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Tuberculosis and the puerperium
320
T H E B R I T I S H J O U R N A L OF T U B E R C U L O S I S
TUBERCULOSIS AND THE P U E R P E R I U M A T R I A L OF C H E M O T H E R A P Y AND (ESTROGENS BY MARY FAR~UHARSON AND BERYL TURNER From the Pregnancy Unit, Grove Park Hospital, London
INTRODUCTION
STUDI~S on tuberculous women in the pucrpcrlum still show disturbing relapse rates, although medical opinion varies on this subject. In this unit intensive chemotherapy and, more recently, the addition of cestrogen therapy in the pucrperium have shown very encouraging results. For the last decade pregnancy in the tuberculous has been regarded as an incident carrying no increased risk. The views of such authors as Cohen (I946), Stewart and Simmonds (I947), and Midgley Turner (I95o), that childbearing has no influence on the progress of active and quiescent cases, are based on long-term follow-up studies. In spite of this the first trimester and the puerperium are still quoted as times of peculiar hazard for the tuberculous. Beven (i952) produced a very detailed paper confirming the grave influence of the puerperium; among his active cases there was a relapse rate of 43 per cent. during the first two months after delivery. Cromie (I954) , in a report from Northern Ireland, found that half his patients with active disease deteriorated either during pregnancy or in the subsquent six months. Beven's paper came from the unit at Grove Park Hospital which deals entirely with antenatal and post-natal patients with pulmonary tuberculosis. This report comes from the same unit, and we have tried to assess the present risks and the results of current treatment. O u r attention has been directed particularly to the possible influence of endocrine factors on the tuberculous process. Browne et al. (I939) estimated the varying blood levels of ~estrogen and chorionic gonadotropin during pregnancy and the puerperium. A notable rise of gonadotropin occurs in early pregnancy and is followed by a fall to near normal levels by the fifth month. The cestrogen level rises steadily from the fourth month, and falls abruptly at parturition. Lurie et al. (I949) found that in mature rabbits ~estrogens retarded the tuberculous process at the site of inoculation into the skin, while gonadotropins increased it: the cestrogens appeared to have a protective effect. It has been suggested that the deterioration in early pregnancy may be related to the high level ofgonadotropin in the blood, and that the puerperal deterioration may be partly attributed to the fall in cestrogens at parturition. Beven's paper was written in the early years of chemotherapy when the drugs were not so freely used as they are to-day. Few of his patients were receiving chemotherapy at the time of delivery nor in the puerperium. It was (Receivedfor publication May ~4, 1956.)
A N D DISEASES O F T H E
CHEST
321
decided, therefore, to attempt to assess and compare the effects of two r6gimes of treatment: 1. Chemotherapy before and after delivery. II. Chemotherapy before delivery, and chemotherapy and eestrin after. MATERIAL The total hospital material comprises 13o cases, treated between J u n e 1953 and December 1955. There were 68 primigravida and 62 multigravida. Fiftyseven patients were under 26 years, and 73 over that age. One hundred and four patients had active disease and a more detailed classification of them is given below: Tuberculosis diagnosed during this pregnancy . . . . . . Chronic active tuberculosis . . . . . . . . . . . . Tuberculosis reactivated during this pregnancy . . . . . .
57 27 2o
O f the newly diagnosed cases 22 (38 per cent.) were found on routine antenatal X-ray. The large majority of the new cases were diagnosed in the first six months of pregnancy. T h e significance of the first trimester in the reactivation of tubercle is shown b y the fact that, of the 20 patients who were admitted because of reactivation of their lesions, this had occurred in the first trimester in IO. There were also 26 patients whose disease was considered by us to be quiescent. It should be noted, however, that all patients entering this unit a r e admitted at least six weeks before the expected date of delivery and remain in for at least six weeks afterwards, so that even quiescent cases m a y be expected to have some disquieting feature warranting this period of care. For our investigation we took two series of active cases, the first consisting of 46 patients treated between J u n e 1953 and September 1954: the second comprising 58 patients treated since October 1954. The two series are comparable as regards age and parity, and their Ministry of Health classification is shown in Table 1, and it m a y be well at this point to compare our type of case with that in Beven's paper. TABLE I.~CLASSIFICATION Of* DISEASE
At
Ai
Bt
Bs
Bs
Series I
. . . . . .
