87097666487Paediatr Perinat EpidemiolPaediatr Perinat EpidemiolPaediatric and perinatal epidemiology0269-50221365-301623061687348210110.1111/ppe.12006NIHMS404540ArticleDescriptive Epidemiology of Nonsyndromic Complete Atrioventricular Canal DefectsAgopianA. J.aMoulikMousumibGupta-MalhotraMoneshabMarengoLisa K.cMitchellLaura E.a*Center for Human Genetics, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TexasDivision of Cardiology, Department of Pediatrics, University of Texas Medical School, Houston, TexasBirth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, TexasCorrespondence: Laura E. Mitchell, Ph.D., University of Texas School of Public Health, 1200 Herman Pressler Dr., Houston, TX 77030, laura.e.mitchell@uth.tmc.edu, Phone: 713-500-9954, Fax: 713-500-99581392012249201211201201112013266515524Background

Complete atrioventricular canal defects (CAVC) are a common heart defect, but few epidemiologic studies have evaluated nonsyndromic CAVC. Risk factors for nonsyndromic CAVC have not been well established.

Methods

To assess the relationship between risk for nonsyndromic CAVC in offspring and several sociodemographic and reproductive parental factors, including maternal diabetes and obesity, we conducted Poisson regression analyses, using data ascertained through the Texas Birth Defects Registry, a large, population-based birth defects registry. Data were evaluated for 563 nonsyndromic cases with CAVC.

Results

Significant associations were observed between nonsyndromic CAVC in offspring and maternal pregestational diabetes (adjusted prevalence ratio (aPR): 6.74, 95% confidence interval (CI): 3.67–12.37), gestational diabetes [aPR: 1.69, 95% CI: 1.03, 2.79], and obesity [aPR: 1.69, 95% CI: 1.24, 2.30].

Comments

Our findings add nonsyndromic CAVC to the growing list of birth defects that appear to be associated with maternal diabetes and obesity.

INTRODUCTION

Birth defects are a leading cause of infant mortality.1 Further, congenital heart defects are the leading cause of birth defect-related mortality and the etiology of heart defects is poorly understood.2 Heart defects represent a heterogeneous group of malformations, and some types of heart defects have been better studied than others. Complete atrioventricular canal defects (CAVC) are the most common type of endocardial cushion defect, and involve deficiencies of the endocardial cushion-derived components of the atrial and ventricular septae and a single common atrioventricular valve ring. CAVC represents approximately 3% of heart defects, occurring in two per 10,000 live births.3 More than 50% of CAVC occur in conjunction with trisomy 21, and 50% of infants with untreated CAVC, whether syndromic or nonsyndromic, will die during the first year of life.3, 4 Few epidemiologic studies have evaluated nonsyndromic CAVC and risk factors for nonsyndromic CAVC have not been well established.

Maternal pregestational diabetes, gestational diabetes, and obesity are independently associated with increased risk for birth defects, including heart defects, in offspring.5, 6 Since more than one-third of adult women in the US are obese or diabetic, and the prevalence of each is rising,7, 8 it is important to delineate the full range of adverse outcomes associated with maternal obesity and diabetes. Although animal models suggest that maternal diabetes may increase offspring risk for CAVC,9 the effects of maternal obesity, diabetes, or other factors on offspring risk for CAVC have not been well studied in humans. Therefore, we conducted a descriptive epidemiologic study of CAVC, evaluating the possible influence of a wide range of sociodemographic and reproductive factors, including maternal diabetes and obesity, on risk for CAVC.

METHODSStudy Population

We conducted descriptive analyses using CAVC data from the Texas Birth Defects Registry. This registry is maintained by the Birth Defects Epidemiology and Surveillance Branch (BDESB) at the Texas Department of State Health Services.10 Active case surveillance is used to identify live births, fetal deaths, and induced pregnancy terminations with birth defects. Cases are included in the registry when the mother resides in Texas at the time of delivery and a diagnosis of a structural malformation or developmental disability is made within the first year of delivery. Case data are abstracted from medical records at all birthing centers, delivery hospitals, midwife facilities, and pediatric hospitals in Texas by BDESB staff. Diagnoses are classified using a six-digit code defined by the Centers for Disease Control and Prevention, based on the British Pediatric Association Classification of Diseases and the International Classification of Diseases, 9th Revision, Clinical Modification system (BPA code).11 Case data from medical records are then linked to sociodemographic and reproductive data from birth and fetal death certificates from the Texas Vital Statistics Unit of the Texas Department of State Health Services.

