Congenital diaphragmatic eventration and hernia sac compared to CDH with true defects: a retrospective cohort study

The clinical presentation of a congenital diaphragmatic hernia (CDH) can be variable, and the prognosis depends on multiple factors, with survival rates ranging from 70 to 80% [1, 2]. The most common type of a diaphragmatic defect is a posterolateral defect also known as Bochdalek hernia, which accounts for about 85% of the cases [3]. Bochdalek hernias occur due to an abnormal pleura-peritoneal fold development, where normally these folds fuse between the 5th and 7th week of gestation [4]. In this type of CDH, organs may herniate into the thorax because of the incomplete diaphragm. Congenital diaphragmatic eventration (CDE) is clinically seen and often treated as another subtype of CDH, although in the worldwide used CDH study group (CDHSG) scoring system, a specific classification for eventration, does not exist [3, 5, 6]. In CDE, there is incomplete muscularization of the (hemi)diaphragm, which results in a weakened muscularized dysfunctional diaphragm causing protrusion of abdominal contents into the thoracic cavity [4]. Clinical manifestations are diverse, varying from asymptomatic to life-threatening respiratory distress. Overall, it is thought to have a relatively good outcome, but exact numbers are not described [7], because most studies do not specify this subtype as a specific entity [2, 8‐12].

CDH type Bochdalek patients can either have a true defect (“classic”) or a hernia sac, which has been described in 14–20% of cases. The latter type is often considered as a common variation of the “classic” CDH [3, 13‐15]. In patients with a hernia sac, a non-muscularized pleuroperitoneal sac covers the herniated organs in the thorax [13, 14]. As however no explanation for the development of a hernia sac has yet been found, the question raises whether these patients with no “classic” true defect are more similar to the other patients with no true defect: CDE patients. Although the three different types described (CDH with a defect, CDH with a hernia sac and congenital diaphragmatic eventration) seem to be part of one spectrum, they may have been caused by different embryological events. The aim of this study is to evaluate whether there is a difference in clinical outcome between Bochdalek CDH with a true defect and patients without a true defect (hernia sac and eventration patients). A subanalysis will be performed to evaluate whether the presence of a hernia sac has more comparable clinical outcomes to CDE rather than Bochdalek type CDH with a true defect.

In the study period, 228 patients were admitted for CDH in this tertiary center. Patients before and after 2010 (after the CDH Euroconsortium paper, as stated in the methods [16]) were compared on demographics, treatment, and outcomes. Comparison showed that there were no significant differences between these parameters during these two periods. The inclusion of the patients and division in the subgroups are demonstrated in Fig. 1, leaving 200 patients eligible for this study. They had a median follow-up of 11 years (range: 1–18). Of the total group, 77% had a CDH Bochdalek with a true defect (CDH_truedefect), 10% had a CDH Bochdalek with a hernia sac (CDH_herniasac), and 9% was diagnosed with an eventration.

This study suggests that CDE and a Bochdalek type CDH with hernia sac could have a more comparable clinical characteristics and surgical or short-term pulmonary outcome than patients with a true defect. This could be explained if the hernia sac is considered as an early form of an eventration. Both an eventration and a hernia sac then occur later in the embryology than the complete true defect in the diaphragm [3, 4, 15, 18]. The pleura-peritoneal fold has been closed in both scenarios, either just as a weak hernia sac or with little muscularization in case of an eventration, and may have been caused by different embryological events.

Patients with eventration have a significant better survival than the Bochdalek type CDH with true defect, which has been previously postulated as well [7, 19‐22]. This was also stated for CDH patients with a hernia sac [13, 14, 23]. Despite the better survival rates, the two major findings of this study were the clinically relevant high recurrence rate (14%) and significantly longer need of respiratory support in patients with an eventration or with a hernia sac compared to (surviving) Bochdalek type CDH patients with a true defect.

