CONGENITAL
TUBERCULOSIS
B;
FREDERICK EUGENE AMIcic,M.D.,
MANNINGW.
ALDEN,M.D.,
AND LEWIS
K.
SWEET, M.D.Huntington,
JV.Va.,
and
Washington,
D.C.
N INFANT with congenital tuberculosis is one who has been infected with tubercle
bacilli during intrauterine life or before passage through the birth canal has been
completed. According to Beitzke’ such a diagnosis can be demonstrated only if both the
tuberculous nature of the lesion and the antenatal origin of the infection can be proved.
The congenital origin of the infection must be assumed if a primary tuberculous complex
is demonstrated in the liver, since such a lesion could have arisen only from tubercle bacilli
in the umbilical vein, Likewise the presence of tuberculous lesions at the time of or within
‘I
few days after birth is indicative of an antenatal infection. In the case of an infant wholives
more
than
a few
days,
a congenital
infection
can
be
proved
only
if a postnatal
infection can be excluded with certainty. This can be done only if the infant has beenseparated immediately and completely from the mother, and has been kept in an
environ-ment known to be free from tuberculosis.
True instances of congenital tuberculosis have been reported infrequently. Beitzke1
in 1935 was able to collect 61 cases of proved congenital tuberculosis with anatomic lesions, and 40 others in whom tubercle bacilli were found without histologic changes.
Hughesdon2 in 1945 collected from the literature 1 1 additional cases that fulfilled
Beitzke’s criteria, and added four of her own. Single cases not included in the preceding
reviews
have
been
reported
by Conrad,
Page!
and
Hall,4’
Buchanon,6
Contreras,7
Harris,
McCullough, Stone and Brock,8 Debr#{233}, Furiet-Laforet and Royer,9 Lesne, Cayla, Roche
and Allard’0 and Hertzog, Chapman and Harring.1’ There are, therefore, 124 cases of
verified congenital tuberculosis on record at the present time. Of these, only nine have
been
reported
in the American literature.The infant reported by Lesne and his associates’#{176} is of particular interest. He was born
to a mother who had been under treatment for tuberculous meningitis for a month before
delivery.
The
mother
died
shortly
thereafter.
The
infant
showed
evidences
of tuberculosis
when he was one month old. He was given a prolonged course of streptomycin therapy
and was in good condition more than one year later, when the report was written. This
is the first infant known to have recovered from congenital tuberculosis.
Four
instances
of
congenital
tuberculosis
have
been
encountered
in the GallingerMunicipal Hospital between 1940 and 1949. Two pf these patients were alive and well
at the
ages
of
17and
24months.
Their tuberculosis apparently has been arrested by streptomycin therapy. The purpose of the present paper is to report these four cases indetail.
CASE REPORTS
Case 1. C. D., a 27 yr. old white female, approximately 8 mo. pregnant, was admitted to the
hospital with a history of a productive cough and weight loss for about 5 mo. Her sputum had
been streaked with blood for 2 wk. before admission and she had become weak and occasionally
From the Departments of Pediatrics and Pathology, Gallinger Municipal Hospital, Washington,
D.C.
dyspneic. She was losing weight in spite of the increasing weight of pregnancy. A fluoroscopic ex-amination at the time of admission revealed infiltration in the left apex near the left axilla. She gave birth to a male infant 4 days after admission. A roentgenogram of the mother’s chest 8 days after delivery revealed mottling and marked fibrosis throughout the left upper lobe, and a cavity 1.5 cm. in diameter in the first left anterior interspace. The remainder of the lung fields showed a miliary distribution of small discreet nodules, the findings being consistent with a miliary type of tuberculo-sis. Examination of the sputum 8 days after delivery revealed tubercle bacilli. The mother ran a febrile course and died on the 22nd day after delivery. Postmortem examination was not performed.
After 18 hr.’ active labor, the patient had been delivered of a male infant who weighed 2000 gm. The infant was taken immediately to the premature nursery. There was no contact with the mother or with any other person with evidence of tuberculosis. The placenta was not described. Physical
examination of the infant at the time of birth revealed no abnormalities. A low weight of 1875 gm was reached on the 6th day of life, and by the 9th day the infant had regained to its birth weight.