2
15
o
x9
xo
Series II
. . . . . .
S
14
x
34
6
5
29
I
53
16
12
20
'7
60
x8
TOTAL
.
.
.
.
.
.
Beven (x952) . . . . . .
.
.
As might bc expected, Bevcn's cases collected five years ago were more advanced than ours. However, our own series are reasonably comparable with each other. There is also close similarity between the two series in the type of disease--e.g., newly diagnosed, chronic active, or reactivated.
322
THE BRITISH JOURNAL
OF TUBERCULOSIS
TREATMENT
The patients in both series were given a minimum period of one month of a suitable combination of antituberculous drugs--e.g., streptomycin, PAS, or I N A H before delivery; these drugs were continued after delivery for a minim u m of six weeks. (In most cases much longer courses of drugs were used both before and after the confinement.) In addition the cases in Series II had a minimum of six weeks of an oestrin preparation, either Stilboestrol 5 rag. t.d.s., or ethinyl oestradiol o'2 rag. t.d.s, from the day of the confinement. The full course of cestrin therapy lasted for three months, and the majority of the patients had this. (On this unit previously an ~estrin preparation was given routinely for ten days post-partum to suppress lactation.) Each patient was X-rayed monthly and had tomograms on admission and six weeks post-partum. Three sputum cultures were set up on admission, and repeated at intervals. Six consecutive sputum cultures were set up post-partum, and three direct examinations made at six weeks after delivery. RESULTS
Active Cases
The relapses in the first two months of the puerperium in our two series and in Beven's cases are given in Table 2. TABLE 2.~Pu~RPERAL
RELAPSE RATES ON DIFFERENT TREATMENT I~GLMES
No. of cases
Beven
Series I
Series I I
Iz4
46
58
49 43%
IO
4 7%
..
No relapsing wlthi two monthg of delivery . . . . . . . . . . % relapse . . . . . . . . . .
Details regarding the 14 relapses in the present trial are given in Tables 3 and 4. TABLE 3.--TYPE
OF RELAPSE
Spread of disease . . . . Cavity enlargement . Positive sputum culture . Breakdown of solid focus . TABLE 4.~TIME Within ,,
,, ,,
.
4 6 8
•.
.
. . . . . . . . . . . . . . .
9 3 I x
OF RELAPSE POST-PARTUM
2 weeks ,, ,. ,~
. . . .
.
.
. .
. .
.
. .
. .
. .
.
.
.
. . . . . .
.
3 ••
. ..
5 2
Relapses occurred in 5 primigravida and 9 multigravida. There were 8 in 46 patients under 26 years, and 6 in 58 patients over 26 years. The younger patient therefore seems to run a slightly greater risk, as one might expect with tuberculosis in women. Their Ministry of Health classification was: 3 A~ cases, IO Bs cases, and I B 3 case.
AND DISEASES O F T H E
CHEST
323
Relapses occurred in both the newly diagnosed cases (8 in 57 cases) and in chronic active cases (5 in 27). There was only one relapse among the 20 patients who reactivated during pregnancy; this would seem to be related to the fact that the disease was probably treated and under control again before delivery. O n the whole, however, mor e prolonged treatment before delivery did not appear to be a safeguard. O f 48 patients treated for more than three months before delivery, 6 relapsed: of 32 treated for two months, 3 relapsed: and of 50 treated for one month, 5 relapsed. It should be mentioned that all the relapses we observed were minimal and the final outcome was probably not affected by them. Possibly the fact that the patients were on treatment minimised such deterioration as occurred. In addition to treatment with chemotherapy, a pneumoperitoneum was induced in 4 cases. Fifteen patients proceeded to excisional surgery, a n d 7 had thoracoplasties. In no case was it found necessary to operate during pregnancy, and surgery was carried out at a suitable time after the second month post-partum.
Quiescent Cases There were in addition 26 patients with quiescent disease, who were treated with the same rdgime as Series I I - - t h a t is, with antenatal and post-natal drugs and oestrin. Among this group there was only one relapse. As a control group for comparison with our hospital figures, we studied a series of Ioo tuberculous women attending Lewisham Chest Clinic, and delivered between I95O and i955. Their disease was considered stable, and they received no special care or treatment over their confinements, beyond the fact that many did not breast feed. Nine of these patients deteriorated within two months of delivery, and details in each year are given in Table 5. TABLE 5.~RELAPSES IN QUIESCENT CLINIG CASES
Tear 195o x95I x95~ x953 x954 x955
. . . . . . . . .
