Dataset Information

Associations of postnatal growth with asthma and atopy: the PROBIT Study.

ABSTRACT: It has been hypothesised that postnatal weight and length/height gain are variously related to wheeze, asthma and atopy; however, supporting evidence is limited and inconsistent.Weights and lengths/heights of 12,171 term infants were measured from birth to 12 months and at 6.5 yr and extracted from polyclinic records prospectively obtained between 12 and 60 months. Atopic phenotypes were ascertained at 6.5 yr with the International Study of Asthma and Allergy in Childhood questionnaire and skin prick tests. Logistic regression models investigated whether rates of weight and length/height gain from infancy to mid-childhood were associated with atopy phenotypes that have occurred ever or in the last 12 months.After controlling for confounders and prior weight and length/height gain, all weight gain variables except birth weight were positively associated with ever having wheezed (p < 0.1). A one s.d. increase in weight gain rate between 0 and 3 months was associated with a 12% increase (2-23%) in allergic rhinitis ever. No other consistent patterns of association were found for weight gain or length/height gain rate between 0 and 60 months with atopic outcomes at 6.5 yr. In contrast, all atopy outcomes except for ever having asthma were associated with current weight and height, even after controlling for prior growth.Current height and weight are more strongly associated with the development of atopic phenotypes in childhood than patterns of infant and early childhood growth, which may well reflect reverse causality (atopy effects on growth) or residual confounding by an unknown common cause of growth and atopy.

SUBMITTER: Anderson EL

PROVIDER: S-EPMC3711479 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Associations of postnatal growth with asthma and atopy: the PROBIT Study.

Anderson Emma L EL Fraser Abigail A Martin Richard M RM Kramer Michael S MS Oken Emily E Patel Rita R Tilling Kate K

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 20130203 2

<h4>Background</h4>It has been hypothesised that postnatal weight and length/height gain are variously related to wheeze, asthma and atopy; however, supporting evidence is limited and inconsistent.<h4>Methods</h4>Weights and lengths/heights of 12,171 term infants were measured from birth to 12 months and at 6.5 yr and extracted from polyclinic records prospectively obtained between 12 and 60 months. Atopic phenotypes were ascertained at 6.5 yr with the International Study of Asthma and Allergy i ...[more]

PMID: 23374010

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Project description:Study questionAre children who were conceived with infertility treatment at an increased risk of developing asthma and atopic conditions?Summary answerInfertility treatment is associated with an elevated risk of asthma and atopic conditions in early and middle childhood, even after adjustment for parental asthma and atopy.What is known alreadyAsthma and atopic conditions are prevalent in childhood. The development of these conditions may be linked to early life exposures, including the use of infertility treatments.Study design, size, durationUpstate KIDS is a prospective cohort study of singletons and multiples born between 2008 and 2010. A total of 5034 mothers and 6171 children were enrolled and followed up until 2019, and 2056 children participated in the middle childhood follow-up.Participants/materials, setting, methodsWomen reported the fertility agents used to become pregnant on a baseline questionnaire. Treatment was categorized as ART (∼22%) use, ovulation induction via oral/injectable medications with or without IUI (OI/IUI, ∼20%), or no treatment (∼58%). Outcomes were assessed by maternal report on questionnaires in early (up to age 3 years, prevalence 9-28%) and middle (7-9 years, prevalence 10-16%) childhood. Weighted Poisson regression models with robust standard errors were used to analyze the risk of atopic outcomes in relation to infertility treatment exposure.Main results and the role of chanceCompared to children conceived without treatment, children conceived with any infertility treatment were at an increased risk of persistent wheeze by age 3 years (relative risk (RR): 1.66; 95% CI: 1.17, 2.33) with adjustments for parental atopy among other risk factors. Around 7-9 years, children conceived with treatment were more likely to have current asthma (RR: 1.30; 95% CI: 0.98, 1.71), eczema (RR: 1.77; 95% CI: 1.25, 2.49) or be prescribed allergy-related medications (RR: 1.45; 95% CI: 1.06, 1.99). Similar effect sizes were found when examining associations by treatment type (i.e. ART versus OI/IUI).Limitations, reasons for cautionChildhood outcomes were based on maternal report and are subject to potential misclassification. There was attrition in this study, which limits the precision of our measures of association.Wider implications of the findingsThough future research is needed to clarify the mechanisms involved, our findings support that both ART and OI/IUI influences the development of asthma and atopic conditions in the offspring from an early age.Study funding/competing interest(s)This work was supported by the National Institutes of Health's Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no relevant conflicts of interest to disclose.Trial registration numberN/A.

Project description:BackgroundEpigenetic mechanisms could alter the airway epithelial barrier and ultimately lead to atopic diseases such as asthma. We aimed to identify DNA methylation profiles that are associated with-and could accurately classify-atopy and atopic asthma in school-aged children.MethodsWe did a genome-wide study of DNA methylation in nasal epithelium and atopy or atopic asthma in 483 Puerto Rican children aged 9-20 years, recruited using multistage probability sampling. Atopy was defined as at least one positive IgE (≥0·35 IU/mL) to common aeroallergens, and asthma was defined as a physician's diagnosis plus wheeze in the previous year. Significant (false discovery rate p<0·01) methylation signals were correlated with gene expression, and top CpGs were validated by pyrosequencing. We then replicated our top methylation findings in a cohort of 72 predominantly African American children, and in 432 children from a European birth cohort. Next, we tested classification models based on nasal methylation for atopy or atopic asthma in all cohorts.FindingsDNA methylation profiles were markedly different between children with (n=312) and without (n=171) atopy in the Puerto Rico discovery cohort, recruited from Feb 12, 2014, until May 8, 2017. After adjustment for covariates and multiple testing, we found 8664 differentially methylated CpGs by atopy, with false discovery rate-adjusted p values ranging from 9·58 × 10-17 to 2·18 × 10-22 for the top 30 CpGs. These CpGs were in or near genes relevant to epithelial barrier function, including CDHR3 and CDH26, and in other genes related to airway epithelial integrity and immune regulation, such as FBXL7, NTRK1, and SLC9A3. Moreover, 28 of the top 30 CpGs replicated in the same direction in both independent cohorts. Classification models of atopy based on nasal methylation performed well in the Puerto Rico cohort (area under the curve [AUC] 0·93-0·94 and accuracy 85-88%) and in both replication cohorts (AUC 0·74-0·92, accuracy 68-82%). The models also performed well for atopic asthma in the Puerto Rico cohort (AUC 0·95-1·00, accuracy 88%) and the replication cohorts (AUC 0·82-0·88, accuracy 86%).InterpretationWe identified specific methylation profiles in airway epithelium that are associated with atopy and atopic asthma in children, and a nasal methylation panel that could classify children by atopy or atopic asthma. Our findings support the feasibility of using the nasal methylome for future clinical applications, such as predicting the development of asthma among wheezing infants.FundingUS National Institutes of Health.

Dataset Information

Associations of postnatal growth with asthma and atopy: the PROBIT Study.

Publications

Associations of postnatal growth with asthma and atopy: the PROBIT Study.

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