The present analyses included cases from the registry with documented postnatal confirmation of diagnoses of endocardial cushion defects (BPA code 745.6) from 1999–2008, including cases that were live births, fetal deaths, and induced pregnancy terminations. Main analyses focused on those cases with CAVC (BPA code 745.620). Data were available for maternal variables (maternal age at delivery, race/ethnicity, history of previous live births, history of previous pregnancies that did not result in live births, onset of prenatal care during the first trimester [yes versus no], education level, birthplace, residence in a county bordering Mexico, residence type [e.g., rural], marital status at time of delivery, pregestational diabetes, gestational diabetes, and prepregnancy body mass index), paternal variables (paternal age at delivery and race/ethnicity), and case variables (delivery year, season of conception, plurality of the pregnancy, and sex). Residence type was defined based on county population size (i.e., rural urban continuum code), as described by Langlois et al.12 Season of conception was based on month of last menstrual period and was categorized as winter (December-February), spring (March-May), summer (June-August), and fall (September-November). Information on overall presence or absence of maternal diabetes, regardless of pregestational or gestational onset, was available for the entire study period. Specific information on maternal pregestational diabetes, gestational diabetes, and prepregnancy body mass index (BMI) was only available for deliveries in 2005–2008. Data on type of pregestational diabetes (i.e., type 1 versus type 2) were not available. For all of these variables, data from vital records were used; however, when data were missing or when a vital record was not available for a case, data abstracted from medical records were used to determine: maternal age at delivery, race/ethnicity, history of previous live births, residence in a county bordering Mexico, and residence type, and infant sex, plurality, and year of delivery. In order to make comparisons, vital records data were obtained from the Texas Vital Statistics unit of the Texas Department of State Health Services for all live births in Texas during the study period.13 The protocol for this study was approved by the Institutional Review Board for the University of Texas Health Science Center at Houston.

Statistical Methods

We conducted descriptive analyses to identify sociodemographic or reproductive characteristics that may increase risk for CAVC. First, we tabulated frequencies of cases with syndromic and nonsyndromic endocardial cushion defects, including CAVC. Syndromic cases were defined as cases with possible or confirmed diagnoses of a chromosome abnormality or malformation syndrome or sequence, based on BPA codes. Patients with visceral heterotaxy were included in the nonsyndromic group. To limit heterogeneity, all subsequent analyses were conducted among cases with nonsyndromic CAVC. Among these nonsyndromic cases, frequencies of additional major birth defects, including heterotaxy, were determined.

We estimated birth prevalence and crude prevalence ratios using data from cases in the numerator and data from all live births in the denominator. Poisson regression was used to estimate prevalence ratios. Variables that were available for the entire study period and were significantly associated (p<0.05) or associated with borderline significance (i.e., lower 95% confidence interval limit ≥0.99 for positive associations or upper 95% confidence limit ≤1.01 for negative associations) with nonsyndromic CAVC in crude analyses were included in the main multivariable model. Multivariable analyses were repeated for deliveries during 2005–2008, using the maternal gestational diabetes, pregestational diabetes, and BMI variables instead of the overall diabetes variable. For this analysis, we included all other variables in the original multivariable model. All analyses were performed using SAS (version 9.1 copyright 2002–2008, SAS, Inc., Cary, NC).

Visceral heterotaxy has been associated with maternal pregestational diabetes and is often observed in conjunction with CAVC.5, 14 Therefore, analyses for 2005–2008 deliveries and the full study period were also repeated among cases without heterotaxy, to ensure that any observed associations were independent of associations with heterotaxy. Further, analyses for the full study period were also repeated among a small subset of cases with isolated CAVC (i.e., those without any additional major [cardiac or non-cardiac] birth defects).

RESULTS

There were 3,806,299 total live births and 1,588 total cases with documented postnatal diagnoses of endocardial cushion defects from 1999–2008 (Table 1). There were 1,335 cases with CAVC; therefore, the total prevalence of CAVC was 3.51 per 10,000 live births. The majority of cases with CAVC (58%) had chromosome abnormalities or malformation syndromes (Table 1), the most common being trisomy 21 (52%, N=693). Cases with heterotaxy syndrome were included under nonsyndromic CAVC (NSCAVC). Subsequent analyses focused on cases with NSCAVC (N=563). The prevalence of NSCAVC was 1.48 per 10,000 live births.