The formula was taken well and the infant appeared to be normal during the 1st 2 wk. of life.
Fifteen days after birth, there was an elevation in the infant’s temperature to 38.7#{176}C. The infant’s respirations became rapid and he took his formula poorly and became listless. On the 16th day of life, chest RG showed several small discreet shadows of increased density throughout both lung fields. The findings were consistent with a miliary tuberculosis. The condition of the infant rapidly became worse and he died 17 days after birth.
Autopsy flndings.-.--The body was that of a white male infant 35 cm. long, weighing 2050 gm.
The positive gross and microscopic findings were confined to the lungs, the genitourinary tract and
the hemopoietic system. Both lungs were distended and their pleural surfaces smooth. Scattered throughout the lung fields were numerous yellowish-white nodules varying in diameter from 1 to
4 mm. These nodules were more profuse in the 2 lower lobes. Some of the nodules appeared to have a central lumen suggesting a clover-leaf arrangement around the bronchioles. The mediastinal lymph nodes were within normal limits.
The kidneys showed the usual fetal markings. The ureters, pelves and calyces of both kidneys were dilated, the right being about 5 times normal size, and the left 3 times normal size.
Microscopically each lung lobule was affected and contained distended alveolar sacs whose lumens were filled with dark blue-staining necrotic material with a few polymorphonuclear and mononuclear cells. Surrounding these areas the adjacent alveoli also contained some debris and more cellular dc-ments of the inflammatory and phagocytic type. The alveolar walls were distinctly outlined, often were completely intact. An occasional bronchiole contained the same material as that present in the alveoli. The bronchial walls and blood vessels appeared intact. The entire picture was one of an intra-alveolar lesion resembling lobular pneumonia except for the far advanced disintegration present in the intra-alveolar material. No epithelioid cells, giant cells or lymphocytes were found in any of the lesions. Ziehl-Neelson stain revealed myriads of acid-fast beaded bacilli in the disintegrated tissue, in the alveolar lumens, and some in the alveolar walls.
No further lesions were found in any of the other organs, and the kidneys showed only the changes consistent with hydronephrosis. There was evidence of extra-medullary hematopoesis in the spleen and adrenal cortex.
The diagnosis was aspiration tuberculous pneumonia contracted in utero, bilateral hydronephrosis
and hydroureter and marked hypochromic anemia.
Case 2. L. J., a 32 yr. old Negro female, was admitted to the hospital at 35 wk.’ gestation. She had attended a prenatal clinic for the first time on the day of admission and was referred to the hos-pital because of early labor and because she had passed a large blood clot. Her pregnancy had been
uneventful except for morning sickness during the first trimester. Her usual weight was 6 1 .8 kg., but at the time of admission was 60.5 kg. Her previous pregnancies were uneventful and both children
were living and well. She had received treatment for syphilis 2 yr. previously and 1 sister was known to have tuberculosis.
At the time of admission her temperature was 37.4#{176}C. About 30 hr. after admission, she was delivered of a 2400 gm. male infant who was immediately taken to the premature nursery. The placenta showed no gross abnormalities. Following delivery the mother continued to maintain an ele-vation in temperature. Chest RG showed miliary tuberculosis 23 days after delivery. Her course was
The infant to L.
J.
did well during the 1st 4 wk. of life. A low weight of 2 100 gm. was reachedon the 5th day after birth. He did well, gaining weight and taking his formula well, until the 37th
day of life, when he weighed 2700 gm. At this time the infant began to have bouts of fever, became listless and anorexic, and developed rapid respirations with periods of apnea. Fine moist rales over
the left lung field were discovered at this time. Chest RG on the 41st day of life showed enlarged tracheo-bronchial lymph nodes on the right side and infiltration in the right upper lobe. First test strength PPD was negative on the 44th day of life. The second strength PPD was positive 2 days later, and at this time the site of the first test strength PPD showed a positive reaction. Repeat RG of the chest 4 days later showed a progression of the lesion in the right lung and there was also in-filtration in the medial portion of the left lung. Tubercle bacilli were found in gastric washings on
the
52nd day of life. The infant became very weak and lost weight. He died 54 days after birth. Autopsy findings-The body was that of a well developed, undernourished Negro male weighing 2810 gm. There was very little subcutaneous fat and the musculature was very thin. Grossly the pleural surfaces of the lungs were smooth and each pleural cavity contained a small amount ofstraw-colored fluid. The lungs were extensively consolidated with confluent areas of yellowish-white necrosis and cavitation. Only very small amounts of aerated lung parenchyma remained. There were many
small foci of yellowish-white caseous material scattered throughout both spleen and liver. No tuber-culous lesions were found in the rest of the viscera, but there was a patent ductus arteriosus and
foramen ovale, and the pericardium contained about 5 cc. of straw-colored fluid.
