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Original Research |
1 Department of Obstetrics, Instituto Central do Hospital das Clinicas da
Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), Av. Dr.
Enéas de Carvalho Aguiar, 225—10o andar—Sala 10.085,
São Paulo, Brasil CEP 05403-000.
2 Department of Maternity, Hôpital Necker-Enfants Malades,
Université de Paris V, Paris, France.
Received August 29, 2007;
accepted after revision October 17, 2007.
Address correspondence to R. Ruano
(rodrigoruano{at}usp.br).
Abstract
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SUBJECTS AND METHODS. Between January 2002 and December 2004, 40 fetuses with isolated CDH and 450 control subjects were prospectively evaluated in two centers. Fetal lung volumes were estimated on 3D sonography using the rotational technique and fetal weight on 2D sonography using the Hadlock equation. The ratio of sonographic fetal lung volume to body weight was calculated in each case and was correlated with neonatal deaths using the Mann-Whitney U test. Accuracies of the ratio in predicting neonatal deaths and pathologic diagnosis of pulmonary hypoplasia were also evaluated.
RESULTS. The ratio of sonographic fetal lung volume to body weight is constant throughout gestation, with a mean value of 0.025. The ratio was significantly lower in neonates that died (median, 0.009; range, 0.004–0.021) than in those that survived (median, 0.011; range, 0.008–0.020) (p = 0.018). Pulmonary hypoplasia was suspected prenatally in 34 of 40 (85.0%) fetuses with CDH, in all cases of death (100%), and in seven of nine (77.8%) neonates that survived. At autopsy, pulmonary hypoplasia was diagnosed in 19 cases (86.4%). Accuracies of the ratio in predicting neonatal deaths and pulmonary hypoplasia were 64.5% (20/31) and 86.4% (19/22), respectively.
CONCLUSION. The sonographic fetal lung volume–body weight ratio can be used more accurately to diagnose pulmonary hypoplasia than to predict neonatal deaths in fetuses with isolated CDH. Further studies are necessary to show the prevalence of pulmonary hypoplasia in fetuses with isolated CDH and its importance for predicting neonatal deaths.
Keywords: congenital diaphragmatic hernia • fetal imaging • prenatal diagnosis • obstetrics • pulmonary hypoplasia • sonography • women's imaging
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Tanigaki et al. [10]
proposed that the ratio of fetal lung volume estimated on MRI and fetal body
weight estimated on sonography be used for the prediction of pulmonary
hypoplasia. These authors' suggestion is based on the pathologic definition of
pulmonary hypoplasia: a ratio of lung weight to body weight of < 0.012 at a
gestational age of 
28 weeks and of < 0.015 at < 28 weeks
[11–14].
In that study [10], a high
accuracy (88%) of this method in predicting pulmonary hypoplasia was observed.
Other investigators have shown that fetal lung volumes can be measured
precisely using 3D sonography in CDH cases with results similar to MRI
estimates of lung volume [7,
8,
15] and to postmortem fetal
lung weights [16]. Ruano et
al. [17] also reported that
the fetal lung volume–body weight ratio can be measured by combining 3D
sonography and 2D sonography with good accuracy when compared with postmortem
examinations.
On the basis of these findings, we prospectively studied the potential of the sonographic fetal lung volume–body weight ratio to predict neonatal deaths and pulmonary hypoplasia in 40 fetuses with isolated CDH, after evaluating the distribution of the ratio against gestational age in 450 healthy control subjects.
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In all fetuses, gestational age was established on the basis of the date of the mother's last period and by sonographic measurement of the crown–rump length in the first trimester. All fetuses with CDH underwent detailed sonographic examination, and fetal amniocentesis for karyotyping was performed. Gestational age at CDH diagnosis ranged from 16 to 32 weeks. Only fetuses with a normal karyotype and without any other associated malformations were included in the study. Among the fetuses with CDH, sonography was performed between 22 and 36 weeks' gestation. All women were informed that the results of the study would not be used to modify perinatal management. The perinatologists, sonographers, and surgeons in charge were unaware of the results of the lung volume measurements. The prenatal diagnostic investigations, obstetrics care, and postnatal treatment were provided with a similar postnatal protocol.
Immediately after birth, neonates with CDH were intubated and
high-frequency oscillatory ventilation was started and was subsequently
changed to conventional ventilation when appropriate. Nitric oxide was used in
infants with pulmonary hyper tension. CDH repair was performed only after
preoperative respiratory and hemodynamic stabi lization. When autopsy was
performed, the patho logic diagnosis of pulmonary hypoplasia was made when the
lung weight–body weight ratio was < 0.012 at a gestational age of
28 weeks and was < 0.015 at < 28 weeks
[11–14].
