Abstract
Background:
Congenital heart disease (CHD) frequently occurs in conjunction with extracardiac developmental anomalies, including cleft malformations. The clinical impact of concomitant cleft disease on the surgical management of CHD has not been studied. We evaluated cardiac surgical outcomes in patients with concomitant CHD and cleft lip and/or palate (CL/P).
Methods:
Patients with CHD + CL/P managed at our institution between January 2004 and December 2018 were included. Demographic, operative, and follow-up data were retrospectively collected and analyzed using SAS 9.4. Chi-square tests were used for categorical variables and t test or Wilcoxon rank sum tests for continuous variables. Significance of P < .05 was used.
Results:
There were 127 patients with CHD + CL/P; 63 (50%) were boys. Compared to the general CHD population, patients with CHD + CL/P demonstrated an enrichment of atrial septal defects (10.5% vs 34%), tetralogy of Fallot/double outlet right ventricle (6.4% vs 15.7%), arch defects (4.5% vs 10.2%), truncus arteriosus (1.2% vs 3.1%), and total anomalous pulmonary venous return (1.0% vs 2.4%). Of 63 patients who underwent CHD repair, 58 (92%) did so prior to CL/P repair at 21.5 (6–114) days of age. Compared to CHD lesion-matched patients undergoing cardiac surgical repair at our institution, patients with CL/P had a 2- to 3.7-fold longer intensive care stay, 1.8- to 2.6-fold longer hospital stay, and 6- to 13.5-fold increase in major morbidity, without a significant difference in mortality.
Conclusions:
Cardiac outflow tract defects are particularly overrepresented in CL/P patients. The presence of CL/P increases the complexity of postoperative care after CHD surgery, without a significant impact on mortality.
Keywords: congenital heart disease, congenital heart surgery, outcomes, postoperative care
Introduction
Congenital heart disease (CHD) affects approximately 7 to 9 per 1,000 live births and is the leading cause of birth defect–associated infant mortality.1 In the United States, nearly 40,000 newborns each year are diagnosed with a congenital cardiac malformation, and in 2010, it was estimated that 2.4 million pediatric and adult patients live with CHD.2 While the majority of these patients have isolated cardiac defects, it is not uncommon for patients with CHD to harbor other extracardiac developmental anomalies.3–5
Cleft lip and/or cleft palate (CL/P) are frequently associated extracardiac anomalies in patients with syndromic and nonsyndromic CHD. Recent reports have found that the prevalence of CHD in cleft patients is up to 14-fold higher than that of the general population.6–10 We have shown that the presence of CHD impacts the management and outcomes of cleft care.11 In contrast, there are limited data concerning the clinical impact of cleft defects on care of CHD. Therefore, the aim of this study is to characterize the phenotypic distribution of cardiac malformations in CL/P patients and to evaluate the impact of concomitant CL/P on the surgical management of CHD.
Patients and Methods
This study is a retrospective analysis of patients diagnosed with combined congenital heart disease and cleft lip and/or palate (CHD + CL/P) who were managed at Children’s Hospital Los Angeles between January 2004 and December 2018. The study protocol was approved by the Children’s Hospital Los Angeles Institutional Review Board.
Data Collection
Patient demographics, operative characteristics, and follow-up data were collected from medical records. To calculate the estimated birth prevalence for cardiac phenotypes in the general CHD population, lesion-specific incidence values were abstracted from data presented in a previous study by Hoffman and Kaplan.1 The comparison cohort comprised a contemporary group of patients with CHD, but without CL/P, who underwent surgery for designated CHD lesions at our institution between 2004 and 2018. Society of Thoracic Surgeons’ (STS) Congenital Heart Surgery Database (CHSD) criteria were used to define cardiac diagnoses, genetic syndromes, chromosomal anomalies, and major morbidity.12
Statistical Analysis
All statistical analyses were performed using SAS version 9.4 software (SAS Institute Inc). Categorical data were presented as frequency counts and percentages and analyzed by χ2 or Fisher exact tests. Continuous data were presented as medians with interquartile ranges (IQRs). Non-normally distributed continuous variables were analyzed by Wilcoxon rank sum tests. All statistical tests were two-sided with significance defined as P < .05.
