Pediatric Cardiology

, Volume 32, Issue 8, pp 1147–1157 | Cite as

The Contribution of Chromosomal Abnormalities to Congenital Heart Defects: A Population-Based Study

  • Robert J. Hartman
  • Sonja A. RasmussenEmail author
  • Lorenzo D. Botto
  • Tiffany Riehle-Colarusso
  • Christa L. Martin
  • Janet D. Cragan
  • Mikyong Shin
  • Adolfo Correa
Original Article


We aimed to assess the frequency of chromosomal abnormalities among infants with congenital heart defects (CHDs) in an analysis of population-based surveillance data. We reviewed data from the Metropolitan Atlanta Congenital Defects Program, a population-based birth-defects surveillance system, to assess the frequency of chromosomal abnormalities among live-born infants and fetal deaths with CHDs delivered from January 1, 1994, to December 31, 2005. Among 4430 infants with CHDs, 547 (12.3%) had a chromosomal abnormality. CHDs most likely to be associated with a chromosomal abnormality were interrupted aortic arch (type B and not otherwise specified; 69.2%), atrioventricular septal defect (67.2%), and double-outlet right ventricle (33.3%). The most common chromosomal abnormalities observed were trisomy 21 (52.8%), trisomy 18 (12.8%), 22q11.2 deletion (12.2%), and trisomy 13 (5.7%). In conclusion, in our study, approximately 1 in 8 infants with a CHD had a chromosomal abnormality. Clinicians should have a low threshold at which to obtain testing for chromosomal abnormalities in infants with CHDs, especially those with certain types of CHDs. Use of new technologies that have become recently available (e.g., chromosomal microarray) may increase the identified contribution of chromosomal abnormalities even further.


Chromosomal abnormality Congenital heart defect Congenital heart disease Prevalence Epidemiology 



We thank Cheryl Broussard, Suzanne Gilboa, Assia Miller, and Sarah Tinker for their assistance with the statistical analyses. The authors acknowledge the dedication and contributions of the abstractors, staff, and scientists who contribute to the MACDP. This research was supported in part by an appointment to the Research Participation Program at the CDC administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the United States Department of Energy and the CDC.


The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).


