Patterns of Co-Occurring Birth Defects in Chinese Infants With Congenital Diaphragmatic Hernia: A National Hospital-Based Surveillance Study

Background: The landscape of co-occurring birth defects among infants with congenital diaphragmatic hernia (CDH) remains underexplored.

Aims: This study aims to elucidate the complex patterns of co-occurring defects in Chinese population.

Materials and methods: We analyzed cases from the Chinese Birth Defects Monitoring Network (2007-2019) with CDH that presented along with at least one additional defect but without a syndromic diagnosis. Adjusted observed-to-expected prevalence (O/E) ratios were calculated for all two- to five-way combinations to discern patterns of co-occurring defects with CDH more frequently than expected by chance.

Results: Among 1235 CDH cases associated with other birth defects, the top 30 combinations with the highest adjusted O/E ratios included musculoskeletal, cardiovascular, central nervous system, facial, and renal defects. Cardiovascular defects were involved in 76.7% of the top combinations, followed by central nervous system (23.3%) and musculoskeletal defects (20.0%). The combination of polydactyly and syndactyly anomalies exhibited the highest adjusted O/E ratio of 5963.37 (95% confidence interval: 5960.00-5966.73).

Discussion: The relationship between musculoskeletal malformation and CDH may be explained from the aspects of epidemiology, embryology and pathogenesis. And mechanisms for the co-occurrence of cardiovascular and CDH may involve disruption of common pathways.

Conclusion: Our analyses describe the co-occurrence patterns of birth defects in CDH infants and reveal several noteworthy patterns. The observed patterns can guide further study and enhance our comprehension understanding of the developmental mechanisms underlying multiple defects.