The proportion of cases with NSCAVC that were live births, fetal deaths, and induced terminations were 98.6%, 0.4%, and 1.1%, respectively. There were two fetal deaths and six induced terminations. Associated major birth defects in the NSCAVC cases are presented by system or structure in Table 2 (and defined in Supplementary Table 1). Heterotaxy syndrome was present in 38.7% (N= 218) of the NSCAVC cases. Additional congenital heart defects commonly reported in the NSCAVC cases included persistent left superior vena cava (25.4%, N=143), transposition of the great vessels (39.4%, N=222), persistent right aortic arch (19%, N=107), ostium secundum atrial septal defect (32.5%, N=183), hypoplastic left ventricle (18.5%, N=104), total anomalous pulmonary venous return (18.5%, N=104), and hypoplastic right ventricle (8.0%, N=45).

The variables that were significantly associated with NSCAVC in offspring in the main crude analyses (i.e., for the entire study period) were maternal age, paternal age, marital status, plurality, and maternal diabetes (i.e., pregestational or gestational) (Table 3). These variables were all included in the main multivariable model (Table 4). A significantly increased prevalence of NSCAVC in offspring was seen among women who were not married at time of delivery compared to those who were married [adjusted prevalence ratio (aPR): 1.31, 95% confidence interval (CI): 1.03, 1.66]. In addition, the prevalence of NSCAVC in offspring was also increased among women with diabetes (pregestational or gestational) compared to those without diabetes [aPR: 2.63, 95% CI: 1.87, 3.70].

To further explore the relationship between maternal diabetes and NSCAVC in offspring, we repeated analyses using data only from 2005–2008, which included maternal gestational diabetes, pregestational diabetes, and BMI variables (Table 4). In the multivariable model, a significantly increased prevalence of NSCAVC in offspring was observed among women with pregestational diabetes [aPR: 6.74, 95% CI: 3.67, 12.37] or gestational diabetes [aPR: 1.69, 95% CI: 1.03, 2.79] as well as among obese (i.e., BMI ≥30 kg/m2) women [aPR: 1.69, 95% CI: 1.24, 2.30], compared to women without these conditions.

Because heterotaxy in offspring has previously been associated with maternal diabetes,5 we repeated analyses among 345 cases without heterotaxy, and in these analyses, similar magnitudes of associations with diabetes and obesity were observed (Table 4). Further, a similar magnitude of association with diabetes was observed in analyses repeated for the full study period among the 47 cases with isolated CAVC (Table 4). Analyses were not repeated for 2005–2008 among cases with isolated CAVC because there were only 18 such cases during this period.

DISCUSSION

The overall prevalence of CAVC in the present study was similar to that reported in previous studies.15, 16 Further, the distribution of syndromes among cases with syndromic CAVC was similar to previous reports, as was the distribution of additional major birth defects among nonsyndromic cases.14, 15

Maternal pregestational diabetes is a known risk factor for congenital heart defects overall, as well as for several specific subtypes of congenital heart defects (e.g, conotruncal defects and heterotaxia).5, 1720 However, many previous studies have been limited by small numbers of cases with specific congenital heart defect subtypes. Due to the rarity of nonsyndromic CAVC, potential risk factors, including maternal diabetes, have not been well studied in relation to nonsyndromic CAVC.

In the present study, we found an increased prevalence of nonsyndromic CAVC in offspring of women with pregestational diabetes, gestational diabetes, obesity (BMI ≥30), or unmarried marital status at delivery. We are aware of only one other study that evaluated the descriptive epidemiology of nonsyndromic CAVC.14 In that study, based on data from the National Birth Defects Prevention Study (N=122 cases), a lower prevalence of CAVC was seen in offspring of Hispanic mothers [crude PR: 0.4, 95% CI: 0.2, 0.7].14 A similar association was not observed in the present study, which used a study population with more than five times as many cases with Hispanic mothers. Although a borderline significant higher prevalence of CAVC was seen among multiple compared to single gestation pregnancies in the present study [aPR: 1.6, 95% CI: 1.0, 2.5] (Table 4), the prevalence among multiple gestation pregnancies was not significantly increased in data from the National Birth Defects Prevention Study [crude PR: 1.1, 95% CI: 0.4, 2.8].14

Significant associations have been reported between pregestational (but not gestational) maternal diabetes and isolated [adjusted OR: 12.4, 95% CI: 3.7, 41.5] and non-isolated [OR: 25.3, 95% CI: 4.2, 152.1] atrioventricular septal defects in data from the National Birth Defects Prevention Study (N=85 cases).5 An association between pregestational diabetes and atrioventricular septal defects has also been reported in data from the EUROCAT registry after adjustment for maternal age, year, and registry [adjusted OR: 2.2, 95% CI: 1.2, 4.0].21 Atrioventricular septal defects and CAVC have also been evaluated in data from the Baltimore-Washington Infant Study, and significant crude associations between pregestational diabetes and CAVC have been reported in analyses involving a small number of cases [N=31 cases, OR: 22.8, 95% CI: 7.4, 70.5].4, 22, 23 To our knowledge, an association between gestational diabetes and CAVC has not been previously reported.

