Abstract
Background Congenital anomalies (CA) are a major contributor to infant mortality worldwide, and the risk of CA differs by maternal and fetal characteristics. Moreover, studies establishing the etiology of CA are methodologically heterogeneous, and its investigation among the Hispanic population is limited. This study aims to investigate the potential etiologies for CA and compare their etiologic profile across pregnancy outcome, fetal/infant sex, and maternal age in a Mexican population-based setting. Methods Potential causes of CA from 2022 to 2024 at Durango General Hospital (northwest Mexico) were investigated through a hospital-based CA surveillance program. Prevalence and 95% confidence intervals (CI) were calculated for known and unknown etiologies and clinical features (live births, fetal losses, males, females, and maternal age of <20, 20-34, and ≥35 years). Pearson's chi-squared test and Fisher's exact test were used to analyze between-group differences. Two-tailed probability values of <0.05 were considered statistically significant. Results Altogether, 497 cases among 11608 births (prevalence, 4.2%; 95% CI, 3.9%-4.6%) were considered. In 155 cases (31.1%, 95% CI: 27.2%-35.3%), a definitive cause was assigned. Pathogenic processes were recognized in 53 cases (10.6%, 95% CI: 8.2%-13.6%) among 342 cases of unknown etiology. Fetal losses, males, and maternal age of <20 years were more prevalent among CA compared to the underlying birth cohort (all P< 0.05). Among recognized etiologies, there were significant differences between fetal losses and pathogenesis classification; males and the environmental etiology group; maternal age of <20 years and the genetic etiology group; single/multiple gene disorders, family history, and multiple exposures; and maternal age of ≥35 years and chromosomal abnormalities, the environmental etiology group, maternal illness, and pathogenesis classification (all P< 0.05). Among unknown etiologies, significant differences were observed in fetal losses and other/multiple categories, live births and craniofacial and musculoskeletal defects, males and cardiovascular and genitourinary defects, females and the unknown etiology group and craniofacial and musculoskeletal defects, maternal age of <20 years and abdominal defects, and maternal age of 20-34 years and the unknown etiology group and craniofacial defects (all P < 0.05). Conclusions The recognized potential nature for CA in this cohort was 41.8%. This study identified causal heterogeneity and provided practical value among its associated clinical features. It emphasizes the relevance of thoughtful clinical investigation into CA despite the predominant unknown causality.