International Journal of Contemporary Pediatrics

Jan M et al. Int J Contemp Pediatr. 2023 Jun;10(6):806-812

http://www.ijpediatrics.com

pISSN 2349-3283 | eISSN 2349-3291

Original Research Article

DOI: https://dx.doi.org/10.18203/2349-3291.ijcp20231482

Extra cardiac birth defects in children with congenital heart anomalies

Muzafar Jan, Parvaiz Rafieq Sohil, Younus Ramzan Khan*, Amber Bashir

Department of Pediatrics, Government Medical College Srinagar, Jammu and Kashmir, India

Received: 28 March 2023

Accepted: 03 May 2023

*Correspondence:

Dr. Younus Ramzan Khan,

E-mail: dr.younusramzan97@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Congenital heart disease (CHD) may be present with a syndrome containing known anomalies with specific physical findings or can be present with manifestations of a systemic defect that affects the heart and other systems. Aim of the study was to determine the prevalence and spectrum of extra-cardiac defects associated with CHD.

Methods: This prospective and observational study was conducted in the age group of 1 day to 12 years with CHD chosen by purposive sampling technique. Informed consent was obtained from parents or guardians. The CHD was diagnosed on the basis of detailed clinical examination, chest X-ray and Electrocardiography and confirmed by 2D echocardiography. The extra-cardiac defects were diagnosed based on standard definitions and various investigations like CBC, LFT, KFT, USG abdomen and skull, CT, MRI, G-Band karyotype, fluorescence in situ hybridization (FISH) studies for micro-deletions, audiometry, ophthalmologic evaluation and thyroid hormone profile.

Results: A total of 61,254 patients were examined during the study and 640 children were identified with CHD. So, the prevalence was 10.14 per 1000 live births. Out 640 children enrolled in the study 352 (55%) were males and 288 (45%) were females with a male female ratio of 1.2:1 and 520 (81.3%) had acyanotic CHD (ACHD) and 120 (18.3%) had cyanotic CHD (CCHD). The majority of the children with CHD belonged to the second birth order 360 (56.2%). The extra-cardiac anomalies were present in 128 (20%) cases. Out of them 77 (12%) cases had extra-cardiac anomalies associated with acyanotic CHD and 51 (8%) cases had extracardiac anomalies associated with cyanotic CHD. Out of 128 cases with extra-cardiac defects 64 (50%) cases were syndromic, 51 (39.8) cases had multiple congenital defects and 13 (10.2%) had laterality defects.

Conclusions: The CHD is often associated with various extra-cardiac abnormalities.

Keywords: CHD, Extra-cardiac defects, Syndrome, Echocardiography

INTRODUCTION

Congenital heart defect (CHD) is the most common congenital malformation among all birth defects leading to morbidity and mortality among children. The burden of CHD is high in developing countries like India, due to the high birth rate and critical nature of CHD requiring expensive surgical and non-surgical interventions. The incidence of moderate to severe structural CHD in live-born infants is 6 to 8 per 1000 live births.1-4 CHD may be present with a syndrome containing known anomalies with specific physical findings or can be present with manifestations of a systemic defect that affects the heart and other systems.5-9 To assess the possible systemic disease or congenital malformations syndromes, all systems of the body are examined. Extra-cardiac abnormalities are found in 20-45% of children with CHDs.10 About 5-10% of patients have known chromosomal abnormalities.11 Extra-cardiac defects are termed as MAJOR if they had medical or surgical significance or serious cosmetic significance and termed as MINOR if there are unusual morphologic features not having any serious medical, surgical, and cosmetic significance. Extra-cardiac defects are divided into three distinct groups: (A). Multiple congenital defects: Multiple congenital defects are defined as those having at least one major or three minor congenital birth defects or malformations that cannot be explained by an underlying syndrome or sequence.12 (B) Syndromes: It is group of signs and symptoms that occur together and characterize a particular abnormality or condition. Those with chromosomal anomalies, single gene defects, or teratogenic syndromes are counted among syndromes for example CATCH 22 syndrome, Williams Beurn, Down, Turer, Noonan, Holtoram, Alagille etc.10,13 (C). Laterality defects; These are also known as embryonic left-right axis patterning or malposition complexes. They include a spectrum of disorders that range in increasing severity from isolated dextrocardia or situs inversus to situs inversus total is or heterotaxy.9,13-17 Thus, recognition of CHD in the newborn is important as this group of abnormalities constitutes a significant proportion of congenital malformations that present in neonatal life, and their early detection is important for appropriate management, and short-term follow up for decision-making regarding a referral or waiting.18-21 The main aim of our study was to determine the various extra-cardiac defects associated with CHD’s.