The association between pregestational diabetes and complex heart defects involving conotruncal septation, cardiac looping, or the endocardial cushion (as reported in our study) points towards an early teratogenic effect on cardiac development (weeks 3–8) by an abnormal metabolic milieu in diabetic mothers.20, 24 The biologic basis for the association between maternal gestational diabetes, which is typically diagnosed after the first trimester, and CAVC is difficult to explain and may reflect cases of undiagnosed pregestational diabetes mellitus diagnosed as gestational diabetes.17, 25

Several previous studies have reported associations between prepregnancy maternal elevated BMI or obesity and offspring risk for heart defects overall, as well as specific heart defects (e.g., left ventricular outflow tract defects, conotruncal defects).2628 However, maternal obesity and CAVC has not been well studied and, to our knowledge, this is the first report of a statistically significant association between maternal obesity and CAVC. Three studies have, however, reported non-significant, elevated associations between elevated BMI and atrioventricular septal defects [adjusted ORs: 1.8, 1.4, and 1.2].6, 26, 27

The novel association between CAVC in offspring and maternal unmarried status may reflect underlying involvement of additional unknown socioeconomic or behavioral factors. Unmarried status has been associated with other adverse pregnancy outcomes in Texas,29 and similar associations between unmarried status and heart defects overall in offspring have been reported 30, 31 but the relationship between marital status and heart defects has not been thoroughly evaluated.

The present study had limitations. Data for maternal obesity, pregestational diabetes, and gestational diabetes was only available for more recent years (i.e., 2005–2008). Similar to other studies of diabetes and birth defects,5, 23 information on type of pregestational diabetes (i.e., type 1 or type 2), diabetes severity, glycemic control, method of diabetes diagnosis, and clinical confirmation of diagnosis was not available. Data for pregestational, gestational, and overall maternal diabetes and obesity were collected from vital records for cases and all livebirths. It seems likely that maternal diabetes and obesity could be underreported on vital records;32 however, the observed prevalence of gestational diabetes, pregestational diabetes, and obesity from 2005–2008 among all live births (i.e., 3.7%, 0.6%, and 20.8%, respectively, data not shown) seems reasonably similar to previous estimates (e.g., 2–10%, 0.5%, and 22%, respectively).5, 3335 Further, previously reported associations between maternal diabetes or obesity and other heart defects support our findings. We cannot rule out the presence of unmeasured confounding by other factors, as our analyses were limited to available data.

There are several strengths to this study, including use of a population-based, multiracial/ethnic sample ascertained by an active surveillance system that includes both liveborn and non-liveborn cases. To our knowledge, this descriptive study contains the largest sample of cases with CAVC described in the literature. We attempted to limit heterogeneity by restricting our case definition to a subset of endocardial cushion defects (i.e., CAVC), and by restricting analyses to nonsyndromic cases. Results for our subgroup analyses also support the main results, and suggest that maternal diabetes and obesity increase offspring risk for CAVC independently of heterotaxy.

In summary, we have identified maternal factors that may increase risk for CAVC. The observed associations between CAVC in offspring and maternal pregestational diabetes, gestational diabetes, and obesity seem consistent with previous findings. Further research is indicated to confirm our findings and better understand the biological mechanisms that underlie these associations.

Supplementary Material

We thank M.A. Canfield and P.H. Langlois and the staff of the Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, for help with collecting data for the Texas Birth Defects Registry. This project was supported in part by the Centers for Disease Control and Prevention (CDC)-funded Texas Center for Birth Defects Research and Prevention (#5U01DD000494) through a cooperative agreement with Texas Department of State Health Services (DSHS), as well as the Title V Office of Texas DSHS. This study is also partially supported by the National Institutes of Health (PI Monesha Gupta, grant number 5K23HL089301-02; PI Mousumi Moulik, grant number 5K08HL091176-04).

