Prenatal phthalate exposure associated with age-specific alterations in markers of adiposity in offspring: A systematic review

Abstract

Childhood obesity and metabolic disorders are of concern and are public health problems globally. Environmental endocrine disruptors, including phthalates, are well known as "obesogens" and "metabolic disruptors". Several studies have investigated the relationships between prenatal phthalate exposure and childhood obesity with inconsistent conclusions. Given the child growth trajectory/pattern as a possible early marker of metabolic disorders, we aimed to assess the effect of prenatal phthalate exposure on offspring growth trajectory. A systematic literature search was conducted using MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) until July 2021. We evaluated the risk of bias for adherence to the prespecified criteria. Fourteen eligible articles were finally included in this systematic review according to the defined PECOS statement. The risk of bias of the included studies was "low" or "probably low", and few were "probably high" and "high". These studies were mostly carried out in the United States (N = 6); others were conducted in China (N = 2), Mexico (N = 2), France (N = 1), Spain (N = 1), Greece (N = 1), and Australia (N = 1) and published from 2015 to 2021. The combined subjects of the 14 studies were 10,396 mother-child pairs. Except for 3 studies not reporting the sex ratio, at least 4001 boys and 3366 girls were included. For the association of prenatal phthalate exposure with an absolute adiposity marker (at a specific visit timepoint), only a few studies were using the same obesity marker as the outcome endpoint and using the same statistical method to explore their associations. However, MEP appeared to be positively associated with several obesity markers, such as the absolute BMI z score, weight-for-age z score, waist circumference, and overweight status. For the association of prenatal phthalate exposure with a repeated measurement of the adiposity marker over the age range, neither associations of adiposity markers with a specific phthalate metabolite nor relationships of a specific adiposity marker with prenatal phthalate exposure were of a consistent result. All four articles reported that phthalate metabolite exposure during pregnancy was associated with children's growth trajectory. Three suggested a sex-specific association between prenatal phthalate exposure and obesity trajectory. In conclusion, the current articles did not show any relationship between prenatal phthalate exposure and children's age-specific outcomes, except for positive associations of prenatal MEP exposure with absolute adiposity markers. However, epidemiological data supported a weak relationship between prenatal phthalate exposure and children's obesity trajectory in a sex-specific manner.

Keywords: Adiposity; Age-specific alteration; Growth trajectory; Phthalate; Prenatal exposure.