased risk of cancer of both the proximal and distal colon.

Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999-2002.

BackgroundAlthough diet and activity are key factors in the obesity epidemic, laboratory studies suggest that endocrine disrupting chemicals may also affect obesity.MethodsWe analyzed associations between six phthalate metabolites measured in urine and body mass index (BMI) and waist circumference (WC) in National Health and Nutrition Examination Survey (NHANES) participants aged 6–80. We included 4369 participants from NHANES 1999–2002, with data on mono-ethyl (MEP), mono-2-ethylhexyl (MEHP), mono-n-butyl (MBP), and mono-benzyl (MBzP) phthalate; 2286 also had data on mono-2-ethyl-5-hydroxyhexyl (MEHHP) and mono-2-ethyl-5-oxohexyl (MEOHP) phthalate (2001–2002). Using multiple regression, we computed mean BMI and WC within phthalate quartiles in eight age/gender specific models.ResultsThe most consistent associations were in males aged 20–59; BMI and WC increased across quartiles of MBzP (adjusted mean BMI = 26.7, 27.2, 28.4, 29.0, p-trend = 0.0002), and positive associations were also found for MEOHP, MEHHP, MEP, and MBP. In females, BMI and WC increased with MEP quartile in adolescent girls (adjusted mean BMI = 22.9, 23.8, 24.1, 24.7, p-trend = 0.03), and a similar but less strong pattern was seen in 20–59 year olds. In contrast, MEHP was inversely related to BMI in adolescent girls (adjusted mean BMI = 25.4, 23.8, 23.4, 22.9, p-trend = 0.02) and females aged 20–59 (adjusted mean BMI = 29.9, 29.9, 27.9, 27.6, p-trend = 0.02). There were no important associations among children, but several inverse associations among 60–80 year olds.ConclusionThis exploratory, cross-sectional analysis revealed a number of interesting associations with different phthalate metabolites and obesity outcomes, including notable differences by gender and age subgroups. Effects of endocrine disruptors, such as phthalates, may depend upon endogenous hormone levels, which vary dramatically by age and gender. Individual phthalates also have different biologic and hormonal effects. Although our study has limitations, both of these factors could explain some of the variation in the observed associations. These preliminary data support the need for prospective studies in populations at risk for obesity.

A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus

This study was designed to evaluate the effects of maternal obesity and diabetes mellitus on the risk of nonchromosomal congenital defects. We used data from 22,951 pregnant women enrolled in a prospective cohort study of early prenatal exposures and pregnancy outcome. The relative risks [prevalence ratios (PRs)] of major nonchromosomal congenital defects associated with obesity and diabetes, alone or in combination, were calculated using multiple logistic regression analysis. In this study, in the absence of diabetes, obese women (body mass index ≥28) had no higher risk, overall, of having an offspring with a major defect [PR = 0.95; 95% confidence interval (CI) = 0.62–1.5[. Their offspring, however, did have a higher prevalence of certain types of defects, including orofacial clefts; club foot; cardiac septal defects; and, to a lesser extent, hydrocephaly and abdominal wall defects. Women with pre-existing or gestational diabetes who were not obese also had no excess risk overall of having offspring affected by a major defect (PR = 0.98; 95% CI = 0.43–2.2), although they did have a higher prevalence of musculoskeletal defects. The pregnancies of women who were both obese and diabetic were 3.1 times as likely (95% CI = 1.2–7.6) to result in an offspring with a defect than were those of nonobese, nondiabetic women, which suggests that obesity and diabetes mellitus may act synergistically in the pathogenesis of congenital anomalies. The defects were largely craniofacial or musculoskeletal.

Intake of Fruits, Vegetables, and Dairy Products in Early Childhood and Subsequent Blood Pressure Change

Background: Diets characterized by high intakes of fruits and vegetables and low-fat dairy products (for example, the DASH diet) have been shown to reduce blood pressure in adults. The effects of similar diets on childrens blood pressure are unknown. Methods: We used 8 years of follow-up data from 95 children, initially 3 to 6 years of age at enrollment in the prospective Framingham Childrens Study in 1986. The yearly clinic visits included 5 measures of blood pressure obtained with an automated device. Diet was assessed by means of replicate sets of 3-day food diaries during each year. Results: Children who consumed more fruits and vegetables (4 or more servings per day) or more dairy products (2 or more servings per day) during the preschool years had smaller yearly gains in systolic blood pressure throughout childhood. By the time of early adolescence, children with higher intakes of fruits and vegetables and dairy products had an adjusted mean (± standard deviation) systolic blood pressure of 106 ± 2.9 mm Hg, whereas those with lower intakes in both food groups had a mean systolic blood pressure of 113 ±1.5 mm Hg. Those with higher intakes of fruits and vegetables alone or dairy alone had intermediate levels of systolic blood pressure in adolescence. The effects on diastolic blood pressure were weaker. Conclusion: These results suggest that a diet rich in fruits, vegetables, and dairy products may have beneficial effects on blood pressure during childhood.