METHODS

This prospective and observational study was conducted in the age group of 1 day to 12 years with CHD chosen by purposive sampling technique in the post graduate department of pediatrics, GB pant children hospital government medical college Srinagar (GMC) over a period of two years between October-2020 to October-2022. Our study was approved by the ethical committee of GMC Srinagar via communication no. F (Min-BOPGS) Acad/KU/22 02-02-2022 held on 29 and 30th September, 2021 under serial number 15. The children with CHDs included as study population after Informed consent obtained from parents or guardians. CHDs was diagnosed on basis of detailed clinical examination, chest X-ray and Electrocardiography and confirmed by 2D Echocardiography. Extra-cardiac defects were diagnosed based on standard definitions and various investigations like CBC, LFT, KFT, USG abdomen and skull, CT, MRI, G-Band karyotype, fluorescence in situ hybridization (FISH) studies for micro-deletions, audiometry, ophthalmologic evaluation and thyroid hormone profile.

Inclusion criteria

Children (age 1 day to 12 years) with CHD with and without extra-cardiac defects were included in study.

Exclusion criteria

Patients with patent ductus arteriosus in preterm neonates, bicuspid aortic valve and patent foramen ovale were excluded.

Statistical analysis

Data was entered in a Microsoft excel spreadsheet and analyzed using SPSS version 22 software. Categorical variables were summarized as frequency and percentage. Continuous variables were summarized as mean and SD.

RESULTS

A total of 61,254 patients were examined during the study. Out of that, 640 children were identified with CHD. So, the prevalence was 10.14 per 1000 live births. A total of 640 children with CHD who satisfied the inclusion criteria were enrolled in this study. Out of them 352 (55%) were males and 288 (45%) were females with a male female ratio of 1.2:1. In this study, 472 (73.8%) belonged to age group <6 years, out of them 260 (55.1%) were male and 212 (44.9%) were female and 168 (26.2%) belonged to age group > 6 years, out of them 92 (54.8%) were males and 76 (45.2%) were females as depicted in table no.1. In this study, the majority of the children with CHD belonged to the second birth order 360 (56.2%) whereas 200 (31.2%) and 80 (12.5%) cases belonged to first and third birth order respectively. In this study only 40 (6.2%) were preterm (<37 weeks) and 600 (93.8%) were term (>37weeks) and 112 (17.5%) children were low birth weight and 528 (82.5%) had normal birth weight. Out of the 640 children enrolled with CHD, 520 (81.3%) had ACHD and 120 (18.3%) had CCHD. In ACHD group, 226 (35%) had VSD, 192 (30%) had ASD, 64 (10%) had PDA and 40 (6.3%) had other heart disease. In CCHD group, 42 (6.5 %) had d-TGA, 32 (5.0%) had TOF and 14 (2.3 %) had TAPVC and 48 (5%) had other heart disease. In this study out of 640 only 8 (1.2%) children had a history of CHD (ASD and VSD) in their family member maternal or paternal side and consanguinity had seen in 132 (20.6%) cases. In this study, 6.2% of the mothers were below 19 years of age, 92.5% belonged to 19-35 years of age and 1.2% were above 35 years of age at the time of conception. In this study, the majority of the children 560 (87.4%) with CHD belonged to the lower class with Upper lower class 424 (66.2%) and lower class 136 (21.2%) respectively.