Results
Demographics and Patient Characteristics
The demographic characteristics of the CHD + CL/P cohort are summarized in Table 1. Our cohort comprised a total of 127 patients. Six patients (4.7%) had a family history of CHD, two tetralogy of Fallot (TOF), one ventricular septal defect (VSD), and three unknown. Isolated cleft palate was the most common cleft diagnosis and was observed in greater than half of the study cohort. In addition, more than half of the CHD + CL/P patients were diagnosed with an associated genetic syndrome, most commonly 22q11 microdeletion (DiGeorge or velocardiofacial syndrome; n = 16, 12.6%), followed by Goldenhar (n = 8, 6.3%), CHARGE (n = 6, 4.7%), and Trisomy 21 (Down syndrome, n = 6, 4.7%). Almost half of the patients had at least one additional extracardiac defect other than CL/P, confirming the frequently observed clustering of birth defects.
Table 1.
Demographic Characteristics of All CHD + CL/P Patients.
| Characteristics | No. (%) Total cohort (n = 127) |
|---|---|
| Sex | |
| Male | 63 (49.6) |
| Female | 64 (50.4) |
| Prematurity | 25 (19.7) |
| Family history of CHD | 6 (4.7) |
| Cleft diagnosis | |
| iCL | 7 (5.5) |
| iCP | 65 (51.2) |
| Combined CL/P | 55 (43.3) |
| Genetic syndrome | 65 (51.2) |
| Noncardiac anatomic abnormalitiesa | 61 (48.0) |
Abbreviations: CHD, congenital heart disease; CL/P, cleft lip and/or cleft palate; iCL, isolated cleft lip; iCP, isolated cleft palate.
Refers to noncleft anatomic abnormalities.
Distribution of Congenital Heart Disease in Cleft Patients
The breakdown of CHD phenotypes in this cohort of patients is shown in Figure 1. The most commonly diagnosed cardiac lesion was atrial septal defect (ASD; n = 43, 33.9%), followed by VSD (n = 26, 20.5%), TOF/double outlet right ventricle (DORV, n = 20, 15.7%), and aortic arch hypoplasia/coarctation ± VSD (n = 13, 10.2%). Using national estimates of CHD birth prevalence,1 we compared the distribution of CHD phenotypes in cleft patients to that observed in the general CHD population (Figure 1). Congenital heart disease phenotypes overrepresented in cleft patients included ASD (CL/P 33.9% vs general population 10.5%), TOF/DORV (15.7% vs 6.4%), arch hypoplasia/coarctation ± VSD (10.2% vs 4.5%), truncus arteriosus (Truncus; 3.1% vs 1.2%), and total anomalous pulmonary venous return (TAPVR; 2.4% vs 1.0%). In contrast, isolated VSD (20.5% vs 39.7%) and isolated pulmonary (2.4% vs 9.6%) or aortic valve stenosis/atresia (2.4% vs 4.5%) appear to be less frequently encountered.
Figure 1.
Distribution of congenital heart disease (CHD) phenotypes in cleft lip and/or cleft palate (CL/P) patients as compared to the general CHD population.
Operative Data
A total of 63 (49.6%) CHD + CL/P patients underwent cardiac surgery in our series (Figure 2; Supplementary Figure 1). All but five (58, 92.0%) underwent cardiac surgery prior to cleft repair at a median age of 21.5 days (IQR: 6.3–113.8). Thirty-two (50.8%) patients underwent cardiac surgery as a neonate (median: 10.0 days, IQR: 5.0–16.8) for arch hypoplasia (n = 13), Truncus (n = 4), patent ductus arteriosus (PDA; n = 4), TAPVR (n = 3), D-transposition of the great arteries (D-TGA; n = 2), hypoplastic left heart syndrome (HLHS; n = 1), and others (n = 5). Twenty-six (41.3%) patients underwent cardiac surgery prior to cleft repair in the postneonatal period (median: 170 days, IQR: 92–272.5) for TOF/DORV (n = 13), VSD (n = 12), and PDA (n = 1). The median time interval was 199 days (IQR: 117.8–238.3) between CHD repair and cleft lip repair in these patients and 499 days (IQR: 367.0–1,526.0) between CHD and cleft palate repairs (Table 2). Five patients had cardiac surgery after initial cleft repair. The median age of this cohort at CHD repair was nearly five years (1,753 days, IQR: 1,703–3,241), and they underwent cardiac surgery for ASD (n = 3), vascular ring (n = 1), and bicuspid aortic valve (n = 1). The time interval between CL/P repair and cardiac surgery was 976 days (IQR: 632–3072).
