Background Atopic disease is a major health problem. Mutations in the filaggrin gene (FLG) confer major susceptibility to eczema and related asthma. Objective We sought to determine the natural ...history and burden of atopic disease conferred by the 2 most common FLG mutations in a large, population-based birth cohort study. Methods We analyzed the effect of the most common null alleles (R501X and 2282del4) on several atopic phenotypes in a cohort of approximately 7000 English children born in 1990-1991. Results FLG null alleles associated strongly with eczema; eczema associated with these mutations presents in early life and is more persistent (hazard ratio for eczema resolution for those with FLG mutations to FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 × 10−8 ). FLG mutations conferred a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P = 1.4 × 10−11 ). Strong associations were identified with sensitization to grass, house dust mite, and cat dander and sensitization to multiple allergens (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 × 10−27 ). Conclusion FLG mutations are strong genetic determinants of eczema, early wheeze, asthma in the context of eczema, and atopic sensitization. They confer risk of a particular trajectory for eczema, with increased duration of disease and greater risk of asthma and multiple allergic sensitizations. FLG alleles help define the risk profile of children with eczema and help define the “eczema plus early wheeze” and “eczema plus asthma” phenotypes.
Background Breast-feeding clearly protects against early wheezing, but recent data suggest that it might increase later risk of atopic disease and asthma. Objective We sought to examine the ...relationship between breast-feeding and later asthma and allergy outcomes by using data from the Avon Longitudinal Study of Parents and Children, a large birth cohort in the United Kingdom. Methods We used adjusted logistic regression models to evaluate the association between breast-feeding and atopy at age 7 years, bronchial responsiveness to methacholine at age 8 years, and wheeze at ages 3 and 7½ years. Bayesian methods were used to assess the possibility of bias caused by an influence of early wheezing on the duration of breast-feeding, as well as selection bias. Results Breast-feeding was protective for wheeze in the first 3 years of life (odds ratio OR of 0.80 95% CI, 0.70-0.90 for ≥6 months relative to never) but not wheeze (OR, 0.98; 95% CI, 0.79-1.22), atopy (OR, 1.12; 95% CI, 0.92-1.35), or bronchial hyperresponsiveness (OR, 1.07; 95% CI, 0.82-1.40) at ages 7 to 8 years. Bayesian models adjusting for the longer duration of breast-feeding among children with wheezing in early infancy produced virtually identical results. Conclusions We did not find consistent evidence for either a deleterious effect or a protective effect of breast-feeding on later risk of allergic disease in a large prospective birth cohort of children with objective outcome measures and extensive data on potential confounders and effect modifiers. Neither reverse causation nor loss to follow-up appears to have materially biased our results.
Introduction The Randot® Preschool Stereoacuity Test is a widely used three-book test for the assessment of binocular status. Using a prototype, we previously reported high testability in children as ...young as 3 years, validity data, and some normative data. Here we report extensive normative and validity data for the final version of the test. In addition, we report normative data for a new, fourth book that adds finer disparities. Methods The Randot® Preschool Stereoacuity Test was administered to 4355 normal children aged 3 to 18 years and 39 adults in multiple settings. In addition, the Randot® Preschool Stereoacuity Test along with the new, fourth book that added 30 arcsec and 20 arcsec disparity levels was administered to 1402 normal children aged 3 to 18 years and 33 normal adults. Both the four-book Randot® Preschool Stereoacuity Test and the Randot circles were administered to 242 patients with amblyogenic conditions aged 3 to 18 years. Results Mean normal stereoacuity improved from 100 arcsec at 3 years of age to 60 arcsec by 5 years and 40 arcsec by 7 years. The lower limit of normal was 400 arcsec at 3 years, 200 arcsec at 4 years, and 60 arcsec at 7 years. Using the new four-book version, further improvement in mean stereoacuity could be appreciated beyond 7 years of age to 30 arcsec in the 11- to 18-year-old and adult groups. Among the 242 patients, Randot® Preschool Stereoacuity Test stereoacuity was strongly associated with Randot circle stereoacuity (χ2 = 261.0, p < 0.001). Conclusions Normative data for the Randot® Preschool Stereoacuity Test show a monotonic improvement of stereoacuity from age 3 years through the teen years. Patient data support the validity of the Randot® Preschool Stereoacuity Test.
