Correspondence

LETTER TO THE EDITOR: VENTRICULARSEPTAL DEFECTS AND THE NATIONALBIRTH DEFECTS PREVENTION STUDY

To the Editor:The National Birth Defects Prevention Study (NBDPS)

is an ongoing, multisite, population-based, case–controlstudy that seeks to identify risk factors for major birthdefects. To respond to advances in clinical care, concernsabout new possible risk factors, resource limitations, andother issues, study methods have undergone severalmodifications since the study’s inception in 1997. Werecently became aware that a modification regardinginclusion criteria for ventricular septal defects (VSDs)might have been misinterpreted in the birth defects com-munity; thus, we want to clarify the modification and itsrationale.

NBDPS case infants have one or more of >30 majorbirth defects ascertained by birth defects surveillance sys-tems (Yoon et al., 2001). Factors considered when select-ing study defects included their public health significanceand likelihood of diagnosis by age 6 weeks. Many birthdefects surveillance systems ascertain more than these>30 defects; for instance, the Centers for Disease Controland Prevention’s (CDC’s) birth defects surveillance sys-tem, the Metropolitan Atlanta Congenital Defects Pro-gram (MACDP), ascertains major structural or geneticbirth defects, including many not in NBDPS (e.g., club-foot, pyloric stenosis, and Down syndrome) (Correa-Vil-lasenor et al., 2003). VSDs, a category of congenital heartdefects initially included in the NBDPS, can be classifiedbased on the location of the opening in the ventricularseptum. The most common type of VSD is muscular;other types include perimembranous/membranous, mal-alignment/conoventricular/outlet, inflow type/subtricus-pid/canal type, and those for which a type or position isnot noted (termed VSDs, not otherwise specified [NOS])(Botto et al., 2007). All VSD types were initially includedin the NBDPS, but after one year of data collection,infants with muscular and NOS VSDs accounted formore than one-sixth of NBDPS-eligible infants (Yoonet al., 2001). Because of the time and costs associatedwith maternal interviews and because some VSDs closespontaneously (Axt-Fliedner et al., 2006), NBDPS investi-gators decided to exclude infants who have muscularand NOS VSDs, without other NBDPS-eligible birthdefects, beginning with estimated dates of delivery >1year after study initiation. Many infants with other VSD

types have accumulated over the ensuing years, leadingNBDPS investigators to further modify the study-specificinclusion criteria to exclude infants with any type of VSDwithout other NBDPS-eligible birth defects, beginningwith estimated dates of delivery on or after January 1,2006.Based on conversations with colleagues, we under-

stand that some investigators might have misinterpretedthis NBDPS-specific modification to indicate that VSDs(or at least certain VSD types) should no longer be con-sidered as major birth defects (i.e., defects of medical,surgical, or cosmetic significance). VSD severity andtreatment depend on their type and size; although manynever need treatment, others require medical manage-ment or surgical or percutaneous closure (Minette andSahn, 2006). Predicting which defects will be of clinicalsignificance shortly after birth is challenging. Thus, weconsider all VSDs to be major birth defects and includethem in CDC’s MACDP. We believe that modifications inNBDPS methodology regarding VSDs should not havebroader implications for birth defects surveillance andresearch, but instead be viewed as a decision made forone specific birth defects research study.

REFERENCES

Axt-Fliedner R, Schwarze A, Smrcek J, et al. 2006. Isolated ventricularseptal defects detected by color Doppler imaging: evolution duringfetal and first year of postnatal life. Ultrasound Obstet Gynecol27:266–273.

Botto LD, Lin AE, Riehle-Colarusso T, et al. 2007. Seeking causes: classify-ing and evaluating congenital heart defects in etiologic studies. BirthDefects Res A Clin Mol Teratol 79:714–727.

Correa-Villasenor A, Cragan JD, Kucik J, et al. 2003. The MetropolitanAtlanta Congenital Defects Program: 35 years of birth defects surveil-lance at the Centers for Disease Control and Prevention. Birth DefectsRes A Clin Mol Teratol 67:617–624.

Minette MS, Sahn DJ. 2006. Ventricular septal defects. Circulation114:2190–2197.

Yoon PW, Rasmussen SA, Lynberg MC, et al. 2001. The National BirthDefects Prevention Study. Public Health Rep 116(Suppl 1):32–40.

Sonja A. Rasmussen*, Tiffany Riehle-Colarusso, StuartK. Shapira, Margaret A. Honein, Jennita Reefhuis, and

the National Birth Defects Prevention Study

National Center on Birth Defects and DevelopmentalDisabilities, Centers for Disease Control and Prevention,

Atlanta, Georgia

Received 3 September 2010; Accepted 20 September 2010

The findings and conclusions in this report are those of the authors and donot necessarily represent the official position of the Centers for Disease Con-trol and Prevention.*Correspondence to: Sonja A. Rasmussen, 1600 Clifton Road NE, Mail StopE-86, Centers for Disease Control, Atlanta, GA 30333. E-mail: skr9@cdc.govPublished online 7 December 2010 in Wiley Online Library (wileyonlinelibrary.com).DOI: 10.1002/bdra.20750

Birth Defects Research (Part A): Clinical and Molecular Teratology 91:66 (2011)

� 2010 Wiley-Liss, Inc. Birth Defects Research (Part A) 91:66 (2011)