Comparing Levels of Urinary Phthalate Metabolites in Egyptian Children with Autism Spectrum Disorders and Healthy Control Children: Referring to Sources of Phthalate Exposure

Background: Evidence supporting environmental risk factors of autism spectrum disorder (ASD) is rising. Phthalates are assumed to contribute to this risk due to their extensive use in daily life as plasticizers and additives in numerous customer products. Phthalates are also accused as a neurotoxic agent affecting brain development. Aim: The main objective of this study is to compare the concentrations of urinary phthalate metabolites as biomarkers of phthalate exposure in children with autism to that of a healthy control group and to compare their exposure to suspected environmental sources of phthalate. Methods: It was a case-control study; conducted over a period of one year. Thirty-eight children with ASD and 99 apparently healthy children comprised the control group, were enrolled in the study. Urinary concentrations of four phthalate metabolites were measured, using a combination of solid phase extraction, high pressure liquid chromatography, and tandem mass spectrometry. Results: Children with ASD comprised 38 children (32 boys and 6 girls), their mean age was 8.95 + 4.17 years. There were significant higher levels of urinary Mono (2ethylhexyl) phthalate (MEHP), mono benzyl, and mono butyl phthalates in cases vs. controls with p value equals (0.006, 0.017 and <0.001) respectively. Regression analysis revealed that male gender and the level of mono butyl are the main predictors of ASD (p<0.001). Conclusion: This study suggested a link between phthalates and ASD with higher urinary levels of phthalate metabolites in children with ASD. These high levels are either due to increased exposure or defective metabolism in children with ASD. The study declined any relationship of the studied sources of phthalate exposure to ASD except the exposure to wall painting with plastic.

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

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.