Special Article

Recent Advances in the Management of Congenital

Diaphragmatic Hernia
V. Jain, S. Agarwala and V. Bhatnagar
Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India

ABSTRACT
The management of congenital diaphragmatic hernia (CDH) is undergoing continual change and refinement, fuelled by
recent advances in this field. Although many studies have documented the benefits of these recent advances but definite
recommendations are lacking. Also, injudicious use of some of these strategies may be counterproductive, underscoring the
importance of evidence based treatment strategy. This article discusses the utility of the recent advances in the management
of CDH. [Indian J Pediatr 2010; 77 (6) : 673-678] E-mail : veereshwarb@hotmail.com

Key words: Congenital diaphragmatic hernia; Surgical repair; Recent advances; Respiratory support; Extra corporeal
membrane oxygenation; High frequency ventilation; Intra uterine management

Congenital diaphragmatic hernia has an incidence of 1

in 2000-5000 live births making it a common anomaly
seen by a pediatric surgeon. The treatment of CDH has
evolved over the last 4 decades, so have the survival
rates. The survival rates have undergone a full circle i.e.,
from 90% in 1950s to 50% in late 1980s and now 80%.
In 1962, in the Swensons Textbook of Pediatric
Surgery it was mentioned The results of surgical
treatment are excellent, and the mortality rate should
not be more than 10%. As most of these infants are
without associated serious anomalies, the results are
gratifying.1 Subsequently it was realized that a large
number of neonates die immediately after birth, before
they can reach a tertiary centre. With routine use of
antenatal ultrasonography, CDH was diagnosed
antenatally. Findings suggestive of CDH include
polyhydramnios, an absent or intrathoracic stomach
bubble, and mediastinal and cardiac shift away from
the side of the hernia. It was subsequently noticed that
many fetuses die in utero or are stillborn. Harrison et al2
coined the term hidden mortality for this phenomenon and
it was realized that the prognosis of this condition was not as
good as thought earlier. Revision and standardization of
management of CDH has resulted in improved
outcomes. The basic management of neonate with CDH
and respiratory distress has remained unchanged and
include immediate intubation and mechanical
Correspondence and Reprint requests : Professor V. Bhatnagar,
Department of Pediatric Surgery, All India Institute of Medical
Sciences, New Delhi-110029, India.
[DOI-10.1007/s12098-010-0094-1]
[Received April 21, 2009; Accepted March 3, 2010]

Indian Journal of Pediatrics, Volume 77June, 2010

ventilation, insertion of nasogastric tube, umbilical vein

and artery catheterization, maintenance of systolic
blood pressure above 50 mmHg. Numerous advances
have been made in other aspects of management of
CDH which are discussed.
The recent advances can be broadly classified as
advances in postnatal care, introduction of fetal
interventions, minimal invasive surgery for repair and
olung transplantation.
ADVANCES IN POSTNATAL CARE
1. Mechanical Ventilation
(a) Concept of Gentle ventilation: Prior to
acceptance of the gentle ventilation, hyperventilation was
the ventilatory strategy used. 3 The patients were
hyperventilated so as to washout CO2 so that pulmonary
hypertension decreases and R to L shunting decreases. On
postmortem examination, significant barotrauma was
noticed in the lungs. The concept of gentle ventilation was
introduced by Wung et al4,5 in 1985. This strategy was
based on minimizing VILI (ventilator induced lung
injury) and ignoring the R to L shunt. The ideal goal is to
achieve a preductal SpO2 > 90mm Hg, but values above 80
mmHg are acceptable while permitting the increase in
pCO 2 to maximum of 60 mmHg (permissive
hypercapnia).
(b) High frequency ventilation: High frequency
oscillatory ventilation is the most common mode of HFV
used in neonates. It is used in various centers as either a
proactive approach or a rescue therapy. High frequency
673

