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K E Y W O R D S: diaphragmatic hernia; lung area; lung to head ratio; prenatal diagnosis; pulmonary hypoplasia
Correspondence to: Prof. J. Deprest, Department of Obstetrics and Gynaecology, Unit of Prenatal and Gynaecological Ultrasound and Fetal
Therapy, UZ Gasthuisberg 3000 Leuven, Belgium (e-mail: Jan.Deprest@uz.kuleuven.ac.be)
The ‘ad hoc’ Antenatal-CDH-Registry Group further includes: D. Van Schoubroeck and G. Naulaers (Leuven, Belgium); F. Molina (London,
UK); V. Datin (Paris, France); J. Matis (Strasbourg, France); A. Delelis (Lille, France); E. Gratacos (Barcelona, Spain); J. Laudy (Rotterdam,
The Netherlands); A. van Heijst (Nijmegen, The Netherlands); V. Eisenberg (Tel Hashomer, Israel).
Accepted: 8 March 2007
Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd. ORIGINAL PAPER
68 Jani et al.
that survived. A study of 650 normal fetuses demonstrated demonstrating the four-chamber view of the heart, and
that the LHR increases exponentially with gestational then multiplying the contralateral lung area’s longest
age3 . Consequently, in the assessment of fetuses with diameter by the longest perpendicular to it1 .
CDH it would be preferable to correct for the gestational
age-related change in LHR.
Statistical analysis
The aim of this extended multicenter study involving
354 fetuses with isolated CDH was to re-examine The data from a previous study, in which we measured the
the value of LHR, corrected for gestational age, in LHR for the left and right lungs of 650 normal fetuses at
the prediction of postnatal survival both in fetuses 12–32 weeks’ gestation3 , were used to establish a normal
with left-sided lesions, with and without intrathoracic range of observed to expected LHR with gestational age.
herniation of the liver, and in those with right- In each fetus the observed LHR in the left and right lungs
sided CDH. was expressed as a percentage of the appropriate expected
mean for gestational age (observed/expected LHR × 100).
PATIENTS AND METHODS Regression analysis was then used to calculate the mean
and the 95% confidence intervals of the observed to
This is an ongoing multicenter study by fetal medicine expected LHR for gestational age for the left and right
units of the antenatal findings and postnatal outcome lungs.
of fetuses diagnosed with isolated CDH. The partic- In each fetus with CDH the observed LHR was
ipating centers provide the necessary data, which are expressed as a percentage of the expected normal mean for
entered in a central antenatal-CDH-registry at the Fetal gestational age. The patients were then divided into three
Medicine Unit in the University Hospital of Leuven, Bel- groups: left-sided CDH with intrathoracic herniation of
gium. the liver, left-sided CDH without intrathoracic herniation
We searched the database to identify all consecutive of the liver and right-sided CDH. Each group was
cases of CDH, diagnosed from the year 1995 onwards, subdivided into those that died postnatally either before
that fulfilled the following criteria: first, no major or after surgery and those that survived. In each subgroup
abnormalities diagnosed either prenatally or postnatally; regression analysis was used to determine whether there
second, live birth after 30 weeks’ gestation and postnatal was a significant association between LHR and observed
follow-up until discharge from the hospital; and third, to expected LHR with gestational age. Regression
determination of liver herniation and measurement of the analysis was used to investigate the effect on survival
fetal LHR. In all the centers measurement of the lung of observed to expected LHR and gestational age at
area was as described by Metkus et al., which essentially delivery as continuous numerical variables, and side of
involves obtaining a transverse section of the fetal chest the diaphragmatic hernia (left or right) and intrathoracic
(b) 160
(a) 6.0
140
5.0
120
Lung area to head circumference ratio
4.0 100
80
3.0
60
2.0
40
1.0
20
0 0
12 16 20 24 28 32 12 16 20 24 28 32
Gestational age (weeks) Gestational age (weeks)
Figure 1 Relationship between right lung area to head circumference ratio (LHR) (a) and observed to expected LHR (b) with gestational age
in normal fetuses. Lines represent mean and 95% CI.
Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2007; 30: 67–71.
