POLIOMYELITIS
IN PREGNANCY: NEWBORN
EFFECT INFANT
MORRIS SIEGEL, M.D., M.P.H., AND MORRIS ~REENBEEG, NEW Y O R K , N. Y. CCORDING to published d a t a on poliomyelitis d u r i n g pregnancy, the fetus m a y be affected either dir e c t l y b y the viral agent or indirectly b y the adverse conditions associated with m a t e r n a l disease. Infection of the fetus can presumably occur d u r i n g the viremia stage of maternal infection. I, 2 Evidence supporting this was recently r e p o r t e d in the case of a fetal death occurring nine days a f t e r the onset of m a t e r n a l symptoms of poliomyelitis. 3 Type I virus was isolated f r o m both the placenta and fetus. The cause of the fetal death was unknown, because secondary or u n r e l a t e d factors could not be ruled out. Most of the fetal deaths reported in the literature in pregnancies complicated by poliomyelitis have followed maternal infection in the first trimester of pregnancy. Infection in later stages of p r e g n a n c y has usually been followed by a live birth. The over-all f r e q u e n c y of fetal deaths has varied f r o m 20 to 35 per cent of maternal infections. ~-~4 These rates were said to be either within or above the average limits of expectancy. W i t h respect to other fetal changes following m a t e r n a l infection, no evi-
A
From
the
Department
of Environmental
1V[edicine a n d C o m m u n i t y H e a l t h , S t a t e U n i v e r s i t y o f :New ~York C o l l e g e of ]Y[edicine a t :New Y o r k C i t y , a n d B u r e a u of P r e v e n t a b i e Diseases, Department of I-Iealth, N e w Y o r k City.
ON
FETUS
AND
M.D., M.S.P.II.
dence of an increased incidence of congenital defects has been cited in the literature. An increase in the f r e q u e n c y of p r e m a t u r i t y has been noted following maternal infection in the first and second trimesters. 11, 14 fn most instances, however, the fetus did not a p p e a r to be underdeveloped. I f the fetus survives the immediate effects of maternal infection, life in utero can be t h r e a t e n e d b y the failure of m a t e r n a l respiration or circulation in cases of bulbar poliomyelitis. F o r t u n a t e l y , such cases are rare, and the life of the baby can usually be saved by adequate medical care. I n r e c e n t years, evidence of an additional hazard has become apparent. W h e n poliomyelitis occurs s h o r t l y before delivery, the fetus m a y be infected from maternal sources, not only in utero but also during delivery by fecal contamination of the birth canal and operative field. I n such cases the i n f a n t m a y develop signs of poliomyelitis early in the neonatal period. 15-21 Extramaternal sources of in~eetion may also be implicated after birth as noted in a report of an outbreak of poliomyelitis among newborn infants. ~2 The foregoing aspects of the problem and others were considered in the present investigation of the effects of maternal infection on the developing fetus. The data were ob-
280
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POLIOMYELITIS
tained in the course of a prospective study of poliomyelitis and p r e g n a n c y in New Y o r k City from 1949 to 1953, inclusive. 23 During this five-year period, eighty-seven cases of poliomyelitis were observed in p r e g n a n t women, of which t w e n t y - t h r e e were nonparalytic and s i x t y - f o u r paralytic types of the disease. The patients were seen by diagnosticians within a week a f t e r notification of the disease for the collection of clinical and epidemiologica] data. Subsequently, they were revisited one to two months a f t e r onset to check on the p r e g n a n c y status, and a y e a r a f t e r delivery for information on the n e w b o r n infant.
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281
for New York City f r o m 1949 to 1953, inclusive. 2' However, a d j u s t m e n t for u n d e r r e p o r t i n g of fetal deaths increases the expected n u m b e r to about 12.5 or more, and reduces the difference between observed and expected results below the level of statistical significance.* ~5 There was no evidence of an increase in cases of congenital d e f e c t - - o n l y one case was rep o r t e d for a f r e q u e n c y of 1.1 per cent. The n u m b e r of p r e m a t u r e infants appeared to be increased. However, the difference between the observed and expected n u m b e r was too small to be considered statistically significant. The a p p a r e n t increase in
TABLE I OUTCOI~E OF DELIVERY Fetal deaths* Live births Congenital defects Premature infants Normal Total
.
