Dear Editor,

We read with interest the paper by Bonfils et al. [1] in which the authors report the prognostic interest of foetal lung volume (FLV) in congenital diaphragmatic hernia (CDH); FLV was measured by magnetic resonance imaging (MRI), and expressed as the ratio of the measured FLV to the expected FLV at the same gestational age given by the normative curve. [2] In this study, including 22 neonates with CDH, the best FLV ratio cut-off was 30%, with a sensitivity of 0.83 (0.55- 0.95), and a specificity of 1 (0.72- 1). Ten neonates had FLV ratio under 30% and all of them died.

We conducted a retrospective study of full term neonates with prenatal diagnosis of isolated CDH between November 2003 and March 2006. FLV ratio was measured by MRI (Siemens Medical System, 1.5-T). All neonates were inborn and managed as previously described [3], the main goal being early postnatal control of persistent pulmonary hypertension of the neonate (PPHN). Seven foetuses were evaluated. Results are expressed as mean+/-SD. The main characteristics of the population are shown in Table 1. FLV ratio was 29+/-10%. One baby died at day 1 of postnatal age and FLV ratio was 17 %. For the other babies, FLV ratio was 31+/-10 % and all of them (86%) survived. Among those six survivors, three had FLV ratio below 30% (17 – 22 – 28 %). MRI characteristics and post natal outcome are shown in table 2.

CDH is traditionally associated with a poor outcome especially when it is associated with polymalformation, abnormal karyotype and prematurity. Prenatal diagnosis permits to delineate early isolated CDH, which are associated with a better outcome. In isolated CDH, the central issue remains PPHN with pulmonary hypoplasia. Since years, ultrasonographists and radiologists have tried to link prenatal measurements to postnatal prognosis. No single antenatal sign has been shown to predict accurately death in foetuses with isolated CDH.

FLV ratio measured by MRI can now be used routinely in clinical practice to evaluate the importance of pulmonary hypolasia. However, in our hands, FLV ratio does not appear to be a good predictor of individual postnatal outcome. Bonfils et al. referred to three investigations: One study [4] reported no statistical difference of FLV between survivors and non survivors in a retrospective study of 41 cases, but FLV were not expressed in percentage of an expected value. Mahieu-Caputo et al. [5] reported a relationship between FLV and survival, in 13 cases of CDH. The FLV ratio was significantly lower in neonates who died (median: 26%, range: 6-63%) compared to those who survived (median: 46%, range: 35-56%). Peak et al. [6], in 11 foetuses with CDH, reported four foetuses with a FLV ratio less than 40%, three of whom died. Another study [7] reported that a 25% FLV ratio appeared to be the threshold below which survival was significantly worse (19%) and above which survival was significantly better (60%) than the global survival rate (40.3%). For this threshold, sensitivity was 0.79 and specificity 0.64. However, the authors pointed out that FLV ratio should be used very carefully notably because of serious ethical issues.

In all these series the survival rate of CDH was between 40% and 73% for FLV ratio between 29% and 42%. In our team, the prenatal discussions with obstetricians and parents never took into account the FLV ratio. Nevertheless, in our series, the survival rate in isolated CDH is now established around 92% [3]. High survival rates may alter the prognostic value of an isolated indicator. Our data do not support the strong association reported between FLV ratio and survival. The FLV ratio does not permit individual prognosis, suggesting again that pulmonary hypoplasia may not be the only determining factor in survival of foetuses with isolated CDH as far as PPHN is controlled.

In conclusion, we think that the determination of measured/expected FLV ratio cut-off alone is not sufficient to delineate very high risk patients with isolated congenital diaphragmatic hernia. The clinical use of this statistical indicator could lead to inaccurate parent’s information or enhanced indication of prenatal intervention. The major issue is ethical. The clinical use of FLV ratio could lead to an inappropriate increased demand for termination of pregnancy.

References:

1 Bonfils M, Emeriaud G, Durand C, Brancato S, Nugues F, Jouk PS, Wroblewski I, Debillon T. Fetal lung volume in congenital diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed. 2006; 0: adc.2005.079392v1.

2 Rypens F, Metens T, Rocourt N, et al. Fetal lung volume: Estimation at MR imaging-initial results. Radiology 2001;219:236-41.

3 Betremieux P, Gaillot T, de la Pintiere A, Beuchee A, Pasquier L, Habonimana E, Le Bouar G, Branger B, Milon J, Fremond B, Wodey E, Odent S, Poulain P, Pladys P. Congenital diaphragmatic hernia: prenatal diagnosis permits immediate intensive care with high survival rate in isolated cases. A population-based study. Prenat Diagn. 2004 Jul;24(7):487-93.

4 Walsh DS, Hubbard AM, Olutoye OO, et al. Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol 2000;183:1067-9.

5 Mahieu-Caputo D, Sonigo P, Dommergues M, et al. Fetal lung volume measurement by magnetic resonance imaging in congenital diaphragmatic hernia. BJOG 2001;108:863-8.

6 Paek BW, Coackley FV, Lu Y, et al. Congenital diaphragmatic hernia: prenatal evaluation with MR lung volumetry - preliminary experience. Radiology 2001;220:63-7.

7 Gorincour G, Bouvenot J, Mourot MG, Sonigo P, Chaumoitre K, Garel C, Guibaud L, Rypens F, Avni F, Cassart M, Maugey-Laulom B, Bourliere- Najean B, Brunelle F, Durand C, Eurin D; Groupe Radiopediatrique de Recherche en Imagerie Foetale (GRRIF). Prenatal prognosis of congenital diaphragmatic hernia using magnetic resonance imaging measurement of fetal lung volume. Ultrasound Obstet Gynecol. 2005 Dec;26(7):738-44.

Tables 1 & 2