MathewsTJMininoAMOstermanMJStrobinoDMGuyerBAnnual summary of vital statistics: 2008Pediatrics201112714615721173001RosanoABottoLDBottingBMastroiacovoPInfant mortality and congenital anomalies from 1950 to 1994: an international perspectiveJournal of Epidemiology and Community Health20005466066610942444CalabroRLimongelliGComplete atrioventricular canalOrphanet Journal of Rare Diseases20061816722604LoffredoCAHirataJWilsonPDFerenczCLurieIWAtrioventricular septal defects: possible etiologic differences between complete and partial defectsTeratology200163879311241431CorreaAGilboaSMBesserLMBottoLDMooreCAHobbsCADiabetes mellitus and birth defectsAmerican Journal of Obstetrics and Gynecology2008199237e23123918674752MillsJLTroendleJConleyMRCarterTDruschelCMMaternal obesity and congenital heart defects: a population-based studyAmerican Journal of Clinical Nutrition2010911543154920375192FlegalKMCarrollMDOgdenCLCurtinLRPrevalence and trends in obesity among US adults, 1999–2008JAMA201030323524120071471LawrenceJMContrerasRChenWSacksDATrends in the prevalence of preexisting diabetes and gestational diabetes mellitus among a racially/ethnically diverse population of pregnant women, 1999–2005Diabetes Care20083189990418223030ZhaoZEndoplasmic reticulum stress in maternal diabetes-induced cardiac malformations during critical cardiogenesis periodBirth Defects Research Part B, Developmental and Reproductive Toxicology201110.1002/bdrb.20330Texas Department of State Health ServicesTexas Birth Defects Epidemiology and Surveillance2011[updated 2011; cited 2011 Dec 17]; Available from: http://www.dshs.state.tx.us/birthdefects/National Center on Birth Defects and Developmental Disabilities CAppendix A: ICD-9 and CDC/BPA codesTeratology200266 Suppl 1S21821912239749LangloisPHScheuerleAHorelSACarozzaSEUrban versus rural residence and occurrence of septal heart defects in TexasBirth Defects Research Part A, Clinical and Molecular Teratology200985764772Texas Department of State Health ServicesTexas Vital Statistics2011[updated 2011; cited 2011 Dec 17]; Available from: http://www.dshs.state.tx.us/VS/HartmanRJRiehle-ColarussoTLinAFriasJLPatelSSDuweKDescriptive study of nonsyndromic atrioventricular septal defects in the National Birth Defects Prevention Study, 1997–2005American Journal of Medical Genetics Part A2011155A55556421337694FerenczCLoffredoCCorrea-VillasenorAWilsonPGenetic and Environmental Risk Factors of Major Cardiovascular Malformations: The Baltimore–Washington Infant Study 1981–1989Armonk, NYFutura Publishing Company, Inc1997RellerMDStricklandMJRiehle-ColarussoTMahleWTCorreaAPrevalence of congenital heart defects in metropolitan Atlanta, 1998–2005Journal of Pediatrics200815380781318657826AbergAWestbomLKallenBCongenital malformations among infants whose mothers had gestational diabetes or preexisting diabetesEarly Human Development200161859511223271Martinez-FriasMLFriasJPBermejoERodriguez-PinillaEPrietoLFriasJLPre-gestational maternal body mass index predicts an increased risk of congenital malformations in infants of mothers with gestational diabetesDiabetic Medicine20052277578115910631BecerraJEKhouryMJCorderoJFEricksonJDDiabetes mellitus during pregnancy and the risks for specific birth defects: a population-based case-control studyPediatrics199085192404255LisowskiLAVerheijenPMCopelJAKleinmanCSWassinkSVisserGHCongenital heart disease in pregnancies complicated by maternal diabetes mellitus. An international clinical collaboration, literature review, and meta-analysisHerz201035192620140785GarneELoaneMDolkHBarisicIAddorMCArriolaLSpectrum of congenital anomalies in pregnancies with pregestational diabetesBirth Defects Research Part A, Clinical and Molecular Teratology201294134140FerenczCRubinJDMcCarterRJClarkEBMaternal diabetes and cardiovascular malformations: predominance of double outlet right ventricle and truncus arteriosusTeratology1990413193262326756LoffredoCAWilsonPDFerenczCMaternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infantsTeratology2001649810611460261ReeceEAHomkoCJWuYKMultifactorial basis of the syndrome of diabetic embryopathyTeratology1996541711829122886Schaefer-GrafUMBuchananTAXiangASongsterGMontoroMKjosSLPatterns of congenital anomalies and relationship to initial maternal fasting glucose levels in pregnancies complicated by type 2 and gestational diabetesAmerican Journal of Obstetrics and Gynecology200018231332010694330GilboaSMCorreaABottoLDRasmussenSAWallerDKHobbsCAAssociation between prepregnancy body mass index and congenital heart defectsAmerican Journal of Obstetrics and Gynecology201020251 e5151 e1019796755CedergrenMIKallenBAMaternal obesity and infant heart defectsObesity Research2003111065107112972676WatkinsMLRasmussenSAHoneinMABottoLDMooreCAMaternal obesity and risk for birth defectsPediatrics20031111152115812728129SullivanKRaleyRKHummerRASchiefelbeinEThe Potential Contribution of Marital-Cohabitation Status to Racial, Ethnic, and Nativity Differentials in Birth Outcomes in TexasMaternal and Child Health Journal201111020824316JosefssonAKernellKNielsenNEBladhMSydsjoGReproductive patterns and pregnancy outcomes in women with congenital heart disease--a Swedish population-based studyActa Obstetricia et Gynecologica Scandinavica20119065966521314820DulskieneVGrazulevicieneREnvironmental risk factors and outdoor formaldehyde and risk of congenital heart malformationsMedicina (Kaunas)20054178779516227712Lydon-RochelleMTHoltVLCardenasVNelsonJCEasterlingTRGardellaCThe reporting of pre-existing maternal medical conditions and complications of pregnancy on birth certificates and in hospital discharge dataAmerican Journal of Obstetrics and Gynecology200519312513416021070KimSYDietzPMEnglandLMorrowBCallaghanWMTrends in pre-pregnancy obesity in nine states, 1993–2003Obesity (Silver Spring)20071598699317426334HuntKJSchullerKLThe increasing prevalence of diabetes in pregnancyObstetrics and Gynecology Clinics of North America200734173199vii17572266Centers for Disease Control and PreventionDiabetes & Pregnancy2011[updated 2011; cited 2011 November 29]; Available from: http://www.cdc.gov/Features/DiabetesPregnancy/

