Review of the Existing Evidence for Sex-Specific Relationships between Prenatal Phthalate Exposure and Children’s Neurodevelopment

Abstract

Phthalates are well-known, ubiquitous environmental contaminants influencing children’s health and their neurodevelopment. However, results of the previously conducted studies are not entirely conclusive. The aim of this review is to present the current state of knowledge with respect to the association between the prenatal phthalate exposure and sex-specific child neurodevelopmental outcomes. A systematic search of the literature was carried out to identify the studies that analyse the sex-specific association between prenatal exposure to phthalates and cognitive, psychomotor outcomes and behavioural and emotional problems. The search was conducted in May 2021, and it was limited to the papers published in English between January 2015 and April 2021. The following databases were used: PubMed, Scopus and Elsevier. The selection process was carried out by two independent authors according to the inclusion criteria. Of a total of 7542 records, 17 epidemiological studies met the inclusion criteria with regards to phthalate exposure and sex-specific differences in child neurobehavioural development. The review shows no clear pattern of association between maternal exposure to phthalates during pregnancy and offspring neurodevelopment. No clearly pronounced sex specific effects, except for BBzP exposure and decreased motor ablates among girls, have been indicated. Inconsistences in the results, as well as unsolved issues related to the interpretation of the results in the context of the exposure level, outcomes, confounders, and biological plausibility highlight the necessity for further research in the field.

Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review

“…However, a recent literature review including 17 epidemiological studies reveals no clear pattern of association between maternal exposures to phthalates during pregnancy and offspring neurodevelopment. This, again, might be caused by inconsistent study protocols, test systems and confounders [ 216 , 217 ].…”

Early childhood exposure to environmental phenols and parabens, phthalates, organophosphate pesticides, and trace elements in association with attention deficit hyperactivity disorder (ADHD) symptoms in the CHARGE study

“…Phthalates are reported to interfere with thyroid functions, which are essential for normal brain development, in a sexually dimorphic manner [ 26 , 28 ], and early thyroid hormone disruption may contribute to the development of ADHD [ 113 ]. Still, regarding phthalate exposure and ADHD-related behaviors, there is inconsistent evidence on effect modification by sex [ 81 , 88 , 90 , 91 , 96 , 97 ] or mediation by thyroid hormone [ 114 ]; therefore, these should be explored in future studies.…”

Prenatal exposures to phthalates and life events stressors in relation to child behavior at age 4–6: A combined cohort analysis

“…The literature on prenatal phthalate exposure and child behavior, in particular, has been both extensive and equivocal. Several recent reviews have evaluated the strength of the literature, generally noting inconsistent patterns of results across studies as well as considerable variation in methods ( Ejaredar et al, 2015 ; Jankowska et al, 2021 ; Lee et al, 2018 ; Minatoya and Kishi, 2021 ; Radke et al, 2020 ). Notably, many studies on prenatal phthalate exposure and child behavior were based on relatively small samples (<400 participants) and may therefore have been underpowered, particularly to detect the sex-specific associations that often occur in relation to prenatal exposures to endocrine disruptors ( Daniel et al, 2020 ; Doherty et al, 2017 ; England-Mason et al, 2020 ; Huang et al, 2019 ; Hyland et al, 2019 ; Kim et al, 2018 ; Li et al, 2020 ; Lien et al, 2015 ).…”