V. Jain et al
ventilation preserves end expiratory volume and
avoids overdistention of the alveoli, therefore decreases
VILI. The Cochrane Group found only 1 randomized trial,
which had enrolled a heterogeneous group of infants with a
wide variety of respiratory pathology. The trial showed no
benefit as compared to conventional ventilation. Many
single institutions experience show benefit of HFV.
Whether HFV is the optimal mode of ventilation for
patients with CDH is still not defined and a larger trial is
needed for clarification.
(c) Liquid Ventilation: Perfluorocarbons have
excellent oxygen and carbon dioxide carrying capacity (50
ml O2/dl and 160210 ml CO2/dl, respectively).6 Liquid
ventilation can be administered as Total Liquid
Ventilation or Partial Liquid Ventilation (PLV), with latter
being more commonly used. PLV involves administration
of intratracheal perfluorocarbon to a volume equivalent to
functional residual capacity followed by standard gas
mechanical ventilation of the perfluorocarbon-filled lung.
PLV is effective by increasing lung compliance, gas
exchange and also by inducing lung growth. There is only
one multicentric, randomized, prospective trial which
evaluated PLV induced lung growth in newborns with
CDH. The study demonstrated better survival in PLV
group as compared to conventional ventilation but it was
not statistically significant and the trial was placed on
hold.7 Recently, there have been no further reports of PLV
in children, so that this procedure seems to be of no
further interest, at least at the moment.
2. Management of Pulmonary Hypertension
(a) Inhalational nitric oxide (iNO) therapy. Nitric
oxide (NO) is an endogenous molecule that induces
production of cyclic GMP from GTP resulting in the
relaxation of vascular smooth muscle. NO proved useful
in the management of PPHN (Persistent Pulmonary
Hypertension) but the efficacy in CDH patients is not as
encouraging. NO therapy can still be tried when
following conditions are fulfilled : RV pressure > 2/3 of
systemic pressure, significant R to L shunt and adequate
LV performance. 8 To evaluate the individual patients
response to treatment, one has to assess the right
ventricular function and systolic pressure serially using
echocardiography. Currently there is no evidence that
iNO changes the outcome in CDH. The largest
randomized, controlled trial of early iNO therapy in
patients with CDH showed no difference in the combined
endpoint of death/ECMO utilization between iNOtreated and controls (Table 1). Moreover, ECMO
utilization was higher in the iNO-treated group.9 Patients
with CDH are poor responders as a group, however
inhaled nitric oxide may have a role in CDH patients
with supra-systemic pulmonary vascular resistance after
establishing optimal lung inflation and demonstrating
adequate left ven-tricular performance (i.e., without
ductal-dependent systemic blood flow).10
674

TABLE 1. Outcomes of Randomized Controlled Trial of iNO

in CDH9
Treatment Group

Control

Inhaled NO

Mortality
Treatment with ECMO

12 (42.9)
15 (53.6)

