is a relatively common birth defect, and long-term healthy
survival in affected fetuses is low.1
For this reason, many avenues of investigation into improving
outcome are warranted. These include investigations into the
mechanisms of development, as well as research to develop
new ways to better predict outcome and to reduce morbidity
and mortality. One approach to determining the cause of these
defects is to investigate the genetic contribution to the
disease. Recent advances have been made in determining multiple
genetic contributors to the spectrum of diaphragmatic defects.2
The articles by Scott et al and Slavotinek et al (reviewed
herein) describe the use of whole genome array hybridization
screens to identify cytogenetic hot spots for CDH patients.
Specific chromosomal deletions are repeatedly associated with
syndromic forms of CDH.3,4
Isolated CDH also has a genetic component supported by mouse
models and by human association, but a single common genetic
cause for CDH has not yet been identified.2,5
Estimates of fetal lung size have been used to predict outcome
in fetuses with CDH. Use of the lung area to head circumference
ratio (LHR) to predict outcome has been used with mixed success.
Since many variables affect the LHR measurement, it is difficult
to compare data across centers or to determine why this measurement
is not effective for all neonates.6
In Europe, FETO is used to promote lung growth in fetuses
with high-risk CDH.7
As synopsized herein, Peralta et al describe the use of 3D
ultrasound to show that lung volume increases after the procedure,
and the increase in lung volume is associated with better
Measurement of lung volume by fetal magnetic resonance imaging
(MRI) has been developed as an alternative to ultrasound.
The articles by Barnewolt et al and Hayakawa et al found that
there was good risk prediction of survival based on fetal
lung volume MRI. Although different measurement and calculation
parameters were used, there was agreement in the ability to
Perhaps lung volume MRI will be a better predictive tool than
lung ultrasound across centers. Prediction of outcome might
also be possible based on the size of the diaphragmatic defect.
In the article from The Congenital Diaphragmatic Hernia Study
Group, it was determined that the size of the defect at the
time of repair was associated with the degree of morbidity
It is still to be determined whether the defect size correlates
well with lung size or whether hernia sizes can be measured
There has been previous debate about surfactant deficiency
in neonates with CDH, largely based on findings of surfactant
deficiency in a large animal model of CDH.12
Boucherat et al studied surfactant maturation in human fetal
lungs in fetuses with and without CDH and compared these findings
to those in the sheep model. They found that human CDH fetal
lungs had normal surfactant maturation and content, and that
the sheep fetal measurements were different from humans.12
This supports not using surfactant therapy in term neonates
with CDH, and highlights the difficulty in assuming a mechanically
generated animal model of CDH matches that of the human disease.
Overall, much progress has been made recently towards stratifying
risk factors in the heterogeneous group of patients categorized
as having "CDH". Hopefully, a future understanding of the
basis for variability in lung size, defect size and type,
and cardiopulmonary function in CDH patients will lead to
the development of therapies to further improve outcome.
J, Bower C, Dickinson JE, Sokol J. Outcomes
of congenital diaphragmatic hernia: a population-based
study in Western Australia. Pediatrics
KG, Pober BR. Congenital
diaphragmatic hernia and pulmonary hypoplasia: new insights
from developmental biology and genetics. Am
J Med Genet C Semin Med Genet 2007;145(2):105-8.
DA, Klaassens M, Holder AM, et al. Genome-wide
oligonucleotide-based array comparative genome hybridization
analysis of non-isolated congenital diaphragmatic hernia.
Hum Mol Genet 2007;16(4):424-30.
AM, Moshrefi A, Davis R, et al. Array
comparative genomic hybridization in patients with congenital
diaphragmatic hernia: mapping of four CDH-critical regions
and sequencing of candidate genes at 15q26.1-15q26.2.
Eur J Hum Genet 2006;14(9):999-1008.
KG, Herron BJ, Vargas SO, et al. Fog2
is required for normal diaphragm and lung development
in mice and humans. PLoS Genet 2005;1(1):58-65.
ME, Jesudason EC, Losty PD. How
useful is the lung-to-head ratio in predicting outcome
in the fetus with congenital diaphragmatic hernia? A
systematic review and meta-analysis. Ultrasound
Obstet Gynecol 2007;30(6):897-906.
J, Jani J, Gratacos E, et al. Fetal
intervention for congenital diaphragmatic hernia: the
European experience. Semin Perinatol 2005;29(2):94-103.
CF, Jani JC, Van Schoubroeck D, et al. Fetal
lung volume after endoscopic tracheal occlusion in the
prediction of postnatal outcome. Am J Obstet
Gynecol 2007.Sep 7; [Epub ahead of print]
CE, Kunisaki SM, Fauza DO, Nemes LP, Estroff JA, Jennings
predicted lung volumes as measured on fetal magnetic
resonance imaging: a useful biometric parameter for
risk stratification in congenital diaphragmatic hernia.
J Pediatr Surg 2007;42(1):193-7.
M, Seo T, Itakua A, et al. The
MRI findings of the right-sided fetal lung can be used
to predict postnatal mortality and the requirement for
extracorporeal membrane oxygenation in isolated left-sided
congenital diaphragmatic hernia. Pediatr Res
KP, Lally PA, Lasky RE, et al. Defect
size determines survival in infants with congenital
diaphragmatic hernia. Pediatrics 2007;120(3):e651-7.
lambs with surgically produced congenital diaphragmatic
hernia (CDH) are deficient in pulmonary surfactant.
J Pediatr Surg 1993;28(9):1218-9.
O, Benachi A, Chailley-Heu B, et al. Surfactant
maturation is not delayed in human fetuses with diaphragmatic
hernia. PLoS Med 2007;4(7):e237.