*Refers to all fetal deaths
OBSERVED RESULTS NUIViBEI~ 1 PEa CENT 19 21.6 69 78.4 ] 1.1 11 12.5 57 64.8 88 100.0 regardless
of d u r a t i o n
Data on the condition of the newborn infant at time of birth were obtained from copies of the eonfidentiaI birth certificate. RESULTS
1. General Considerations.--A total of eighty-eight products of conception were studied in the eighty-seven pregnancies complicated b y poliomyelitis. There were eighty-six single births and one set of twins. The outcome of these pregnancies as compared with the expected outcome based on data reporteci in the general pregnant population d u r i n g the period under consideration is shown in Table I. The observed n u m b e r of fetal deaths was more t h a n twice t h a t expected based on n a t a l i t y statistics
EXPECTED RESULTS NUI~BER I PER CENT 8.6 9.7 79.4 90.3 0.7 0,8 6.4 7.3 72.3 82.2 88,0 100.0
of g e s t a t i o n .
fetal deaths and in premature infants was not related to racial factors, because only six of the eighty-eight births were Negroes. Of these six births, one was premature, three were normal, and two were fetal deaths. Thus, they represented 7 per cent of the total sample and I0 per cent of the fetal deaths and premature infants, respectively. An analysis of the foregoing data by clinical type of maternal disease during gestation is given in Table II. There were relatively fewer fetal deaths and more premature infants following an attaek of paralytic poliomyelitis during pregnancy than nonparalytie poliomyelitis. I-Iowever, *A D r o b a b i l i t y o f l e s s t h a n 0.05 w a s s i d e r e d s i g n i f i c a n t in t h e p r e s e n t s t u d y .
con-
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THE JOURNAL OF PEDIATRICS
the respective differences were not considered statistically significant for the number of cases in each group, particularly the few cases in the nonparalytic group. The effects of other factors on the results observed at birth were considered, such as parity and the degree of epidemicity or incidence of poliomyelitis in the general popula-
women. However, the differences were not sl/atistically significant for the, small samples considered. Thus, the groups studied were too small to exclude the likelihood of sampling variation, and larger samples would be needed to evaluate adequately the effect of the foregoing factors.
2. Poliomyelitis in the New,born Infant.--Three cases of paralytic pc-
TABLE I I CLINICAL TYPE OF MATERNAL DISEASE OUTCOME OF DELIVERY Fetal deaths Live b i r t h s Congenital defects Premature infants Normal Total
PAI%ALYTICP E R
I
NUMBER
NONFARALYTIC NUMBEI% [ PER CENT
CENT
lI 54
16.9 83.1
1 10 43
8 15
1.5 15.4 66.2
34.8 65.2
0 1 14
65
100.0
0.0 4.3 60.9 23
100.0
TABLE I I I . OUTCOME OF :PREGNANCY FOLLOWING POLIOMYELITIS DUllING GESTATION IN I~ELATION TO DEGREE OF ]~PIDEMICITY AND PARITY AT TIME OF ONSET OUTCOME OF PREGNANCY LIVE BIRTttS FETAL CONGENITAL DEATItS DEFECTS PRE2CLATUI~E
TOTAL IVACTO~ CONSIDEI~ED
NO.
PER CENT
NO.
PEI~ CENT
NO.
PER CENT
NO.
PER CENT
NOP~MAL PER NO.