12 (48)
20 (80)*

Data expressed as n (%); *, p = 0.043

(b) Type 5 PDE inhibitor e.g., Sildenafil. Silde nafil is

a type 5 PDE inhibitor, and has already been used in the
treatment of PPHN and pulmonary hypertension in
children with congenital heart disease. There are no
randomized controlled trials or prospective studies on the
use of Sildenafil in infants with CDH. It has been used in
individual patients in CDH through oral and intravenous
routes. The usual starting dose is 0.1 to 0.2 mg/kg every
6 to 8 hr, and can be increased up to 1 to 1.5 mg/kg/dose
every 6 hr. It has been shown to increase cardiac output
(RV>LV) and decrease pulmonary hypertension.11 Further
studies are required to delineate the role of sildenafil in
management of pulmonary hypertension associated with
CDH.
(c) Prostaglandins: Prostaglandin E1 may be useful to
maintain duct patency in patients with left ventricular
dysfunction and having right ventricle dependent
systemic circulation. However, in a recent study there
was no additional benefit of PGE1 over NO.12
(d) Endothelin (ET) receptor blockers: Bosentan is a
non selective ET receptor blocker and has been safely
used in two neonates with pulmonary hypertension due
to transposition of great arteries. Sitaxsentan and
ambrisentan are specific ET-A receptor antagonists which
may be more effective and less hepatotoxic than
bosentan.13
(e) RhoA and Rho-kinase pathways: These pathways
are involved in maintaining the pulmonary vascular tone
and their downstream effectors form a key pathway for
the regulation of the vascular tone. In animal models,
Fasudil, a Rho-kinase inhibitor, showed promising results
in the treatment of pulmonary hypertension.14
3. Extracoporeal Membrane Oxygenation (ECMO) : In
the late 1970s, the first reports of ECMO for infants with
CDH provided a potential therapy for these children with
severely hypoplastic lungs. Since that time, the strategy
for use of ECMO in patients with CDH has undergone
continual refinement and critical ex-amination.
Approximately one-third of infants born with CDH will
be treated with ECMO during their initial course of
management.
The indications for ECMO are:15,16

Oxygenation Index (OI) >40 (OI = Mean airway
pressureFiO2100PaO 2)

Indian Journal of Pediatrics, Volume 77June, 2010

Recent Advances in the Management of Congenital Diaphragmatic Hernia

Alveolar to arterial oxygen difference >600 (AaDO2=([PB-PH2O]FiO2) PaCO2PaO 2)

Failure to respond- most common indication
The

contraindications to ECMO are:17

<34 weeks or weight < 2000 gms
ICH > grade I
Severe congenital/ chromosomal abnormality
Highest preductal PaO2< 80-100mm Hg

Significant coagulopathy or uncontrolled bleeding

Traditionally, infants with CDH who require ECMO
support have been preferentially placed on venoarterial
(VA) ECMO. However, in a single center study,
Kugleman and coworkers18 also showed no difference
between infants treated with VV when compared with
VA ECMO for CDH. Based on these studies, it would be
prudent to assume that most infants with CDH can be
treated with VV ECMO if an adequate cannula (such as a
14Fr) can be placed. A recent Cochrane review looked at
randomized controlled trials of ECMO use in infants with
respiratory failure.19 Two of the 4 cited trials included
subgroup analyses examining ECMO in CDH infants,
with no apparent survival benefit. The CDH study group
has observed higher than predicted mortality when
ECMO was used in a low mortality risk group, and higher
than expected survival in a high mortality risk (>80%)
group.20
4. Miscellaneous : These include the use of surfactant
therapy and the concept of delayed repair.
(a) Surfactant : Animal studies and human clinical
trials suggest that term infants with CDH have surfactant
deficiency and that surfactant composition may be
altered. 21 The use of a bovine-derived surfactant was
evaluated in a small, randomized controlled trial of 17
infants > 34 wks gestation with CDH already on ECMO.22
No clinical benefit was observed in lung compliance, time
to extubation, or duration of oxygen therapy. A recent
report suggests that surfactant therapy in the
management of CDH, even after correcting for use of
ECMO, iNO and postnatal steroids, results in increased
risk of mortality. 23 Therefore, based on the lack of
definitive evidence and the availability of only limited
observational studies, administration of surfactant to
infants with CDH cannot be recommended with the
exception of participation in well-designed clinical trials,
or in a significantly premature neonate where respiratory
distress may be in part due to true surfactant deficiency.24
(b) Delayed repair : Although considered a surgical
emergency from the 1940s, through the 1980s CDH is
now considered as medical emergency which requires
cardio-pulmonary stabilization, followed by definitive
surgical repair. The change from emergency to delayed
repair was initiated in 1987, when Sakai and coworkers25
showed that the respiratory system compliance frequently
Indian Journal of Pediatrics, Volume 77June, 2010