Microscopic.-Sections of lung showed large areas in which there was complete replacement of lung parenchyma by a fibrosing inflammatory process. The lesions were surrounded by thin
collage-nous connective tissue bands and their centers were often completely necrotic. In the midzones there were numerous polymorphonuclear cells, lymphocytes and congested capillaries. Epithelioid and giant cells were absent. About these fibrous enclosed areas the adjacent alveoli contained polymorphonuclear cells, lymphocytes, plasma cells, large macrophages and debris. Many of the bronchioles were
cen-trally located in these lesions and their mucosal cells were completely destroyed. The bronchiolar
walls were often necrotic so as to suggest that the initial pulmonary process originated in the air
passages and spread to involve contiguous tissues. There was also definite evidence of invasion and destruction of small arteries in the most heavily involved regions. There were varied amounts of fibrin on the pleural surface and the tissues were markedly edematous.
The picture was that of a tuberculous bronchopneumonia following aspiration of infected material.
Acid-fast beaded organisms were demonstrated in these tissues.
Sections of liver and spleen both contained small rounded lesions scattered throughout the parenchyma. These lesions were composed of caseating centers and had lymphocytes and polymorpho-nuclear cells at the periphery. In a rare instance Langhan’s type giant cells were present. Acid-fast stains revealed abundant beaded bacilli identical with M. tuberculosis.
Since the lesions in the liver and spleen had miliary distribution, were composed of definite
casea-tion necrosis, and did contain rare Langhan’s giant cells, it was felt they were of a more recent oc-currence than those in the lungs.
Case 3. M. H., an 18 yr. old Negro female in the 7th month of gestation, was admitted to the obstetric service in active labor. About 14 hr. before admission she began to have uterine contrac-tions and vaginal bleeding, and 2 hr. before admission she passed 3 large clots of blood. Her
tempera-ture on admission was 38.4#{176}C. There was a moderate pharyngitis, and the lungs were clear. One brother of this patient died with tuberculosis, a nephew had primary tuberculosis and her 1 child was being treated for primary tuberculosis. The patient had been followed in the District of Columbia
Chest Clinic for 7 yr. because of her family contacts. RGs 22 mo. before admission showed no evidence of tuberculosis. The day before admission RGs showed far advanced pulmonary tuberculosis. Two
hours after admission she was delivered of a 1 560 gm. female infant who was taken immediately
to the premature nursery. There was no contact with the mother after birth. Chest RG of the mother,
made 2 days after delivery, showed miliary tuberculosis. The following day the mother was started
on streptomycin 3 gm/day by intramuscular injection. This was continued for 47 days. Chest RG 2 mo. after delivery showed complete clearing of the miliary lesions. All laboratory work, including sputums, were essentially negative. Because of low abdominal pain, a gynecologist who saw her was of the opinion that she had a tuberculous salpingitis. Five months after delivery she was restarted
was in the hospital 2 yr. after delivery. She showed no evidence of miliary tuberculosis, and was
con-valescing from her pelvic tuberculosis.
