Radiographic Diagnosis of Hyaline Membrane Disease'

SORRELL L. WOLFSON, M.D., ROBERT FRECH, M.D.,2 CARLYSLE HEWITT, M.D.,

and D. R. SHANKLIN, M.D.

T of hyaline membrane(clinical)
HE ANTEMORTEM diagnosis
disease remains
difficult because of the lack of a definitive
test. This lack affects the assessment of
ancillary diagnostic technics and the evalu-
ation of treatment. Until a satisfactory
testbecomes available, further effort must be
made to improve existing technics through
comparison with the ultimate criterion of
autopsy confirmation. Because radiog-
raphy of the thorax offers a two-dimen-
sional view of anatomical changes within
the lung, we determined to analyze our Fig. 1. Typical appearance of Stage I chest film.
radiographic experience, which was part of Pattern is nonspecific, suggesting merely the possibility
an intensive study of premature newborn of pulmonary change.
infants at the Tampa General Hospital.
This paper describes our criteria for seen. A chest film was obtained to exclude
clinical and radiological diagnosis, makes any intrathoracic component.
correlations between radiographic findings By inspection, respiratory distress would
and clinical distress, survival, and maturity, include dyspnea, tachypnea, generalized
and analyzes the findings in relation to cyanosis, retractions of the costal margins,
autopsy proof of the lesion complex of and abdominal protrusion with a "see-
hyaline membrane disease. This experi- saw" motion during inspiration; ausculta-
ence suggests that when certain criteria are tion would reveal expiratory grunt, de-
applied, radiographic study of the thorax creased entry of air into lungs, and rales.
of the infant with respiratory distress be- All signs were not present in every case.
comes a nearly ideal tool per se for diagnosis A diagnosis of idiopathic respiratory dis-
of severe distress with a high intrinsic tress syndrome was made when one or
mortality rate. This study also contrib- more of the auscultatory signs and/or
utes to an understanding of the rate of abdominal protrusion were present.
evolution of the disease complex itself. Our analysis is based on the initial film.
A repeat film was obtained in accordance
CLINICAL STUDY
with clinical indication. The films were
During the twenty-month interval from read by two radiologists CR. F., C. H.) and
October 1964 through May 1966 inclusive, classified according to the following criteria.
328 premature infants were admitted to the The significance of each stage is given
Newborn Intensive Care Unit of Tampa immediately after each criterion.
General Hospital. A chest film was ob- Stage 0: Clear lungs. Condition nor-
tained if the Apgar score was 0-6 or if mal.
respiratory distress was clinically apparent. Stage I : Air bronchogram pattern
In one patient, a large cervical mass was greater than normal, involving a combina-
1 From the Departments of Pediatrics (S. L. W., Teaching Chief) and Radiology (R. F. and C. H., Radiologists)
of Tampa General Hospital, Tampa, Fla., and the Laboratory of Pathology (D. R. S., Professor of Pathology and
Obstetrics-Gynecology, Pritzker School of Medicine), The Chicago Lying-In Hospital, University of Chicago,
Chicago, Ill. Accepted for publication in March 1969.
Supported in part by grants-in-aid from Ayerst Laboratories, New York, N. Y.
2 Present address: Department of Radiology, Washington University School of Medicine, St. Louis, Mo.
RADIOLOGY 93: 339-343, August 1969. ah

339
340 SORRELL L.
Fig. 2. Typical appearance of Stage II chest film.
The air bronchogram is diffuse, accentuated by peri-
bronchial atelectasis or peribronchial opacity.
tion of at least two lobes. Nonspecific;
might be consistent with early hyaline
membrane disease, early bronchopneu-
monia, anectasis neonatorum, tracheo-
esophageal fistula with atresia of the
esophagus, pulmonary lymphangiectasis, or
congestive failure of congenital heart dis-
ease. Requires repeat films, more detailed
correlation with clinical findings, etc., for
proper evaluation.
Stage II : Diffuse air bronchogram.
Definite but not always striking peri-
bronchial atelectasis or thickening involv-
ing all the lobes. Faint alveolar opacifica-
tion. Mild to moderate hyaline membrane
disease.
Stage III: Pattern of definite alveolar
opacification in addition to air broncho-
gram. Confluent opacification or unequiv-
ocal and fairly dense reticular pattern in-
volving less than half the total lung field.
Advanced, severe hyaline membrane disease.
Stage IV: Same as Stage III, but with
alveolar opacification involving the major-
ity of the lung field. Advanced, severe
hyaline membrane disease.
There were 75 infants whose chest
roentgenograms were obtained within the
first one hundred and twenty hours after
birth, with the times of the films recorded.
Films were made for 11 others, but the
timing could not be verified. Seventy-one
had initial films in the first forty-eight
hours after birth.
The initial films were all viewed prospec-
WOLFSON AND OTHERS August 1969
tively during the study and then reviewed
for consistency of interpretation by three
of us (S. L. W., R. F., C. H.). All patho-
logical materials were independently re-
diagnosed (D. R. S.). After all clinical
diagnoses were reviewed (S. L. W.), the
three sets of interpretations were concur-
rentlyanalyzed (S. L. W., D. R. S.).
Fig. 3. Typical appearance of Stage III chest film.
Alveolar opacification is definite; diffuse air broncho-
gram.
RESULTS
The overall mortality was 29/75, or
38.7 per cent. Fifty infants had clinical
respiratory distress by the above criteria.
In this group the mortality was 25/50, or
50 per cent. In the group not considered
to have clinical respiratory distress, the
mortality was 4/25, or 15 per cent. This
distribution is highly significant, chi square
being 8.2, 0.01 > P > O.OOL
Infants Thought to Have Clinical Respira-
tory Distress Syndrome. 1. The survivors:
There were 22 single births and 3 twins,
each from different pairs. There were 14
males and 11 females; 7 Caucasians,
17 Negroes, and 1 Indian. Twenty-four
weighed less than 2,500 g at birth; one
weighing 2,600 g was considered premature
by gestation and length. Five were born
in the months of September to December,
11 in January to April, and 9 in May to
August.
In 7 infants the chest film was Stage 0;
in 18 it was positive, with the following
profile: 6 in Stage I, 9 in Stage II, 3 in
Stage III, and 0 in Stage IV.
Vol. 93 RADIOGRAPHIC DIAGNOSIS OF HYALINE MEMBRANE DISEASE 341

