Journal Articles

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Pediatric Research


BACKGROUND: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood.

METHODS: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects.

RESULTS: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula).

CONCLUSIONS: Our analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects).

IMPACT: In this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common.


Anal Canal, Esophagus, Heart Defects, Congenital, Humans, Infant, Kidney, Limb Deformities, Congenital, Registries, Spine, Texas, Trachea

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