Prevalence of congenital heart disease among patients with down syndrome in Southwestern Saudi Arabia.

Background: There is a paucity of data on the prevalence and pattern of congenital heart disease (CHD) among patients with Down syndrome (DS) in Bisha, Saudi Arabia. The aim of the study was to determine the prevalence and patterns of CHD in patients with DS and explore the association of participants' sex with CHD in DS patients. Methodology: A total of 42 patients with confirmed DS were enrolled in the study. Relevant data were obtained from the patients' records. The spectrum of CHD was analyzed and classified accordingly. Pearson's Chi-square was used to determine the association of gender with CHD.
Results: Approximately 81% of the study participants had CHD. The most common CHD was atrial septal defect (28.5%), followed by ventricular septal defect (25%), patent ductus arteriosus (16%), and atrioventricular septal defect (14.3%). No significant association was found between CHDs and sex.
Conclusion: The prevalence of CHD in the study group was consistent with reports from other regions of Saudi Arabia and globally. Participants' sex was not associated with the occurrence of CHD in DS patients in this study.

INTRODUCTION

Down syndrome (DS) is a genetic disorder characterized by mental disability, developmental delay, characteristic facial appearance, congenital malformations, and hypotonia at infancy.[12] The prevalence of DS varies among the populations, which could be due to differences in maternal age, ethnicity, and parental consanguinity.[34] The incidence of DS in Saudi Arabia is estimated at 1 in 554 live births.[5] The probability of having a child with DS increases with maternal age and hence that by the age of 42 years, the chance is 1 in 60 and by the age of 49 years, it is 1 in 12.[6]

Congenital heart disease (CHD), such as hypoplastic left heart and heterotaxy syndrome, are among the leading causes of death in patients with DS.[789] The association of DS with CHD has been well documented in the literature. In the last few decades, the frequency of CHD among persons DS was reported to be approximately 20%, but in recent years, the frequency has increased by more than two-fold, to approximately 50%. This increase could be due to improvement in diagnostic tools and in the clinical care of these patients.[10] Improved management of CHD has contributed significantly to an increase in life expectancy for patients with DS from 30 years to 60 years within the past four decades.[11] Atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), and atrioventricular septal defect (AVSD) are the most common congenital heart defects associated with DS.[121314] These heart defects have serious consequences on the health and survival of affected persons. It is, therefore, important that persons with DS undergo cardiac evaluation as early as possible, especially since the outcomes in patients with the same cardiac defects after primary reconstructive surgery were similar between patients with and without DS.[15]

The frequency and pattern of CHD in DS differs between populations. There are few published studies on CHD and DS in Saudi Arabia. These studies showed a frequency of CHD in Saudi Arabia, ranging from 35% to 86%, with different patterns of CHD.[161718] No data, however, have been reported on the frequency of CHD on DS patients from Bisha, Southwestern Saudi Arabia, hence the need for this study. The aims of this study were to: (1) Assess the prevalence and pattern of CHD among persons with DS in Bisha, Saudi Arabia, and to compare the findings with other national and international data; (2) Explore the association of sex with CHD among persons with DS in Bisha, Saudi Arabia.

METHODOLOGY

Study area

This study was conducted in Bisha, southwestern Saudi Arabia.

Study design

This is a cross-sectional study.

Inclusion criteria

All children and adolescents (aged 1 month–15 years) genetically confirmed as having DS registered from 2016 to 2019.

Exclusion criteria

DS patients not confirmed genetically (whose karyotyping was not available) were excluded from the study.

Screening (echocardiography)

Confirmation of DS in suspected cases was performed in an accredited laboratory in Saudi Arabia using cytogenetic analysis (trypsin-Giemsa banding technique). All the confirmed children and adolescents with DS underwent echocardiography, chest X-ray, and electrocardiogram (ECG) during screening. Other indications for CHD screening include one or more of the following symptoms; heart murmurs, signs of heart failure or cyanosis, abnormal chest radiograph, or ECG abnormality.

The presence of CHD was confirmed using echocardiography approach by a trained pediatric cardiologist. The echocardiography examination was carried out using M-mode, colored two-dimensional (2D) pulse, and continuous-wave Doppler echocardiogram. Two-dimensional echocardiographic pictures were recorded in the standard parasternal long-axis, short-axis, apical four chamber, subcostal, and suprasternal views. Diagnosis, severity, and classification of the CHD were determined based on the American Society of Echocardiography guidelines.[1920]

Ethical approval

Permission to conduct the research was obtained from the Research and Ethics Committee of the College of Medicine, University of Bisha where the research was conducted. Informed consent from the patients was not required, as only secondary data were used, and no identifying information of any participant was disclosed.

