Post-operative anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery

Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094). Conclusions: A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center. What is Known: • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. What is New: • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. What is Known: • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. What is New: • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.


Introduction
Morgagni hernia is a retrosternal diaphragmatic hernia named after the famed Italian anatomist Giovanni Batista Morgagni (1682-1771).Morgagni hernias are rare and account for less than 2-5% of congenital diaphragmatic hernias [1,2] and are due to failure of fusion of the crural and central portions of the diaphragm at the 8th week of gestation [3].They can be located bilaterally behind the sternum, with the right side usually appearing more prominent [2].The natural history of this hernia is not well studied, but life-threatening situations have been described [4,5].Most cases of Morgagni hernia are found incidentally during chest radiographs performed for upper respiratory tract infections.When symptomatic, the presentation may be of a bowel obstruction due to incarcerated loops, respiratory distress due to occupation of the thoracic space by the bowel, cardiac compression, or failure to thrive [5].
Trisomy 21 (Down syndrome, DS) is the most common chromosomal abnormality in live births [6] and typically manifests as dysmorphism with characteristic appearance, intellectual and developmental disabilities, heart defects, hypotonia, poor wound healing, and additional congenital anomalies [7].Nearly half of infants born with DS are born with a congenital heart defect [8,9], which in many cases requires surgical intervention [10].
Several studies have reported an association between Morgagni hernias and DS [11][12][13], especially in patients with a heart defect [14].In one retrospective study, 15 of 21 patients (76%) who underwent surgery for an anterior diaphragmatic hernia had DS, and nine of them (43%) had previously undergone cardiac surgery [15].The authors postulated that there may be an association between anterior diaphragmatic hernia and cardiac surgery in children with DS; however, the study made no comparison with a control group.
Only a few of the studies reporting post-operative diaphragmatic hernia discuss children [16,17], and only several cases of children with anterior diaphragmatic hernia following cardiac surgery have been reported to date [15,18,19].These articles did note, however, that the phenomenon is likely much more prevalent, but that it is not reported, or else not attributed to an iatrogenic etiology [16].
The hypothesis that cardiac surgery is one of the causes of diaphragmatic hernias resembling Morgagni hernias in children with DS is reinforced in light of accumulated evidence of connective tissue problems and tissue healing defects in patients with DS, as well as an impaired immune system [19][20][21].These can explain why this rare defect can occur more frequently in children with DS after cardiac surgery than it does in other post-cardiac operation children.
There is a paucity of literature regarding anterior diaphragmatic hernias resembling Morgagni hernias as a sequel of cardiac surgery in patients with DS.The purpose of this study was to investigate the possible association between surgical repair of heart defects in children with DS and the subsequent appearance of an anterior diaphragmatic hernia.

Patients and methods
This study is a retrospective observational cohort study.The study was approved by the Hadassah Medical Organization institutional review board (HMO-0124 -19).

Study population
The study group included 92 children with DS who underwent cardiac surgery in our institution between 2011 and 2019.This study group was compared with a control group of 100 children of similar ages without DS who underwent cardiac surgery during the same period (and by the same surgeon) in our institution.

Data collection
All available chest radiographs (CXRs) of the children from the study group and the control groups were blindly evaluated for the presence of a diaphragmatic hernia by a pediatric radiologist.Each CXR was categorized by orientation (AP only, Lateral only or AP and Lateral) and whether there is evidence of a hernia (marked as 1) or no evidence of a hernia (marked as 0).The CXR categorizations were correlated with the patients' clinical course, which was collected from patient's electronic medical records, in order to verify whether they had been diagnosed with, or operated for, an anterior diaphragmatic hernia.

Statistical analysis
The comparison between the groups was made using Fisher's exact test.

