Congenital Diaphragmatic Hernia (CDH) is a rare disorder that occurs in 2–3 per 10,000 births [1] and is characterized by a defect in the diaphragm that allows herniation of abdominal contents into the thorax during development. Additional congenital anomalies and underlying genetic disorders are present in about one-third of patients [1]. Secondary pulmonary hypoplasia and pulmonary hypertension of varying severity occur in almost all patients. These factors result in mortality rates of around 37% [1], with only slight improvement over the last 20 years. Approximately 30% of patients with CDH are treated with Extracorporeal Membrane Oxygenation (ECMO), and mortality in these patients is ~50–60% [2, 3].

Given the significant morbidity and mortality associated with CDH, and the complex intensive care options to treat patients with CDH, extensive effort has been made to identify predictors of outcome. Predictors available prenatally can be used to counsel parents, guide decisions regarding the management of the pregnancy, and determine candidacy for trials of fetal interventions such as fetoscopic endoluminal tracheal occlusion (FETO) [4, 5]. Predictors available prenatally, in conjunction with others derived postnatally, can guide decisions about candidacy for neonatal interventions such as ECMO, and can facilitate comparisons of outcomes between centers with differing patient populations.

Predictors of outcome in CDH patients available prenatally are often derived from fetal ultrasound (US) and magnetic resonance imaging (MRI), and usually assess the degree of pulmonary hypoplasia. These include the lung:head ratio (LHR) and observed:expected LHR derived from fetal ultrasound, and percent predicted lung volume, observed:expected total lung volume (o/e TLV), and the percentage of intrathoracic liver herniation derived from fetal MRI. The utility of these prenatal markers has been determined primarily from data derived from patients with left-sided CDH, who comprise ~75% of cases [6]. In this issue of the Journal of Perinatology, members of the Congenital Diaphragmatic Study Group, utilizing data from their CDH Registry, provide two of the largest clinical series of CDH patients to date, and describe the relationship between prenatal US and MRI findings and postnatal outcomes in both left and right CDH.

In 929 patients with left-sided CDH, Perrone et al. provide further evidence that prenatal US and MRI measurements of lung volume correlate with postnatal outcomes, including survival, ECMO use, defect size, and liver position. Given the large dataset and the statistical significance of the correlations, providers should feel comfortable using these results to assist in counseling their patients and determining interventions.

In contrast, in 156 patients with right-sided CDH, Danzer et al. found that prenatal measurements of lung volume did not correlate with survival. However, measurements consistent with more severe pulmonary hypoplasia did correlate with greater use of ECMO. These data are important in counseling families and in determining the aggressiveness of medical care. Data regarding the relationship between lung volume and survival derived from patients with left CDH are not applicable to those with right CDH. Also, in contrast to data derived in patients with left CDH, survival in patients with right CDH was independent of liver position. This may not be surprising, given the fact that nearly all (90%) right-sided CDH patients had an intrathoracic liver.

It is unclear why measurements of fetal lung volume and liver position should have different relationships with outcome for right versus left CDH. It is possible that the assessments differ in their accuracy based on CDH side, as noted by the authors. It seems more likely, as also noted, that right and left CDH may be the result of different pathophysiological mechanisms. We agree with the authors that continued research is needed to assist in counseling parents and directing fetal and neonatal care.

One similarity between the series of right and left-sided CDH patients is that patients with the largest, “type D” diaphragmatic defects, (whose survival rate was 59% and 81% for left and right-sided CDH, respectively), could not be differentiated by assessments of lung volume from patients whose CDH was not repaired (of whom none survived). It is clear that the degree of pulmonary hypoplasia is not the only factor determining intervention and survival.

Both of these studies are limited in that they are retrospective. However, they consist of the largest number of CDH patients studied to date. Both studies are of great clinical importance and will help guide providers caring for patients with CDH and their families, but the study on right-sided lesions raises numerous questions. If prenatal US and MRI measurements do not predict survival in right-sided CDH, do commonly used postnatal predictors predict survival? For example, does the best PaCO2 achieved after birth, or an inability to achieve a PaCO2 < 70 predict mortality in right-sided lesions, as has been shown in some studies of populations composed primarily of left-sided lesions [7,8,9]? Do prenatal assessments of lung volumes in the lower range of the lowest category (for example, o/e TLV on MRI < 15%) predict mortality? Is there an absolute lowest prenatal measurement of pulmonary hypoplasia that predicts 100% mortality? If a low o/e TLV on fetal MRI predicts the need for ECMO but not survival, could the early initiation of ECMO, including in the delivery room, improve outcome, as some suggest [10]?

These questions, and others, are best answered by studies of large series of patients with CDH, like the two published in this journal evaluating patients from the Congenital Diaphragmatic Study Group’s CDH Registry. We look forward to further studies evaluating pre and postnatal predictors of outcome, and the best management strategies for patients with CDH, including the possible use of prenatal therapies such as FETO or postnatal therapies such as ECMO. For now, among CDH patients with the most severe lesions, there continues to be uncertainty regarding which patients to treat and which patients to withhold therapy, particularly if the diaphragmatic defect is on the right.