Data management and statistical analysis

Hospital charts of eligible participants were reviewed by a pediatrician who was familiar with medical records of the study group and an experienced researcher conversant with data management. The prevalence of CHD was recorded using a structured instrument (with Cronbach alpha value of 0.87), which included age, sex, clinical features, echocardiographic findings, congenital heart defects, and other congenital malformations. The data were computed by a statistician by calculating the proportion of all eligible patients with echocardiographic findings suggestive of CHD. Pearson's Chi-square was used to determine the association of sex with CHD. The level of statistical significance was set at 5%.

RESULTS

We found a total of 42 (19 males and 23 females) confirmed DS cases, age range 1 month–15 years (median: 2.0). Of this number, a total of 34 participants (81%) had CHD [Table 1]. Of the participants who presented with CHD, 58.8% were female.

Table 1

Prevalence of congenital heart disease among patients with Down syndrome in Bisha, Saudi Arabia (n=42)

	Frequency (%)
Presence of CHD	34 (81.0)
Absence	8 (19.0)
Total	42 (100)

CHD=Congenital heart disease

Five major types of CHD were observed, which occurred either in isolation or in association with other CHD. The most frequent was ASD (28.5%), followed by VSD (25%) [Table 2].

Table 2

Major types of congenital heart disease in patients with Down syndrome in Bisha, Saudi Arabia

CHD	Frequency (%)
ASD	16 (28.5)
VSD	14 (25)
AVSD	8 (14.3)
PDA	9 (16)
TOF	3 (5.4)
Other CHD	6 (10.8)
Total	56 (100)

CHD=Congenital heart disease, ASD=Atrial septal defect, VSD=Ventricular septal defect, AVSD=Atrioventricular septal defect, PDA=Patent ductus arteriosus, TOF=Tetralogy of fallot

Table 3 shows the association of CHD and sex among patients with DS in Bisha. The most frequent CHD types were ASDs and VSD, with higher frequency in females. The least common type was the tetralogy of Fallot, which was observed only among males. Tetralogy of Fallot and patent foramen ovale occurred more frequently in females. However, the overall association of CHD type and sex was not statistically significant.

Table 3

Association of congenital heart disease with gender among patients with Down syndrome in Bisha Saudi Arabia

CHD	Gender		Total
	Male (EF)	Female (EF)
ASD	7 (8.31)	11 (9.69)	18
AVSD	1 (0.46)	4 (2.34)	5
PDA	3 (2.31)	2 (2.69)	5
TOF	0 (0.92)	2 (1.08)	2
VSD	2 (2.31)	3 (2.69)	5
Absence of CHD	5 (3.69)	3 (4.31)	8

Pearson χ2=4.59, df=5, P=0.469. CHD=Congenital heart disease, ASD=Atrial septal defect, AVSD=Atrioventricular septal defect, PDA=Patent ductus arteriosus, TOF=Tetralogy of fallot, VSD=Ventricular septal defect, EF=Expected frequency

DISCUSSION

CHD, respiratory tract infections, and leukemia are the leading cause of death in DS patients.[2122] While CHD has been reported to cause most deaths in early childhood among patients with DS, respiratory infection has been attributed to be the cause of deaths in both children and adults with DS.[11] Compared to other regions in Saudi Arabia, the percentage of CHD among people with DS in our study (81%) was higher than reports from Riyadh (49%), Al-Madina (58.6%), and Asir (61.3%), but similar to reports from Albaha (83.3%) and Jeddah (86.8%).[910] The similarity with other parts of Saudi Arabia could be due to common cultural practices dietary intake and or genetic factors linked to consanguineous marriage, which is prevalent across the country.