deteriorates after CDH repair. They recommended that

repair should be deferred until after initial resuscitation
improves physiologic function, achieving a period of
cardiorespiratory stability. Two small randomized trials
(total of 86 infants enrolled) comparing early (< 24 hours)
vs late (>24 hours) surgical correction of CDH among
infants who were symptomatic at or shortly after birth,
have been published.26,27 Neither showed any significant
difference between groups in mortality, the primary
outcome. These data were incorporated into a recent
Cochrane systematic review on the effects of late (defined
as more than 24 hr of age) vs early (defined as within the
first 24 hrs after birth) surgical correction of CDH on
survival to hospital discharge. The authors of this review
concluded that there is no clear evidence favoring delayed
(when stabilized) as compared with immediate (within 24
hrs of birth) surgical repair of CDH, but a substantial
advantage to either one could not be ruled out.28 Even
though there is lack of evidence to support it, the current
routine in most centers includes preoperative stabilization
before surgery.
(c) Predictors of outcome and risk stratification
(i) Anatomic Factors
Side- Right sided CDH have worse prognosis
Position of stomach and liver- Survival better in cases
with intra-abdominal stomach and liver
LHR (Lung to head ratio)- defined as ratio of
contralateral lung cross-sectional area-to-head
circumference. Based on LHR fetus with CDH can be
classified as follows. Group A: A LHR lower than 0.6
points to a very poor outcome for the fetus, with extreme
lung hypoplasia and a mortality rate of almost 100%.
Group B: a ratio between 0.6 and 1 gives the fetus which
has a severe lung hypoplasia a predictive survival rate of
15 to 60%. FETO is normally proposed for these babies.
Group C: a ratio in the range of 1.0 to 1.6 gives the child a
66% chance of survival and a predictive survival rate of
more than 83%.29 To nullify the changes in value of LHR
with variation in gestational age, the ratio of observed to
expected LHR is being preferred.
Fetal lung volume (FLV)- Fetal MRI can be used to
calculate the absolute and relative FLV. A definite cutoff
value for good prognosis is lacking but higher values are
related with better prognosis. There is significant increase
in mortality if relative FLV is less tan 25-40%.30
McGoon index (MGI) and Pulmonary artery index
(PAI)- These are calculated during echocardiography.
MGI is calculated as diameter of right and left pulmonary
artery divided by the diameter of descending aorta while
PAI is calculated as area of right and left pulmonary
artery divided by body surface area. MGI (cutoff value,
1.31) and PAI (cutoff value, 90) are reliable indices for
predicting mortality in CDH.31
675

V. Jain et al
(ii) Physiological factors
Apgar score at 5 minutes
Oxygenation index (OI) = MAP FiO2/PaO2
Lower OI correlated with better survival. In a recent
study the best OI on day 1 of life was found to be the best
prognostic index in the CDH infants.32
Modified Ventilation index (MVI)MVI = (RR PIP PaCO2)/1000
Lower MVI associated with better survival. In infants
with MVI less than 40 the survival rate with conventional
ventilation approaches 96%.
FETAL INTERVENTIONS
Fetal intervention has undergone 3 phases in the last 2
decades :

Open definitive repair

Tracheal occlusion with open

technique

Tracheal occlusion with Fetoscopy:
FETENDO and FETO

PLUG
Plug the lung
until it grows

Open definitive repair : In utero repair in fetal CDH

models showed reversal of pulmonary hypoplasia,
restoration of normal lung function and survival. The role
of fetal surgery for fetuses without liver herniation (liverdown) was examined with a prospective trial. 33 Four
fetuses with isolated left-sided CDH underwent open
repair. Although, preterm labor led to delivery at 29 to 34
wk, three of four infants survived with good outcome,
and no infant required ECMO. In the control group of
patients that were treated with standard postnatal care,
six of seven survived, and only one infant required
ECMO. The authors concluded that in utero repair does
not improve survival rate over standard postnatal
treatment in the subgroup of CDH fetuses without liver
herniation, primarily because survival in this subgroup is
very favorable without prenatal intervention.
Tracheal occlusion (PLUG) : After observating that
tracheal atresia results in lung hyperplasia, therapeutic
tracheal occlusion (TO) was suggested as a potential
method to overcome lethal pulmonary hypoplasia
associated with CDH. Many observations were made
after study in fetal models.34
Lung growth increased in normal and CDH models
after TO
Lung growth because of increased cell division (with
increased alveoli and capillaries)
Tracheal occlusion can be achieved in the following
ways.35
Open tracheal occlusion : Open tracheal clipping is
676

