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Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management
G Model JOBCR 313 No. of Pages 4
Journal of Oral Biology and Craniofacial Research xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral Biology and Craniofacial Research journal homepage: www.elsevier.com/locate/jobcr
Original Article
Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management Akash Kasatwar* , Rajiv Borle, Nitin Bhola, Rajanikanth K, G.S.V. Prasad, Anendd Jadhav Sharad Pawar Dental College & Hospital, DMIMS, Wardha, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 April 2017 Received in revised form 19 July 2017 Accepted 28 September 2017 Available online xxx
Background: Cleft lip and palate is one of the most common congenital craniofacial deformities seen in children. Various congenital anomalies are reported in the literature to be associated with cleft lip and palate. Cardiac anomalies are one of the most common congenital disorders associated in cleft lip and palate patientsIt includes Cyanotic and acyanotic cardiac diseases likel fallot’s tetralogy, transposition of greater vessels, atresia of tricuspid, total anomalous pulmonary venous return (TAPVR), truncus arteriosus, ebstein’s anomaly, hypoplastic left heart syndrome and pulmonary atresia, patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary stenosis, aortic stenosis and coarctation of aorta. Aim: To study the prevalence of congenital cardiac anomalies in cleft lip and palate patients. Objectives: To study different types of congenital cardiac anomalies/defects in patients with cleft lip and palate and its implications in surgical management. Materials and Methods: This is a retrospective study carried out for a period of one year. In the present study medical records of 200 patients with cleft lip and palate were evaluated and analyzed for presence of congenital cardiac anomalies. Results: Out of 200 patients of cleft lip and palate, 30 patients (15%) were associated with congenital cardiac anomalies with male to female ratio of 1:1. Associated congenital cardiac anomalies were most frequently seen in unilateral cleft palate patients (21.05%) The most common cardiac anomaly was Ventricular septal defect (36.6%). © 2017
Keywords: Cleft lip & palate Congenital anomalies Cardiac anomalies Surgical implications
1. Introduction Defective embryogenesis leading to structural and functional abnormalities of prenatal origin is referred to as congenital malformations. Congenital malformations may be caused by environmental factors, genetic and of unknown origin. The mode of the cause of such defects in most of the cases is uncertain. Various congenital abnormalities reported in the literature includes skeletal system disorders, nervous system(central) disorders, congenital cardiac diseases, respiratory system abnormalities, polydactyly, eyes and ear anomalies, limb anomalies, chromosomal disorders, talipes equinovarus, cleft of lip and palate, anencephaly, spina bifida, and many more.1,2
* Corresponding author at: Department of Oral & Maxillofacial surgery, Sharad Pawar Dental College & Hospital, DMIMS, Sawangi (Meghe), Wardha 442001, Maharashtra, India. E-mail addresses: [email protected] (A. Kasatwar), [email protected] (R. Borle), [email protected] (N. Bhola), [email protected] (R. K), [email protected] (G.S.V. Prasad).
Congenital anomalies or malformations are often associated with certain types of secondary major defects. In an epidemiologic study by Vallino-Napoli,one third of the cleft patients were associated with other birth related defects in Victoria, Australia, and the prevalence rate of cleft lip and palate (CL/P) was higher than that of cleft palate(CP).3 Associated deformities of cleft lip and palate patients with other congenital malformations was around 32.2% as reported by Beriaghi in USA and patients with CP (38.7%) were having more congenital anomalies than in patients with CL/P (26.4%).4 In another study by Luijsterburg, 10% of patients with clefts had other anomalies of the craniofacial region and congenital defects involving the other systems were 13%.5 Congenital cardiovascular anomalies are the structural flaws in the heart predisposing the patients to various complications. According to the study done by Hoffman, congenital heart disease (CHD) had incidence of about 4 to 5 per 1000 live births.6 Various studies in the literature has reported the relations of CHD with extra-cardiac malformations. Many of these patients may require noncardiac surgeries. This study was intended to determine the prevalence of congenital cardiac anomalies in patients with cleft
https://doi.org/10.1016/j.jobcr.2017.09.009 0976-5662/© 2017
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
G Model JOBCR 313 No. of Pages 4
2
A. Kasatwar et al. / Journal of Oral Biology and Craniofacial Research xxx (2017) xxx–xxx
lip and palate, to analyze their association and its surgical implications in the management of patients with cleft lip and palate. 2. Materials and method All the patients operated for cleft lip and palate between October 2015 to September 2016 in the Oral and Maxillofacial Surgical Centre at Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha, India, were retrospectively analyzed for the presence of congenital cardiac anomalies (CCA’s). The data of 200 patients was collected from Medical Record Department. All the patients showing features of CCA’s were included in the study. The data of the discharged patients signifying clinical signs and symptoms like shortness of breath, palpitations, failure to thrive, digital clubbing, cyanosis, abnormal cardiac murmur, history of recurrent chest infections, abnormal chest x-ray and other diagnostic investigations including ECG & echocardiography were selected for the study.