Prediction of survival in diaphragmatic hernia 69
Table 1 Relationship between lung area to head circumference ratio (LHR) and observed to expected (O/E) LHR with gestational age in
fetuses with congenital diaphragmatic hernia
3.5 80
Lung area to head circumference ratio
70
3.0
Observed : expected LHR (%)
60
2.5
50
2.0
40
1.5
30
1.0
20
0.5 10
0 0
18 22 26 30 34 38 18 22 26 30 34 38
Gestational age (weeks) Gestational age (weeks)
Figure 2 Relationship between lung area to head circumference ratio (LHR) (a) and observed to expected LHR (b) with gestational age in
fetuses with left-sided congenital diaphragmatic hernia. The closed circles and solid regression lines are the values for the babies that died
and the open circles and dashed regression lines represent the survivors.
position of the liver (yes or no) as categorical variables. CI, 61–139%; right lung: r = −0.039, P = 0.320; mean
A receiver–operating characteristics (ROC) curve was observed to expected LHR 100%, 95% CI, 67–133%,
constructed for the prediction of survival by the observed Figure 1).
to expected LHR. The search of the antenatal-CDH-registry identified
Statistical analysis of the data was performed with SPSS 354 fetuses that fulfilled the entry criteria2 . The median
for Windows (V.13, Chicago, IL, USA) and Excel for gestational age at prenatal sonographic assessment was
Windows 2003 (Microsoft Corp., Redmond, WA, USA). 27 (range, 18–38) weeks and the median gestational
A P-value of less than 0.05 was considered statistically age at delivery was 38 (range, 31–42) weeks. In each
significant. of the four subgroups of fetuses with left-sided CDH
there was a significant association between LHR and
gestational age, but not between observed to expected
RESULTS
LHR and gestational age (Table 1; Figure 2). For the two
In normal fetuses, in both the left and right lungs the subgroups with right-sided CDH there was no significant
LHR increased significantly with gestational age3 , but association of either LHR or observed to expected LHR
the observed to expected LHR did not change sig- with gestational age (Table 1).
nificantly with gestational age (left lung: r = −0.029, In the group with left-sided CDH and intrathoracic
P = 0.464; mean observed to expected LHR 100%, 95% herniation of the liver, 85 of the 161 (52.8%) babies
Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2007; 30: 67–71.
70 Jani et al.
Table 2 Regression analysis in the prediction of survival in fetuses with isolated diaphragmatic hernia
Multivariate analysis
n (%) or
Variable median (range) OR (95% CI) P
LHR, lung area to head circumference ratio; NS, not significant; OR, odds ratio.
60 Survival (%) 60
50 50
40 40
30 30
20 20
10 10
0 0
≤ 25 26−35 36−45 46−55 > 55 ≤ 25 26−35 36−45 46−55 >55
Observed : expected LHR (%) Observed : expected LHR (%)
Figure 3 Survival rate according to the fetal observed to expected lung area to head circumference ratio (LHR) in fetuses with isolated
left-sided (a) and right-sided (b) diaphragmatic hernia. The filled bars represent fetuses with intrathoracic herniation of the liver and the
open bars represent those without herniation.
60
weeks. Regression analysis demonstrated that significant
predictors of survival were the side of diaphragmatic
hernia, the observed to expected LHR and the gestational 40
age at delivery (Table 2). The relationship between
observed to expected LHR and survival in each group
is shown in Figure 3. 20
In our previous report on expectantly managed fetuses
with isolated, left-sided CDH, we found that postnatal
survival was very poor when the LHR at 22–28 weeks’ 0
gestation was less than 1.0, which is equivalent to an 0 20 40 60 80 100
observed to expected LHR of ≤ 25% in the present study2 . False-positive rate (%)
The area under the ROC curve for prediction of
survival from the observed to expected LHR in fetuses Figure 4 Receiver–operating characteristics curve for the
prediction of survival in fetuses with left-sided congenital
with left-sided CDH was 0.761 (P < 0.001; standard
diaphragmatic hernia according to cut-off values of observed to
error = 0.027) and for a false positive rate of 10% the expected lung area to head circumference ratio (continuous line).
sensitivity was 46% (Figure 4). The dashed line is the reference line.
Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2007; 30: 67–71.
Prediction of survival in diaphragmatic hernia 71
Copyright 2007 ISUOG. Published by John Wiley & Sons, Ltd. Ultrasound Obstet Gynecol 2007; 30: 67–71.