performed through a small hysterotomy. The EXIT

procedure (ex utero intrapartum treatment) was
developed to safely deliver fetuses that had been treated
with tracheal occlusion. In this procedure, a low
transverse hysterotomy is made, and the fetal head is
delivered. The tracheal obstruction is relieved and the air
way is secured, while the fetus receives gas exchange
from the placental circulation. Flake and colleagues 36
reported results from a prospective study comparing
open fetal tracheal occlusion to standard postnatal care.
The study evaluated fetuses with CDH, including a LHR
< 1.0, liver herniation, and the absence of other anomalies.
Fifteen fetuses underwent tracheal occlusion at 24 - 28 wk
of gestation. Of the original 15, 5 (33%) fetuses survived to
discharge. The results were favorable compared with 0%
survival in a matched cohort of similar fetuses that did
not have this therapy.
Fetal endoscopy (FETENDO) : Video and ultrasound
assisted fetal endoscopy was performed to occlude the
trachea by a clip or a balloon. This procedure avoided
maternal hysterotomy, although maternal laparotomy
was still performed. Therefore maternal general
anesthesia was required. Reversal was done by the EXIT
procedure.
Harrison et al 37 conducted a randomized controlled
trial to determine if FETENDO had any survival benefit
over the standard postnatal group. The inclusion criteria
was LH ratio < 1.4 and presence of liver herniation. The
trial was terminated early as there was no difference in
survival benefits among the two groups. The authors
argued that the beneficial effects of TO were negated by
premature delivery.
FETO (Fetoscopic Endoluminal Tracheal Occlusion):
It is the least invasive of all options of TO. The procedure
is performed percutaneously and therefore general
anesthesia is not required. The procedure is performed
under epidural or spinal anesthesia combined with local
anaesthesia. A thin-walled flexible Teflon cannula is
inserted into the amniotic cavity directed toward the fetal
mouth. The trocar is then withdrawn and fetoscopic
instruments are inserted. The endoscope is introduced
into the fetal mouth and advanced through the vocal
cords to identify the carina, and the catheter is positioned
to deliver the balloon just above it. The balloon is inflated.
Reversal of TO, in view of experimental data is performed
at around 34 wk, either by fetal tracheoscopy, or by
puncturing the balloon using an ultrasound-guided 20G
needle. Prepartum removal also avoids the inherent need
for hysterotomy and allows vaginal delivery, as well as
referral back to the initial tertiary referral unit, which may
pose less psychological and financial burden on the
patient.
The efficacy of FETO was evaluated by the FETO task
group. They conducted a nonrandomized prospective
trial. 38 The inclusion criteria was LH ratio < 1.0 and
Indian Journal of Pediatrics, Volume 77June, 2010

