Orofacial clefts associated with cardiac anomalies: 27 years of experience of a multidisciplinary group in a tertiary hospital

METHODS: Retrospective study of patients attended in the Cleft Lip and Palate Multidisciplinary Group outpatient clinic at Hospital Universitario São João, Porto-Portugal. Medical records from January 1992 through December 2018 were reviewed. Patients were divided into four groups according to the Spina classification: cleft lip (CL), cleft lip and palate (CLP), isolated cleft palate (CP) and atypical cleft (AC). Further categorization included gender, affected relatives, associated congenital anomalies and syndromes.

Available data present cardiovascular malformations as one of the most common congenital defects in CLP patients. Furthermore, congenital heart disease is more prevalent in OFC children than in the general pediatric population (5-15%) (8,9). These cardiovascular conditions included: atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), tetralogy of Fallot, truncus arteriosus, transposition of the great vessels, aortic stenosis and pulmonary stenosis. Patent foramen oval was not included because is considered an anatomical variation and not a cardiac malformation (10,11).
The study of the association between OFC and other congenital defects is of major importance, helping to provide the appropriate multidisciplinary management and to improve prognosis too. Taking the previous into account, we aim to describe our population of OFC with associated CHD (12). combined cardiac defects (two or more).

Methods
All patients were followed-up in a multidisciplinary group, which included pediatrics, cardiology, otorhinolaryngology, genetics, pediatric surgery, orthodontics and speech therapy.
The analysis was performed using IBM SPSS Statistics 21. The chi-square test was applied to study the association between CHD and the occurrence of additional congenital anomalies in OFC (significant if the p value below 0.05).

Results:
There was a total of 588 patients, 338 (57.4%) were males. Associated congenital anomalies The main groups of cardiac anomalies were left-to-right shunt (n=47) and right ventricular outflow tract obstruction (n=14). VSD and ASD were the most prevalent diagnosis (33.8% and 19.4% respectively. See on Table 1). Five patients had dysrhythmias, three of them associated with structural cardiac anomalies.
Eleven patients (14.3%) combined two or more cardiac conditions. The most frequent one was the association of bicuspid aortic valve and VSD.

Discussion:
Clefts and craniofacial malformations are commonly seen around the world, considered by the WHO as a public health problem, requiring a multidisciplinary approach due to its frequent association with other organic abnormalities. This was the highlight of this study: to claim attention to the not rare association of these malformations, which carry important comorbidities and a relevant impact on patient's lives.
In our study, we found a higher frequency of male patients, which may possibly be in agreement with other international studies that established a higher risk of OFC in men (5,9,11).
According to the type of OFC distribution, more than half of the patients had CP, as reported in other studies (3,9). CLP and CL alone are typically more common in boys and CP is traditionally more prevalent among girls, with a boy to girl ratio of 1.6: 1 for CLP, 1.2: 1 for CL and 0.9: 1 for CP ( 18).
However, several studies reported other prevalence rates, which shows that there isn't an established relation between OFC type and associated comorbidities. These differences may also be explained by different target populations, different methods and objectives around worldwide studies.
It is important to reinforce the association with other organic malformations and also genetic syndromes in about 90% (p<0.05). The syndromes most implied in our study overlap with international data about this issue. An attempt diagnosis is essential for adequate follow-up and genetic counseling, including prenatal appointments (13).
We found an important prevalence of cardiac anomalies in OFC patients (13%), similar to the existing studies (14). However, the prevalence is higher than published in countries like Brazil or England (11, 15).
The most frequent cardiac pathology found was left-right shunts (58%), more specifically ASD and VSD, which is in accordance with other results (14,16,17). We must be aware of the high percentage of combined cardiac defects, which may reflect a higher complexity in the approach of OFC patients. Every time an OFC is suspected during pregnancy, a fetal echocardiogram should be performed, aiming to get a "full picture" of the problem and, in that way, allowing to achieve a timely and correct approach to the patient and his family.
In our center, the multidisciplinary approach and the follow-up are performed throughout many years, sometimes into adulthood, focusing on the individualization of medical care, which includes sometimes multiple surgeries and long-term treatments. We believe that the long course follow-up is crucial to improve the prognosis of these patients.

Funding
This study did not receive financial support from external sources

Conflicts of interest disclosure
The authors declare no competing interests relevant to the content of this study.