Physical ecamination of the infant to M. H. at the time of birth revealed no abnormalities. On the second day after birth a low weight of 1284 gm. was reached. After this the infant began to gain weight. Second test strength purified protein derivative was questionably positive on the 14th day of life. The same test repeated the 21st day of life was definitely positive. When the infant was 56 days old and weighed 2143 gm., it was noted that there was an enlarged anterior cervical lymph node, and that small pre-auricular lymph nodes were palpable. At the same time both the liver and spleen became palpable, the edge of each being felt about 3 cm. below the costal margin. On the 63rd day of life, chest RG first showed some haziness in both lung fields. On the 72nd day there was diffuse mottling throughout both lung fields, the findings being consistent with a miliary tuberculosis. Gastric washings taken at this time were positive for acid-fast bacilli on culture. Streptomycin was given by intramuscular injection in doses of 60 mg. every 4 hr., starting on the 72nd day of life. This was continued for 4 mo. When the infant was 127 days old, and had been on streptomycin for 55 days, her weight had increased to 3277 gm. and chest RG was first reported as showing clear-ing of the miliary infiltration. Subsequent RGs showed complete clearing. She had several upper respiratory infections with catarrhal otitis media and elevations in temperature which were treated satisfactorily with sulfadiazine and/or penicillin. Her liver and spleen continued to be palpably en-larged. From the 3rd to the 5th month of life several blood transfusions were given for a moderate anemia. Thereafter the infant maintained a satisfactory RBC count and hemoglobin without trans-fusions. She gained and developed fairly well though caloric tests showed complete absence of vestibular function. She was discharged at 83/4 mo. of age weighing 5.9 kg. At 2 yr. of age she weighed 1 1.1 kg. and her chest was clear by roentgenographic examination. Her liver edge was felt 1 cm. below the costal margin and her spleen tip was barely palpable. She walked well and showed little gross evidence of vestibular damage. She was mentally retarded, with an intelligence quotient of 58 by the Kuhlman infant scale. The authors were uncertain as to the causal relationship between the congenital miliary tuberculosis and the mental retardation.
Case 4. V. G., a Negro female aged 22 yr., was admitted to the Gallinger Municipal Hospital in the 33rd wk. of gestation. She was admitted because of false labor produced by a mild diarrhea. Her labor subsided but she developed an elevation of temperature. Simultaneously with the fever she
de-veloped pain in the right flank and mild pyuria. These symptoms continued. One week after admis-sion, chest RG showed increased lung markings and accentuated hilar shadows that were compatible with tuberculosis of the tracheo-bronchial glands. During the period of fever she went into labor and was delivered of a male infant. The placenta was normal on gross and microscopic examinations. She continued to run a febrile course and gradually developed bilateral adnexal masses. Twenty-eight days after admission she developed evidence of intestinal obstruction. After appropriate
sup-portive measures had been employed, an exploratory laparotomy was performed. The findings were
characteristic of tuberculous peritonitis and salpingitis. A biopsy of peritoneum showed only sub-acute inflammation, but the peritoneal fluid showed organisms typical of M. tuberculosis on both smear and culture.
Following operation, the patient was given streptomycin in a dosage of 2.0 gm/day for 6 wk.
During this time her condition improved remarkably. She became afebrile after 4 wk. of therapy. She was discharged 3 mo. after admission. She subsequently returned to the hospital and 1#{189}yr. after the birth of the infant was under treatment for moderately advanced, active pulmonary tuberculosis.
The patient, V. G., was delivered of a male infant after a labor that lasted 18 hr. The infant’s weight at birth was 1770 gm. The infant was transferred from the delivery room 1 hr. after birth and had no subsequent contact with the mother or with anyone else who showed evidence of
tuberculo-sis. He was given the usual care provided for a normal premature infant. His early response was
good. He reached a low weight of 1500 gm. on the 8th day of life, then regained his birth weight on
the 23rd day. The tuberculin test (P.P.D. #2) was negative at that time, and chest RG showed no
abnormality.
the tuberculin test still was negative. Because of the continuation of the discharge from the right ear, and the right facial palsy, a right antrotomy was performed on the 71st day of life. The antrum was filled with greenish caseous material, and the antrum and the mastoid cells were enlarged from pres-sure necrosis. A large lymph node from the right cervical chain was removed for biopsy. On histo-logic study the node contained conglomerate granulomata which were typical of tuberculosis. A
cul-ture from this node showed a dense growth of acid-fast bacilli typical of M. tuberculosis. Tubercle bacilli were recovered also on culture of the ear discharge. A specimen of tibial bone marrow ex-amined on the day of operation also showed tubercle bacilli on both smear and culture.
Beginning the day of operation, after a definite diagnosis of tuberculosis had been established,
the infant was given streptomycin 0.25 gm. by intramuscular injection every 6 hr. ( 1.0 gm/day).