Table 1 Prevalence of CCA in Cleft Lip & Palate Patients. Type of cleft
No of patients Cases of CCA %
Male (%)
Female (%)
7.50 9.09 7.84
1(33.33%) 0(0%) 1(25%)
2(66.67%) 1(100%) 3(75%)
4(2.25,S) 1(1.10,NS) 5
21.05 16.67 20.00
2(50%) 1(100%) 3(60%)
2(50%) 0(0%) 2(40%)
61 63 124
11(3.66,S) 10(3.45,S) 21
18.03 15.87 16.94
2(18.18%) 8(80%) 10(47.62%)
200
30
15.00
9(81.82%) 2(20%) 11 (52.38%) 15(50%)
Cleft Lip Unilateral Bilateral Total
40 11 51
3(1.80,NS) 1(1.05,NS) 4
Cleft Palate Unilateral Bilateral Total
19 6 25
Both(CLAP) Unilateral Bilateral Total Grand Total
15(50%)
3. Results
Graph 2. Prevalence of Different Types of CCA in Cleft Lip And Palate Patients.
40% 36.67% 35% 30%
% of Cases
In the present study, the medical report of 200 patients of cleft lip and palate were analyzed of which 134 (67%) were males and 66 (33%) were females. The frequency, type and sex distribution of the patients with cleft lip and palate are highlighted in Graph 1. The occurrence of bilateral cleft lip and cleft palate was 32.5%(n = 63) the most frequent subtype, followed by unilateral cleft lip with palate 30.5%(n = 61), unilateral lip 20%(n = 40), unilateral cleft palate 9.5%(n = 19), bilateral cleft lip 5.5%(n = 11) and bilateral cleft palate3%(n = 6). Congenital cardiac anomalies were associated with 30 patients (15%) of congenital clefts. Patient’s with unilateral cleft palate (21.05%) were more frequently born with CCA’s followed by those with unilateral (one side) cleft lip alveolus and palate(18.03%), bilateral(two side) cleft palate(16.67%),bilateral cleft lip alveolus and palate(15.87%),bilateral cleft lip (9.09%) and unilateral cleft lip (7.5%) in that order (Table 1). Various types of CCA’s associated with Cleft lip and palate is summarised in Graph 2. The different type of CCA reported in the study were VSD (ventricular septal defect)(36.67%), PDA(patent ductus arteriosus) (13.33%),TOF (tetralogy of fallot)(13.33%), TGV(transposition of greater vessels) (6.67%),MVP (mitral valve prolapse)(6.67%), ASD (Atrial septal defect) (3.33%), ASD associated with VSD(6.67%) and ASD + VSD + PDA (3.33%) and others which included two patients with rheumatic heart disease and mitral regurgitation and one patient with mitral regurgitation with associated aortic regurgitation (10%) Graph 3. Statistical analysis was done by using descriptive and inferential statistics using z-test for single proportions. The software used in the analysis was SPSS 17.0
25% 20% 15%
13.33%
13.33% 10%
10% 6.67%
6.67%
5%
6.67% 3.33%
3.33%
0%
Types of CCA
Graph 3. Prevalence of different types of Congenital Cardiac Anomalies.
and Graph Pad Prism 5.0 and p < 0.05 was considered as level of significance 4. Discussion
Graph 1. Showing Type, Frequency And Sex Distribution Of The Patients with Cleft Lip & Palate.
Cleft and craniofacial malformations are the most common anomalies in head and neck region results due to an inborn error in structural morphogenesis .They may invariably occur with other congenital defects.7 Congenital malformations are commonly seen in almost all parts of the world. The prevalence of cleft and craniofacial anomalies is relatively higher in central region of India.
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
G Model JOBCR 313 No. of Pages 4
A. Kasatwar et al. / Journal of Oral Biology and Craniofacial Research xxx (2017) xxx–xxx
This study was undertaken to evaluate the prevalence of congenital cardiac anomalies in patients with cleft lip and palate and to study their implications in surgical management. Several essential non-genetic causative factors can lead to severe congenital cardiac anomalies. These influencing factors are active as well as passive smoking during pregnancy, binge drinking, women’s with high body mass index, gestational diabetes mellitus and folate deficiency.8 The neural crest cells and the cephalic mesoderm are essential for the formation and development of the cranio-maxillofacial tissues. Neural crest cells influences the development of both cardiac tissues and craniofacial tissues simultaneously. These neural crest cells contribute to the conotruncal endocardial cushions which separate the outflow tract of the heart into pulmonary and aortic channels. This may be the reason many infants with severe craniofacial anomalies also have cardiac abnormalities.9 Out of the 200 patients of cleft lip and palate, 30 (15%) of the patients were found out to have different type of CCA’s. Out of 30 patients of CCA’s, 15(50%) were male and 15(50%) were female. The prevalence of CCA’s in CP (20%) was higher than that in CL (7.84%) and CLAP (16.94%). The frequency of CCA’s was found to be more in unilateral cleft palate (21.05%) followed by those with unilateral (one side) cleft lip alveolus and palate (18.03%), bilateral (two side) cleft palate (16.67%), bilateral cleft lip alveolus and palate (15.87%), bilateral cleft lip (9.09 %) and unilateral cleft lip (7.5 %) as shown in Table 1. In the study done by Nancy Geis et al the percentage of CCA’s were more in bilateral cleft lip, alveolus and palate patients (12.5%).10 In another study done by Barbara E Otaigbe et al the number of CCA patients were equally distributed in all the subtypes of cleft patients.11 Ting Sun et al. reported an incidence of CHD in CP (20%) which was higher than that in CL (3.1%) and CLP (16.3%).12 In the current study there is higher prevalence of CCA’s in patients with unilateral cleft palate (Table 1). The prevalence of association