Background Animal data suggest that tobacco smoke exposure of a mother when she is in utero influences DNA methylation patterns in her offspring and that there is an effect on the respiratory system, ...particularly airway responsiveness. The only study, to our knowledge, in humans suggests that there is a similar effect on asthma. The present study tests whether an association with respiratory problems can be confirmed in a large population study and aims to determine whether in utero exposure of the father has similar effects on his offspring. Methods Information from the Avon Longitudinal Study of Parents and Children was used to compare the offspring of women and of men who had themselves been exposed to cigarette smoke in utero; separate analyses were performed for children of women smokers and nonsmokers. The outcome measures were trajectories of history of early wheezing, doctor-diagnosed asthma by age 7 years, and results of lung function and methacholine challenge tests at 8 years. A variety of social and environmental factors were taken into account; offspring sexes were examined separately. Results There was no association with any outcome in relation to maternal prenatal exposure. There was some evidence of an increase in asthma risk with paternal prenatal exposure when the study mother was a nonsmoker (adjusted OR, 1.17; 95% CI, 0.97-1.41). This was particularly strong for girls (adjusted OR, 1.39; 95% CI, 1.04-1.86). Conclusions We did not find that maternal prenatal exposure to her mother's smoking had any effect on her children's respiratory outcomes. There was suggestive evidence of paternal prenatal exposure being associated with asthma and persistent wheezing in the granddaughters.
Stature at a particular age can be considered the cumulative result of growth during a number of preceding growth trajectory periods. We investigated whether height and weight growth trajectories ...from birth to age 10 years were related to refractive error at ages 11 and 15 years, and eye size at age 15 years.
Prospective analysis in a birth cohort.
Children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) U.K. birth cohort (minimum N = 2676).
Growth trajectories between birth and 10 years were modeled from a series of height and weight measurements (N = 6815). Refractive error was assessed by noncycloplegic autorefraction at ages 11 and 15 years (minimum N = 4737). Axial length (AXL) and radius of corneal curvature were measured with an IOLMaster (Carl Zeiss Meditec, Welwyn Garden City, U.K.) at age 15 years (minimum N = 2676). Growth trajectories and an allelic score for 180 genetic variants associated with adult height were tested for association with refractive error and eye size.
Noncycloplegic autorefraction at ages 11 and 15 years, and AXL and corneal curvature at age 15 years.
Height growth trajectory during the linear phase between 2.5 and 10 years was negatively associated with refractive error at 11 and 15 years (P<0.001), but explained <0.5% of intersubject variation. Height and weight growth trajectories, especially shortly after birth, were positively associated with AXL and corneal curvature (P<0.001), predicting 1% to 5% of trait variation. Height growth after 2.5 years was not associated with corneal curvature, whereas the association with AXL continued up to 10 years. The height allelic score was associated with corneal curvature (P = 0.03) but not with refractive error or AXL.
Up to the age of 10 years, shared growth mechanisms contribute to scaling of eye and body size but minimally to the development of myopia.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Objective To investigate dietary patterns and nutritional intake in children of mothers with eating disorders. Study design Mothers (N = 9423) from a longitudinal general population birth cohort ...study, the Avon Longitudinal Study of Parents and Children, completed Food Frequency Questionnaires on their children at 3, 4, 7, and 9 years of age. Macronutrient intake was estimated, and dietary patterns were obtained using principal components analysis. Linear regression and mixed-effects models were used to assess dietary patterns and nutritional intake among children of women with lifetime anorexia nervosa (AN, n = 140), bulimia nervosa (BN, n = 170), or AN+BN (n = 71), compared with children of women without eating disorders (unexposed women, n = 9037). Results Children in the maternal AN and BN groups had higher scores on the “health conscious/vegetarian” dietary pattern compared with unexposed children. Less adherence to the “traditional” dietary pattern was observed in children of exposed mothers, with more pronounced differences in early childhood. Children of women with AN and BN had higher intake of energy and children of women with BN had higher intake of carbohydrates and starch and lower intake of fat, compared with children in the unexposed group. Conclusions Maternal eating disorders are associated with altered offspring dietary patterns and macronutrient intake. Longitudinal changes in patterns of diet in children of women with eating disorders may increase the risk of weight gain or disordered eating later in life.
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