Figure 2.
Staged surgical management of combined congenital heart disease and cleft lip and/or palate (CHD + CL/P) patients (n = 127).
Table 2.
Sequence of Surgical Interventions for All CHD + CL/P Patients.
| No. (%) |
|
|---|---|
| Surgical interventions | Total cohort (n = 127) |
| Type of surgery | |
| CHD only | 13 (10.2) |
| CL/P only | 64 (50.4) |
| CHD and iCL | 6 (4.7) |
| CHD and iCP | 26 (20.5) |
| CHD and CL/P | 18 (14.2) |
| First lesion repaired | |
| CHD | 58 (45.7) |
| CL | 34 (26.8) |
| CP | 35 (27.6) |
| Interval between CHD and CL repair, daysa | 199 (117.8–238.3) |
| Interval between CHD and CP repair, daysa | 499 (367.0–1,526.0) |
| Interval between CL/P and CHD repair, daysa | 976 (632.0–3,072.0) |
| Age at first repair, daysa | |
| CHD | 21.5 (6.3–113.8) |
| CL | 157 (119.8–214.5) |
| CP | 608 (415.0–1,657.0) |
Abbreviations: CHD, congenital heart disease; CL, cleft lip; CL/P, cleft lip and/ or cleft palate; CP, cleft palate; iCL, isolated cleft lip; iCP, isolated cleft palate.
Data are expressed as median (interquartile range).
Three patients underwent cardiac surgery at an outside hospital. Operative data for the remaining 60 patients whose CHD was surgically managed at our institution are summarized in Table 3. Two-thirds of the patients underwent CHD intervention on cardiopulmonary bypass. The remainder included patients who had PDA ligation, systemic-to-pulmonary shunt, and vascular ring repair. All patients who went on pump required cross-clamping, and about a quarter of the patients in the cohort required deep hypothermic circulatory arrest for their repair. Delayed sternal closure was undertaken in 16 (26.7%). There were two operative deaths. One was a 1.4-kg premature baby who had DORV and a large PDA with significant overcirculation. He underwent PDA ligation but died of extreme prematurity-related complications. The second was a term neonate with DORV/AV canal and pulmonary atresia who underwent systemic–pulmonary shunting. The child developed sepsis-related multi-organ failure 22 days postsurgery. There were 40 (67%) patients who experienced a major morbidity event. This was primarily driven by unplanned noncardiac reintervention in the form of feeding tube placement in more than half of the patients. There was a 15% rate of unplanned cardiac reintervention. Median postoperative ventilator days was 2.0 (IQR: 1.0–4.0) and intensive care unit (ICU) stay was 6 (IQR: 3.0–10.0) days, whereas median hospital stay was 17 days (IQR: 8.0–35.0).
Table 3.
