Home            Past Issues            About IP            About IAP           Author Information            Subscription            Advertisement              Search  

Research brief

Indian Pediatr 2014;51: 389-391

Extracardiac Birth Defects in Children with Congenital Heart Defects


Sunil Karande, Varsha Patil, Archana Kher and Mamta Muranjan

From Genetic Clinic, Department of Pediatrics, Seth GS Medical College and KEM Hospital, Parel, Mumbai, India.

Correspondence to: Dr Sunil Karande, Professor, Department of Pediatrics, Seth GS Medical College and KEM Hospital, Parel, Mumbai 400 012, India.
Email: karandesunil@yahoo.com

Received: September 24, 2013;
Initial review: December 09, 2013;
Accepted: March 03, 2014.

To assess the proportion and pattern of extracardiac birth defects in children with congenital heart defects referred to a tertiary care institute.

Methods: Cross-sectional observational study from January 2010 to June 2011.

Results: Out of 560 children with congenital heart defects, 98 (17.5%) had extracardiac birth defects. Fifty-six had multiple congenital defects; 36 were syndromic cases and 6 had laterality defects. A total of 386 extracardiac birth defects (103 major and 283 minor) were documented, with craniofacial and skeletal birth defects being the commonest.

Conclusion: Extracardiac birth defects are common in children with congenital heart defects.

Keywords: Congenital heart disease, Craniofacial abnormalities, Syndrome.

Congenital heart defects (CHDs) are a common variety of birth defects, with an overall prevalence of 8.1/1000 births [1]. They account for approximately one third of all congenital anomalies, and are the single largest contributor to infant mortality attributable to birth defects [2]. Clinical studies have reported that up to 30% of children with CHDs may have additional extracardiac birth defects that may further add to the morbidity and mortality [3,4]. Data regarding proportion and pattern of these defects in Indian children with CHDs are scarce. We planned this study to assess the proportion and profile of extracardiac birth defects in children with CHDs to referred to a tertiary care hospital in Mumbai, India.


This cross-sectional observational study was conducted at a tertiary care institute in Mumbai after approval from its Institutional Ethics Committee. The study was conducted over a period of 18 months (from January 2010 to June 2011). Children (age 1 day to 12 years) with CHDs from pediatric outpatient department, genetic clinic, pediatric wards, pediatric and neonatal intensive care units; and cardiology and cardiovascular and thoracic surgery outpatient departments and wards), both symptomatic and those incidentally detected, were examined for extracardiac defects . The CHDs were diagnosed on basis of detailed clinical examination, chest X-ray, and electrocardiography (ECG); and confirmed by 2D-echocardiography or cardiac catheterization.

The extracardiac defects were diagnosed based on standard definitions [5-11]. Wherever indicated, further investigations like ultrasound (abdomen/skull), computed tomography (CT), audiometry, ophthalmologic evaluation and thyroid hormone profile were done. G-banded karyotype and fluorescence in situ hybridization (FISH) studies (for microdeletions) were performed whenever indicated. Defects were termed as ‘major’ if they had medical or surgical significance, or serious cosmetic significance [6]. ‘Minor’ defects were defined as unusual morphologic features not having any serious medical, surgical or cosmetic significance [6].

Only patients with CHDs having associated extracardiac defects were included as study population and were classified into three distinct groups: (i) multiple congenital defects (MCDs), (ii) syndromes, and (iii) laterality defects. MCDs comprised those having at least one major or three minor extracardiac congenital birth defects [6,12]; were further classified into: (a) those having an unrecognized pattern, and (b) those having a recognized pattern of unknown etiology [12]. Those with chromosomal anomalies, single-gene defects or teratogenic syndromes were counted among syndromes [6,13]. Children having laterality defects (e.g., heterotaxy syndromes) were grouped separately [6,13]. The extracardiac defects documented in this study were also grouped into organ systems [14,15].


Out of a total 560 children diagnosed with CHDs during the study period, 98 (17.5%) (52 boys) had associated extracardiac birth defects. The mean (SD) ages at time of diagnosis of CHD and at time of enrolment were 6.5 (16.9) months and 24.2 (34) months, respectively. Thirteen (13.3%) patients were born of a third-degree consanguineous marriage; 33 (33.7%) had global developmental delay.

Sixty-four children had acyanotic CHD and 34 had cyanotic CHD (Table I). In the acyanotic CHD, 14 had ventricular septal defect, 11 had atrial septal defect and 10 had patent ductus arteriosus. In the cyanotic CHD group, tetralogy of Fallot was the commonest defect (n=23). Table I presents the profile of extracardiac defects in study children. Patients with ‘MCDs with unrecognized patterns’ formed the largest group of cases. All six patients of ‘MCDs with recognized pattern of unknown etiology’ had VACTERL association. The 36 ‘syndromic cases’ included Down syndrome (n=25), velocardiofacial syndrome (n=3); Noonan syndrome, CHARGE syndrome, Lenz microphthalmia syndrome, CCGE (cleft palate, cardiac defect, genital anomalies, and ectrodactyly) syndrome, achondroplasia and congenital rubella syndrome (1 each); and two children with undefined syndromes with abnormal karyotype patterns. Among the six children with laterality defects, 5 had situs inversus (without polysplenia/asplenia) and one had heterotaxia (asplenia syndrome).