Recent Advances in the Management of Congenital Diaphragmatic Hernia

presence of liver herniation. The controls were those
who met the inclusion criteria but declined FETO.
FETO was performed at median gestation age of 26 wks.
Reversal was done at 34 wks. They noted that survival
till discharge was 50% (10/20) as compared to only 8%
survival (1/12) in the control group. With experience the
incidence of premature rupture of membranes is
decreasing and gestational age at delivery is increasing so
that the beneficial effect may become more apparent. A
recent multicentre prospective trial evaluating FETO, in
210 patients reported that in fetuses with left CDH treated
with FETO, the survival rate increased from 24.1% to
49.1%, and in right CDH survival increased from 0% to
35.3% (p< 0.001), even in presence of high incidence of
PPROM and preterm delivery.39
Fetal Surgery for CDH is not feasible at present in our
country, as it requires a specialized team of Pediatric
surgeon, perinatologist, obstetrician, anesthesiologist,
radiologist and trained nursing and paramedical staff,
which at present is available in only few centres in the
world. But before starting fetal surgery programme at a
tertiary care centre, other requirements for management
of high risk cases like a high frequency ventilator,
availability of NO and ECMO should be looked into.
MINIMAL INVASIVE SURGERY FOR REPAIR
Laparoscopy was first described in 1995 by Van der Zee et
al.40 At present thoracoscopy is preferred over laparoscopy
for repair of CDH.Minimal invasive surgery has still not
gained popularity because of high failure rate (14%),
prohibitive increases in PCO2 and acidemia.41
LUNG TRANSPLANTATION
Van Meurs et al42 performed the first lung transplantation
in CDH in 1994. Not much progress has been made after
that in this field because of improved survival with other
more viable options.
These recent advances have improved the survival of
CDH in the western world but in developing countries
like India, where most nurseries are not equipped with
iNO, HFV or ECMO the survival rates are still dismal. The
published data form India pertaining to CDH outcome is
scant. The survival of neonates who presented within first
24 hr of life ranges from 0 to 46% whereas the survival for
those who presented after 24 hr was more than 80%.43,45
CONCLUSIONS
Recent advances in management of congenital
diaphragmatic hernia have led to increased survival. The
benefits of some of these advances remain uncertain and
larger multicentric trials are required to clearly define
Indian Journal of Pediatrics, Volume 77June, 2010

their role.
Contributions: VJ, SA and VB; collectively searched the literature,
sifted the data and prepared the manuscript.
Conflict of Interest : None.
Role of Funding Source: None.

REFERENCES
1. Swenson O. Chalasia, achalasia, hiatus hernia, and
diaphragmatic hernia. In Swenson O, ed. Pediatr Surg, 2nd ed.
New York; Appleton-Century-Crofts Inc, 1962; 189-201.
2. Harrison MR, Bjordal RI, Langmark F, Knutrud O. Congenital
diaphragmatic hernia: The hidden mortality. J Pediatr Surg
1978; 13: 227-230.
3. Drummond W, Gregory G, Heyman M. The effect of alkalosis
on pulmonary artery pressure, systemic artery pressure and
PaO2 in infants with persistent pulmonary hypertension.
Pediatr Res 1979; 13: 493-495.
4. Wung JT, James LS, Kilchevsky E, James E. Management of
infants with severe respiratory failure and persistence of the
fetal circulation, without hyperventilation. Pediatrics
1985;76:488-494.
5. Wung JT, Sahni R, Moffitt ST, Lipsitz E, Stolar CJ. Congenital
diaphragmatic hernia: survival treated with very delayed
surgery, spontaneous respiration, and no chest tube. J Pediatr
Surg 1995;30: 406409.
6. Shaffer TH, Wolfson MR, Clark Jr L. State of the art review:
liquid ventilation. Pediatr Pulmonol 1992; 14: 102-109.
7. Hirschl RB. Current experience with Liquid Ventilation.
Pediatr Respir Rev 2004; 5: S339-S345.
8. Mohseni-Bod H, Bohn D. Pulmonary hypertension in
congenital diaphragmatic hernia. Semin Pediatr Surg 2007; 16:
126-133.
9. Neonatal Inhaled Nitric Oxide Study Group. (No authors
listed). Inhaled nitric oxide and hypoxic respiratory failure in
infants with congenital diaphragmatic respiratory failure.
Pediatrics 1997; 99: 838-845.
10. Kinsella JP, Ivy DD, Abman SH. Pulmonary vasodilator
therapy in congenital diaphragmatic hernia: acute, late, and
chronic pulmonary hypertension. Semin Perinatol 2005; 29:
123-128.
11. Noori S, Friedlich P, Wong P, Garingo A, Seri I.
Cardiovascular effects of sildenafil in neonates and infants
with congenital diaphragmatic hernia and pulmonary
hypertension. Neonatology 2007; 91: 92-100.
12. Shiyanagi S, Okazaki T, Shoji H et al. Management of
pulmonary hypertension in congenital diaphragmatic hernia:
nitric oxide with prostaglandin-E1 vs nitric oxide alone. Pediatr
Surg Int 2008; 24: 1101-1104.
13. van den Hout L, Sluiter I, Gischler S et al. Can we improve
outcome of congenital diaphragmatic hernia? Pediatr Surg Int
2009; 25: 733-743.
14. Abe K, Shimokawa H, Morikawa K et al. Long-term treatment
with a Rho-kinase inhibitor improves monocrotaline-induced
fatal pulmonary hypertension in rats. Circ Res 2004; 94: 385393.
15. Khan AM, Lally KP. The role of extracorporeal membrane
oxygenation in the management of infants with congenital
diaphragmatic hernia. Semin Perinatol 2005; 29: 118-122.
16. Lally KP. Extracorporeal membrane oxygenation in patients
with congenital diaphragmatic hernia. Semin Pediatr Surg
1996; 5: 249-255.
17. Bahrami KR, Van Meurs KP. ECMO for neonatal respiratory
failure. Semin Perinatol 2005; 29: 15-23.