Operative Characteristics and Outcomes for CHD + CL/P Patients Undergoing Cardiac Surgery at Our Institution.
| No. (%) |
|
|---|---|
| Operative variables | Total cohort (n = 60) |
| Cardiac surgery prior to cleft intervention | 55 (91.7) |
| Cardiopulmonary bypass utilized | 39 (65.0) |
| Bypass time (minutes)a | 57 (40.5–78) |
| Cross-clamp time (minutes)a | 41 (34.5–50.8) |
| DHCA utilized | 14 (23.3) |
| DHCA (minutes)a | 29 (22.0–33.5) |
| Days on ventilatora | 2 (1.0–4.0) |
| 30-day mortality | 2 (3.3) |
| Major morbidity | 40 (66.7) |
| ECMO | 3 (5.0) |
| Unplanned cardiac reintervention | 9 (15.0) |
| Phrenic nerve palsy | 2 (3.3) |
| Pacemaker implantation | 1 (1.7) |
| Surgical feeding tube placement | 31 (51.7) |
| Postoperative ICU stay (days)a | 6 (3.0–10.0) |
| Postoperative hospital stay (days)a | 17 (8.0–35.0) |
Abbreviations: CHD, congenital heart disease; CL/P, cleft lip and/or cleft palate; DHCA, deep hypothermic circulatory arrest; ECMO, extracorporeal membrane oxygenation; ICU, intensive care unit.
Data are expressed as median (interquartile range).
To assess the impact of CL/P on CHD management, we sought to compare surgical outcomes between CHD + CL/P patients and CHD lesion-matched patients without CL/P, managed surgically at our institution over the same time period. This analysis included two CHD procedures usually performed in the neonatal period (Truncus and d-TGA) and two during infancy (VSD, TOF/DORV; Table 4). The presence of CL/P did not impact the duration of bypass or cross-clamp, as expected. There was also no significant difference in mortality. However, the median ICU stay was 2- to 3.7-fold longer in patients with CL/P (statistically significant in all subtypes), and the median hospital stay was 1.8- to 2.6-fold longer (statistically significant in all but VSD). Major morbidity was 6- to 13.5-fold higher in CL/P group (statistically significant in all but Truncus). The individual morbidity events in the CL/P cohort included unplanned noncardiac intervention (placement of surgical feeding tube: 8 [22%], airway evaluation/intervention: 4 [11%]); postoperative mechanical support, 2 (6%); and diaphragm plication, pacemaker implantation, thoracic duct ligation, and reoperation for bleeding in 1 (3%) patient each. In contrast, in patients without CL/P, there were 102 morbidity events in 60 (3.9%) patients. This included 47 (3%) unplanned noncardiac interventions (37 [2.3%] surgical feeding tube placement), 26 (1.6%) unplanned cardiac interventions, 13 (0.8%) reoperation for bleeding, 7 (0.4%) pacemaker implantation, and 9 others.
Table 4.
Comparative Data Between CHD + CL/P Patients and a Cohort of Lesion-Matched CHD Patients Without CL/P From Our Institution.
| VSD |
TOF/DORV |
Truncus |
TGA |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Category | CL/P (n = 11) | No CL/P (n = 812) | P value | CL/P (n = 18) | No CL/P (n = 378) | P value | CL/P (n=4) | No CL/P (n = 67) | P value | CL/P (n = 3) | No CL/P (n = 291) | P value |
| Age at surgerya | 4 (2–8) months | 7 (5–11) months | .128 | 5 (1–7) months | 7 (3–8) months | .361 | 6 (6–6) days | 7 (4–9) days | .536 | 9 (8–9) days | 5 (3.5–7) days | .460 |
| Female sex (%) | 5(45) | 341 (42) | .817 | 9(50) | 163 (43) | .565 | 3(75) | 34 (51) | .346 | 3 (100) | 105 (36) | .022 |
| Prematurity (%) | 3(27) | 104 (13) | .157 | 4(22) | 49 (13) | .260 | 0 | 5(7) | .571 | 1 (33) | 46 (16) | .418 |
| Genetic syndrome (%) | 5(45) | 243 (30) | .265 | 7(39) | 30 (8) | <.001 | 3(75) | 40 (60) | .543 | 1 (33) | 5(2) | <.001 |
| Preoperative mechanical ventilation (%) | 1 (9) | 49(6) | .673 | 3(17) | 30 (8) | .190 | 0 | 6(9) | .532 | 2(67) | 196 (67) | .980 |
