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Updated: Jun 18, 2025
Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Effect of prenatal phthalate exposure on fetal development and maternal/neonatal health consequences: A systematic
Laura Almeida-Toledano1, Elisabet Navarro-Tapia2, Giorgia Sebastiani3
1Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; BCNatal, Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, Universitat de Barcelona, 08950 Barcelona, Spain.
Insights
Prenatal exposure to phthalates, common in plastics and personal care items, is linked to pregnancy complications and neurodevelopmental issues in children. Further research is needed to understand specific mechanisms and safe exposure levels.
Area of Science:
- Environmental Health
- Reproductive Toxicology
- Developmental Pediatrics
Background:
- Phthalates are widespread in consumer products, leading to significant human exposure.
- Prenatal exposure to phthalates is a growing concern due to potential adverse effects on maternal and fetal health.
- Existing research indicates a link between phthalate exposure and various health issues, necessitating a comprehensive review.
Purpose of the Study:
- To systematically review the impact of prenatal phthalate exposure on major pregnancy complications.
- To analyze the role of phthalates in fetal neurodevelopmental disorders.
- To discuss molecular mechanisms and critical exposure windows for phthalate-induced effects.
Main Methods:
- Systematic literature review adhering to PRISMA methodology.
- Inclusion of over 100 articles published within the last 10 years.
- Analysis of studies investigating phthalate exposure and pregnancy outcomes/fetal development.
Main Results:
- Maternal exposure to phthalates is associated with an increased risk of gestational diabetes, pregnancy-induced hypertension, fetal growth restriction, and preterm birth.
- Prenatal phthalate exposure negatively impacts children's motor skills, memory, and language acquisition, and increases risks for autism spectrum disorder traits and ADHD.
- Di(2-ethylhexyl) phthalate and its metabolites are frequently implicated in these adverse outcomes.
Conclusions:
- Prenatal phthalate exposure poses significant risks to pregnancy and fetal neurodevelopment.
- Endocrine disruption, oxidative stress, inflammation, and DNA methylation are key molecular mechanisms involved.
- The first trimester is a critical window for exposure, highlighting the need for further research into specific effects and long-term consequences.
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.
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