When this medication was started the infant’s weight was 2724 gm. and his condition was poor.
Following the streptomycin therapy the mastoid wound healed well, the facial paralysis improved
slowly, and the weight gain became more rapid. The chest remained clear as determined by fre-quently repeated roentgen examinations. Streptomycin was discontinued after 124 days of therapy. At that time the infant weighed 5056 gm. The infant has continued to do well. At 18 mo. of age he weighed 10.2 kg., and measured 89 cm. in length. His cervical adenopathy had receded. His chest was clear by roentgenographic examination. The infant had normal dentition and was in good gen-eral physical condition. He showed retardation in development in that he did not talk or walk, though he occasionally pulled up to a standing posture. He showed evidence of vestibular damage in that he sat uncertainly. His locomotor retardation may have been caused by vestibular damage, which was expected. The lack of speech may have been due to nothing more than lack of stimulation in an
institutional environment, though general mental retardation may have been a factor.
COMMENT
All four of the infants described fulfill the criteria for congenital tuberculosis as
out-lined by Beitzke.1 None of the infants had postnatal contact with his mother or with any
other
infected
person
since
all
were
cared
for
in the
nursery
for
premature
infants
until
they showed evidence of illness. Case 1 developed a severe tuberculous bronchopneumonia
with intra-alveolar necrosis before death on the 17th day of life. This extensive lesion in
so young an infant would seem to be possible only on the basis of intrauterine aspiration
of infected amniotic fluid. The infants in Cases 2 and 3 may have been infected during
intrauterine
life
or
intranatal
passage.
Repeated
tuberculin
tests
were
not
done
on
the
second infant whose diagnosis was established only when there was advanced evidence of
clinical
illness
after
5 wk.
of life.
The
chest
RG
and
the
intradermal
tuberculin
test
were
positive
at that
time.
Therefore,
the
diagnosis
was
established
late
in the
course.
The
third
infant showed a positive tuberculin test after three weeks of life, with positive RG and
bacteriologic tests only after two months. The primary lesion in both these infants was in
the lungs (in Case 3 by roentgenographic evidence only) . It would seem highly probable
that both these infants were infected by the aspiration of infected amniotic fluid in utero,
though the possibility of intranatal aspiration cannot be excluded. Since the mothers of all
three of these infants had acute miliary tuberculosis at the time of delivery, it is reasonable
to assume an infection of the amniotic fluid without demonstrable gross abnormalities
in the placenta.
The infant in Case 4 apparently was infected during birth. The mother had pelvic
tuberculosis
and
tuberculous
peritonitis
rather
than
acute
miliary
tuberculosis.
The
infant
remained
symptom
free
for seven
weeks,
and
the tuberculin
test
was
negative
at nine
weeks,
two weeks after the onset of symptoms. The primary lesion appears to have been an otitis
media, followed by tuberculous cervical lymphadenitis and a hematogenous tuberculosis
as demonstrated by the finding of tubercle bacilli in the bone marrow. The lungs remained
was no
evidence
of
liver
involvement.
These
findings
make
an
intranatal
infection
seem
almost certain.The patients in this group comprise the only infants born to mothers who were
suffer-ing from acute miliary tuberculosis at the time of delivery in this hospital during the past
10 years. Since every infant the authors have seen who was born during the acute stage of acute miliary tuberculosis has developed tuberculosis without subsequent exposure, it
would seem that all infants born to mothers with acute miliary or pelvic tuberculosis
should be watched very closely with frequently repeated tuberculin tests. This should be
done with the view of establishing the diagnosis in the earliest possible stage of the
disease. This belief is enhanced by the fact that two of these patients apparently have had
their tuberculosis arrested for periods of 15 and 21 months after the institution of
strep-tomycin therapy. Treatment in these infants was started late in the disease because the
authors
wanted
to
delay
until
the
diagnosis
of
tuberculosis
was
established
beyond
a
peradventure of a doubt. Earlier treatment in subsequent patients would seem to be more
advantageous.
