Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights

Meredith M Howley; Eva Williford; A J Agopian; Angela E Lin; Lorenzo D Botto; Christopher M Cunniff; Paul A Romitti; Eirini Nestoridi; Marilyn L Browne; National Birth Defects Prevention Study

doi:10.1002/bdr2.2003

Back

Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights

Journal article

Open access

Peer reviewed

Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights

Meredith M Howley, Eva Williford, A J Agopian, Angela E Lin, Lorenzo D Botto, Christopher M Cunniff, Paul A Romitti, Eirini Nestoridi, Marilyn L Browne and National Birth Defects Prevention Study

Birth defects research, Vol.115(1), pp.43-55

01/01/2023

DOI: 10.1002/bdr2.2003

PMCID: PMC9464263

PMID: 35277952

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/9464263View

Open Access

Abstract

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. 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. 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. 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.

multiple congenital anomalies

co-occurrence

multiple birth defects

observed-to-expected ratio

Details

Title: Subtitle: Patterns of multiple congenital anomalies in the National Birth Defect Prevention Study: Challenges and insights
Creators: Meredith M Howley - Birth Defects Registry, New York State Department of Health, Albany, New York, USA
Eva Williford - Birth Defects Registry, New York State Department of Health, Albany, New York, USA
A J Agopian - Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth School of Public Health, Houston, Texas, USA
Angela E Lin - Medical Genetics Unit, Department of Pediatrics, MassGeneral Hospital for Children, Boston, Massachusetts, USA
Lorenzo D Botto - University of Utah
Christopher M Cunniff - Division of Medical Genetics, Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA
Paul A Romitti - University of Iowa
Eirini Nestoridi - Massachusetts Department of Public Health
Marilyn L Browne - Department of Epidemiology and Biostatistics, School of Public Health, Rensselaer, New York, USA
National Birth Defects Prevention Study
Resource Type: Journal article
Publication Details: Birth defects research, Vol.115(1), pp.43-55
DOI: 10.1002/bdr2.2003
PMID: 35277952
PMCID: PMC9464263
NLM abbreviation: Birth Defects Res
ISSN: 2472-1727
eISSN: 2472-1727
Publisher: Wiley
Grant note: FOA #DD09-001 / CDC HHS PA #02081 / CDC HHS FOA #DD13-003 / CDC HHS Centers for Birth Defects Research and Prevention NOFO #DD18-001 / CDC HHS PA #96043 / CDC HHS R01 HD093660 / NICHD NIH HHS Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS)
Language: English
Electronic publication date: 03/11/2022
Date published: 01/01/2023
Academic Unit: Epidemiology; Biostatistics
Record Identifier: 9984226810702771

Metrics

108 Record Views

12 Times Cited - Web of Science