TABLE I	Profile of Extracardiac Birth Defects in Children with Congenital  Heart Defects 
Congenital Multiple congenital Syndromic Laterality
heart defect defects n (%)  n (%) defects n (%)
Unrecognized Recognized
pattern pattern
Acyanotic 29 (29.6) 3 (3.1) 28 (28.6) 3 (3.1)
Cyanotic 21 (21.4) 3 (3.1) 8 (8.2) 3 (3.1)

A total of 386 extracardiac birth defects (103 major and 283 minor) were documented (Web Table I).


In the present study, almost one-fifth of children with CHDs had associated extracardiac birth defects. Majority belonged to MCDs group, and craniofacial birth defects were the most frequent. Miller, et al. [13] conducted a population based surveillance study of 7984 live-born and stillborn infants and fetuses with CHDs: 1080 (13.5%) had multiple, 1048 (13.1%) had syndromic and 161 (2.0%) had laterality defects [13]. Tennstedt, et al. [14] conducted a necropsy study in 815 fetuses; 85 (66%) had extracardiac birth defects with central nervous system birth defects being the most frequent. Gucer, et al. [15] conducted autopsies in 305 children with CHDs; 140 (46%) had extracardiac birth defects with craniofacial birth defects being the most frequent.

The present study had some potential limitations. The study was based on convenience sampling, and was conducted in a tertiary care hospital setting wherein most of the patients were referred cases. Moreover, we could not do autopsy studies in children with CHDs who died at our institute. Due to financial constraints, small structural cytogenetic abnormalities and single-gene mutations might have remained undiagnosed, resulting in the inadvertent inclusion of some genetically determined cases in the MCDs group.

The treating pediatrician needs to be aware that extracardiac birth defects are common in children with congenital heart defects. Identification of extracardiac birth defects may have implications for clinical practice (such as surgical management of associated anomalies), early intervention therapy for developmental delay, and genetic counseling for future pregnancies.

Contributors: SK: conceptualized the study, monitored data collection, wrote the manuscript and will act as the guarantor of the paper. VP: collected and analyzed the data, literature review and writing of manuscript. AK: conceived the study and revised the manuscript. MM: revised the manuscript for important intellectual content. The final manuscript was approved by all authors.

Funding: None; Competing interests: None stated.


1. National Birth Defects Prevention Network. Guidelines for Conducting Birth Defects Surveillance. Atlanta, GA: National Birth Defects Prevention Network, Inc; 2004.

2. Reller MD, Strickland MJ, Riehle-Colarusso T, Mahle WT, Correa A. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr. 2008;153:807-13.

3. Copeland GE, Kirby RS. Using birth defects registry data to evaluate infant and childhood mortality associated with birth defects: an alternative to traditional mortality assessment using underlying cause of death statistics. Birth Defects Res A Clin Mol Teratol. 2007;79:792-7.

4. Kramer HH, Majewski F, Trampisch HJ, Rammos S, Bourgeois M. Malformation patterns in children with congenital heart disease. Am J Dis Child. 1987;141:789-95.

5. Hoffman JI, Christianson R. Congenital heart disease in a cohort of 19,502 births with long-term follow-up. Am J Cardiol. 1978;42:641-7.

6. Rasmussen SA, Olney RS, Holmes LB, Lin AE, Keppler-Noreuil KM, Moore CA. Guidelines for Case Classification for the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol. 2003;67:193-201.

7. Allanson JE, Cunniff C, Hoyme HE, McGaughran J, Muenke M, Neri G. Elements of morphology: standard terminology for the head and face. Am J Med Genet. 2009;149A:6-28.

8. Hall BD, Graham JM Jr, Cassidy SB, Opitz JM. Elements of morphology: standard terminology for the periorbital region. Am J Med Genet. 2009;149A:29-39.

9. Hunter A, Frias JL, Gillessen-Kaesbach G, Hughes H, Jones KL, Wilson L. Elements of morphology: standard terminology for the ear. Am J Med Genet. 2009;149A:40-60.

10. Carey JC, Cohen MM Jr, Curry CJ, Devriendt K, Holmes LB, Verloes A. Elements of morphology: standard terminology for the lips, mouth, and oral region. Am J Med Genet A. 2009;149A:77-92.

11. Biesecker LG, Aase JM, Clericuzio C, Gurrieri F, Temple IK, Toriello H. Elements of morphology: standard terminology for the hands and feet. Am J Med Genet A. 2009;149A:93-127.

12. Jones KL. Smith’s Recognizable Patterns of Human Malformation, 6th ed. Philadelphia, PA: Elsevier Saunders; 2006.

13. Miller A, Riehle-Colarusso T, Alverson CJ, Frías JL, Correa A. Congenital heart defects and major structural noncardiac anomalies, Atlanta, Georgia, 1968 to 2005. J Pediatr. 2011;159:70-8.

14. Tennstedt C, Chaoui R, Korner H, Dietel M. Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: Results of a seven year necropsy study. Heart. 1999;82:34-9.

15. Gucer S, Ince T, Kale G, Akcoren Z, Ozkutlu S, Talim B, et al. Noncardiac malformations in congenital heart disease: a retrospective analysis of 305 pediatric autopsies. Turk J Pediatr. 2005;47:159-66.


Copyright © 1999-2014  Indian Pediatrics/font>