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. 2021 Feb;17(1):64.e1-64.e8.
doi: 10.1016/j.jpurol.2020.11.015. Epub 2020 Nov 12.

Patterns of co-occurring birth defects among infants with hypospadias

Katherine L Ludorf  1 , Renata H Benjamin  1 , Maria Luisa Navarro Sanchez  1 , Scott D McLean  2 , Hope Northrup  3 , Laura E Mitchell  1 , Peter H Langlois  4 , Mark A Canfield  4 , Angela E Scheuerle  5 , Daryl A Scott  6 , Christian P Schaaf  7 , Joseph W Ray  8 , Omobola Oluwafemi  1 , Han Chen  9 , Michael D Swartz  10 , Philip J Lupo  11 , A J Agopian  12
Affiliations

Patterns of co-occurring birth defects among infants with hypospadias

Katherine L Ludorf et al. J Pediatr Urol. 2021 Feb.

Erratum in

Abstract

Introduction: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally.

Objective: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects.

Study design: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA).

Results: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias.

Discussion: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified.

Conclusion: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.

Keywords: Birth defects; Co-occurrence; Epidemiology; Hypospadias; Observed-to-expected ratio.

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Conflict of interest statement

Conflict of interest None.

Figures

Figure 1.
Figure 1.
Venn diagram of the top 30 birth defect combinations, where counts represent the number of the top 30 combinations that include the indicated defects (e.g., 6 of the top 30 combinations include urogenital and cardiovascular defects) in cases with hypospadias, Texas Birth Defect Registry, 1999-2014
See this image and copyright information in PMC

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