677

V. Jain et al
18. Kugelman A, Gangitano E, Pincros J, Tantivit P, Taschuk R,
Durand M. Venovenous versus venoarterial extracorporeal
membrane oxygenation in congenital diaphragmatic hernia. J
Pediatr Surg 2003; 38: 1131-1136.
19. Elbourne D, Field D, Mugford M. Extracorporeal membrane
oxygenation for severe respiratory failure in newborn infants.
Cochrane Database Syst Rev 2002: CD001340.
20. The Congenital Diaphragmatic Hernia Study Group. (No
authors listed). Does extracorporeal membrane oxygenation
improve survival in neonates with congenital diaphragmatic
hernia? J Pediatr Surg 1999; 34: 720-724.
21. Cogo PE, Zimmermann LJ, Meneghini L et al. Pulmonary
surfactant disaturated-phosphatidylcholine (DSPC) turnover
and pool size in newborn infants with congenital
diaphragmatic hernia (CDH). Pediatr Res 2003; 54: 653-658.
22. Lotze A, Knight GR, Anderson KD et al. Surfactant (beractant)
therapy for infants with congenital diaphragmatic hernia on
ECMO: evidence of persistent surfactant deficiency. J Pediatr
Surg 1994;29:407-412.
23. Van Meurs K. Congenital Diaphragmatic Hernia Study
Group. Is surfactant therapy beneficial in the treatment of the
term newborn infant with congenital diaphragmatic hernia? J
Pediatr 2004; 145: 312-316.
24. Moya FR, Lally KP. Evidence-based management of infants
with congenital diaphragmatic hernia. Semin Perinatol 2005;
29: 112-117.
25. Sakai H, Tamura M, Hosokawa Y, Bryan AC, Barker GA,
Bohn DJ. Effect of surgical repair on respiratory mechanics in
congenital diaphragmatic hernia. J Pediatr 1987; 111: 432-438.
26. de la Hunt MN, Madden N, Scott JE et al. Is delayed surgery
really better for congenital diaphragmatic hernia?: a
prospective randomized clinical trial. J Pediatr Surg 1996; 31:
1554-1556.
27. Nio M, Haase G, Kennaugh J, Bui K, Atkinson JB. A
prospective randomized trial of delayed versus immediate
repair of congenital diaphragmatic hernia. J Pediatr Surg 1994;
29: 618-621.
28. Moyer V, Moya F, Tibboel R, Losty P, Nagaya M, Lally KP.
Late versus early surgical correction for congenital
diaphragmatic hernia in newborn infants. Cochrane Database
Syst Rev 2002; CD001695.
29. de Buys Roessingh AS, Dinh-Xuan AT. Congenital
diaphragmatic hernia: current status and review of the
literature. Eur J Pediatr 2009; 168: 393-406.
30. Kilian AK, Bsing KA, Schuetz EM, Schaible T, Neff KW et al.
Fetal MR lung volumetry in congenital diaphragmatic hernia
(CDH): prediction of clinical outcome and the need for
extracorporeal membrane oxygenation (ECMO). Klin Padiatr
2009; 221: 295-301.