cENT
Epidemicity at Time of Onset o/ Maternal Poliomyelitis Onset i n e p i d e m i c y e a r (1949) Onset in n o n e p i d e m i c yea~s (1950-1953) Total
28
100.0
7
25.0
0
0.0
4
14.3
17
60.7
60 88
100.0 100.0
12 19
20.0 21.6
1 t
1.6 1.1
7 11
11.7 12.5
40 57
66.7 64.8
Primiparas Multiparas Total
19 69 88
100.0 100.0 100.0
3 8 11
15.8 11.6 12.5
11 46 57
57.9 66.7 64.8
Parity at Tithe of Infection 5 14 19
tion when maternal infection occurred. A summary of the analysis of the data by these factors is given ill Table III. The percentage of fetal deaths and premature infants was slightly greater in the epidemic year of 1949 than in the succeeding nonepidemic years. These percentages also appeared to be greater among primiparous women than multiparons
26.3 20.3 21.6
0 1 1
0.0 1.4 1.1
liomyelitis were reported in the neonatal period among the sixty-nine live births in the study, a rate of 43 per 1,000 live births. The three cases occurred among the fifty-four newborn infants of mothers with paralytic poliomyelitis, a rate of 56 per 1,000 live births in this group. The attack rate of paralytic poliomyelitis exceeded that recorded for
SIEGEL AND GREENBERG:
POLIOMYELITIS IN PREGNANCY
any age group of familial contacts in New York City during the period considered, and is more than 1,000 times greater than the rate of paralytic poliomyelitis observed under 1 year of age in the general population.26, 27 The three cases observed in the study occurred among nine newborn infants following maternal infection in the last month of gestation. All three infants were delivered within twenty-four to forty-eight hours of the onset of .neurological signs of poliomyelitis in the mother. Symptoms of paralysis in the newborn infant were observed from six to ten days after delivery. Two died at age 11 and 13 days, respectively, and one recovered with mild paralysis of the right arm. 3. Neonatal Mortality.--There were five deaths in the neonatal period among the sixty-nine live births, a death rate of 72.5 per 1,000 live births as compared with an" expected neonatal death rate of 18.6 per 1,000 live births. 24 All of the deaths were associated with the paralytic type of poliomyelitis in the mother during gestation. When based on these cases only, the neonatal death rate was 92.6 per 1,000 live births. One of the deaths occurred in the single ease of congenital defect reported in the study, that of a monstrosity weighing 2,150 grams at birth who lived a few minutes only. The mother was 27 years of age, had had one normal delivery and no fetal deaths previously. She developed paralytic poliomyelitis during the sixth month of gestation and delivered at term three months after infection.
283
All the other deaths in the neonatal period were related directly or indirectly to poliomyelitis in the mother. Two died within twentyfour hours of " a n o x e m i a , " following post-mortem cesarean delivery in mothers dying of bulbar poliomyelitis in the eighth and ninth months of gestation, respectively. Two other deaths occurred in newborn infants with neonatal poIiomyelitis who developed paralysis ten days after birth and died at ages 11 and 13 days, respectively, as already noted. In these two cases, the mothers developed characteristic symptoms of poliomyelitis on the day of delivery or witt~in twenty-four hours after delivery. No deaths occurred in the post-neonatal period. The total number of newborn infants alive at I year of age was sixty-four or 72.7 per cent of all the products of gestation in the study. None showed any gross evidence of congenital deformity, and all were well developed at the end of their first year. No c]inlcal evidence of poliomyelitis was reported in the post-neonatal period. From the results described above, there was evidence of an increased incidence of neonatal poliomyelitis and mortality which was associated with the onset of maternal infection in the last months of pregnancy. No conclusions could be drawn as to the over-all incidence of fetal deaths and premature births following poliomyelitis in pregnancy since the data were inconclusive. The results observed were studied more closely for a possible relationship to the period of gestation at onset of infection.
4. Period of Gestation at Onset of Poliomyelitis.--An analysis of tile
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OF
d a t a a c c o r d i n g to l e n g t h of g e s t a t i o n r e v e a l e d t h a t t h e t i m e of onset of clinical i n f e c t i o n w a s a m a j o r influence in t h e o u t c o m e o f p r e g n a n c y . T h i s is a p p a r e n t f r o m t h e d i s t r i b u t i o n of t h e p r o d u c t s of g e s t a t i o n s h o w n in T a b l e I V b y t h e t r i m e s t e r of i n f e c t i o n , f o r a l l c l i n i c a l cases of p o l i o m y e l i t i s i n t h e m o t h e r , a n d f o r p a r a l y t i c cases TABLE I V .