Table 1: Age and gender distribution of study population.
Table reproduced from source PDF page 2

In our study extra-cardiac anomalies were present in 128 (20%) cases where as 512 (80%) cases had no extra-cardiac anomalies. Out of them 77 (12%) cases had extra-cardiac anomalies associated with acyanotic CHD and 51 (8%) cases had extra-cardiac anomalies associated with cyanotic CHD as depicted in Table 2. Out of 128 cases with extra-cardiac defects 64 (50%) cases were syndromic, 51 (39.8) cases had multiple congenital defects and 13 (10.2%) had laterality defects. The various syndromes associated with CHD in our study (Table 3).

Table 2: Type of CHD and associated extra-cardiac anomalies.
Table reproduced from source PDF page 3
Table 3: Distribution of syndromes in CHD'S, (n=64).
Table reproduced from source PDF page 3
Figure 1: Patient with downs syndrome and echo documented nonrestrictive inlet VSD and karyotyping showing Trisomy 21, 47XY.
Figure 1: Patient with downs syndrome and echo documented nonrestrictive inlet VSD and karyotyping showing Trisomy 21, 47XY.
Figure 2: Patient with Edward syndrome having clenched hand, overlapping fingers, rocker bottom feet and echo documented Peri-membranous VSD and TOF.
Figure 2: Patient with Edward syndrome having clenched hand, overlapping fingers, rocker bottom feet and echo documented Peri-membranous VSD and TOF.

In laterality defects 7 (53.8%) had right sided isomerism and 6 (46.2%) had left sided isomerism. Asplenia was present in 7 cases while interrupted inferior vena cava with polysplenia was seen in 6 cases. In multiple congenital defects musculoskeletal defects were commonest associated defect seen in 22 patients [43.1%]. The other systems affected were gastrointestinal system in 9 (17.6%) cases, genitourinary system in 7 (13.7%) cases, respiratory system in 4 (7.8%) cases, central nervous system in 3 (5.9%) cases and other systems in 6 (11.7%) cases as depicted in Table 4.

Table 4: Various extracardiac anomalies in CHD.
Table reproduced from source PDF page 3

Among musculoskeletal defects 8 had club foot, 7 had cleft lip with cleft palate, 5 had polydactyly and syndactyly, 4 had eye and ear deformities, 3 had congenital dysplasia of hip, 3 had choanal atresia, 3 had ankyloglossia, 2 had scoliosis and 2 had arthrogryposis. Among gastrointestinal anomalies 3 had hernia (inguinal and umbilical), 2 had congenital hypertrophic pyloric stenosis, 1 had duodenal atresia, 1 had biliary atresia and 1 had malrotation of gut. Among genitourinary anomalies 3 had cryptorchidism, 2 had hypospadias, 2 had posterior urethral value and 1 had polycystic kidney disease. Among respiratory anomalies 2 had laryngomalacia, 1 had trachea-esophageal fistula and 1 had diaphragmatic hernia. Among CNS anomalies 2 had neural tube defects, 1 had hydrocephalus and corpus callosum agenesis.

Figure 3: Patient with cleft lip and palate with echo documented 7 mm ASD and 2.5 mm PDA.
Figure 3: Patient with cleft lip and palate with echo documented 7 mm ASD and 2.5 mm PDA.
Figure 4: Patient with polydactyly and CTEV with echo documented inlet VSD with perimembranous extrusion.
Figure 4: Patient with polydactyly and CTEV with echo documented inlet VSD with perimembranous extrusion.
Figure 5: Patient with arthrogryposis with echo documented large inlet VSD and ASD.
Figure 5: Patient with arthrogryposis with echo documented large inlet VSD and ASD.
Figure 6: Patient with congenital diaphragmatic hernia and echo documented bicuspid aortic valve, mild aortic stenosis with tortuous arch.
Figure 6: Patient with congenital diaphragmatic hernia and echo documented bicuspid aortic valve, mild aortic stenosis with tortuous arch.