of cleft lip and palate patients with CCA’s varies in different parts of the world. According to Barbosa et al. from Brazil, 9.5% of patients with congenital cleft lip and palate had an additional congenital heart disease.13 In the prospective study done by Shafi T and Atiq M in cleft lip and palate cases in Pakistan, 29% of the patients had various congenital malformations and 51% of them were found to be linked with cardiac anomalies.14 In a retrospective study done in cleft patients, Liang reported prevalence of 5.4% of the patients with CHD in China.15 In the current study, Cleft lip and palate patients had associated CCA’s in 15% (30 patients) of the cases. The present study has sample size slightly higher than that observed by Otaigbe et al who also reported a similar prevalence rate of 15% among 20 children of oral clefts.11 The prevalence in this study is however higher than 6.7% and 9.5% as established by Geiset al from England and Barbosa et al from Brazil respectively and Aimede et al from Abeokuta, South-western Nigeria reported a lowest prevalence of 1.6%.10,13,16 The prevalence in our study is much lower than the 45.1% and 45.5% as reported by Sun et al from Eastern China and Rawashd eh from Jordan.12,17 CCA’s are further classified into two main categories cyanotic and acyanotic types based on how the blood circulates through the heart due to abnormal opening or defects in the heart. Cyanotic heart diseases includes fallot’s tetralogy, transposition of greater vessels, atresia of tricuspid, total anomalous pulmonary venous return (TAPVR), truncus arteriosus, ebstein’s anomaly, hypoplastic left heart syndrome and pulmonary atresia. Various types of acyanotic heart diseases are patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary stenosis, aortic stenosis, coarctation of aorta. In the present study, amongst all the congenital cardiac malformations, Ventricular septal defect (VSD) was amongst the most commonly associated cardiac anomaly, accounting for 36.67% in patients with cleft lip and palate (Graph
3
3). Patent ductus arteriosus (13.33%) and tetralogy of fallot (13.33%) were the next common cardiac anomalies followed by transposition of greater vessels (TGV) (6.67%%), mitral valve prolapse (MVP) (6.67%). Atrial septal defect (ASD) as a single defect (3.33%), ASD + VSD (6.67%) and ASD + VSD + PDA in combination (3.33%) and others which included two patients with rheumatic heart disease and mitral regurgitation and one patient with mitral regurgitation and aortic regurgitation accounting for 10%. The result of this study is similar to that of Barbara E Otaigbe11, Mileradet al 18 and Chan et al.19 who found VSD to be the predominant congenital cardiac anomalies in cleft lip and palate cases. Cardiac anomalies have significant impact on morbidity, mortality, and medical care cost in childrens and adults. It is one of the leading causes of mortality in early childhood.20 In India, the mortality rate of the infants during 6–18 month of follow-up was 34.9% in the study done by Khalil et al.21 Congenital cardiac disease accounts for about 10% of infant mortality rate in India.22 Although there is some variation in reported incidence in different studies, its prevalence in patients with cleft lip and palate is of concern as the child may be syndromic or may have various other associated congenital anomalies. Poor physical and mental growth is common in children’s with cleft lip and palate associated with CCA. Patients has to undergo multiple corrective surgeries for regaining normal function and esthetics, Any surgical intervention may lead to deprived metabolic response, delayed wound healing and impaired growth and development of the child. Intraoperatively or postoperatively, patients with CCA’s may have increased risk of developing certain complications like arrhythmias, pulmonary hypertension, infective endocarditis, respiratory tract infections, increased risk of stroke due to blood clots and congestive cardiac failure .23 Hence, before undergoing any medical or surgical intervention there should be a mandatory preoperative evaluation of the patient by a multidisciplinary team which includes pediatricians, physicians, cardiologist, anesthetists, and maxillofacial surgeons. Certain precautions has to be taken preoperatively in patients with CCA’s associated with cleft lip and palate. Careful clinical examination, medical history, essential diagnostic evaluation and necessary laboratory investigations should be done to identify various other systemic abnormalities. Blood investigations including complete blood count, coagulation profile such as prothrombin time,activated partial thromboplastin time and International Normalised Ratio (INR) are mandatory as the patient may be on antiplatelet medications .C reactive protein and WBC count will determine the potential diagnosis of infections. Patient may be taking certain medications like aspirin, clopidogrel (dual antiplatelet therapy), warfarin, diuretics antiarrythmics, and antihypertensives. All the necessary medications related to CCA ’s should be continued even during the surgical management of cleft patients. For simple and short time surgeries, low dose aspirin can be continued. However for major complex surgeries prior cardiologist and anesthetist opinion should always be done to avoid uncontrolled bleeding. CCA patient’s on warfarin should be preoperatively monitored and should be shifted on heparin before surgery. All the patients with infective endocarditis associated with cleft lip and palate should be mandatorily undergo antibiotic prophylaxis according to American Heart Association (AHA) guidelines to further reduce the magnitude of the postoperative risk. Cardiac risk assessment should be done for all patients undergoing non-cardiac surgery as a critical part of preoperative evaluation as they may have associated cardiac anomalies. Small form of VSD’s without pulmonary hypertension and other CCA’s that are asymptomatic can be managed conservatively and surgical intervention is not needed in most of the patients. Larger CCA’s requires surgical management because they may cause difficulty in
