Faculty, Staff and Student Publications
Language
English
Publication Date
1-1-2023
Journal
Birth Defects Research
DOI
10.1002/bdr2.2003
PMID
35277952
PMCID
PMC9464263
PubMedCentral® Posted Date
1-1-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
Background: About 20%-30% of children with birth defects have multiple major birth defects in more than one organ system, often referred to as multiple congenital anomalies (MCAs). Evaluating the patterns of MCAs can provide clues to the underlying causes, pathogenic mechanisms, and developmental pathways. We sought to explore selected patterns of MCAs within the National Birth Defects Prevention Study (NBDPS), a population-based, case-control study that excluded cases attributed to known chromosomal or single-gene abnormalities.
Methods: We defined MCAs as having two or more NBDPS-eligible birth defects and calculated the adjusted observed-to-expected ratio for all observed MCA patterns using co-occurring defect analysis.
Results: Of the 50,186 case infants eligible for NBDPS, 2,734 (3.7%) had at least two eligible birth defects. We observed 209 distinct 2-way combinations of birth defects, 297 distinct 3-way combinations, 179 distinct 4-way combinations, and 69 distinct 5-way combinations. Sacral agenesis had the largest proportion of cases with MCAs (70%), whereas gastroschisis had the lowest (3%). Among the cases with MCAs, 63% had a heart defect, 23% had an oral cleft, and 21% had anorectal atresia/stenosis. Of the patterns with adjusted observed-to-expected ratios in the top 20%, most were consistent with the known associations or syndromes, including VATER/VACTERL association and CHARGE syndrome.
Conclusions: Most but not all patterns that had the highest adjusted observed-to-expected ratios were instances of known syndromes or associations. These findings highlight the importance of considering birth defect combinations that suggest syndromic patterns in the absence of a formal syndromic diagnosis. New approaches for screening for sequences and associations, and VATER/VACTERL in particular, in surveillance systems with limited resources for manual review may be valuable for improving surveillance system quality. The observed MCA patterns within NBDPS may help focus future genetic studies by generating case groups of higher yield.
Keywords
Infant, Child, Humans, Case-Control Studies, Abnormalities, Multiple, Nervous System Malformations, Gastroschisis, Heart Defects, Congenital, co-occurrence, multiple birth defects, multiple congenital anomalies, observed-to-expected ratio
Published Open-Access
yes
Recommended Citation
Howley, Meredith M; Williford, Eva; Agopian, A J; et al., "Patterns of Multiple Congenital Anomalies in the National Birth Defect Prevention Study: Challenges and Insights" (2023). Faculty, Staff and Student Publications. 1123.
https://digitalcommons.library.tmc.edu/uthsph_docs/1123