PEDIATRICS
t r i m e s t e r of i n f e c t i o n w e r e 35, 12, a n d 5 p e r cent, r e s p e c t i v e l y . O n t h e o t h e r h a n d , t h e p e r c e n t a g e of n o r m a l infants at birth increased progress i v e l y w i t h t r i m e s t e r o f o n s e t of p a r a l y t i c m a t e r n a l i n f e c t i o n f r o m 50 p e r c e n t in t h e first t r i m e s t e r to 85 p e r c e n t i n t h e last. T h e f r e q u e n c y of p r e m a t u r e i n f a n t s f l u c t u a t e d be-
OUTCOME OF P R E G N A N C Y BY T R I M E S T E R OF G E S T A T I O N AT T I M E OF O N S E T OF POLIOMYELITIS PERIOD OE GESTATION AT ONSET OF POLIOMYELITIS
OUTCOME OF PREGNANCY
FIRST TRIMESTER NUMBER
SECOND T R I M E S T E R
I PEi% CENT
NUMBER
THIRD TRIMESTER
] PER CENT
NUMBER
I PER CENT
All Clinical Cases
Fetal deaths Live births Congenital defects Premature infants l~ormal Total
14 16
46.7 53.3
4 3]
11.4 88.6
] 22
4:3 95.7
0
0.0
1
2.9
0
0:0
3 13
10.0 43.3
6 24
17.1 68.6
2 20
8.7 87.0
30
100.0
35
100.0
23
100.0
12.0 88.0
1 19
5.0 95.0
Paralytic Cases Only
Fetal deaths IAve births Congenital defects Premature infants Normal Total
7 13
35.0 65~0
3 22
0
0.0
1
4.0
0
0.0
3 10
15.0 50.0
5 16
20.0 64.0
2 17
10.0 85.0
20
]00.0
25
]00.0
20
100.0
TABLE V INTERVAL
PERIOD OF GESTATION AT O N S E T O F POLIOMYELITIS
First trimester Second trimester Third trimester Total
BETWEEN ONSET OF POLIOMYELITIS AND ONSET OF LABOR
NUMBER OF FETAL DEATHS
LESS T H A N 2 WK.
2 TO 4 ~TK.
I OR MORE MO.
14 4 1 19
9 1 0 10
1 0 1 2
4 3 0 7
only. A s n o t e d i n T a b l e I V , t h e f r e quency of fetal deaths decreased m a r k e d l y w i t h t r i m e s t e r of o n s e t of p o l i o m y e l i t i s f r o m 46.7 p e r c e n t o f a l l c l i n i c a l i n f e c t i o n s i n t h e first t r i m e s t e r to 11.4 p e r c e n t of t h o s e i n t h e s e c o n d t r i m e s t e r a n d t o 4.3 p e r c e n t in t h e t h i r d . B a s e d on p a r a l y t i c cases o n l y , t h e f e t a l d e a t h r a t e s b y
t w e e n 10 a n d 20 p e r c e n t p e r t r i m e s t e r of o n s e t of p o l i o m y e l i t i s w i t h t h e h i g h e s t r a t e a f t e r m a t e r n a l infection in the second trimester. The results obtained by trimester of i n f e c t i o n w e r e f u r t h e r e x a m i n e d to d e t e r m i n e t h e t i m e r e l a t i o n s h i p bet w e e n t h e o n s e t of m a t e r n a l d i s e a s e a n d t h e d e l i v e r y o f t h e p r o d u c t of
SIEGEL
AND
GREENBERG:
POLIOI~YELITIS
conception. A s u m m a r y of the int e r v a l elapsing b e t w e e n the onset of poliomyelitis and l a b o r w h e r e f e t a l deaths occurred is given in Table V. I n ten of the nineteen cases where fetal deaths resulted, l a b o r occurred within two weeks a f t e r the onset of poliomyelitis in the first and second trimesters. These deaths m a y have been r e l a t e d to the occurrence of poliomyelitis in the m o t h e r . No other specific causes were m e n t i o n e d in the records examined. I n addition, two fetal deaths occurred f r o m two to f o u r weeks a f t e r onset of m a t e r n a l infection in the first and t h i r d trimesters, respectively. The f o r m e r was not associated w i t h a n y other corn-
IN
285
PREGNANCY
teen deaths to s u g g e s t a direct relationship b e t w e e n infection and the e n s u i n g fetal death. Ten of these eleven deaths were associated with infection in the first trimester. The eleven deaths included f o u r out of eight f e t a l deaths following nonp a r a l y t i c poliomyelitis and seven out of eleven fetal deaths a f t e r p a r a l y t i c disease. W i t h respect to the p r e m a t u r e infants, the i n t e r v a l b e t w e e n infection and the onset of l a b o r in the m o t h e r was usually m o r e t h a n a m o n t h as s u m m a r i z e d in Table VI. I n the case of nine of the eleven p r e m a t u r e infants, m a t e r n a l infection occurred in the first and second trimesters, and
TABLE V I
PERIOD OF GESTATION AT ONSET OF POLIOMYELITIS
First trimester Second trimester Third trimester Total
NU 1V~BER OF FRE!~ATURE INFANTS
INTERVAL BETWEEN ONSET OF LABOtr AND ONSET OF POLIOMYELITIS
LESS TITAN 2 wK.