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
G Model JOBCR 313 No. of Pages 4
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feeding, growth retardation and life threatening problems. According to European Society of Cardiology (ESC) and The European Society of Anaesthesiology (ESA) guidelines for noncardiac surgeries, patients with stable cardiac disease can undergo low and intermediate risk surgeries which include head and neck surgeries.24 Patients with complicated CCA’s have to be critically evaluated by the cardiologist to reduce postoperative complications. High risk cardiac patient’s categorized as ASA III, IV and V are at a relatively higher operative risk and require superior degree of monitoring and care. In a high-risk group if the underlying cardiac anomaly is of great concern and if it is significant, it is advisable to treat the congenital cardiac disease first and then the cleft lip and palate surgeries to reduce further medical and surgical complications. Prompt diagnosis and intime management may not only reduce further co-morbidities but will also help in proper development of the child. Hospitals or an institutions should be well supported with the necessary equipments and backup for all the patients with congenital heart disease undergoing noncardiac surgeries for any potential complications if arise. Before the conduction of anesthesia and intraoperatively, continuous ECG monitoring and pulse oximetry is needed. The variations in the reported prevalence of congenital cardiac anomalies in cleft patients are largely due to disparity in identifying minor lesions. It is necessary to identify cardiac comorbidity in cleft lip and palate patients preoperatively at the earliest possible age. With increasing use of echocardiography, diagnostic rate has been enhanced leading to increasing prevalence of CCA’s.25 Nowadays echocardiography is a preferred investigative tool for initial assessment of the infants with CCA ’s. Even the complex anatomy of the cardiac anomalies can be delineated with 2D echo. As it is non-invasive method, echocardiography is also an important imaging modality for proper management and to improve the survival of patients with various CCA’s by early medical and surgical intervention. 5. Conclusion The evaluation and management of the patients with cleft lip and palate associated with cardiac anomalies is complex issue. Early identification of the problems and early intervention for the same is indicated in the childrens with this type of conditions. Conflict of interest None. Acknowledgement
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This work was supported by Dr Apoorva Mishra. References
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multiplicity of environmental and genetic factors. Pediatricse. 2004;54(4 Suppl):957–968. Francine Rizk, Pascale Salameh, Aline Hamadé. Congenital anomalies: prevalence and risk factors. Univ J Publ Health. 2014;2(2):58–63. Vallino-Napoli LD, Riley MM, Halliday JL. An epidemiologic study of orofacial clefts with other birth defects in Victoria, Australia. C left Palate Craniofac J. 2006;43:571–576. Beriaghi S, Myers SL, Jensen SA, Kaimal S, Chan CM, et al. Cleft lip and palate: association with other congenital malformations. J Clin Pediatric Dent. 2009;33:207–210. Luijsterburg AJ, Vermeij-Keers C. Ten years recording common oral clefts with a new descriptive system. Cleft Palate Craniofac J. 2011;48:173–182. Julien I, Hoffman E, Kaplan Samuel. JACC. 2002;12:1890–1900. Sekhon PS, Ethunandan M, Markus AF, Gopal Krishnan, Bhasker Rao C. Congenital anomalies associated with cleft lip and palate—an analysis of 1623 consecutive patients. Cleft Palate Craniofac J. 2011;48:371–378. Mozaffarian D, et al. eart disease andstroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38–e360. Keyteand Anna, Hutson MaryRedmond. The neural crest in cardiac congenital anomalies. Differentiation. 2012;84:25–40. Geis Nancy, BooneSeto Louis Bartoshesky, Lewis Michael B, Pashayan ermine M. Prevalence of Congenital heart disease among the population of metropolitan cleft lip and palate clinic. Cleft Palate J. 1981;18:19–23. Barbara Otaigbe E, Oladimeji Akadiri A, Joycelyn Eigbobo O. Clinical and echocardiographic findings in an African pediatric population of cleft lip palate patients: a preliminary report. Nig J Cardiol. 2013;10:6–8. Ting Sun, HuaTian, Changqian Wang, Ping Yin, Yaqin Zhu, Xianghua Chen, Zhengde Tang A Survey of Congenital Heart Disease and Other Organic Malformations Associated with Different Types of Orofacial Clefts in Eastern China; January 2013;8: e54726. Barbosa MM, Rocha CM, Katina T, Caldas M, Codorniz A. Prevalence of congenital heart diseases in oral cleft patients. Pediatr Cardiol. 