Association of Early Life Exposure to Phthalates With Obesity and Cardiometabolic Traits in Childhood: Sex Specific Associations

Abstract

Few studies have investigated longitudinal associations between early life phthalate exposure and subsequent obesity and cardiovascular risks in children with inconsistent results. We aimed to evaluate the associations between phthalate exposure during gestation and childhood with offspring obesity and cardiometabolic risk factors in 500 mother-child pairs from the Rhea pregnancy cohort in Crete, Greece. Seven phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)] were quantified in spot urine samples collected from mothers (1st trimester) and their children at 4 years of age. We calculated the molar sum of DEHP metabolites (MEHP, MEHHP, MEOHP). We measured child weight, height, waist circumference, skinfold thicknesses, blood pressure (BP), and lipids at 4 and 6 years and leptin, adiponectin, and C-reactive protein at 4 years. We used generalized estimating equations to examine associations at each age and tested for interaction by sex. Child exposure to phthalate metabolites was associated with lower BMI z-scores in boys and higher BMI z-scores in girls. Each 10-fold increase in ΣDEHP was associated with a change in waist circumference of −2.6 cm (95% CI: −4.72, −0.48) in boys vs. 2.14 cm (95% CI: −0.14, 4.43) in girls (p-sex interaction = 0.003) and a change in waist-to-height ratio of −0.01 (95% CI: −0.03, 0.01) in boys vs. 0.02 (95% CI: 0.01, 0.04) in girls (p-sex interaction = 0.006). Phthalate metabolite concentrations at age 4 were negatively associated with systolic and diastolic blood pressure. MEP was associated with lower systolic BP z-scores (adj. β = −0.22; 95% CI: −0.36, −0.08) at 4 years. MnBP and MBzP were associated with lower diastolic BP z-scores (adj. β = −0.13; 95%CI: −0.23, −0.04, and adj. β = −0.11; 95% CI: −0.21, −0.01, respectively). A 10-fold increase in MiBP was associated with 4.4% higher total cholesterol levels (95% CI: 0.2, 8.7). Prenatal phthalate exposure was not consistently associated with child adiposity and cardiometabolic measures. Our findings suggest that early life phthalate exposure may affect child growth and adiposity in a sex-specific manner and depends on the timing of exposure.

Ultra-processed food intake in association with BMI change and risk of overweight and obesity: A prospective analysis of the French NutriNet-Santé cohort

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Early-life exposures and cardiovascular disease risk among Ghanaian migrant and home populations: the RODAM study

“…Early-life exposures might have different effects in male and female biology, and the influence of possible confounders such as age at menarche might also be different for men and women. 43,44 Male and female puberty might differ in terms of behavior, hormonal factors, and changes in body composition. Both men and women put in fat mass.…”

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“…The downstream effects of maternal DEHP exposure on the developing fetus remain less clear. Valvi et al and Vafeiadi et al have reported that maternal DEHP exposure is associated with a decrease in systolic blood pressure in children aged <7 years (Vafeiadi et al, 2018; Valvi et al, 2015). Similarly, Sol et al reported that maternal phthalate exposure was associated with a decrease in systolic and diastolic blood pressure in girls, but not boys (mean age 9.7 years) (Sol et al, 2020).…”