Food group intake and central obesity among children and adolescents in the Third National Health and Nutrition Examination Survey (NHANES III)

OBJECTIVE To explore mean food group intakes associated with central obesity anthropometry among children and adolescents enrolled in the Third National Health and Nutrition Examination Survey (NHANES III). DESIGN Cross-sectional study. SETTING Representative sampling of the US population (1998-2002). SUBJECTS Subjects were 3761 children (5-11 years) and 1803 adolescents (12-16 years) with single 24 h dietary recalls and anthropometric measures of central body fat (waist circumference and sum of subscapular and suprailiac skinfold thicknesses). RESULTS Results were controlled for confounding by age, height, race/ethnicity, Tanner stage, television viewing and parental education. In younger children, there was no relationship between central adiposity and mean intakes of dairy, fruit, vegetables or grains, while a positive association with meat intake was found among boys. In adolescent boys and girls, central body fat measures were inversely associated with mean dairy and grain intakes. Adolescent boys in the highest quartile of central adiposity consumed less fruit and fewer vegetables; those in the lowest central adiposity quartile consumed less meat. Finally, adolescents who met the criteria for central obesity (waist circumference >or=85th percentile for age and sex) reported consuming significantly less total dairy (as well as milk and cheese separately), total grains (whole and refined) and total fruit and vegetables. There was no association with meat consumption. To test the stability of these findings, the final analysis was replicated in 2541 same-aged adolescents from NHANES 1999-2002; the results were very similar. CONCLUSIONS These cross-sectional analyses suggest that intakes of dairy, grains and total fruits and vegetables are inversely associated with central obesity among adolescents.

Low Dairy Intake in Early Childhood Predicts Excess Body Fat Gain

Objective: To estimate the effect of dairy intake in early childhood on the acquisition of body fat throughout childhood.

Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus

Although rates of adult-onset diabetes mellitus increase with increasing obesity, there is little evidence that weight loss in overweight individuals can reduce their risk of developing diabetes. Using data from the Framingham Study, we examined the effects of sustained and nonsustained weight loss on risk of diabetes mellitus among 618 overweight (body mass index > or =27) subjects 30-50 years of age. To separate sustained from nonsustained weight loss, we examined weight change in two consecutive 8-year periods. Subjects who had stable weight (+/- 1 lb per year) during both periods served as the referent group for all analyses. Sustained weight loss led to a 37% lower risk of diabetes [relative risk (RR) = 0.63; 95% confidence interval = 0.34-1.2], and this effect was stronger for more obese (body mass index > or =29) subjects (RR = 0.38; 95% confidence interval = 0.18-0.81). Those who lost 8.1-15 lb had a 33% reduction in diabetes risk, whereas those losing more had a 51% reduction in risk. Regardless of the amount of weight lost, those who regained the lost weight had no reduction in diabetes risk (RR = 1.1 and 1.2 for those who lost 8.1-15 and >15 lb, respectively). We conclude that a modest amount of sustained weight loss can substantially reduce the risk of diabetes mellitus in overweight individuals.

Folate Intake and the Risk of Neural Tube Defects: An Estimation of Dose-Response

Background. Studies have shown that folic acid supplementation in early pregnancy markedly reduces the risk of neural tube defects (NTDs). Investigation of the relation between relative dose of supplemental folic acid or total folate intake and NTD risk is limited. Methods. We used data from 23,228 women, predominantly from the northeastern United States, enrolled between October 1984 and June 1987 in a prospective study of early prenatal exposures and pregnancy outcomes. Diet and vitamin intake data were gathered in the early second trimester. NTDs were ascertained through prenatal testing and by report of the delivering physician. Data analyses included multiple logistic regression and restricted spline regression modeling. Results. For each additional 500 dietary folate equivalents consumed per day, the prevalence of NTDs decreased by 0.78 cases (95% confidence interval [CI] = 0.47–1.09) per 1,000 pregnancies. Compared with women having the lowest total folate intakes (0–149 folate equivalents per day), the prevalence of NTDs declined by 34%, 30%, 56% and 77% among the offspring of those women consuming 150–399, 400–799, 800–1199 and ≥ 1200 folate equivalents per day, respectively (P-value for linear trend = 0.016). Conclusions. Our results suggest that NTD risk declines markedly with modest increases of total folate in early pregnancy. Total folate dose, rather than supplemental folate alone, should be considered in formulating public health guidelines for NTD prevention.