| Preoperative risk factor present (%) | 2(18) | 65 (8) | .220 | 4(22) | 49 (13) | .260 | 2(50) | 21 (31) | .439 | 2(67) | 201 (69) | .929 |
| CPB time, minutesa | 63 (44–93) | 60 (48–73) | .440 | 68 (55–97) | 70 (47–87) | .510 | 64 (52–72) | 82 (48–78) | .420 | 99 (77–124) | 107 (61–132) | .390 |
| Cross-clamp time, minutesa | 44 (29–66) | 39 (30–51) | .470 | 45 (36–63) | 44 (28–65) | .450 | 39 (37–40) | 53 (38–66) | .440 | 79 (58–96) | 83 (58–93) | .440 |
| ICU LOS, daysa | 6 (5–23) | 2(1–3) | .040 | 11 (5–23) | 3 (2–4) | .014 | 14 (11–65) | 7(4–11) | .001 | 13 (11–17) | 5 (3–13) | .020 |
| Hospital LOS, daysa | 8 (6–30) | 4(2–61) | .080 | 13 (9–26) | 6 (5–8) | .003 | 32 (24–90) | 18 (9–26) | .002 | 39 (25–41) | 15 (6–32) | .001 |
| Major morbidity (%) | 3(27) | 14(2) | .001 | 6(34) | 10(3) | .002 | 2(50) | 4(6) | .258 | 2(67) | 32(11) | .036 |
| Mortality (%) | 0(0) | 3 (0.5) | .999 | 1 (6) | 7(2) | .313 | 0(0) | 2(3) | .999 | 0 (0.0) | 5(2) | .999 |
Abbreviations: CHD, congenital heart disease; CL/P, cleft lip and/or cleft palate; CPB, cardiopulmonary bypass; ICU, intensive care unit; LOS, length of stay; TGA, D-transposition of the great arteries; TOF/DORV, tetralogy of Fallot/double outlet right ventricle; VSD, ventricular septal defect.
Data are expressed as median (interquartile range). The rest of the data are number (percentage).
Follow-Up Data
The longitudinal outcome data following cardiac surgery in the CHD + CL/P cohort are shown in Table 5. The median duration of follow-up was 1.8 years (IQR: 0.2–4.9). There were no deaths during follow-up. Overall, 10 (16.7%) patients underwent 12 surgical reinterventions at a median of 6.9 years (IQR: 2.4–11.0) from initial intervention. These included five right ventricle to pulmonary artery conduit exchanges, one pulmonary valve replacement, four right ventricular outflow tract reconstructions, one valve-sparing aortic root repair, and one Bentall procedure. No patient had significant unplanned residual lesions at the last follow-up.
Table 5.
Longitudinal Follow-Up for CHD + CL/P Patients Who Underwent Cardiac Surgery at Our Institution.
| No. (%) |
|
|---|---|
| Outcomes | Total cohort (n = 60) |
| Follow-up period (years)a | 1.8 (0.2–4.9) |
| Postdischarge mortality | 0 (0.0) |
| Surgical interventions | 10 (16.7) |
| RV-PA conduit/pulmonary valve replacement | 6 |
| RVOT reconstruction | 4 |
| Aortic valve reintervention | 2 |
| Time to intervention (years)a | 6.9 (2.4–11.0) |
Abbreviations: RV-PA, right ventricle to the pulmonary artery; RVOT, right ventricular outflow tract.
Data are expressed as median (interquartile range).
Comment
Congenital heart disease remains the most common birth defect in the United States. While CHD frequently exists as an isolated lesion, it can occur in conjunction with other extracardiac abnormalities. Recent studies have investigated the clinical impact of extracardiac malformations in patients with CHD. Collectively, these reports have shown that in addition to increasing the burden of surgical interventions, extracardiac anomalies elevate the risk for unplanned reoperation, expanded resource utilization, and reduced overall survival following cardiac surgery.13,14 Though informative, the inclusion of heterogeneous patient cohorts with variable noncardiac lesions has precluded the ability to evaluate the clinical impact of specific extracardiac anomalies in patients with CHD. Given the growing interest in developing more personalized prognostic and therapeutic approaches to children with CHD, efforts to understand the influence of specific extracardiac malformations on CHD management are of intrinsic scientific merit.