The percentage CHD in the present study was 81% compared to Oman 60%, Sudan 41%, Morocco 100%, Libya 45%, Nigeria 78%, Malaysia 49.3%, Sweden 54%, France 64.3%, Japan 50.5%, and Ohio 38%.[2324252627] When compared with the above countries, the percentage of CHD among people with DS in our study was a little higher, with the exception of Morocco. The average global prevalence of CHD in people with DS was around 50%. The difference could be due to genetic factors linked to consanguineous marriage, which is common in Saudi Arabia or due to advancing maternal age. In other countries such as India, Pakistan, and Morocco, the practice of consanguineous marriages has been shown to range between 20% and 50%. In parts of India, while in Saudi Arabia it is higher.[28]

ASD, VSD, PDA, and AVSD were the most common congenital heart defects in patients with DS. In the present study, ASD had the highest frequency of 28.5%, followed by VSD (25%) and PDA (16%). In Albaha and Almadina, for example, AVSD had the highest frequency, while VSD was the most common CHD in Abha and Riyadh, with PDA being the most common congenital heart defect in Jeddah. This finding shows a regional variation in the prevalence of CHD within Saudi Arabia, which may be due to differences in geographical features of different parts of Saudi Arabia. Some parts like Abha are high altitude, as high as 2200 meters above sea level, while others like Dammam are only about 10 m above sea level. Since effective oxygen percentage decreases with an increase in altitude, the difference in altitude levels coupled with other factors, may cause variation in the oxygen saturation of pregnant mothers of regions at different altitudes. In the high-altitude areas, this may predispose to intrauterine hypoxia, which may, in turn, lead to CHD in the unborn child.

When compared with results from other countries, ASD had the highest frequency in Oman (33.3%), Libya (23%), Korea 30.6%, and the current study in Bisha, Saudi Arabia (28.5%). Our finding of 28.5% lies within the range of what obtained in these countries. Other similar VSD prevalence findings were seen in Malaysia (20%), Sweden (22.1%), France (22%), and the United States (35% in Ohio).[29303132]

AVSD was highest in seven countries; Egypt (2.7%), Oman (27.7%), Kashmir (14%), Japan (7%), France (30%), Atlanta (USA) (45%), and Guatemala (9.5%).[83334] The AVSD value obtained in the present study was within the range of what was obtained from studies in the above countries.

In the case of PDA, our findings show that 14.7% of patients with DS had PDA, making it the third most prevalent CHD in our study. This was consistent with reports from other countries, such as Morocco (16.7%), Japan (12%), and South Korea (17.5%), but lower than findings from Guatemala, which had a prevalence of PDA of 28.5%.[825343536] In comparison with our findings, of the common CHD reported in patients with DS, the frequency of VSD was highest in Kashmir (India) (24%), Japan (33.3), Malaysia (20%) and Ohio (USA) (32.4%). Our study identified ASD as having the highest frequency in DS patients. This finding is similar to reports from Oman, Libya, and Korea. The similarity of the result of the present study with Oman where ASD had the highest frequency may be due to the geographical proximity of Oman to Saudi Arabia, with a higher probability of population admixture from migration or intermarriage between the people of the two countries.

We found no statistically significant correlation between the reported CHDs and sex.

We recommend further research to explore reasons for variations in the presentation of CHD in persons with DS that may guide the development of measures to reduce the incidence of CHD in DS and enable the early detection of CHD in persons with DS. Health-care providers, families, and the community should cooperate to give more support to persons with DS to enable these individuals to achieve their goals.

Limitations of the study

This study has limitations. First, we had a relatively small sample size, which increases the likelihood of a type 2 error in our assessment of the association between participants’ sex and CHD in DS. Second, our findings are based on secondary data analysis. We were, therefore, constrained by the range of data variables that were available. Relevant information, such as household income, dietary intake, pregnancy history, was not available. Finally, the cross-sectional nature of our study design limits causal inferences.

Strength of the study

While most of the previous studies focused attention on the clinical diagnosis of DS and others on the genetic aspects, our study combined both clinical diagnosis and genetic confirmation of the status of the participants, improving the validity of our diagnosis. In addition, we were able to highlight the screening (using echocardiography approach) carried out on the patients for the diagnosis and severity of CHD. The study also provides insight into the possible role of geographic locations such as altitude on the occurrence of CHD in persons with DS, which has not been reported previously.

CONCLUSION

Consistent with reports from other parts of the world, we found that the most common forms of CHD in patients with DS in Bisha Saudi Arabia were ASD and VSD, with a frequency of 28.5% and 25%, respectively. There was no significant association between the reported CHDs and sex. Future larger investigations on cardiovascular and other diseases in people with DS are recommended.

Financial support and sponsorship

The study was funded by the Deanship of Scientific Research, University of Bisha.

Conflicts of interest

There are no conflicts of interest.