2003;24:369– 374. Shafi T, Khan MR, Atiq M. Congenital heart disease and associated malformations in children with cleft lip and palate in Pakistan. Br J Plast Surg. 2003;56:106–109. Liang CD, Huang SC, Lai JP. A survey of congenital heart disease in patients with oral clefts. Acta Paediatr Taiwan. 1999;40:414–417. Aimede OS, Olalere GO, Adedayo O, Adeshola S. Orofacial clefts: our experience in two suburban health facilities. Dentistry. 2013;3:155. Rawashdeh MA, Jawdat Abu-Hawas B. Congenital associated malformations in a sample of Jordanian patients with cleft lip and palate. J Oral Maxillofac Surg. 2008;66:2035–2041. Milerad J, Larson O, PhD D, Hagberg C, Ideberg M. Associated malformations in infants with cleft lip and palate: a prospective, population-based study. Pediatrics. 1997;100:180–186. Chan KW, Lee KH, Pang KK, Mou JW, Tam YH. Clinical characteristics of children with orofacial cleft in a tertiary centre in Hong Kong. Hong Kong J Paediatr. 2013;18:147–151. Suzanne M., Gilboa, Jason L., Salemi, Wendy N., Nembhard, David E., Fixler Adolfo Correa. United States, 1999 to 2006 Mortality Resulting From Congenital Heart Disease Among Children and Adults in the Circulation. 2010; 122:2254-2263. Khalil A, Aggarwal R, Thirupuram S, Arora R. Incidence of congenital heart disease among hospital live births in India. Indian Ped. 1994;31:519–527. Saxena Anita. Congenital heart disease in India: a status report. Indian J Pediatr. 2005;72(7):595–598. Jagdish Menghraj Shahani. Anaesthetic considerations in children with congenital heart disease undergoing non-cardiac surgery. Indian J Anaesth. 2012;56:491–495. Kristenson SD, et al. ESC/ESA guidelines on non-cardiac surgery: cardiovascular assessment and management: the joint task force on noncardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur Heart J. 2014;35:2383–2431. Giuseppe Pacileo, Di Salvo Giovanni, Giuseppe Limongelli, Tiziana Miele, Raffaele Calabrò. Echocardiography in congenital heart disease: usefulness, limits and new techniques. J Cardiovasc Med. 2007;(January):17–22.
1. Brent RL. Environmental causes of human congenital malformations: the pediatrician’s role in dealing with these complex clinical problems caused by a
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
Journal of Oral Biology and Craniofacial Research xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Journal of Oral Biology and Craniofacial Research journal homepage: www.elsevier.com/locate/jobcr
Original Article
Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management Akash Kasatwar* , Rajiv Borle, Nitin Bhola, Rajanikanth K, G.S.V. Prasad, Anendd Jadhav Sharad Pawar Dental College & Hospital, DMIMS, Wardha, India
A R T I C L E I N F O
A B S T R A C T
Article history: Received 3 April 2017 Received in revised form 19 July 2017 Accepted 28 September 2017 Available online xxx
Background: Cleft lip and palate is one of the most common congenital craniofacial deformities seen in children. Various congenital anomalies are reported in the literature to be associated with cleft lip and palate. Cardiac anomalies are one of the most common congenital disorders associated in cleft lip and palate patientsIt includes Cyanotic and acyanotic cardiac diseases likel fallot’s tetralogy, transposition of greater vessels, atresia of tricuspid, total anomalous pulmonary venous return (TAPVR), truncus arteriosus, ebstein’s anomaly, hypoplastic left heart syndrome and pulmonary atresia, patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary stenosis, aortic stenosis and coarctation of aorta. Aim: To study the prevalence of congenital cardiac anomalies in cleft lip and palate patients. Objectives: To study different types of congenital cardiac anomalies/defects in patients with cleft lip and palate and its implications in surgical management. Materials and Methods: This is a retrospective study carried out for a period of one year. In the present study medical records of 200 patients with cleft lip and palate were evaluated and analyzed for presence of congenital cardiac anomalies. Results: Out of 200 patients of cleft lip and palate, 30 patients (15%) were associated with congenital cardiac anomalies with male to female ratio of 1:1. Associated congenital cardiac anomalies were most frequently seen in unilateral cleft palate patients (21.05%) The most common cardiac anomaly was Ventricular septal defect (36.6%). © 2017
Keywords: Cleft lip & palate Congenital anomalies Cardiac anomalies Surgical implications
1. Introduction Defective embryogenesis leading to structural and functional abnormalities of prenatal origin is referred to as congenital malformations. Congenital malformations may be caused by environmental factors, genetic and of unknown origin. The mode of the cause of such defects in most of the cases is uncertain. Various congenital abnormalities reported in the literature includes skeletal system disorders, nervous system(central) disorders, congenital cardiac diseases, respiratory system abnormalities, polydactyly, eyes and ear anomalies, limb anomalies, chromosomal disorders, talipes equinovarus, cleft of lip and palate, anencephaly, spina bifida, and many more.1,2
* Corresponding author at: Department of Oral & Maxillofacial surgery, Sharad Pawar Dental College & Hospital, DMIMS, Sawangi (Meghe), Wardha 442001, Maharashtra, India. E-mail addresses: [email protected] (A. Kasatwar), [email protected] (R. Borle), [email protected] (N. Bhola), [email protected] (R. K), [email protected] (G.S.V. Prasad).
