Association between endocrine disruptors and surgical congenital malformations: Systematic review and meta-analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 41308826 · doi:10.1016/j.jpedsurg.2025.162829
What was done
A systematic review and meta-analysis (PROSPERO CRD420251158778) following PRISMA 2020 guidelines searched PubMed, Embase, Web of Science, and gray literature from 2010 to 2025. It evaluated observational studies on prenatal exposure to endocrine disruptors (phthalates, bisphenols, PFAS, organochlorines) and surgical congenital malformations. Quality was assessed via the Newcastle-Ottawa Scale and GRADE methodology, with random-effects meta-analysis performed.
What was found
Across 66 included studies (35,732 participants), 42 (64%) were high quality, 18 (27%) moderate, and 6 (9%) low quality. Endocrine disruptor exposure was significantly associated with: - Hypospadias: pooled OR 2.21 (95% CI: 1.15-3.27; I² = 65.4%, p = 0.003) - Cryptorchidism: OR 1.85 (95% CI: 1.02-3.36; I² = 58.2%, p = 0.041) - Congenital heart disease: OR 1.39 (95% CI: 1.09-1.76; I² = 42.1%, p = 0.008) DEHP and DBP phthalates conferred the highest risk for urogenital malformations (OR 3.12, 95% CI: 1.45-6.72). First-trimester exposure showed the strongest associations. GRADE evidence was rated moderate-to-high for urogenital and cardiac anomalies, but low for gastrointestinal and neural defects.
Why it matters
This study provides synthesized evidence linking prenatal chemical endocrine disruptor exposures during early fetal development to structural birth defects requiring surgical correction.
Limits
All included data derive from observational studies, precluding causal inference and leaving open residual confounding. Substantial heterogeneity was present across outcomes (I² between 42.1% and 65.4%), 36% of studies were moderate or low quality, and evidence certainty for neural and gastrointestinal defects remained low.
Cited by
- supports Maternal exposure to high levels of phthalates during pregnancy is linked to abnormal male fetal genital development, specifically hypospadias and undescended testicles (cryptorchidism).