# Maternal Phthalate Exposure and Allergic Diseases in Children: A Meta-Analysis and Network Toxicology

**Authors:** Yi Xiang, Yanming Lv, Wenhao Fu, Jie Wen, Baixiang Li, Xueting Li

PMC · DOI: 10.3390/ijms26136103 · International Journal of Molecular Sciences · 2025-06-25

## TL;DR

This study finds that exposure to phthalates during and after pregnancy is linked to an increased risk of childhood allergic diseases and identifies key biological pathways involved.

## Contribution

The study introduces a novel integration of meta-analysis and network toxicology to explore phthalate effects on childhood allergies.

## Key findings

- Prenatal phthalate exposure is associated with higher odds of childhood wheezing and eczema.
- Postnatal phthalate exposure is linked to wheezing, eczema, and rhinitis in children.
- Phthalate-targeted genes are enriched in pathways critical to allergic diseases, with strong molecular interactions to key immune proteins.

## Abstract

Several studies suggest a relationship between phthalates (PAEs) and allergic diseases in children. Therefore, we speculated that PAE exposure may be an important environmental factor causing allergic diseases. The present study employed meta-analysis and network toxicology to analyze the interactions and assess potential pathogenic pathways between prenatal and postnatal PAE exposure and childhood allergic diseases. This study found that prenatal PAEs exposure was positively associated with childhood wheezing and eczema (OR = 1.03, 1.05), and postnatal PAEs exposure was positively associated with childhood wheezing, eczema, and rhinitis (OR = 1.10, 1.05, 1.06). PAE exposure from dust may elicit distinct effects compared to direct exposure to PAEs. Furthermore, a large number of overlapping genes between disease targets and PAEs were identified. Enrichment analysis highlighted the association of PAE-targeted genes with biological pathways integral to allergic diseases. Molecular docking results indicated a strong link between the PAEs and the core proteins, such as SRC, AKT1, and HSP90AA1. These proteins are critically involved in the regulation of immune–inflammatory processes underlying allergic diseases. This discovery not only enhances our understanding of the relationship between environmental pollutants and child health but also provides a robust reference for experimental studies on the induction of childhood diseases by early-life exposure to environmental pollutants.

## Linked entities

- **Genes:** SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207], HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320]
- **Chemicals:** PAEs (PubChem CID 37013)
- **Diseases:** eczema (MONDO:0004980), rhinitis (MONDO:0003014)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SRC (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 6714] {aka ASV, SRC1, THC6, c-SRC, p60-Src}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}
- **Diseases:** rhinitis (MESH:D012220), wheezing (MESH:D012135), Allergic Diseases (MESH:D004342), inflammatory (MESH:D007249), eczema (MESH:D004485)
- **Chemicals:** PAE (MESH:C032279)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12250265/full.md

## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12250265/full.md

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Source: https://tomesphere.com/paper/PMC12250265