Distribution of Endocardial Cushion Defects and Specified Syndromic and Nonsyndromic Subgroups.

Endocardial cushion defect type and subgroupN (%)
CAVCa1,335
 Syndromic772 (57.8)
  Trisomy 21693 (51.9)
  Trisomy 1831 (2.3)
  Trisomy 1310 (0.7)
  Other chromosome abnormalities16 (1.2)
  Other syndromes33 (2.5)
 Nonsyndromic563 (42.2)
  Additional cardiac or non-cardiac malformation516
   Additional cardiac malformation only223
    Visceral heterotaxy218
  Isolated CAVCa47
 CAVCa and single or hypoplastic ventricle variants287
  Trisomy 2149 (17.1)
  Nonsyndromic221 (77.0)
Ostium primum defects without CAVCa143
 Trisomy 2134 (23.8)
 Nonsyndromic95 (66.4)
Single common atrium106
 Trisomy 213 (2.8)
 Nonsyndromic86 (81.1)
Other endocardial cushion defect62
 Trisomy 2127 (43.5)
 Nonsyndromic30 (48.4)

Complete atrioventicular canal defects

Additional Major Birth Defects Among Nonsyndromic Cases with Complete Atrioventricular Canal Defects (N=563)

Major birth defectaN%
Additional cardiovascular anomalies
Septal defects
 Additional ventricular septal defect6110.8
 Secundum atrial septal defect18332.5
Conotruncal defects
 Tetralogy of Fallot183.2
 Pulmonary infundibular stenosis, not otherwise specified569.9
 Transposition of great vessels22239.4
 Common truncus81.4
Aortic arch abnormalities
 Coarctation of aorta6611.7
 Hypoplasia of aorta7813.9
 Persistent right aortic arch10618.8
Anomalies of great veins
 Persistent left superior vena cava14325.4
 Total anomalous pulmonary venous return10418.5
 Partial anomalous pulmonary venous return203.6
Hypoplastic or single ventricle variants
 Hypoplastic left ventricle10418.5
 Hypoplastic right ventricle458.0
 Hypoplastic ventricle, not otherwise specified50.9
 Single ventricle, not otherwise specified6711.9
Additional specified abnormality of common atrioventricular valve
 Congenital stenosis of ‘mitral’ component7112.6
 Atresia or stenosis of ‘tricuspid’ component254.4
Anomalies of aortic valve
 Congenital stenosis of aortic valve305.3
 Congenital insufficiency of aortic valve10.2
Anomalies of pulmonary valve
 Atresia, hypoplasia, or absence of pulmonary valve7513.3
 Stenosis of pulmonary valve8314.7
 Unspecified pulmonary atresia, stenosis, or hypoplasia5810.3
Anomalies of pulmonary artery14826.3
Anomalies of coronary artery or sinus325.7
Additional non-cardiac birth defects
Visceral heterotaxy21838.7
Anomalies of nervous system386.7
Anomalies of eye101.8
Anomalies of ear, face, and neck346.0
Anomalies of respiratory system223.9
Anomalies of digestive system
 Anomalies of intestinal fixation9316.5
 Anomalies of gallbladder, bile ducts, and liver223.9
 Other specified anomalies of stomach6211.0
Anomalies of urinary system and genital organs7613.5
Anomalies of musculoskeletal system
 Polydactyly142.5
 Anomalies of spine295.2
 Other anomalies of ribs and sternum285.0