3 6 2 11
plication of p r e g n a n c y a n d m a y have been r e l a t e d to the infection. The latter, however, o c c u r r e d in a m o t h e r who died of eclampsia in the last m o n t h of gestation and cannot be directly a t t r i b u t e d to poliomyelitis. I n seven other cases the i n t e r v a l between the onset of polio and delivery was one or more months. I n these cases, the onset of l a b o r a p p e a r e d to be too f a r r e m o v e d f r o m the onset of poliomyelitis for the infection to be a direct p r e c i p i t a t i n g f a c t o r and other complications of p r e g n a n c y should be considered. I n s u m m a r y , therefore, the time relation between the occurrence of poliomyelitis and f e t a l d e a t h was suf"ficiently close in eleven of the nine-
0 0 2 2
I
2TO 4 WK.
0 0 0 0
l
10RlV[ORE ~0.
3 6 0 9
delivery followed m o r e t h a n a month a f t e r infection. Six of these nine infants were delivered between the t h i r t y - e i g h t h a n d f o r t i e t h weeks of gestation, and one each at twentynine, t h i r t y - f o u r , a n d t h i r t y - s i x weeks of gestation. Two p r e m a t u r e infants were .born w i t h i n a w e e k a f t e r the onset of poliomyelitis in the mother. In b o t h cases, infection occurred in the t h i r t y - n i n t h w e e k of gestation. In only two instances, therefore, did the onset of l a b o r follow shortly a f t e r infection, b u t these occurred in p r e g n a n t w o m e n infected at term. In all other cases of p r e m a t u r e infants gestation did not a p p e a r to be int e r l ~ p t e d b y infection and usually continued to term. All b u t one of the
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T H E J O U R N A L OF PEDIATRICS
mothers of the premature infants had the paralytic type of poliomyelitis. In addition to the two premature infants mentioned, nine normal infants were born shortly after the occurrence of poliomyelitis in the last trimester of pregnancy. In most instances, symptoms of poliomyelitis occurred in the ninth month of gestation or near term, and labor began spontaneously less than a week after the onset of disease. The significance of the onset of labor early in the acute stage of maternal disease is that the newborn infant is exposed to a high risk of clinical infection, as noted in the section on neonatal poliomyelitis. DISCUSSION
The present study represents a prospective investigation of the effects of poliomyelitis during gestation on the fetus and newborn infant. Because of the r ar i t y of poliomyelitis in females of childbearing age, it was necessary to plan the study over a period of years, beginning with the epidemic of 1949 in New York City and continuing through the succeeding four nonepidemic years. During this period, the annual attack rate of poliomyelitis in women from 15 to 44 years of age varied from 4.9 to 13.5 per 100,000 in endemic and epidemic years, respectively. These variations allowed for a comparison of the effects of different rates in the same community. There appeared to be no statistically significant difference in the outcome of delivery as measured by the frequency of fetal deaths, premature infants, and normal live births between years of high and low incidence. Nor was the outcome signifi-
eantly affected by the clinical type of disease in the pregnant woman except for the occurrence of bulbar poliomyelitis. However, the number of cases studied was too small for adequate evaluation of these factors. Similarly, inconclusive results were obtained in the analysis of the cases observed by such contributory factors as race, parity, and previous fetal deaths. There was no evidence of an association between poliomyelitis in pregnancy and the occurrence of congenital defects. Only one such case was reported in eighty-eight deliveries in the study, that of a monstrosity associated with paralytic poliomyelitis in the mother in the sixth month of gestation, and born at term weighing 2,150 grams. The data reported included eight maternal cases of poliomyelitis with onset of disease in the first two months of pregnancy, when the expected incidence of congenital defect is highest, twenty-two cases infected in the third month of gestation, and fourteen in the fourth month, a total of forty-four cases in the first four months of gestation, thirtY-one with paralytic disease, and thirteeu with nonpara]ytic disease. 23 It was possible to establish a definite relationship between some of the results observed in the fetus and newborn infant and the period of pregnancy in which infection occurred. Infection in the first trimester was associated with fetal deaths in almost half of the cases infected at this time and with immature live births in an additional 10 per cent. The frequency of fetal deaths dropped sharply from 46.7 per cent following infection in the first three months of pregnancy to 13.8 per cent for infec-