DISCUSSION

CHD is the most common congenital malformation among all birth defects leading to morbidity and mortality among children. The burden of CHD is high in developing countries like India, due to the high birth rate and critical nature of CHD requiring expensive surgical and non-surgical interventions. The estimated prevalence of 8 per 1000 live births is accepted as the best approximation.22 Available Indian studies had reported a wide variation in the prevalence of CHD from 2.25 to 26 per 1000 live births.23-25 A recent systemic review also reported a higher prevalence in Asia due to a high birth rate and consanguinity, especially in Iran and India. In this study, the prevalence is 10.14 per 1000 live births. This may be high by being the largest referral center in Kashmir, availability of better diagnostic modalities, improved survival of premature infants, and high birth rate.

In this study, out of 640 cases 352 (55%) were male and 288 (45%) were female children with a male female ratio of 1.2:1. In a study by Begum et al, Singh et al, male to female ratio was found to be 0.9:1 and 1.1:1 respectively, and a study by Vaidyanathan et al and Tandan et al observed male to female ratio of 1:1 and 0.8:1.26-29 Out of the 640 children enrolled with CHD, the majority 520 (81.3%) had ACHD and 120 (18.7%) had CCHD. The majority had VSD (35%) followed by ASD in (30%) and PDA in (10%) which was in accordance with similar studies by Smitha et al who reported (40.7%) had VSD, (19.06%) had ASD and (9.53%) had PDA.30 In this present study, the majority of the children with congenital heart disease belonged to the lower (87.4%) class with Upper lower class (66.2%) and lower class (21.2%) according to modified Kuppusamy Socio-Economic Scale. A study by Agha et al and Tandon et al also reported a high prevalence of CHD in children belonging to low socio-economic status. In this study out of 640 only 8 (1.2%) children had a history of congenital heart disease (ASD and VSD) in their family member maternal or paternal side.29,31 According to Nelson textbook of pediatrics, the risk of occurrence increases if a 1st degree relative (parent/sibling) is affected in (2-6%) whereas when two first degree relatives are affected with CHD, the risk of subsequent child may reach to 20-30%.32

In this study, 6.2% of the mothers were below 19 years, 92.5% belonged to 19-35 years and 1.2% were above 35 years at the time of conception. Similarly Best et al reported that advanced maternal age is not a risk factor for CHD however there was a marginal risk of infants developing certain types of CHD among mothers aged more than 35 years.33 Our results were also supported by Miller et al who also observed that infants born to mothers older than 35 years of age seemed to be at 20% increased risk of CHDs, while infants born to younger mothers tended to be at decreased risk of CHDs.13 In the present study, consanguinity was noted in 20% of cases. Similarly Gnanalingam et al also observed that parental consanguinity was noted in 12.5% of the control group compared to 31.1% of the CHD group.34 In our study extra-cardiac anomalies were present in 128 cases [20.0%] which was in accordance with retrospective study done by Pradat et al who observed the data of children with major CHD in Sweden, and found extra-cardiac malformation was identified in 25.7% of patients after excluding 15% of the children with chromosomal anomalies.35 Similarly Bosi et al retrospectively evaluated CHD in Italy and found 24% of these patients had extra-cardiac malformations.36 Similarly study done by Abdullah et al in Saudi Arabia reported 28.5% incidence of extra-cardiac anomalies.37