Frequent additional major birth defects reported by system/structure

Prevalence Estimates and Unadjusted Prevalence Ratios for Cases with Nonsyndromic Complete Atrioventricular Canal Defects in TX, 1999–2008

VariableCases (N=563)Total live births (N=3,806,299)Prevalence (/10,000 live births)Unadjusted prevalence ratio [95% CIa]
Maternal age (years)
 <20795385341.471.0 Reference
 20–2414410706421.340.9 [0.7, 1.2]
 25–2914910195641.461.0 [0.8, 1.3]
 30–341167620171.521.0 [0.8, 1.4]
 35–39573437761.661.1 [0.8, 1.6]
 ≥4018713772.521.7 [1.0, 2.9]
Paternal age (years)b
 <20231833101.251.0 Reference
 20–24846837881.231.0 [0.6, 1.6]
 25–291248728541.421.1 [0.7, 1.8]
 30–341067836981.351.1 [0.7, 1.7]
 35–39724586631.571.3 [0.8, 2.0]
 ≥40542678142.021.6 [1.0, 2.6]
Marital status
 Married33424429351.371.0 Reference
 Unmarried22013607771.621.2 [1.0, 1.4]
Plurality
 Singleton53836957931.461.0 Reference
 Multiple251102992.271.6 [1.0, 2.3]
Any diabetes
 Yes481310103.662.7 [2.0, 3.6]
 No50336752871.371.0 Reference
Gestational diabetesc
 Yes15595972.521.6 [0.9, 2.7]
 No24515379441.591.0 Reference
Pre-gestational diabetesc
 Yes12969012.387.9 [4.4, 14.2]
 No24815878511.561.0 Reference
Body mass index (kg/m2)c
 Underweight (<18.5)9724411.240.9 [0.5, 1.8]
 Normal (18.5–24.9)1057885371.331.0 Reference
 Overweight (25.0–29.9)703930531.781.3 [1.0, 1.8]
 Obese (≥30)753298132.271.7 [1.3, 2.3]
Previous live births
 No22214430811.541.0 Reference
 Yes34022716401.501.0 [0.8, 1.2]
Previous pregnancies that did not result in live births
 No42829919261.431.0 Reference
 Yes1197545711.581.1 [0.9, 1.4]
Year of delivery
 1999513491571.461.0 Reference
 2000423633251.160.8 [0.5, 1.2]
 2001493650921.340.9 [0.6, 1.4]
 2002573723691.531.1 [0.7, 1.5]
 2003433773741.140.8 [0.5, 1.2]
 2004573814411.491.0 [0.7, 1.5]
 2005553855371.431.0 [0.7, 1.4]
 2006713993091.781.2 [0.9, 1.7]
 2007634074531.551.1 [0.7, 1.5]
 2008754052421.851.3 [0.9, 1.8]
Sex
 Male28819458411.481.0 Reference
 Female27518604581.481.0 [0.9, 1.2]
Maternal education
 >High school19914732791.351.0 Reference
 High school17511099451.581.2 [1.0, 1.4]
 <High school17311834771.461.1 [0.9, 1.3]
Maternal Residence (Texas-Mexico border)
 No48233180051.451.0 Reference
 Yes814882941.661.1 [0.9, 1.4]
Maternal race/ethnicity
 Non-Hispanic white20513879341.481.0 Reference
 Non-Hispanic black674249641.581.1 [0.8, 1.4]
 Hispanic28018441031.521.0 [0.9, 1.2]
Paternal race/ethnicityc
 Non-Hispanic white17612227031.441.0 Reference
 Non-Hispanic black463304611.391.0 [0.7, 1.3]
 Hispanic22515637801.441.0 [0.8, 1.2]
Season of conception
 Winter1589231811.711.0 Reference
 Spring1228735931.400.8 [0.6, 1.0]
 Summer1178491111.380.8 [0.6, 1.0]
 Fall1509161321.641.0 [0.8, 1.2]
First trimester prenatal care
 Yes37626962361.391.0 Reference
 No1459197491.581.1 [0.9, 1.4]
Residence type
 Metropolitan urbanized50233878861.481.0 Reference
 Non-metropolitan urbanized301553281.931.3 [0.9, 1.9]
 Less urbanized312630851.180.8 [0.6, 1.1]
Maternal birthplaced
 United States1489222181.601.1 [0.9, 1.4]
 Outside United States1329218851.431.0 Reference
Total56338062991.48