678

31. Takahashi S, Oishi Y, Ito N et al. Evaluating mortality and

disease severity in congenital diaphragmatic hernia using the
McGoon and pulmonary artery indices. J Pediatr Surg 2009; 44:
2101-2106.
32. Sinha CK, Islam S, Patel S, Nicolaides K, Greenough A,
Davenport M. Congenital diaphragmatic hernia: prognostic
indices in the fetal endoluminal tracheal occlusion era. J
Pediatr Surg 2009; 44: 312-316.
33. Harrison MR, Adzick NS, Bullard KM et al. Correction of
congenital diaphragmatic hernia in utero VII: a prospective
trial. J Pediatr Surg 1997; 32: 1637-1642.
34. Kitano Y. Prenatal intervention for congenital diaphragmatic
hernia. Semin Pediatr Surg 2007; 16: 101-108.
35. Cass DL. Fetal surgery for congenital diaphragmatic hernia:
the North American experience. Semin Perinatol 2005;29:104111.
36. Flake AW, Crombleholme TM, Johnson MP, Howell LJ,
Adzick NS. Treatment of severe congenital diaphragmatic
hernia by fetal tracheal occlusion: clinical experience with
fifteen cases. Am J Obstet Gynecol 2000; 183: 1059-1066.
37. Harrison MR, Keller RL, Hawgood SB et al. A randomized
trial of fetal endoscopic tracheal occlusion for severe fetal
congenital diaphragmatic hernia. N Engl J Med 2003; 349:
1916-1924.
38. Deprest J, Jani J, Van Schoubroeck D et al. Current
consequences of prenatal diagnosis of congenital
diaphragmatic hernia. J Pediatr Surg 2006; 41: 423-430.
39. Jani JC, Nicolaides KH, Gratacs E et al. Severe diaphragmatic
hernia treated by fetal endoscopic tracheal occlusion.
Ultrasound Obstet Gynecol 2009; 34: 304-310.
40. van der Zee DC, Bax NM. Laparoscopic repair of congenital
diaphragmatic hernia in a 6-month-old child. Surg Endosc
1995; 9: 1001-1003.
41. Arca MJ, Barnhart DC, Lelli JL Jr et al. Early experience with
minimally invasive repair of congenital diaphragmatic
hernias: results and lessons learned. J Pediatr Surg 2003; 38:
1563-1568.
42. Van Meurs KP, Rhine WD, Benitz WE et al. Lobar lung
transplantation as a treatment for congenital diaphragmatic
hernia. J Pediatr Surg 1994; 29: 1557-1560.
43. Bhat YR, Kumar V, Rao A. Congenital diaphragmatic hernia
in a developing country. Singapore Med J 2008; 49: 715-718.
44. Jain A, Singh V, Sharma M. Congenital diaphragmatic hernia:
our experience - a brief review. Indian J Anaesth 2002; 46: 426429.
45. Pandey A, Tandon RK, Kureel SN, Wakhlu A, Rawat J.
Evaluation of congenital diaphragmatic hernia in a tertiary
health center of a developing country: management and
survival. Hernia 2008;12:189-192.

Indian Journal of Pediatrics, Volume 77June, 2010