  1. 1.
    Baldwin EL, Lee JY, Blake DM, Bunke BP, Alexander CR, Kogan AL et al (2008) Enhanced detection of clinically relevant genomic imbalances using a targeted plus whole genome oligonucleotide microarray. Genet Med 10:415–429PubMedCrossRefGoogle Scholar
  2. 2.
    Bondy CA (2007) Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 92:10–25PubMedCrossRefGoogle Scholar
  3. 3.
    Bosi G, Garani G, Scorrano M, Calzolari E (2003) Temporal variability in birth prevalence of congenital heart defects as recorded by a general birth defects registry. J Pediatr 142:690–698PubMedCrossRefGoogle Scholar
  4. 4.
    Botto LD, May K, Fernhoff PM, Correa A, Coleman K, Rasmussen SA et al (2003) A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics 112:101–107PubMedCrossRefGoogle Scholar
  5. 5.
    Centers for Disease Control (2007) Hospital stays, hospital charges, and in-hospital deaths among infants with selected birth defects—United States, 2003. MMWR Morbid Mortal Wkly Rep 56:25–29Google Scholar
  6. 6.
    Centers for Disease Control (2010) Statistical analysis battery for epidemiologic research (SABER). Available at: Accessed 31 Mar 2010
  7. 7.
    Correa A, Cragan JD, Kucik JE, Alverson CJ, Gilboa SM, Balakrishnan R et al (2007) Reporting birth defects surveillance data 1968–2003. Birth Defects Res A Clin Mol Teratol 79:65–186PubMedGoogle Scholar
  8. 8.
    Cragan JD, Gilboa SM (2009) Including prenatal diagnoses in birth defects monitoring: experience of the Metropolitan Atlanta Congenital Defects Program. Birth Defects Res A Clin Mol Teratol 85:20–29PubMedCrossRefGoogle Scholar
  9. 9.
    Dadvand P, Rankin J, Shirley MD, Rushton S, Pless-Mulloli T (2009) Descriptive epidemiology of congenital heart disease in Northern England. Paediatr Perinat Epidemiol 23:58–65PubMedCrossRefGoogle Scholar
  10. 10.
    Ferencz C, Loffredo CA, Correa-Villasenor A, Wilson PD (eds) (1997) Genetic and environmental risk factors of major cardiovascular malformations: the Baltimore-Washington Infant Study 1981–1989. Futura Publishing Armonk, NYGoogle Scholar
  11. 11.
    Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW (1989) Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. J Pediatr 114:79–86PubMedCrossRefGoogle Scholar
  12. 12.
    Freeman SB, Bean LH, Allen EG, Tinker SW, Locke AE, Druschel C et al (2008) Ethnicity, sex, and the incidence of congenital heart defects: a report from the National Down Syndrome Project. Genet Med 10:173–180PubMedCrossRefGoogle Scholar
  13. 13.
    Grech V, Gatt M (1999) Syndromes and malformations associated with congenital heart disease in a population-based study. Int J Cardiol 68:151–156PubMedCrossRefGoogle Scholar
  14. 14.
    Harris JA, Francannet C, Pradat P, Robert E (2003) The epidemiology of cardiovascular defects, part 2: a study based on data from three large registries of congenital malformations. Pediatr Cardiol 24:222–235PubMedCrossRefGoogle Scholar
  15. 15.
    Johnson MC, Hing A, Wood MK, Watson MS (1997) Chromosome abnormalities in congenital heart disease. Am J Med Genet 70:292–298PubMedCrossRefGoogle Scholar
  16. 16.
    Kidd SA, Lancaster PA, McCredie RM (1993) The incidence of congenital heart defects in the first year of life. J Paediatr Child Health 29:344–349PubMedCrossRefGoogle Scholar
  17. 17.
    Lammer EJ, Chak JS, Iovannisci DM, Schultz K, Osoegawa K, Yang W et al (2009) Chromosomal abnormalities among children born with conotruncal cardiac defects. Birth Defects Res A Clin Mol Teratol 85:30–35PubMedCrossRefGoogle Scholar
  18. 18.
    Lu XY, Phung MT, Shaw CA, Pham K, Neil SE, Patel A et al (2008) Genomic imbalances in neonates with birth defects: high detection rates by using chromosomal microarray analysis. Pediatrics 122:1310–1318PubMedCrossRefGoogle Scholar
  19. 19.
    Marino B, Digilio MC (2000) Congenital heart disease and genetic syndromes: specific correlation between cardiac phenotype and genotype. Cardiovasc Pathol 9:303–315PubMedCrossRefGoogle Scholar
  20. 20.
    Mathews TJ, MacDorman MF (2008) Infant mortality statistics from the 2005 period linked birth/infant death data set. Natl Vital Stat Rep 57:1–32PubMedGoogle Scholar
  21. 21.
    Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP et al (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86:749–764PubMedCrossRefGoogle Scholar