CI, confidence interval

Data were missing for 17.8% of cases for paternal age and 20.6% for paternal race/ethnicity

Data available for cases delivered in 2005–2008 only

Maternal birthplace was only analyzed among cases with Hispanic mothers

Adjusted Prevalence Ratios for Nonsyndromic Cases with Complete Atrioventricular Canal Defects in TX, 1999–2008

CAVC (N=563)CAVC without heterotaxy (N=345)Isolated CAVC (N=47)

Variable1999–2008 Adjusted prevalence ratio [95% CIa]2005–2008 Adjusted prevalence ratio [95% CIa]1999–2008 Adjusted prevalence ratio [95% CIa]2005–2008 Adjusted prevalence ratio [95% CIa]1999–2008 Adjusted prevalence ratio [95% CIa]
Maternal age (years)
 <201.0 Reference1.0 Reference1.0 Reference1.0 Reference1.0 Reference
 20–241.0 [0.7, 1.5]0.8 [0.5, 1.4]1.3 [0.7, 2.4]1.5 [0.6, 4.0]0.6 [0.2, 1.7]
 25–290.9 [0.6, 1.5]0.6 [0.4, 1.2]1.2 [0.6, 2.4]1.2 [0.4, 3.5]0.1 [0.02, 0.4]
 30–340.9 [0.5, 1.5]0.7 [0.4, 1.2]1.2 [0.6, 2.6]1.3 [0.4, 3.9]0.1 [0.02, 0.5]
 35–390.9 [0.5, 1.6]0.6 [0.3, 1.1]1.3 [0.6, 2.9]0.8 [0.2, 2.8]0.1 [0.02, 0.9]
 ≥401.4 [0.7, 2.9]1.0 [0.4, 2.4]2.1 [0.8, 5.7]1.7 [0.4, 6.9]-
Paternal age (years)b
 <201.0 Reference1.0 Reference1.0 Reference1.0 Reference1.0 Reference
 20–241.1 [0.6, 1.8]1.1 [0.6, 2.2]0.7 [0.3, 1.5]0.6 [0.2, 1.9]1.0 [0.2, 4.9]
 25–291.3 [0.7, 2.3]1.3 [0.6, 2.7]1.0 [0.4, 2.2]1.0 [0.3, 3.2]2.5 [0.5, 12.5]
 30–341.3 [0.7, 2.4]1.6 [0.7, 3.4]1.0 [0.4, 2.4]1.2 [0.4, 4.3]4.0 [0.7, 21.5]
 35–391.5 [0.8, 2.8]2.0 [0.9, 4.5]1.2 [0.5, 3.0]1.9 [0.5, 6.9]3.7 [0.6, 24.9]
 ≥401.7 [0.9, 3.3]2.3 [1.0, 5.3]1.4 [0.5, 3.4]2.1 [0.6, 8.0]-
Marital status
 Married1.0 Reference1.0 Reference1.0 Reference1.0 Reference1.0 Reference
 Unmarried1.3 [1.0, 1.7]1.4 [1.0, 1.8]1.3 [0.9, 1.8]1.5 [1.0, 2.3]0.7 [0.3, 1.6]
Plurality
 Singleton1.0 Reference1.0 Reference1.0 Reference1.0 Reference1.0 Reference
 Multiple1.6 [1.0, 2.5]1.7 [0.9, 2.9]1.8 [1.0, 3.2]1.6 [0.7, 3.8]2.8 [0.7, 10.5]
Any diabetes
 Yes2.6 [1.9, 3.7]3.1 [2.0, 4.7]2.5 [0.7, 9.5]
 No1.0 Reference1.0 Reference1.0 Reference
Gestational diabetesc
 Yes1.7 [1.0, 2.8]2.0 [1.0, 4.0]
 No1.0 Reference1.0 Reference
Pre-gestational diabetesc
 Yes6.7 [3.7, 12.4]8.7 [3.9, 19.5]
 No1.0 Reference1.0 Reference
Body mass index (kg/m2) c
 Underweight (<18.5)1.1 [0.5, 2.1]1.1 [0.4, 3.1]
 Normal (18.5–24.9)1.0 Reference1.0 Reference
 Overweight (25.0–29.9)1.3 [0.9, 1.8]1.2 [0.8, 2.0]
 Obese (≥30)1.7 [1.2, 2.3]1.5 [0.9, 2.4]

CI, confidence interval

Data were missing for 17.8% of cases for paternal age

Data available for cases delivered in 2005–2008 only