Congenital anomalies or malformations are often associated with certain types of secondary major defects. In an epidemiologic study by Vallino-Napoli,one third of the cleft patients were associated with other birth related defects in Victoria, Australia, and the prevalence rate of cleft lip and palate (CL/P) was higher than that of cleft palate(CP).3 Associated deformities of cleft lip and palate patients with other congenital malformations was around 32.2% as reported by Beriaghi in USA and patients with CP (38.7%) were having more congenital anomalies than in patients with CL/P (26.4%).4 In another study by Luijsterburg, 10% of patients with clefts had other anomalies of the craniofacial region and congenital defects involving the other systems were 13%.5 Congenital cardiovascular anomalies are the structural flaws in the heart predisposing the patients to various complications. According to the study done by Hoffman, congenital heart disease (CHD) had incidence of about 4 to 5 per 1000 live births.6 Various studies in the literature has reported the relations of CHD with extra-cardiac malformations. Many of these patients may require noncardiac surgeries. This study was intended to determine the prevalence of congenital cardiac anomalies in patients with cleft
https://doi.org/10.1016/j.jobcr.2017.09.009 0976-5662/© 2017
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
G Model JOBCR 313 No. of Pages 4
2
A. Kasatwar et al. / Journal of Oral Biology and Craniofacial Research xxx (2017) xxx–xxx
lip and palate, to analyze their association and its surgical implications in the management of patients with cleft lip and palate. 2. Materials and method All the patients operated for cleft lip and palate between October 2015 to September 2016 in the Oral and Maxillofacial Surgical Centre at Acharya Vinoba Bhave Rural Hospital, Sawangi (Meghe), Wardha, India, were retrospectively analyzed for the presence of congenital cardiac anomalies (CCA’s). The data of 200 patients was collected from Medical Record Department. All the patients showing features of CCA’s were included in the study. The data of the discharged patients signifying clinical signs and symptoms like shortness of breath, palpitations, failure to thrive, digital clubbing, cyanosis, abnormal cardiac murmur, history of recurrent chest infections, abnormal chest x-ray and other diagnostic investigations including ECG & echocardiography were selected for the study.
Table 1 Prevalence of CCA in Cleft Lip & Palate Patients. Type of cleft
No of patients Cases of CCA %
Male (%)
Female (%)
7.50 9.09 7.84
1(33.33%) 0(0%) 1(25%)
2(66.67%) 1(100%) 3(75%)
4(2.25,S) 1(1.10,NS) 5
21.05 16.67 20.00
2(50%) 1(100%) 3(60%)
2(50%) 0(0%) 2(40%)
61 63 124
11(3.66,S) 10(3.45,S) 21
18.03 15.87 16.94
2(18.18%) 8(80%) 10(47.62%)
200
30
15.00
9(81.82%) 2(20%) 11 (52.38%) 15(50%)
Cleft Lip Unilateral Bilateral Total
40 11 51
3(1.80,NS) 1(1.05,NS) 4
Cleft Palate Unilateral Bilateral Total
19 6 25
Both(CLAP) Unilateral Bilateral Total Grand Total
15(50%)
3. Results
Graph 2. Prevalence of Different Types of CCA in Cleft Lip And Palate Patients.
40% 36.67% 35% 30%
% of Cases
In the present study, the medical report of 200 patients of cleft lip and palate were analyzed of which 134 (67%) were males and 66 (33%) were females. The frequency, type and sex distribution of the patients with cleft lip and palate are highlighted in Graph 1. The occurrence of bilateral cleft lip and cleft palate was 32.5%(n = 63) the most frequent subtype, followed by unilateral cleft lip with palate 30.5%(n = 61), unilateral lip 20%(n = 40), unilateral cleft palate 9.5%(n = 19), bilateral cleft lip 5.5%(n = 11) and bilateral cleft palate3%(n = 6). Congenital cardiac anomalies were associated with 30 patients (15%) of congenital clefts. Patient’s with unilateral cleft palate (21.05%) were more frequently born with CCA’s followed by those with unilateral (one side) cleft lip alveolus and palate(18.03%), bilateral(two side) cleft palate(16.67%),bilateral cleft lip alveolus and palate(15.87%),bilateral cleft lip (9.09%) and unilateral cleft lip (7.5%) in that order (Table 1). Various types of CCA’s associated with Cleft lip and palate is summarised in Graph 2. The different type of CCA reported in the study were VSD (ventricular septal defect)(36.67%), PDA(patent ductus arteriosus) (13.33%),TOF (tetralogy of fallot)(13.33%), TGV(transposition of greater vessels) (6.67%),MVP (mitral valve prolapse)(6.67%), ASD (Atrial septal defect) (3.33%), ASD associated with VSD(6.67%) and ASD + VSD + PDA (3.33%) and others which included two patients with rheumatic heart disease and mitral regurgitation and one patient with mitral regurgitation with associated aortic regurgitation (10%) Graph 3. Statistical analysis was done by using descriptive and inferential statistics using z-test for single proportions. The software used in the analysis was SPSS 17.0
25% 20% 15%
13.33%
13.33% 10%
10% 6.67%
6.67%
5%
6.67% 3.33%
3.33%
0%
Types of CCA
Graph 3. Prevalence of different types of Congenital Cardiac Anomalies.
and Graph Pad Prism 5.0 and p < 0.05 was considered as level of significance 4. Discussion
Graph 1. Showing Type, Frequency And Sex Distribution Of The Patients with Cleft Lip & Palate.