  22. 22.
    Obler D, Juraszek AL, Smoot LB, Natowicz MR (2008) Double outlet right ventricle: aetiologies and associations. J Med Genet 45:481–497PubMedCrossRefGoogle Scholar
  23. 23.
    Pierpont ME, Basson CT, Benson DW Jr, Gelb BD, Giglia TM, Goldmuntz E et al (2007) Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 115:3015–3038PubMedCrossRefGoogle Scholar
  24. 24.
    Pradat P (1992) Epidemiology of major congenital heart defects in Sweden, 1981–1986. J Epidemiol Community Health 46:211–215PubMedCrossRefGoogle Scholar
  25. 25.
    Rauch R, Hofbeck M, Zweier C, Koch A, Zink S, Trautmann U et al (2010) Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot. J Med Genet 47:321–331PubMedCrossRefGoogle Scholar
  26. 26.
    Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A (2008) Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005. J Pediatr 153:807–813PubMedCrossRefGoogle Scholar
  27. 27.
    Riehle-Colarusso T, Strickland MJ, Reller MD, Mahle WT, Botto LD, Siffel C et al (2007) Improving the quality of surveillance data on congenital heart defects in the metropolitan Atlanta congenital defects program. Birth Defects Res A Clin Mol Teratol 79:743–753PubMedCrossRefGoogle Scholar
  28. 28.
    Roskes EJ, Boughman JA, Schwartz S, Cohen MM (1990) Congenital cardiovascular malformations (CCVM) and structural chromosome abnormalities: a report of 9 cases and literature review. Clin Genet 38:198–210PubMedCrossRefGoogle Scholar
  29. 29.
    Schellberg R, Schwanitz G, Gravinghoff L, Kallenberg R, Trost D, Raff R et al (2004) New trends in chromosomal investigation in children with cardiovascular malformations. Cardiol Young 14:622–629PubMedCrossRefGoogle Scholar
  30. 30.
    Shaffer LG, Kashork CD, Saleki R, Rorem E, Sundin K, Ballif BC et al (2006) Targeted genomic microarray analysis for identification of chromosome abnormalities in 1500 consecutive clinical cases. J Pediatr 149:98–102PubMedCrossRefGoogle Scholar
  31. 31.
    Stoll C, Alembik Y, Roth MP, Dott B, De Geeter B (1989) Risk factors in congenital heart disease. Eur J Epidemiol 5:382–391PubMedCrossRefGoogle Scholar
  32. 32.
    Strickland MJ, Riehle-Colarusso TJ, Jacobs JP, Reller MD, Mahle WT, Botto LD et al (2008) The importance of nomenclature for congenital cardiac disease: implications for research and evaluation. Cardiol Young 18(Suppl 2):92–100PubMedCrossRefGoogle Scholar
  33. 33.
    Tinkle BT, Walker ME, Blough-Pfau RI, Saal HM, Hopkin RJ (2003) Unexpected survival in a case of prenatally diagnosed non-mosaic trisomy 22: clinical report and review of the natural history. Am J Med Genet A 118A:90–95PubMedCrossRefGoogle Scholar
  34. 34.
    Torfs CP, Christianson RE (1998) Anomalies in Down syndrome individuals in a large population-based registry. Am J Med Genet 77:431–438PubMedCrossRefGoogle Scholar
  35. 35.
    van Karnebeek CD, Hennekam RC (1999) Associations between chromosomal anomalies and congenital heart defects: a database search. Am J Med Genet 84:158–166PubMedCrossRefGoogle Scholar
  36. 36.
    Waitzman NJ, Romano PS, Scheffler RM (1994) Estimates of the economic costs of birth defects. Inquiry 31:188–205PubMedGoogle Scholar
  37. 37.
    Yang Q, Chen H, Correa A, Devine O, Mathews TJ, Honein MA (2006) Racial differences in infant mortality attributable to birth defects in the United States, 1989–2002. Birth Defects Res A Clin Mol Teratol 76:706–713PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA)  2011

Authors and Affiliations

  • Robert J. Hartman
    • 1
    • 2
  • Sonja A. Rasmussen
    • 1
    Email author
  • Lorenzo D. Botto
    • 3
  • Tiffany Riehle-Colarusso
    • 1
  • Christa L. Martin
    • 4
  • Janet D. Cragan
    • 1
  • Mikyong Shin
    • 1
    • 5
  • Adolfo Correa
    • 1
  1. 1.National Center on Birth Defects and Developmental DisabilitiesCenters for Disease Control and PreventionAtlantaUSA
  2. 2.Oak Ridge Institute for Science and EducationOak RidgeUSA
  3. 3.Department of PediatricsUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.Department of Human GeneticsEmory UniversityAtlantaUSA
  5. 5.RTI InternationalTriangle Research ParkUSA

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