Our center has established expertise in the care of both pediatric cardiac and craniofacial lesions, thus providing a relatively large cohort of patients with concomitant CHD and cleft malformations. Cleft defects are seen in only a small proportion of patients with CHD; conversely, our analysis has revealed that the prevalence of CHD in cleft patients is about 14-fold greater than that observed in the general population.11 One potential explanation for the enrichment of CHD in CL/P patients is that these disease processes manifest as part of a larger genetic syndrome. In support of this notion, cleft and cardiac anomalies are described features in several genetic disorders, including 22q11 deletion (DiGeorge/velocardiofacial) and CHARGE syndromes. In our own series, over half of the patients were diagnosed with a defined syndrome or known genetic defect, and 48% of patients had at least one more congenital anatomic abnormality, implicating a more global developmental derangement. That said, the causative mechanisms for at least one half of this cohort of CHD + CL/P patients remain unexplained by traditional genetic defects. With recent advancements in next-generation and single-cell sequencing platforms, unbiased genomic analyses in nonsyndromic CHD + CL/P cohorts may help uncover novel genetic and molecular etiologies in these patients.
Another approach to understanding disease pathogenesis in CHD + CL/P patients is to investigate molecular derangements in niche patient subsets. To specifically address this approach, we began by characterizing the distribution of CHD phenotypes in patients with CL/P. We found that the overrepresentation of CHD in this population is driven by selective enrichment of a subset of cardiac lesions, resulting in a profile of cardiac phenotypes in cleft patients that differs from that of the general CHD population (Figure 1). We interpret the higher prevalence of ASD in this cohort to represent a screening bias. This broad diagnosis likely includes a significant number of patent foramen ovale and lesions of limited hemodynamic significance, as evidenced by the fact that a large proportion of patients with “ASD” have not required any intervention to date. The next set of overrepresented cardiac lesions includes TOF/DORV, aortic arch abnormalities, and truncus arteriosus, all of which are outflow tract or conotruncal anomalies. During cardiac development, both outflow tracts and the proximal aortic arch develop from the same set of second heart field cardiac progenitor cells that arise in the pharyngeal mesoderm.15 The selective enrichment of various types of conotruncal anomalies suggests that common cellular or molecular events concurrently orchestrate the maturation processes that govern craniofacial and cardiac outflow tract development. Total anomalous pulmonary venous return was also more prevalent in this cohort. Pulmonary veins develop at the venous or inflow pole of the developing heart, and hence, it is conceivable that a different set of overlapping molecular pathways are involved in craniofacial and pulmonary venous development.
We then sought to analyze the clinical impact of these concomitant defects. As would be expected, the presence of CHD increases the complexity of caring for patients with CL/P. Along these lines, our previous work has shown that a significant additional resource burden is required to care for CL/P patients who also harbor heart defects.11 The current study adds additional perspective to this finding. The overwhelming majority of patients who required surgical intervention for their cardiac lesion underwent CHD repair roughly six months prior to cleft lip repair or 1.4 years prior to cleft palate repair. This difference in time interval represents contemporary practice patterns to undertake cleft lip repair during infancy and cleft palate repair during the second and third years of life. Patients who underwent neonatal cardiac repair had lesions such as truncus arteriosus, HLHS, arch hypoplasia, and so on, that would have generally precluded survival without intervention. Patients with progressively cyanotic lesions (TOF) or significant VSD causing failure to thrive underwent surgery within the first few months of life. Thus, at least in the Western world, by the time a child is being considered for cleft repair, it is highly likely that complex and/or cyanotic CHD has been addressed. In contrast, when cleft care is provided in areas of the world with more limited access to medical care, our data can be used to direct examination to rule out the more complex heart defects of relevance in this patient population.
