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Fetal lung assessment in congenital diaphragmatic hernia: evidence for growth

Congenital diaphragmatic hernia (CDH) occurs in 1/4000 births, with a neonatal mortality of 47–60% of affected cases1. Arguably, this is one of few fetal conditions which has justified the relentless efforts over the last 30 years to discover an efficient intrauterine treatment. Indeed, in the case of isolated CDH there is a high risk of perinatal death and morbidity, mainly because of pulmonary hypoplasia and pulmonary hypertension that cannot be treated efficiently postnatally. Although the natural history of the disease has been elucidated only partially, there is strong evidence to support the hypothesis that the condition worsens throughout pregnancy due to lung compression. Accurate prognostic evaluation is critical to define the forms of CDH likely to benefit from intrauterine therapy. Adverse outcome can be independently predicted prenatally by the ultrasonographic measurement of the contralateral lung as well as by assessing the position of the fetal liver2. Lung measurements are performed by ultrasound and are related to head circumference in the lung-to-head ratio (LHR), which increases with gestational age, both lungs growing faster than does the head circumference in normal fetuses3. The trace method, which delineates the lung perimeter in a transverse section of the thorax at the level of the cardiac fourchamber view, has proved more reproducible than are the anteroposterior diameter or multiplication of the two longest axes of the lungs, in both normal fetuses and those with CDH4,5. Although the trace method is not widely used, optimal measurements would be obtained using this method, reported with respect to the expected measurement for gestational age (observed to expected (O/E)-LHR)3. Use of magnetic resonance imaging (MRI) does not significantly improve assessment of lung growth or hypoplasia6. Similarly, diffusion-weighted MRI has not so far significantly improved the prognostic value of biometric lung assessment, although this early experience was in fewer than 20 cases7. MRI does, however, have a role in the quantitative assessment of liver herniation, a method that Cannie et al. have suggested overcomes the subjectivity of ultrasound evaluation8. In cases with severe left CDH, defined by an O/E-LHR of less than about 25% and intrathoracic herniation of the fetal liver, the predicted survival rate with traditional expectant antenatal management and postnatal ventilatory support for stabilization followed by surgery is less than 30%5. Furthermore, morbidity in survivors is high, with evidence of bronchopulmonary dysplasia in more than 70% of cases, and this also relates to prenatally measured LHR9 (Table 1). A recent systematic review of the literature emphasized, however, that LHR alone was not discriminant in predicting survival10. This may reflect the heterogeneity of the series reviewed, particularly with reference to the cut-off used to measure LHR in absolute values, where a cut-off of 1 applies in earlier gestation and one of 1.4 applies for assessment at ≥ 26 weeks. This underlines the importance of using the O/E values. The high rates of perinatal mortality and severe morbidity in survivors with isolated CDH have not been improved as a result of open fetal surgery aimed at complete anatomical correction of the anomaly. Over the last 10 years, the target of fetal surgery has therefore moved towards securing temporary fetal tracheal occlusion (FETO) using an inflatable device, in an attempt to cause transient lung overgrowth in order to counteract the process leading to lung hypoplasia and hypertension, while allowing normal lung function. Although in animal models such palliative endoscopic fetal surgery was successful in restoring lung growth and function, the efficacy of this strategy in humans is still debated. By 2009, the European FETO consortium had performed over 200 of these procedures, with consistent results: a survival rate of 50% following FETO, while the estimated survival in untreated cases was less than 30%. The rate of bronchopulmonary dysplasia also apparently decreased, from an estimated rate of more than 70% to less than 40% in the same severity group. However, FETO is associated with a risk of PPROM (15% within 3 weeks) and an earlier gestational age at delivery (mean, 35.3 weeks)11. In the first randomized controlled trial (RCT) in human fetuses, FETO failed to show any clinical benefit12. A possible explanation for the inconclusive results is the heterogeneity of both the severity of the cases as well as the techniques used. Cases were recruited if their preoperative LHR was below 1.4. However, LHR increases with gestational age and a cut-off of 1.4 before 28 weeks cannot necessarily be categorized as reflecting a poor prognosis. As such, a large proportion of the cases included in this RCT are likely to have had a good prognosis without antenatal intervention. The FETO technique used was not only percutaneous but also by laparotomy and hysterotomy, invasive techniques that are associated with a high risk of preterm birth. Three new articles published in this issue of the Journal suggest that additional prognostic factors could be used in case selection for FETO. Moreno-Alvarez et al.13 studied fetuses with left CDH in which lung tissue perfusion was assessed by analysis of fractional