2. The deaths: There were 19 single

births and 6 twins, 2 of whom constituted
one pair. There were 15 males and 10
females; 13 Caucasians and 12 Negroes.
All weighed less than 2,500 g at birth and
were considered premature by gestational
age. Twelve were born in the months of
September to December, 5 in January to
April, and 8 in May to August.
In all 25 infants the chest film was read
as positive, with the following profile:
o in Stage I, 9 in Stage II, 10 in Stage III,
and 6 in Stage IV. There were 21 autop-
sies on these infants; hyaline membrane
disease was found in 20 (95.2 per cent). Fig. 4. Typical appearance of Stage IV chest film.
Alveolar opacification over majority of lung field.
The exception was a 765-g white male Air bronchogram may be obscured by increasing fluid.
living thirty-six hours and showing early
acute pneumonia. TABLE I summarizes 0; in the other 7 it was Stage 1. Both
these data. degrees were considered as essentially
I nfants Thought Not to Have Clinical negative.
Respiratory Distress Syndrome. 1. The 2. The deaths: There were 4 single
survivors: There were 19 single births and births: 3 males and 1 female; 3 Caucasians
2 twins, both from different pairs. There and 1 Negro. All weighed between 1,000
were 13 males and 8 females; 5 Caucasians and 2,000 g at birth. Two were born in
and 16 Negroes. All weighed less than the months of September to December,
2,500 g at birth. Eleven were born in with 1 in each of the other periods.
the months of September to December, 3 In all 4 the chest films were negative.
in January to April, and 7 in May to Autopsies on 3 surviving eleven, ninety-
August. eight, and one hundred and fifteen
In 14 infants the chest film was Stage hours, respectively, showed no evidence of

TABLE I: PARTICULARS IN NEWBORN INFANTS WITH TIMED CHEST FILMS

Consideration Infants with Clinical Infants Without Clinical

Distress Syndrome Distress Syndrome

Total No. 50 25
Survivors 25 (50% survival) 21 (84% survival)
Singletons 22 (54 % survival) 19 (83% survival)
Twins 3 (33% survival) 2 (100% survival)
Males 14 (48% survival) 13 (81 % survival)
Females 11 (52% survival) 8 (100% survival)
Stage ofilm 7 (100% survival) 14 (77% survival)
Stage I film 6 (100% survival) 7 (100% survival)
Stage II film 9 (50% survival) o
Stage III film 3 (23% survival) o
Stage IV film o (0% survival) o
Deaths 25 4
Singletons 19 4
Twins 6 o
Males 15 3
Females 10 1
Stage ofilm o 4
Stage I film o o
Stage II film 9 o
Stage III film 10 o
Stage IV film 6 o
342 SORRELL L. WOLFSON AND OTHERS August 1969