Results
We reviewed 3247 CXRs of 192 patients: 1482 CXRs of 92 children with DS after cardiac surgery (the study group), and 1765 CXRs of 100 patients in the control group of children without DS who underwent cardiac surgery.The characteristics of the children and the two groups, including the number of CXRs and the duration of the follow-up periods, are presented in Table 1.
In the study group, four patients with an anterior diaphragmatic hernia were found.In three children, the findings were identified in a CXR, both in the AP and in the Lateral view (Fig. 1) and in two cases findings were confirmed by an upper gastrointestinal (UGI) series (Fig. 2).In one case (a hernia containing liver) the diagnosis was made by CT (Fig. 3).In all the cases that were treated surgically, the diaphragmatic defect was located in the left diaphragm, contrary to the classic Morgagni hernia.
In the control group, no known or suspected cases of an anterior diaphragmatic hernia were found (P = 0.0094, CI of 95%).
Of the 4 patients who were identified with an anterior diaphragmatic hernia, one patient had a recurrent hernia about a year after the initial hernia diagnosis and surgical repair.This hernia was also detected on CXR, so a total of 5 cases of diaphragmatic hernia were found.
All hernia patients were diagnosed when the patients were referred to the emergency room.All of them had breathing difficulties (5/5).Other complaints included fever (3/5), desaturation (2/5) or vomiting (2/5).Time between cardiac surgery and presentation of the hernia symptoms was 9 months (3/4) to 13 months (1/4) (average = 15.5 months, median = 15.5 months, IQR = 9.5 months).The case of the recurrent hernia appeared a year after the repair of the first hernia.In none of the cases found in this study was there evidence of a hernia in CXR obtained prior to and immediately after the cardiac operation.

Discussion
Several case studies have reported the association between cardiac surgery in children with DS and anterior diaphragmatic hernia [15,17,18].However, this association has not been thoroughly investigated, hence no recommendations have been made regarding the assessment and the duration of follow-up required to detect these cases and to prevent their potential complications.
Our study found that there is indeed a higher incidence of anterior diaphragmatic hernia in children with DS who have undergone cardiac surgery (4/92, compared with 0/100 in the control group, P = 0.0094, CI of 95%).In addition, one of the children suffered a recurrent hernia a year after the first hernia was repaired.In four out of five cases, the hernia was detected on a CXR (Fig. 1).In the remaining case the hernia was detected only by CT (a hernia that contained liver but not the intestine, Fig. 3).All cases were detected when the patients attended the emergency room with respiratory and concomitant complaints within 9-13 months after cardiac surgery.In contrast to the right-sided predominance of congenital Morgagni hernia [2], in 4 of our 5 cases with post-operative hernia, it occurred on the left.No cases of a congenital hernia were detected in any of the children in the study group or in the control group.Our findings support a strong association between cardiac surgery in children with DS and an anterior diaphragmatic hernia that appears after surgery.The higher incidence in the study group versus the control group can be explained by a combination of several causes.These include opening of the abdominal cavity while opening of the sternum and pericardium (Fig. 4).Both the experience of surgeons at our institution and the cases reported in the literature indicate that the location of the hernias corresponds with the end of the surgical incision [17,18].In many cases, surgical drains and pacemaker wires are inserted at this location.These are removed by pulling, without a specific suturing or surgical closure, a few days after surgery -presumably prior to the complete healing of the tissues.However, no similar incidence was observed in children without DS who underwent cardiac surgery using similar surgical technique.In addition, in all children operated in our institution, chest drains were located under the right costal margin, rather than at the end of the surgical incision.Hence, it seems that reduced tissue healing in children with DS has an important part in the development of these defects [15,[19][20][21].
As a consequence of the findings of this study, the surgical technique has been modified in patients with DS in our medical center.It currently includes suturing the diaphragmatic pericardium to the upper abdominal fascia so that there will be no potential connection left between the thoracic and abdominal cavities.Since this change was implemented 39 additional children with DS had cardiac surgery in our institution, and as of submission of this paper we have not encountered any additional cases of post-operative anterior diaphragmatic hernia.
In light of these findings, it appears that there is no need for special preoperative evaluation (beyond a routine AP and Lateral CXR, as is common prior to cardiac surgery).As shown in our study and as reported in the literature [2,4,22], anterior diaphragmatic hernias are very rare, and not a single case was found in a a similar-size group of Fig. 2 Antero-posterior (a) and lateral (b) views of the upper abdomen after contrast ingestion of a 16-month-old girl with DS, 9 months after VSD repair, with breathing difficulties.Follow-up radiographs reveal passage of colon into the thorax (arrows), emphasizing the need to demonstrate the entire gastrointestinal tract if hernia is suspected Fig. 1 AP (a) and Lateral (b) CXR of an 18-month-old boy with Trisomy 21, with respiratory distress 13 months after cardiac surgery.A radiolucent finding passing from the abdomen to the chest anteriorly to the liver and immediately posterior to the sternum (arrows) overlies the heart on the left 1 3 patients with DS who had not undergone cardiac surgery.All our patients with an anterior diaphragmatic hernia were diagnosed when they referred for medical assistance (Table 2), and no other asymptomatic patients were found in our survey.Considering the symptomatic presentation, no special follow-up for children with DS who had undergone cardiac surgery appears to be necessary.It should be noted, however, that in 2 cases the radiographic findings were initially attributed to pneumonia and the suspected diagnosis of a hernia was verified by an upper gastrointestinal series (UGI) performed after antibiotic treatment did not resolve their symptoms.Nevertheless, 4 out of our 5 cases were detected by a regular CXR in which the diagnosis was clearly evident to medical practitioners with different levels of training, experience and expertise.
We therefore recommend that in any referral of a child with DS after cardiac surgery to a physician due to respiratory complaints, vomiting or suspected bowel obstruction, a high level of suspicion for an anterior diaphragmatic hernia should be maintained.If the findings on a CXR are not clear enough, it is recommended to continue with gastrointestinal imaging after ingestion of a contrast agent (Fig. 2), and if necessary, by a CT scan, for cases of diaphragmatic hernias that do not contain intestine and therefore are not well demonstrated on CXRs.
Our study is not free of possible biases, above all the fact that this study was conducted based on data obtained from a single medical center.It is certainly possible that a patient who underwent cardiac surgery at our institution was later diagnosed and/or operated for an anterior diaphragmatic hernia at another institution and therefore would not be included in our results.However, if such cases (unknown to us) exist, then the incidence of the reported association is even higher.
In addition, we assumed that the study group could be compared to the control groups, but it can be argued that the surgeries performed in the study group of patients with DS that have characteristic cardiac defects [8,9], differ from those performed in the control group of children without DS.However, the surgical techniques of the initial sternotomy as well as the chest wall closure at the end of the surgery were similar in both groups.
Another difference between the groups is the number of CXRs performed for each patient in the different groups (Table 1).The number of CXRs in the group of children with DS who did not undergo surgery was significantly lower when compared to the other two groups.Theoretically, then, there may have been diaphragmatic hernias in this group that were not detected.Liver tissue is seen anterior to the heart protruding the chest at the level of the Xyphoid (arrows) Fig. 4 Image from surgery, a view from the chest to the abdomen after opening the sternum and pericardium.The triangle within which the probe is located is a diaphragmatic opening to the abdominal cavity, through which the intestine can rise into the thoracic cavity behind the sternum