Our data show that the majority of patients requiring surgical intervention for their CHD will have unrepaired CL/P at the time of their cardiac surgery. In this regard, cleft disease differs from other congenital anomalies, such as tracheoesophageal fistula or congenital diaphragmatic hernia. The STS CHSD mortality risk model has traditionally included noncardiac anatomic abnormalities as a binary all-or-none variable, without regard to the exact nature of the defect.16 A more recent analysis clearly demonstrated that the associated mortality risk varied based on the individual noncardiac abnormality, such that an enhanced model that utilized the individual noncardiac defects, as opposed to a generic binary variable, was more discriminatory.17 Cleft disease was not one of the seven defects analyzed in that study, and our current results would concur that concomitant CL/P does not confer an additional mortality risk. However, compared to contemporary lesion-matched patients undergoing cardiac surgery at our institution without cleft malformations, the presence of concomitant CL/P was associated with longer ICU and hospital stay and increased morbidity. Cleft disease brings unique challenges to patient care without directly affecting cardiac physiology. The difficulty with securing and managing the airway can be particularly problematic in these patients, forcing a deviation from routine institutional practices with ventilator and potentially inotropic management. We speculate that this underlies the longer ICU stay observed in these patients. In addition, among the neonates in our cohort, three patients required reintubation and unplanned airway intervention in the postoperative period, contributing to increased morbidity events. Similarly, feeding issues are further complicated by cleft disease, especially in a neonate who has undergone major cardiac surgery. Patients with cleft disease require specific alterations to feeding approaches, including the need for modified nipples and duration and frequency of feeding. Consequently, maintaining adequate nutrition is often more challenging in this patient population. Given the additional difficulties with establishing and safely maintaining access with nasoenteral tubes in these patients, our institutional preference favors early placement of enteral feeding tubes. Our data reflect this practice, as over half of the CHD + CL/P patients in this series underwent enteral feeding tube placement, another unplanned noncardiac intervention. The requirement for these focused additional efforts to ensure adequate nutrition is likely responsible for the prolonged hospital stay noted in this cohort of patients. Stated differently, our work suggests that the primary driver of increased morbidity and hospital stay in CL/P patients is the need for unplanned noncardiac interventions, including feeding tube placement and airway interventions. As the STS CHSD transitions to a composite risk model that includes morbidity and length of stay outcomes,18 the impact of associated noncardiac defects like CL/P will gather greater relevance, and it is in this regard also that we believe work such as ours is significant.
The current study suffers from limitations inherent to any retrospective observational analysis. First, all patients included in this study were managed at the same institution. Therefore, the demographic findings presented here are subject to selection bias and would need to be generalized with caution. The outcome measures described are also heavily influenced by institutional process measures, such as duration of intubation, decision to place enteral feeding tube, and so on. While there is internal consistency between our comparison groups, direct extrapolation to centers with different practice patterns may not be feasible. In addition, although our cohort includes a relatively large series of patients with concomitant CHD + CL/P, the sample size is still limited, particularly with respect to individual CHD lesions, and additional studies across multiple centers are warranted. Finally, our short follow-up precludes the evaluation of long-term outcomes.
In conclusion, our work demonstrates that the overrepresentation of CHD in patients with CL/P is primarily driven by the enrichment of cardiac outflow tract defects. This suggests that craniofacial and cardiac outflow tract systems share a common developmental basis. In addition, the presence of concomitant CL/P increases the complexity of postoperative care and length of stay in children undergoing surgery for CHD, without impacting surgical mortality.
Supplementary Material
Acknowledgments
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by NIH award K08HL121191 to S.R.K.
Abbreviations and Acronyms
- ASD
atrial septal defect
- CHD
congenital heart disease
- CL/P
cleft lip and/or cleft palate
- d-TGA
d-transposition of the great arteries
- HLHS
hypoplastic left heart syndrome
- ICU
intensive care unit
- IQR
interquartile range
- PDA
patent ductus arteriosus
- STS CHSD
Society of Thoracic Surgeons Congenital Heart Surgery Database
- TAPVR
total anomalous pulmonary venous return
- TOF/DORV
tetralogy of Fallot/double outlet right ventricle
- Truncus
truncus arteriosus
- VSD
ventricular septal defect
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Supplemental Material
Supplemental material for this article is available online.
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