Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Vitamin supplement use and incident cataracts in a population-based study.

OBJECTIVE: To determine the relationship between vitamin supplement use and the 5-year incidence of nuclear, cortical, and posterior subcapsular cataract in the Beaver Dam Eye Study cohort. DESIGN: The 5-year incidence of cataract, determined from slitlamp (nuclear cataract) and retroillumination (cortical and posterior subcapsular cataract) photographs, was assessed in a population-based cohort of persons participating in baseline (1988-1990) and follow-up (1993-1995) examinations. Detailed data regarding the type, dosage, and duration of supplement use were obtained by in-person interviews at follow-up. PARTICIPANTS: Residents of Beaver Dam, Wis, aged 43 to 86 years, were identified by private census. Of the 3684 participants in both baseline and follow-up examinations, 3089 were eligible for incident cataract analysis in the present study. RESULTS: Compared with nonusers, the 5-year risk for any cataract was 60% lower among persons who, at follow-up, reported the use of multivitamins or any supplement containing vitamin C or E for more than 10 years. Taking multivitamins for this duration lowered the risk for nuclear and cortical cataracts but not for posterior subcapsular cataracts (odds ratios [95% confidence intervals] = 0.6 [0.4-0.9], 0.4 [0.2-0.8], and 0.9 [0.5-1.9], respectively). Use of supplements for shorter periods was not associated with reduced risk for cataract. Measured differences in lifestyle between supplement users and nonusers did not influence these associations, nor did variations in diet as measured in a random subsample. CONCLUSIONS: These data add to a body of evidence suggesting lower risk for cataract among users of vitamin supplements and stronger associations with long-term use. However, the specific nutrients that are responsible cannot be ascertained at this time, and unmeasured lifestyle differences between supplement users and nonusers may explain these results. Arch Ophthalmol. 2000;118:1556-1563

Dietary fat and age-related maculopathy.

OBJECTIVE: To describe the relationship between type and level of fat in the diet and the prevalence of age-related maculopathy. DESIGN: Retrospective population-based study. SETTING AND PARTICIPANTS: Residents of Beaver Dam, Wis, between the ages of 45 and 84 years, participating in the Beaver Dam Eye Study and Nutritional Factors in Eye Disease Study. DATA COLLECTION: Presence and severity of age-related maculopathy were determined from masked grading of fundus photographs taken from 1988 through 1990. Diets in the past (1978 through 1980) were assessed retrospectively using a food frequency questionnaire during in-person home interviews. RESULTS: Persons with intake of saturated fat and cholesterol in the highest compared with the lowest quintile had 80% and 60% increased odds for early age-related maculopathy, respectively, after adjusting for age and intake of beer. These relationships were not influenced by adjusting for several other potential confounding variables (carotenoid intake, intake of vitamins C or E in supplements, smoking, body mass index, time spent outdoors in the summer, gender, and history of diabetes, hypertension, or cardiovascular disease). Odds ratios for late age-related maculopathy were in similar directions but were not statistically significant. CONCLUSIONS: High intake of saturated fat and cholesterol is associated with increased risk for early age-related maculopathy in the Beaver Dam population. This supports the hypothesis that atherosclerosis or its risk factors are related to age-related maculopathy. Confirmation of this finding in other populations and in prospective studies is needed.

Diet and nuclear lens opacities.

Relations between diet and nuclear opacities in the lens of the eye were investigated in a population-based cohort of middle-aged and older adults who lived in Beaver Dam, Wisconsin. Nuclear sclerosis was assessed from photographs of the lens taken during 1988-1990 in 1,919 persons in the Beaver Dam Eye Study. Diets in the past (1978-1980) were assessed retrospectively with the use of a food frequency questionnaire in home interviews. Relations with intake of foods and nutrients were evaluated using logistic regression analyses. In men, after controlling for age, smoking, and heavy drinking, intakes of numerous nutrients in the highest versus lowest quintile were associated with 40-50 percent reduced odds of more severe nuclear sclerosis. Relations with some nutrients (vitamins A, C, and E, riboflavin, thiamin, niacin) were at least partly explained by previously identified inverse associations with multivitamin use. Relations with other nutrients (folate, alpha-carotene, and dietary fiber) appeared to reflect associations with intake of foods, particularly vegetables. Inverse associations with individual nutrients and foods were often weaker or nonexistent in women. These data indicate that the intake of vitamin supplements (in men and women) and certain foods (particularly in men) may explain associations of several nutrients with risk for nuclear sclerosis.

Essential fatty acid deficiency in premature infants.

To better characterize essential fatty acid (EFA) deficiency in neonates, we assessed 63 premature infants by serial determinations of plasma fatty acids for the level of linoleic acid, the presence of an abnormal trienoic acid (5,8,11-eicosatrienoic acid [20:3 omega 9]), and the ratio of this compound to arachidonic acid, ie, the triene-tetraene ratio. The data indicated that at age 7 d, 67% of these infants had low plasma linoleic acid levels, 62% showed readily detectable 20:3 omega 9, and 44% had a high triene-tetraene ratio. Infants fed by age 2 d had a normal mean linoleate level at 7 d and none showed detectable 20:3 omega 9 by 10 d. In contrast, infants who were not fed until 7 d showed a very high incidence of abnormal fatty acid status. By maintaining a daily record of linoleate intake, we calculated from regression models that the average amount required to achieve normal fatty acid nutrition was 1.19 g.kg-1.d-1.

Some considerations in the analysis of rates of change in longitudinal studies.

This paper discusses and compares several estimators of mean rate of change in unbalanced longitudinal data based on a model with randomly distributed regression coefficients across individuals. The estimators are unweighted and weighted means of these coefficients. The paper also evaluates commonly used variance estimates corresponding to the estimators. Results show that in situations of very slight imbalance, the choice of method is not critical. When imbalance is substantial, however, one should weight the regression coefficients by their estimated precision. An example using data from a nutritional study on premature neonates illustrates some issues encountered in the analysis of longitudinal clinical data sets.