SUMMARY
Four patients with congenital tuberculosis, all prematurely born infants, are
de-scribed. Three infants born of mothers with acute miliary tuberculosis apparently
con-tracted the disease by aspiration of infected amniotic fluid in utero. The fourth infant,
who was born to a mother with acute pelvic tuberculosis and tuberculous peritonitis, seems
to have
been
infected
during
passage
through
the
birth canal. Two of the infants weretreated
by
intramuscular injections of streptomycin. In both instances the tuberculousinfection appears to have been arrested ; the infants are in good condition at the ages of 18 and 24 months, respectively. It is recommended that all infants born to mothers with
acute miliary or pelvic tuberculosis be followed with frequently repeated tuberculin tests
to insure an early diagnosis and adequate treatment.
ADDENDUM
The
infants
now
are
26
and
32 months of age. They have shown no further evidenceof
tuberculous
activity.
They
still
show
mental
retardation
and
absent
vestibular
function.
REFERENCES
1. Beitake, H., Uber die angioborene tuberkulose infektion, Ergebn. d. ges. Tuberk. Forsch. 7:1, 1935.
2. Hughesdon, Mary R., Congenital tuberculosis, Arch. Dis. Childhood 21:121, 1946.
3. Conrad, C. E., Chairman’s address, Section on Pediatrics, Oklahoma City, Nov. 15-18,
J.
South. MA. 32:169, 1938.4. Pagel, W., and Hall, S., Aspiration type of congenital tuberculosis, Tubercle 27:153, 1946.
5. Pagel, W., and Hall, S., Aspiration type of congenital tuberculosis: Further communication, Tubercle 29:32, 1948.
6. Buchanon,
J.,
Neonatal tuberculosis: Two cases, Glasgow M.J.
27:13, 1946.7. Contreras, R. E., Tuberculosis congenita, Bol. med. del. Hosp. Inf. (Mexico) 4:74, 1947. S. Harris, E. A., McCullough, G. C., Stone,
J.
J., and Brock, W. M., Congenital tuberculosis:Re-view of disease with report of case,
J.
Pediat. 32:311, 1948.9. Debr#{233}, R., Furiet.Laforet, Mme., and Royer, P., Tuberculose cong#{233}nitale transplacentaire
a
forme ict#{233}rique, Arch. franc. p#{233}diat.5:225, 1948.10. Lesne, E., Cayla, Roche and Allard, Tuberculose cong#{233}nitale transplacentaire avec m#{233}ningite
I 1. Hertzog, A.
J.,
Chapman, S., and Harring,J.,
Congenital pulmonary aspiration tuberculosis: Report of case, Am.J.
Clin. Path. 19: 1 1 39, 1949.SPANISH ABSTRACT
Tuberculosis
Congenita
El diagnostico de Ia tuberculosis congenita solo puede establecerse cuando la naturaleza y origen congenito de las lesiones tuberculosas puede demonstrarse. La presencia de un complejo primario
en el higado es prueba evidente del origen congenito de la infecciOn tuberculosa, asi como lo es la presencia de un complejo primario pulmonar o en otro sitio en aquellos casos que fallecen al nacer 0 en los primeros dias de nacimiento. En un ni#{241}oque surviva varios dias, el diagnostico de Ia infecci#{243}n congenita solo puede postularse solo en caso que el ni#{241}osea separado de la madre y mantenido en un ambiente libre de tuberculosis.
Los autores revisan Ia literatura m#{233}dica reciente de Ia tuberculosis congenita y reportan 4 casos adicionales de tuberculosis congenita ocurrida en ni#{241}osprematuros. Tees de ellos nacieron de madres
con tuberculosis miliar y aparentemente contrajeron Ia infecci#{243}n por aspiracion uterina del liquido
anniotico infectado. En el cuarto paciente, Ia madre padecia de una tuberculosis pelvica aguda con peritonitis y Ia infecciOn parece haberse contraido durante el pasage del ni#{241}oa traves del canal pelvico. Dos casos fueron tratados con estreptomicina con buenos resultados y arresto aparente de Ia
infecci#{243}ntuberculosa; ambos ninos continuan saludables a la edad de 18 y 24 meses respectivamente. Se recomienda que ninos rtacidos de madres con tuberculosis miliar o pelvica deben examinarse fre-cuentemente con pruebas de tuberculina para segurar un diagnostico temprano y un tratamiento adecuado.