Conclusion
Our findings show that there is a higher incidence of anterior diaphragmatic hernias resembling Morgagni hernias in children with DS after cardiac surgery, when compared both with children without DS who underwent cardiac surgery, and with children with DS who did not have cardiac surgery.In light of this finding, cardiac surgeries administered to this cohort at our medical center now include the additional, integral step of suturing the diaphragmatic pericardium to the upper abdominal fascia after repair of the cardiac defect.No special follow-up is needed for children with DS who undergo cardiac surgery before or after surgery.A high index of suspicion for anterior diaphragmatic hernias should be maintained when children with DS who have had cardiac surgery seek medical attention due to breathing difficulties, vomiting or suspected bowel obstruction.If findings on CXR are not diagnostic, additional imaging exams should be performed, including upper gastrointestinal imaging and/or CT, if necessary.

Fig. 3
Fig.3Axial (a) and sagittal (b) reformats of an unenhanced CT scan of a 14-month-old child with Trisomy 21, who had fever and shortness of breath, 9 months after cardiac repair.Liver tissue is seen anterior to the heart protruding the chest at the level of the Xyphoid (arrows)

Table 1
Patients data.Characteristics of the two study groups.The duration of follow-up is determined as the time elapsed from the first CXR in the system to the last CXR in the system Numbers in bold represent the most significant results

Table 2
Hernia case data.