The recurrence rate of CDH_notruedefect within 1 year was higher than in previous statements, where no recurrences in CDE were reported [7, 19‐22]. Then again, the total number of recurrences found in the Bochdalek type CDH in this cohort (5%) is relatively low in comparison to other studies, and the sample sizes of both eventration and hernia sac patients are relatively small [8, 24]. Previous studies suggested that the severity or defect size of CDH would be a prognostic value for recurrence rates [24‐27], but these cohorts were not adjusted for CDE and CDH with hernia sacs. The current study shows that during follow-up of the surviving patients, patients with no true defects have a higher recurrence rate than patients with a true defect. Recurrence rates of CDH_notruedefect even remain higher than Bochdalek patients with a patch, being a surrogate for large defect sizes in classic CDH. The higher recurrence rate might be explained by the fact that the use of a diaphragm patch for repair in patients with eventration or hernia sac is low, suggesting an underestimation of the strength of the repair. The native diaphragm may have been too weak for a reliable primary closure. The non- or partially muscularized tissue is probably not as strong as normal diaphragm and stretches more easily in the long run, causing more recurrences or new eventration. A lower threshold to use of patch closure in patients and resection of the hernia sac or part of the eventration may prevent the recurrences in both CDH patients with hernia sac or eventration of the diaphragm. However, due to the retrospective nature of these studies, confounding for the manner of hernia sac repair was not possible, a question for which prospective trial would possibly be required.

Another remarkable finding was that the patients with no true defect had a higher need for respiratory support, oxygen supplementation, both at 30 days of life and at time of discharge. For the groups separately, this clinically relevant difference was similar at discharge, however, not significant probably due to the small number of patients in the hernia sac and eventration group. These patients in this study initially had a better outcome but improved clinically less extensive than expected at 30 days and at discharge or even deteriorated. Because the numbers of pulmonary hypertension, treatment with inhaled nitric oxide, and ECMO were relatively low, pulmonary hypertension did not seem to explain this worse outcome for eventration patients of CDH patients with a hernia sac. Other explanations may be the presence of a more pronounced or underestimated pulmonary hypoplasia, a lesser functional diaphragm than previously thought (with higher recurrences) or the higher presence of other birth defects, which was shown in this study. Whatever the cause, the poor pulmonary condition with higher need for respiratory support at 30 days and at discharge warrants close pulmonary follow-up in this group of patients. In a future prospective study on this subject, it would be interesting to look for diaphragm motility disorder during follow-up, not only to explain difference in clinical follow-up but also to correct the outcomes for type of repair and its consequence on the function of the diaphragm. This could give us new insights in the type of surgery, type of defect, and functional outcome on the requirement of more ventilation and oxygen. Two previous studies by Levesque et al. (2019) and Oliver et al. (2019) showed a lower oxygen dependency after 28 respectively 30 days for hernia sac patients [28, 29]. However, all of these studies (including this study) are retrospective single center studies; therefore differences in diagnostics and treatment could give a bias (e.g., a difference in ECMO rate). Moreover, there may also be differences in the comparison to the patient groups of both centers in the non-hernia sac group, as, for example, in this study, eventration patients were excluded from the non-hernia sac group. Despite the differences between the patient groups, the rate of oxygen supply for hernia sac patients in our study seems to be comparable to the study by Oliver et al. (2019) (39% versus 44%). For the long-term follow-up, pulmonary function does seem to improve, as was also shown in other studies [13, 14, 23]. Wu et al. (2015) proved that the symptoms of their 86 symptomatic eventration patients resolved after surgery so timely diagnosis and treatment are related to lower respiratory morbidity (such as respiratory chest infection and cough) in these patients [19].

Due to the retrospective nature, data collection was incomplete and may be less reliable. Examples were the lack of access to data from the prenatal period such as the observed lung-to-head ratio (O/E LHR). For example, patch repair had to be used as surrogate for the size of the defect. The pooling of the data in the combined CDH hernia sac group and eventration group for subanalysis of comparison between a true and non-true defect may hypothetically be right but may have given a bias as well, based on the relatively small sample sizes of especially hernia sac and eventration patients. Although no significant differences in characteristics and outcome of these patients were found, a larger prospective cohort needs to confirm that these groups can be seen as one and give definite conclusions of the data given in this study. Also, the fact that some of the patients did not survive, mainly in the true Bochdalek group, could give a bias in the long-term outcome; however this group was not the focus of this study.

The recurrence rate for patients without a true congenital diaphragmatic hernia defect (hernia sac and eventration) seems to be higher than for patients with a true Bochdalek type congenital diaphragmatic hernia. The similarities in these patients without a true defect found in this study can be an indication that these defects are often underestimated. The short-term outcomes of these patients are comparable to patients with a small true diaphragmatic defect, while the long-term prognosis is more comparable to patients with a large defect. Further studies are needed to evaluate whether the surgical techniques (to use or patch or not) for these specific defects need to be adjusted to prevent recurrences and improve the pulmonary outcome at 30 days of age and at discharge.