TABLE II: CUMULATIVE PERCENTAGES OF DISCUSSION

POSITIVE CHEST FILMS
The radiographic and prognostic aspects
Time Total Films Positive Films
of hyaline membrane disease are well
Interval Taken Found* known. The interested reader should con-
sult in particular the monograph edited by
0-1 hr. 7(9.3%) 3(8.1%)
1-2 hr. 22(29.3%) 11 (29.7%) Kaufmann (6), the reference monograph
2-3 hr. 39(52.0%) 21 (56.7%) by Avery (1), and the reports of Harris
3--4 hr 54(72.0%) 29(78.4%)
4-5 hr. 62 (82.6%) 34 (91.9%) (4), Nadelhaft and Ellis (7), Stahlman
et al. (12), Steiner (13), and Weintraub
* Stages II, III, and IV.
etal. (14).
TABLE III: PERCENTAGE OF POSITIVE FILMS DURING The radiographic frequency of hyaline
EACH HOURLY INTERVAL membrane disease in our series was 37/
328 prematures (11.3 per cent). The
Positive Films Positive Films mortality rate was 25/37 (67.6 per cent)
Time
Interval Total Patients Severely Dis- with 21 autopsies. In only one case was a
tressed Patients
lesion other than hyaline membrane disease
0-1 hr. 3/7 (43%) 3/5(60%) found at autopsy. When considered as a
1-2 hr. 8/15 (57%) 8/10(80%) single population (an assumption not
2-3 hr. 10/17 (39%) 10/13 (77%)
3--4 hr. 8/15 (57%) 8/10(80%) necessarily valid per se), the group with
4-5 hr. 5/8(62%) 5/7 (71 %) positive radiographic findings (Stage 11-
IV films) has a mortality rate identical to
hyaline membrane disease. A white male that reported by Hutchison et al. (5),
weighing 1,985 g at birth and living seven- whose criteria for diagnosis are similar to
teen and a half hours was not subjected to ours.
autopsy. The negative chest film was In the present study, two features were
taken at the age of two hours. TABLE I noted: (a) a high correlation with the
summarizes these data. radiographic criteria, which established the
The Interval Between Birth and Time of disease proved by autopsy and (b) early
Chest Film: The interval between birth strongly positive films which accounted
and time of chest roentgenography varied for 90 per cent of all positives by the age of
greatly but was basically dependent on the five hours.
appearance and apparent clinical signifi- Of the entire series of 75 cases, 3 were
cance of respiratory distress. The finding possibly classifiable as false-positives and
of definitely positive films (Stages II, 1 as false-negative, an overall correlation
III, and IV) closely parallels the timing of of 71/75 (95 per cent). The 3 false-
radiographic exposure, suggesting the positives were Stage III films in survivors
pulmonary process is of rapid onset and of with definite severe clinical distress.
early maximum interference with ventila- Alternatively, these could represent true
tion. As seen in TABLE II, 82.6 per cent of examples of healing with survival (2).
all chest films were made by five hours after The possible false-negative was the infant
birth; 91.9 per cent of positive films had described above with a negative film at
been obtained by that time. Beginning two hours, no real clinical distress, and,
with films taken between two and three unfortunately, no autopsy. We have on
hours, the proportion of positives exceeds occasion found typical hyaline membrane
that of total films. disease in infants with no real distress.
The percentage yield of positive films The survival for this child is almost exactly
at each hourly interval was similar. the median from our general experience,
TABLE III shows an increase in yield after and we wonder whether the film was taken
the first hour, which remains essentially too early. The lack of distress led us
higher throughout the final four hours of away from a repeat film.
this study period. The finding of 9 Stage II infants among
Vol. 93 RADIOGRAPHIC DIAGNOSIS OF HYALINE MEMBRANE DISEASE
those dying after severe distress and the
autopsy proof of hyaline membrane disease
are also of interest. The question arises
whether these were films taken dispro-
portionately early in the evolution of the
lesion. As one test, the ratio of birth-
film interval to total survival time was
calculated for all 25 deaths in the group.
The Stage II cases had an average ratio
of 0.14, and the Stage III and IV cases
had an average ratio of 0.28. This sug-
gests that the Stage II films were taken
disproportionately early with respect to
total survival. The STAGE II infants also
lived twice as long on the average, forty-
six hours compared to twenty-three hours
for Stages III and IV. Stage IV cases
showed the shortest survival average (nine
and a half hours) and the highest ratio as
defined above, 0.41.
These findings allow the inference that
early severe distress portends a poor
prognosis with respect to both eventual sur-
vival beyond the neonatal period and the
average postnatal course of those infants
dying of the disease. In the great majority
of cases, the radiographic lesion is well
developed in the first five hours. Infer-
entially, the anatomic equivalent of the
radiographic lesion is well developed in the
first five hours. Of the elements of the
lesion seen at autopsy (9, 10), it is likely
that resorptive atelectasis, vascular conges-
tion, and edema occur early, with the
definitive membranes a rather late de-
velopment (8). Although seen early and
frequently, the focal necroses of bronchiolar
epithelium (11) probably have no radio-
graphic importance. This sequential
analysis reduces the importance of the
actual membranes to our understanding of
the lesion and lends support to Gruenwald's
conclusions on their significance (3).
SUMMARY
Chest roentgenographic findings in new-
343
born infants with respiratory distress
showed a high degree of correlation with
autopsy findings. It is suggested that x-
ray examination offers an ideal diagnostic
technic for respiratory distress in newborn
infants. In the authors' series of 75 cases,
more than 90 per cent of positive films were
obtained by the age of five hours, emphasiz-
ing the early onset of this disease after
birth.
D. R. Shanklin, M.D.
Chicago Lying-In Hospital
5841 Maryland Ave.
Chicago Ill. 60637
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