title: Laterality defects in the national birth defects prevention study (1998-2007): birth prevalence and descriptive epidemiology.
abstract: Little is known epidemiologically about laterality defects. Using data from the National Birth Defects Prevention Study (NBDPS), a large multi-site case-control study of birth defects, we analyzed prevalence and selected characteristics in children born with laterality defects born from 1998 to 2007. We identified 517 nonsyndromic cases (378 heterotaxy, 73.1%; 139 situs inversus totalis [SIT], 26.9%) resulting in an estimated birth prevalence of 1.1 per 10,000 live births (95% confidence interval 1.0–1.2). Prevalence did not differ significantly across sites, over time, or by inclusion of pregnancy termination. Laterality defects were more common among preterm cases compared to term cases, and in children born to mothers who were non-white or younger than 20 years compared to white mothers or those age 25–29 years. The distribution of associated cardiac and extra-cardiac defects, excluding the expected heterotaxy anomalies, varied by type of laterality defect. Cases with heterotaxy were significantly more likely than those with SIT to have double outlet right ventricle, atrioventricular canal defects, pulmonary stenosis, non-tetralogy of Fallot pulmonary atresia with ventricular septal defect, totally and partially anomalous pulmonary venous return; also more likely to have orofacial clefts, esophageal atresia, bowel atresias, and omphalocele, though not reaching statistical significance. Relatively more common among cases with SIT were Dandy- Walker malformation, anotia/microtia, and limb deficiency. The similarity in the demographic characteristics of heterotaxy and SIT supports the hypothesis that they are part of a continuum of abnormal left-right axis patterning. These findings on laterality defects may help guide clinical care, future research, and prevention strategies.
authors.affiliation: Medical Genetics, MassGeneral Hospital for Children, Boston, Massachusetts; Massachusetts Center for Birth Defects Research and Prevention, Boston, Massachusetts.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Lin
authors.forename: Sergey
authors.initials: S
authors.lastname: Krikov
authors.forename: Tiffany
authors.initials: T
authors.lastname: Riehle-Colarusso
authors.forename: Jaime L
authors.initials: JL
authors.lastname: Frías
authors.forename: John
authors.initials: J
authors.lastname: Belmont
authors.forename: Marlene
authors.initials: M
authors.lastname: Anderka
authors.forename: Tal
authors.initials: T
authors.lastname: Geva
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Getz
authors.forename: Lorenzo D
authors.initials: LD
authors.lastname: Botto
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000453:epidemiology*; D004310:Double Outlet Right Ventricle / Q000453:epidemiology; D005260:Female; D006345:Heart Septal Defects, Ventricular / Q000453:epidemiology; D059446:Heterotaxy Syndrome / Q000453:epidemiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D015995:Prevalence; D012857:Situs Inversus / Q000453:epidemiology; D044465:White People; D055815:Young Adult
keywords: asplenia; cardiovascular malformations; congenital heart defects; dextrocardia; heterotaxy; isomerism; laterality defects; malposition; prevalence; race/ethnic disparities; situs ambiguous; situs inversus
references.citation: Genet Med. 2009 Jul;11(7):473-87
references.pmid: 19606528
references.citation: Orphanet J Rare Dis. 2011 Oct 03;6:64
references.pmid: 21968022
references.citation: Birth Defects Res A Clin Mol Teratol. 2014 Feb;100(2):79-91
references.pmid: 24523198
references.citation: Am J Med Genet. 2001 Mar 1;99(2):142-6
references.pmid: 11241474
references.citation: Genet Med. 2000 May-Jun;2(3):157-72
references.pmid: 11256661
references.citation: Hum Genet. 2000 Mar;106(3):277-87
references.pmid: 10798355
references.citation: Circulation. 2007 Jun 5;115(22):2814-21
references.pmid: 17515466
references.citation: Am J Epidemiol. 2009 Oct 15;170(8):975-85
references.pmid: 19736223
references.citation: Am J Cardiol. 2000 Mar 15;85(6):729-34
references.pmid: 12000048
references.citation: Am J Med Genet. 1995 Mar 13;56(1):12-5
references.pmid: 7747776
references.citation: Dev Biol. 2013 Jul 1;379(1):1-15
references.pmid: 23583583
references.citation: Obstet Gynecol. 1996 Feb;87(2):163-8
references.pmid: 8559516
references.citation: Am J Med Genet. 2001 Jul 15;101(4):345-55
references.pmid: 11471158
references.citation: Nat Genet. 1997 Nov;17(3):305-8
references.pmid: 9354794
references.citation: Public Health Rep. 2001;116 Suppl 1:32-40
references.pmid: 11889273
references.citation: Eur J Hum Genet. 2006 Jan;14(1):17-25
references.pmid: 16251896
references.citation: J Pediatr. 2008 Dec;153(6):807-13
references.pmid: 18657826
references.citation: Birth Defects Res A Clin Mol Teratol. 2012 Jun;94(6):449-58
references.pmid: 22473636
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Oct;79(10):714-27
references.pmid: 17729292
references.citation: Pediatrics. 1980 Feb;65(2 Pt 2):375-461
references.pmid: 7355042
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2915-20
references.pmid: 21282601
references.citation: Birth Defects Res A Clin Mol Teratol. 2003 Mar;67(3):193-201
references.pmid: 12797461
references.citation: J Am Coll Cardiol. 2002 Jun 19;39(12):1890-900
references.pmid: 12084585
references.citation: Birth Defects Res A Clin Mol Teratol. 2007 Feb;79(2):65-186
references.pmid: 17278144
references.citation: Circulation. 2012 May 8;125(18):2178-80
references.pmid: 22499951
references.citation: Circulation. 2011 Mar 1;123(8):841-9
references.pmid: 21321151
references.citation: Pediatr Cardiol. 2008 May;29(3):536-44
references.pmid: 18004616
references.citation: Heart. 2012 Nov;98(22):1667-73
references.pmid: 22888161
references.citation: Am J Med Genet A. 2012 Dec;158A(12):2981-98
references.pmid: 23132826
references.citation: Circulation. 2007 Jun 5;115(22):2793-5
references.pmid: 17548739
references.citation: J Pediatr. 2011 Jul;159(1):70-78.e2
references.pmid: 21329942