Indian Pediatr 2014;51: 389-391
Extracardiac Birth Defects in Children with
Congenital Heart Defects
Sunil Karande, Varsha Patil, Archana Kher and Mamta
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.
Received: September 24, 2013;
Initial review: December 09, 2013;
Accepted: March 03, 2014.
Objective: To assess the proportion and pattern of extracardiac
birth defects in children with congenital heart defects referred to
a tertiary care institute.
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
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
. They account for approximately one third of all congenital
anomalies, and are the single largest contributor to infant mortality
attributable to birth defects . 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
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 . ‘Minor’ defects were defined as
unusual morphologic features not having any serious medical, surgical or
cosmetic significance .
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 . 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
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
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
defects n (%)
defects n (%)
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.  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 . Tennstedt, et al.  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.  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
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