Association between endocrine disruptors and surgical congenital malformations: Systematic review and meta-analysis

Abstract

Background: Prenatal exposure to endocrine disruptors (EDs) represents a growing public health concern due to its potential association with congenital malformations requiring pediatric surgical intervention. The ubiquity of these chemicals in modern environments and their ability to interfere with normal hormonal development during critical fetal windows raises significant concerns for pediatric surgeons. This systematic review was registered prospectively in PROSPERO (CRD420251158778).

Methods: We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. We searched PubMed, Embase, Web of Science, and gray literature from 2010 to 2025 for observational studies evaluating prenatal exposure to phthalates, bisphenols, perfluorinated compounds (PFAS), and organochlorines, with outcomes of surgical congenital malformations. Quality was assessed using the Newcastle-Ottawa Scale and GRADE methodology. Random-effects meta-analysis was performed using R software.

Results: Of 4121 studies identified, 66 met inclusion criteria (total population: 35,732). According to the Newcastle-Ottawa Scale, 42 studies (64 %) had high quality (≥7 points), 18 (27 %) moderate quality (5-6 points), and 6 (9 %) low quality (<5 points). Significant associations were found between ED exposure and 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), and congenital heart disease (OR: 1.39, 95 % CI: 1.09-1.76; I² = 42.1 %, p = 0.008). DEHP and DBP phthalates showed the highest risks for urogenital malformations (OR: 3.12, 95 % CI: 1.45-6.72). First trimester exposure demonstrated the strongest associations across malformation types. GRADE evidence was rated as moderate to high for urogenital and cardiac anomalies but low for gastrointestinal and neural defects.

Conclusions: Prenatal ED exposure is significantly associated with increased risk of surgical congenital malformations, particularly male urogenital and cardiac anomalies. These findings support implementing preventive strategies during pregnancy and justify stricter regulatory policies to protect fetal health and reduce the surgical burden in pediatric populations.

Level of evidence: II (Systematic Review and Meta-Analysis).

Keywords: Bisphenol A; Congenital malformations; Endocrine disruptors; PROSPERO; Pediatric surgery; Phthalates; Prenatal exposure.