Cleft and craniofacial malformations are the most common anomalies in head and neck region results due to an inborn error in structural morphogenesis .They may invariably occur with other congenital defects.7 Congenital malformations are commonly seen in almost all parts of the world. The prevalence of cleft and craniofacial anomalies is relatively higher in central region of India.
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
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This study was undertaken to evaluate the prevalence of congenital cardiac anomalies in patients with cleft lip and palate and to study their implications in surgical management. Several essential non-genetic causative factors can lead to severe congenital cardiac anomalies. These influencing factors are active as well as passive smoking during pregnancy, binge drinking, women’s with high body mass index, gestational diabetes mellitus and folate deficiency.8 The neural crest cells and the cephalic mesoderm are essential for the formation and development of the cranio-maxillofacial tissues. Neural crest cells influences the development of both cardiac tissues and craniofacial tissues simultaneously. These neural crest cells contribute to the conotruncal endocardial cushions which separate the outflow tract of the heart into pulmonary and aortic channels. This may be the reason many infants with severe craniofacial anomalies also have cardiac abnormalities.9 Out of the 200 patients of cleft lip and palate, 30 (15%) of the patients were found out to have different type of CCA’s. Out of 30 patients of CCA’s, 15(50%) were male and 15(50%) were female. The prevalence of CCA’s in CP (20%) was higher than that in CL (7.84%) and CLAP (16.94%). The frequency of CCA’s was found to be more in unilateral cleft palate (21.05%) followed by those with unilateral (one side) cleft lip alveolus and palate (18.03%), bilateral (two side) cleft palate (16.67%), bilateral cleft lip alveolus and palate (15.87%), bilateral cleft lip (9.09 %) and unilateral cleft lip (7.5 %) as shown in Table 1. In the study done by Nancy Geis et al the percentage of CCA’s were more in bilateral cleft lip, alveolus and palate patients (12.5%).10 In another study done by Barbara E Otaigbe et al the number of CCA patients were equally distributed in all the subtypes of cleft patients.11 Ting Sun et al. reported an incidence of CHD in CP (20%) which was higher than that in CL (3.1%) and CLP (16.3%).12 In the current study there is higher prevalence of CCA’s in patients with unilateral cleft palate (Table 1). The prevalence of association of cleft lip and palate patients with CCA’s varies in different parts of the world. According to Barbosa et al. from Brazil, 9.5% of patients with congenital cleft lip and palate had an additional congenital heart disease.13 In the prospective study done by Shafi T and Atiq M in cleft lip and palate cases in Pakistan, 29% of the patients had various congenital malformations and 51% of them were found to be linked with cardiac anomalies.14 In a retrospective study done in cleft patients, Liang reported prevalence of 5.4% of the patients with CHD in China.15 In the current study, Cleft lip and palate patients had associated CCA’s in 15% (30 patients) of the cases. The present study has sample size slightly higher than that observed by Otaigbe et al who also reported a similar prevalence rate of 15% among 20 children of oral clefts.11 The prevalence in this study is however higher than 6.7% and 9.5% as established by Geiset al from England and Barbosa et al from Brazil respectively and Aimede et al from Abeokuta, South-western Nigeria reported a lowest prevalence of 1.6%.10,13,16 The prevalence in our study is much lower than the 45.1% and 45.5% as reported by Sun et al from Eastern China and Rawashd eh from Jordan.12,17 CCA’s are further classified into two main categories cyanotic and acyanotic types based on how the blood circulates through the heart due to abnormal opening or defects in the heart. Cyanotic heart diseases includes fallot’s tetralogy, transposition of greater vessels, atresia of tricuspid, total anomalous pulmonary venous return (TAPVR), truncus arteriosus, ebstein’s anomaly, hypoplastic left heart syndrome and pulmonary atresia. Various types of acyanotic heart diseases are patent ductus arteriosus, ventricular septal defect, atrial septal defect, pulmonary stenosis, aortic stenosis, coarctation of aorta. In the present study, amongst all the congenital cardiac malformations, Ventricular septal defect (VSD) was amongst the most commonly associated cardiac anomaly, accounting for 36.67% in patients with cleft lip and palate (Graph
3
3). Patent ductus arteriosus (13.33%) and tetralogy of fallot (13.33%) were the next common cardiac anomalies followed by transposition of greater vessels (TGV) (6.67%%), mitral valve prolapse (MVP) (6.67%). Atrial septal defect (ASD) as a single defect (3.33%), ASD + VSD (6.67%) and ASD + VSD + PDA in combination (3.33%) and others which included two patients with rheumatic heart disease and mitral regurgitation and one patient with mitral regurgitation and aortic regurgitation accounting for 10%. The result of this study is similar to that of Barbara E Otaigbe11, Mileradet al 18 and Chan et al.19 who found VSD to be the predominant congenital cardiac anomalies in cleft lip and palate cases. Cardiac anomalies have significant impact on morbidity, mortality, and medical care cost in childrens and adults. It is one of the leading causes of mortality in early childhood.20 In India, the mortality rate of the infants during 6–18 month of follow-up was 34.9% in the study done by Khalil et al.21 Congenital cardiac disease accounts for about 10% of infant mortality rate in India.22 Although there is some variation in reported incidence in different studies, its prevalence in patients with cleft lip and palate is of concern as the child may be syndromic or may