Assessment of Fetal Lung Volumes on 3D Sonography
Fetal lung volumes were estimated using the rotational technique (virtual
organ computer-aided analysis [VOCAL]) on a sonography machine (Kretztechnik
Voluson 730, GE Healthcare) with a 4- to 8-MHz transducer for 3D volume
scanning. A transverse section of the fetal thorax at the level of the
four-chamber view, with the fetal heart proximal to the transducer, was
identified on 2D sonography, and the volume box was adjusted to scan the
entire fetal thorax. After scanning the volume, the three orthogonal
sonography sections were analyzed and stored on a removable hard disk. Each
lung was carefully identified in the three orthogonal multiplanar imaging
sections. A transverse section of the fetal thorax was chosen, and each lung
volume was measured using the rotational technique, which consists of
outlining the contour of the lung repeatedly after rotating the image six
times by 30°. Left and right lung volumes were automatically measured four
times by the same operator, and the total fetal lung volumes were then
calculated in cubic centimeters (cm3)
(Fig. 1).
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Statistical Analyses
The ratio of sonographic fetal lung volume to body weight was calculated as
the ratio between estimated fetal lung volumes on 3D sonography and estimated
fetal body weights on 2D sonography. The ratio values were plotted against
gestational age in control subjects. In fetuses with CDH, the ratio was
compared with neonatal deaths using the Mann-Whitney U test (SPSS
version 13, SPSS) for Windows (Microsoft). Pulmonary hypoplasia was suspected
using the same cutoffs for fetal lung weight–body weight ratios that
were considered at autopsy. Accuracies of the ratio in predicting neonatal
deaths and pathologic diagnosis of pulmonary hypoplasia were evaluated after
calculating the receiver operating characteristic curve. Statistical
differences were considered to be significant when the p value was
less than 0.05.
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Pulmonary hypoplasia is characterized pathologically by the fetal lung weight–body weight ratio in macroscopic analysis and by the radial alveolar count in microscopic specimens [11–14, 19]. The ratio is considered the simplest, most frequently used parameter for the diagnosis of pulmonary hypoplasia [11–14, 19]. On the basis of these observations, Tanigaki et al. [10] proposed the use of the ratio of fetal lung volume estimated on MRI and fetal body weight estimated on sonography for the prediction of pulmonary hypoplasia, with good results. Recently, it was shown that the sonographic fetal lung volume–body weight ratio can be precisely measured when these measurements were compared with those obtained at autopsy of 35 fetuses after termination of pregnancy [17]. Good accuracy of the ratio in predicting and diagnosing pulmonary hypoplasia was also reported [17]. Because neonatal deaths in isolated CDH may be related to the degree of pulmonary hypoplasia, we decided to evaluate the potential of the ratio to predict neonatal deaths and pulmonary hypoplasia in fetuses with isolated CDH.
Many efforts have been made to predict and diagnose pulmonary hypoplasia correctly and to predict neonatal deaths in fetuses with isolated CDH. As we mentioned earlier, the main problem of many studies is the confusion in concepts between the diagnosis of pulmonary hypoplasia and the prediction of neonatal outcome. This occurs particularly in CDH, in which pulmonary hypoplasia is present in almost all cases and the main prenatal aim is to predict outcome—that is, to identify which fetuses will have more severe pulmonary hypoplasia and will consequently die. In the present study, fetal lung volumes were related to the neonatal outcome given that low ratios were observed in cases of death and pulmonary hypoplasia was diagnosed on sonography in all fetuses with CDH. However, the accuracy of the ratio in predicting neonatal deaths was low (64.5%), confirming the suspicion that the sonographic fetal lung volume–body weight ratio is not the best parameter for this purpose. This finding may be explained also by the fact that pulmonary hypoplasia is not the only cause of neonatal deaths in CDH cases. Other abnormalities in these lungs, such as severe pulmonary arterial hypertension, are involved too [20]. On the other hand, the ratio is a good parameter to use to predict pulmonary hypoplasia (accuracy = 86.4%), which seems to be present in approximately 85.0% of all fetuses with CDH.
In conclusion, the sonographic fetal lung volume–body weight ratio can be used to diagnose pulmonary hypoplasia in fetuses with isolated CDH, but this ratio lacks sufficient accuracy to reliably predict neonatal deaths. Further studies are necessary to show the prevalence of pulmonary hypoplasia in fetuses with isolated CDH and its importance for predicting neonatal deaths.
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), were terminated (
), and died as neonates (x). Mean
sonographic fetal lung volume–body weight ratio (solid line) was 0.025;
10th centile (lower dashed line) and 90th centile (upper dashed line) were
0.020 and 0.032, respectively.