SIEGEL AND GREENBERG:
POLIOMYELITIS IN PREGNANCY
tions in the fourth and fifth months and to 3.4 per cent after that. Not only was there a preponderance of fetal deaths following infection in the first trimester but about 65 per cent of these occurred within two weeks of the infection and were apparently directly related to the occurrence of poliomyelitis in the mother. F o r infections occurring after the first trimester, the interval between the onset of infection and the onset of labor was usually one or more months, thus implicating other factors in pregnancy as the possible causes of the fetal deaths. 1V[ost of the premature infants observed in the study were associated with infection in the first and second trimesters. In most of these cases, gestation proceeded to term, labor usually occurred more than a month after the onset of infection, and other complications of pregnancy were not reported. I n view of the many causes of prematurity, one can only speculate on the possibility t h a t the effect of infection on the fetus was not marked enough to kill it, but did influence its growth. The onset of poliomyelitis in the last trimester was associated with a live birth in 96 per cent of the pregnancies. There was only one fetal death in twenty-three cases in this group. This occurred sixteen days after the onset of poliomyelitis in the last month of gestation, in a woman who died of eelampsia. Two additional observations of clinical and epidemiologieal interest were noted among those infected in the last stages of pregnancy. First, neonatal poliomyelitis occurred only in infants whose mothers developed poliomyelitis near term, and who
287
were born shortly after onset of the disease in their mothers. This group is presumably unprotected by maternal antibodies, and may be heavily exposed to maternal infection in utero, during delivery and after birth. Second, two newborn infants delivered by post-mortem cesarean section died of " a n o x e m i a " in less than fourteen hours. The mothers had died of bulbar poliomyelitis in the eighth and ninth months of gestation, respectively. The occurrence of bu]bar poliomyelitis is a serious complication which threatens the life of both the mother and child. Death of the child may be avoidable by timely cesarean section. 14 There were four deaths in the neonatal period which were attributable to the onset of poliomyelitis in the mother toward the end of pregnancy. In two, the mothers died before delivery and a post-mortem cesarean section was done in a vain effort to save the child. In two others, the infant developed poliomyelitis shortly after birth. SUMI~ARY
1. A prospective study was made of the outcome of gestation following the occurrence of poliomyelitis in New York City from 1949 to 1953, inclusive. During this period eightyseven pregnancies, which resulted in eighty-eight products of gestation, were investigated. Sixty-five fetuses were associated with paralytic poliomyelitis during gestation and twentythree with nonparalytic poliomyelitis. 2. There was no evidence of an increase in congenital defects, a n d ] n conclusive evidence of an increase in prematurity. 3. Fetal deaths were observed in from 35 to 46 per cent of the preg-
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THE JOURNAL OF PEDIATRICS
nancies complicated b y the onset of poliomyelitis in the first t ~ m e s t e r of gestation. !V[ost of these fetal deaths were delivered within two weeks of the onset of clinical infection, and app e a r e d to be d i r e c t l y r e l a t e d to the occurrence of poliomyelitis in the mother. 4. An increase in the incidence of neonatal poliomyelitis was observed which w a s associated with p a r a l y t i c m a t e r n a l infection s h o r t l y before delivery. 5. An increase in the neonatal mort a l i t y r a t e was noted which was related to n e o n a t a l poliomyelitis and to anoxemia f o 1 1 o w i n g post-mortem cesarean section in w o m e n d y i n g of bulbar poliomyelitis. REFERENCES
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