Asthma and obesity are two of the most common chronic and disabling conditions of childhood. While both are multifactorial (risk factors include genetics, race, socioeconomic status, diet, and physical activity), most of these risk factors are not amenable to modification or avoidance. However, environmental factors are amenable to change and are plausible contributing factors to both. Given documented rapid increases in both conditions over the past three decades, it is imperative to find ways to reduce both asthma and obesity.

Phthalates, chemicals used to produce a diverse array of consumer products including shampoos, plastic bottles and cosmetics, have been found to interact withperoxisome proliferator-activated receptors that play critical roles in lipid and carbohydrate metabolism.Di-2-ethylhexylphthalate (DEHP) is of particular concern, because mono-(2-ethylhexyl) phthalate,a DEHP metabolite,increases expression of threeperoxisome proliferator-activated receptors(PPARs) which play key roles inlipidand carbohydrate metabolism, providing biological plausibility for a role of DEHP metabolites in childhood obesity and insulin resistance. Additionally, DEHP metabolites induce the release of pro-inflammatory cytokines from lung cells, and activation of PPARs can also modulate immune response.

Investigators have found associations of exposure to plastic wall materials with the development of bronchial obstruction, persistent wheeze, cough, and phlegm in children.Prenatal exposure to butylbenzylphthalate, a high molecular weight (HMW) phthalate used in flooring, has been associated with the development of eczema in one urban longitudinal birth cohort, and a cross-sectional study has associated urinarymono-carboxyoctyl phthalate and mono-carboxynonyl phthalate with asthma.Cross-sectional studies and one longitudinal cohort study have associated lower-molecular weight phthalates with child and adolescent obesity. It is plausible that fetal vulnerability to DEHP is greater, and that this earlier life exposure is more likely to disrupt endocrine processes that maintain dietary balance, leading to obesity. Measurement of phthalates at a single timepoint in pregnancy has moderate sensitivity (56-67%) and high specificity (83-87%) for four phthalate metabolites to estimate exposure tertile over a three-month period, but past studies have been unable to assess a developmental window of vulnerability to phthalate exposure.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal population-based birth cohort study of 14,541 UK mothers enrolled during pregnancy in 1991 and 1992, with data collected at multiple time points during pregnancy and in childhood, through review of hospital records, clinical and laboratory examination, and surveys of parents and children.This population is well-characterized with regard tosociodemographic and behavioral risk factors for obesity, and represents an efficient method to examine ubiquitous environmental chemical exposures as separate risks. We propose to analyze 1500 banked maternal urine samples from each of three trimesters of pregnancy for urinary phthalates, and assess associations with standardized measures of infant, child and adolescent body mass, allergy, and respiratory outcomes.

Aim 1. To examine whether prenatal urinary phthalate metabolites are associated with weight-for-length and Body Mass Index Z-scores in childhood, fat mass, and cardiovascular risks in the school age years and adolescence.

H1. Prenatal urinary phthalates are independently associated with increases in standardized measures of body mass and obesity in childhood, as well as increases in fat mass, adjusting for maternal, sociodemographic and other lifestyle factors.

Aim 2. To examine whether prenatal urinary phthalate metabolites are associated with wheeze, allergy, and asthma phenotype in childhood.

H2a. Prenatal urinary phthalates are associated with increased odds of wheeze in children, adjusting for potential confounding factors.

H2b. Prenatal urinary phthalates are associated with increased odds of allergic phenotype (eczema, rhinitis, or allergy) in children, adjusting for potential confounding factors.

H2b. Prenatal urinary phthalates are associated with asthma phenotype (asthma diagnosis or bronchodilator responsiveness) in children, adjusting for potential confounding factors.

Aim 3. To examine whether prenatal urinary phthalate metabolites are associated with decrements in pulmonary function in the school-age years.

H3. Prenatal urinary phthalates are independently associated with decrements in pulmonary function (forced expiratory volume in the first second (FEV1) and the ratio of FEV1 to forced vital capacity.