have various other associated congenital anomalies. Poor physical and mental growth is common in children’s with cleft lip and palate associated with CCA. Patients has to undergo multiple corrective surgeries for regaining normal function and esthetics, Any surgical intervention may lead to deprived metabolic response, delayed wound healing and impaired growth and development of the child. Intraoperatively or postoperatively, patients with CCA’s may have increased risk of developing certain complications like arrhythmias, pulmonary hypertension, infective endocarditis, respiratory tract infections, increased risk of stroke due to blood clots and congestive cardiac failure .23 Hence, before undergoing any medical or surgical intervention there should be a mandatory preoperative evaluation of the patient by a multidisciplinary team which includes pediatricians, physicians, cardiologist, anesthetists, and maxillofacial surgeons. Certain precautions has to be taken preoperatively in patients with CCA’s associated with cleft lip and palate. Careful clinical examination, medical history, essential diagnostic evaluation and necessary laboratory investigations should be done to identify various other systemic abnormalities. Blood investigations including complete blood count, coagulation profile such as prothrombin time,activated partial thromboplastin time and International Normalised Ratio (INR) are mandatory as the patient may be on antiplatelet medications .C reactive protein and WBC count will determine the potential diagnosis of infections. Patient may be taking certain medications like aspirin, clopidogrel (dual antiplatelet therapy), warfarin, diuretics antiarrythmics, and antihypertensives. All the necessary medications related to CCA ’s should be continued even during the surgical management of cleft patients. For simple and short time surgeries, low dose aspirin can be continued. However for major complex surgeries prior cardiologist and anesthetist opinion should always be done to avoid uncontrolled bleeding. CCA patient’s on warfarin should be preoperatively monitored and should be shifted on heparin before surgery. All the patients with infective endocarditis associated with cleft lip and palate should be mandatorily undergo antibiotic prophylaxis according to American Heart Association (AHA) guidelines to further reduce the magnitude of the postoperative risk. Cardiac risk assessment should be done for all patients undergoing non-cardiac surgery as a critical part of preoperative evaluation as they may have associated cardiac anomalies. Small form of VSD’s without pulmonary hypertension and other CCA’s that are asymptomatic can be managed conservatively and surgical intervention is not needed in most of the patients. Larger CCA’s requires surgical management because they may cause difficulty in
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009
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feeding, growth retardation and life threatening problems. According to European Society of Cardiology (ESC) and The European Society of Anaesthesiology (ESA) guidelines for noncardiac surgeries, patients with stable cardiac disease can undergo low and intermediate risk surgeries which include head and neck surgeries.24 Patients with complicated CCA’s have to be critically evaluated by the cardiologist to reduce postoperative complications. High risk cardiac patient’s categorized as ASA III, IV and V are at a relatively higher operative risk and require superior degree of monitoring and care. In a high-risk group if the underlying cardiac anomaly is of great concern and if it is significant, it is advisable to treat the congenital cardiac disease first and then the cleft lip and palate surgeries to reduce further medical and surgical complications. Prompt diagnosis and intime management may not only reduce further co-morbidities but will also help in proper development of the child. Hospitals or an institutions should be well supported with the necessary equipments and backup for all the patients with congenital heart disease undergoing noncardiac surgeries for any potential complications if arise. Before the conduction of anesthesia and intraoperatively, continuous ECG monitoring and pulse oximetry is needed. The variations in the reported prevalence of congenital cardiac anomalies in cleft patients are largely due to disparity in identifying minor lesions. It is necessary to identify cardiac comorbidity in cleft lip and palate patients preoperatively at the earliest possible age. With increasing use of echocardiography, diagnostic rate has been enhanced leading to increasing prevalence of CCA’s.25 Nowadays echocardiography is a preferred investigative tool for initial assessment of the infants with CCA ’s. Even the complex anatomy of the cardiac anomalies can be delineated with 2D echo. As it is non-invasive method, echocardiography is also an important imaging modality for proper management and to improve the survival of patients with various CCA’s by early medical and surgical intervention. 5. Conclusion The evaluation and management of the patients with cleft lip and palate associated with cardiac anomalies is complex issue. Early identification of the problems and early intervention for the same is indicated in the childrens with this type of conditions. Conflict of interest None. Acknowledgement
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This work was supported by Dr Apoorva Mishra. References
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1. Brent RL. Environmental causes of human congenital malformations: the pediatrician’s role in dealing with these complex clinical problems caused by a
Please cite this article in press as: A. Kasatwar, et al., Prevalence of congenital cardiac anomalies in patients with cleft lip and palate – Its implications in surgical management, J Oral Biol Craniofac Res. (2017), https://doi.org/10.1016/j.jobcr.2017.09.009