Effect of prenatal phthalate exposure on fetal development and maternal/neonatal health consequences: A systematic review

Abstract

The ubiquitous presence of phthalate compounds in cosmetics, personal care products and plastics commonly used in toys, food packaging or household products, results in human exposure with adverse effects on reproductive health and fetal development. Following the PRISMA methodology, this systematic review analyzes the effect of prenatal phthalate exposure on major pregnancy complications, such as gestational diabetes, pregnancy-induced hypertension, fetal growth restriction and preterm birth, and its role in fetal neurodevelopment. This review includes >100 articles published in the last 10 years, showing an association between maternal exposure to phthalates and the risk of developing pregnancy complications. Phthalates are negatively associated with motor skills and memory, and also increase the risk of delayed language acquisition, autism spectrum disorder traits, and behavioral deficits, such as attention deficit hyperactivity disorder in children prenatally exposed to phthalates. Di (2-ethylhexyl) phthalate and its metabolites (mono(2-ethylhexyl) phthalate, mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-hydroxyhexyl) phthalate, mono(2-ethyl-5-oxohexyl) phthalate) are the main compounds associated with the above-mentioned pregnancy complications and fetal neurodevelopmental disorders. In addition, this review discusses the molecular mechanisms responsible for various pregnancy complications and neurodevelopmental disorders, and the critical window of exposure, in order to clarify these aspects. Globally, the most common molecular mechanisms involved in the effects of phthalates are endocrine disruption, oxidative stress induction, intrauterine inflammation, and DNA methylation disorders. In general, the critical window of exposure varies depending on the pathophysiology of the complication being studied, although the first trimester is considered an important period because some of the most vulnerable processes (embryogenesis and placentation) begin early in pregnancy. Future research should aim to understand the specific mechanism of the disruptive effect of each component and to establish the toxic dose of phthalates, as well as to elucidate the most critical period of pregnancy for exposure and the long-term consequences for human health.