In our study out of 128 cases with extra-cardiac defects 64 (50%) were syndromic, 51 (39.8) cases had multiple congenital defects and 13 (10.2%) had laterality defects. Laterality defects were the least common found only in 13 cases of which 7 cases were right isomerism and 6 cases were left isomerism. 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.48 Similarly Tennstedt et al conducted a necropsy study in 815 fetuses and found 85 (66%) had extracardiac birth defects with central nervous system birth defects being the most frequent.38 Gucer et al conducted autopsies in 305 children with CHDs and reported 140 (46%) had extracardiac birth defects with craniofacial birth defects being the most frequent.39 In all these studies the multiple congenital defects were more than syndromes. Downs syndrome was the commonest syndrome associated with CHD in our study occurring in 35 cases comprising 54.7%. The prevalence of congenital heart disease in downs syndrome was similar to the findings from other studies, which have been between 44% and 62%.40 The study done by Greenwood et al found that 137 of 1566 infants (8.8%) had congenital heart disease associated skeletal abnormalities.41 Similarly Wallgren et al found such an association in 161 out of 1000 children with congenital heart disease (16.1%), with an excess of tetralogy of Fallot (27% of affected infants).42 In our Study Among musculoskeletal anomalies, the most common was club foot (8 cases), followed by cleft lip with or without cleft palate (7 cases) followed by polydactyly and syndactyly (5 cases). In our study out of 640 patients with CHD 7 (13.7%) had genitourinary anomalies which was similar to study done by Wallgren et al who reported out of 1000 patients with CHD 131 (13.1%) had genitourinary anomalies, out of these 131 patients, 30 (23%) had hydronephrosis, 24 (18%) had renal agenesis, 15 (11%) had horseshoe kidney, 28 (21%) had genital malformations, and 56 (43%) had other anomalies.48 In our study 9 (17.6%) cases had gastrointestinal anomalies, among them 3 had hernia (inguinal and umbilical), 2 had congenital hypertrophic pyloric stenosis, 1 had duodenal atresia, 1 had biliary atresia and 1 had malrotation of gut. Similarly study by Touloukiarr reported that four of five infants with both trisomy 21 and duodenal atresia had malformations of the atrioventricular septum.43 Fonkalsrud et al noted that 17% of infants with duodenal obstruction had coexisting congenital heart disease. On the other hand, congenital heart disease is only found in 5.2% of infants with jejunal or ileal atresia.44,45 This difference may result from the varying causes of the lesions. Similarly, Gallo et al found 14 cases of esophageal atresia in 1354 cases of congenital heart disease (1.0%) but also did not report the frequency of trachea-esophageal fistula.46 In our study CNS lesions were present in 3 (5.9%), out of them 2 had neural tube defects and 1 had hydrocephalus plus corpus callosum agenesis. Similarly, Greenwood et al found central nervous system abnormalities in 6.9% of 1566 infants with congenital heart disease, while Gallo et al reported an association in 3.2% of 1354 cases.41,46 Wallgren et al in a study of 1000 children with congenital heart disease in a combination of clinical and autopsy findings, reported that 6% had associated central nervous system malformations.42 Of the 60 affected infants, 22 had unspecified brain anomalies, 17 had hydrocephalus, 12 had a meningomyelocele, and 17 had abnormalities of the sensory organs (eyes or ears). No specific pattern of relationships was found between the types of congenital heart disease and central nervous system abnormalities.

Limitations

The main limitation of the study was we could not establish the exact incidence of congenital heart disease with or without extra-cardiac defects as our study didn’t include all live births, fetal deaths and abortions and we couldn’t do autopsy studies in children with CHD who died at our institute.

CONCLUSION

The prevalence of CHD in our study was 10.14% per 1000 live births. Out of 128 cases with extra-cardiac anomalies, majority were syndromic in 64 cases followed by multiple congenital defects in 51 cases and laterality defects in 13 cases. Musculoskeletal defects were commonest associated defects seen in 23 cases. The 54.7% of down syndrome cases were associated with CHD and the most common cardiac lesion was atrioventricular septal defect. The pediatrician must be well aware of association between congenital cardiac diseae and chromosomal abnormalities to facilitate early surgical treatment of defects, early intervention for developmental delay and genetic counseling for offspring.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

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