.
.
.
. . . . . . . . . . . .
Wo. ofeas~
Relapsesinpuerperium
7 8 i6 i8 20 ~9
o 2 2 o I 4
In such a study as this, it is desirable to have figures of the average relapse rates for tubercle treated with modern antibiotic and chemotherapeutic drugs. Such figures are difficult to obtain and it is for this reason that we have included for comparison a short series of non-pregnant women in the same age group, treated at the same hospital, and observed by one of us (B.T.). All were active cases, and various r6gimes of treatment were used. The results in Table 6 show relapses that occurred in the second to the fourth months of hospital treatment, this being a period comparable in time with the first two months of the puerperjure in our cases. There were 5 ° cases, with 2 relapses, giving a relapse rate of 4 per cent.
324
T H E B R I T I S H J O U R N A L OF T U B E R C U L O S I S TABLE
6.~RELAPSES
Deterioration o n ,, ,, ,, ,, TOTAL RELAPSES R e l a p s e rate .
IN N O N - P R E G N A N T
ACTIVE
CASES
b e d rest only . . . . . . . . single c h e m o t h e r a p y .... combined chemotherapy .... . . . . . . . . . . . . . . . . . . . . . . . . .
x x o 2 4°/o
Discussion The problem of a peculiar risk for the tuberculous during pregnancy is still unsolved. When approaching this subject on the basis of our results, there are two significant facts to bear in mind. Firstly, these relapses are occurring within the very short period of two months, and secondly, all the patients were on active treatment at the time. Papcrs such as those of Beven and Cromie suggest that there is a definite danger, whereas those of Stewart and Simmonds maintain that in the long run there is no significant effect. Possibly data obtained from in-patients where observation is closer will give higher relapse rates. It may be that discrepancies between the reports arise because the first two authors collected their data shortly after delivery, whereas Stewart and Simmonds' follow-up was carried out eighteen months later. This would suggest that the tendency to deteriorate may be self-limiting. This further report from the Grove Park Unit supports the view that the puerperium is an unfavourable period. Puerperal relapses may be duc to one (or both) of two main factors, mechanical and constitutional, including hormonal. Those occurring immediately after delivery (within hours or days) may have a mechanical basis, and such instances might be prcventcd by a large pneumoperitoneum. Earlier diagnosis and more effective treatment have wholly altered the prognosis in tuberculosis; hence comparison with previous findings are unreliable. The figures set out below can only be used to show current results. For active cases Beven found a puerperal relapse rate of 43 per cent., on Sanatorium rdgime. Our relapse rate was 22 per cent. on chcmotherapy (Scries I), and 7 per cent with the addition of cestrin in the puerperium (Series II). This latest figure is so low, and the character of the relapses so minor, that we have not considered termination justifiable on the grounds of pulmonary tuberculosis in any of our cases. The difference bctwecn the results of Series I and Series II is considerable and would strongly suggest that the administration of high doses of cestrin in the puerperium has a marked effect in reducing the numbcr of relapses. As regards the quiescent cases, the clinic figure of a 9 per cent. relapse rate compares unfavourably with that for quiescent cases treated with drugs and ccstrin (one relapse in 26 cases), especially when bearing in mind that the quiescent cases would not have been in our unit unless there was some cause for anxiety. The findings in this unit suggest that, as with the active cases, so with the quiescent cases, the best results may be achieved with antenatal and post-natal drugs and cestrin. Apart from the material used for this report there have bcen a few quiescent cases on the unit treated by variations of our standard r6gime; they are included in Table 7.
AND DISEASES OF THE CHEST
325
TABL]~ 7.'--RELAPSES IN O UIESG~NT CASES
Type of treatment
No. of cases
Relapses
No active treatment (clinic cases) . . . . . . No active treatment (hospital cases) . . . . . . Post-natal o~strinonly . . . . . . . . . . Post-natal chemotherapy and cestrin . . . . . . Ante-natal and post-natal chemotherapy and post-natal oestrin . . . . . . . . . . . . . .
IOO
9
8
5 6
I
3 I
06
There seems little justification for the use of cestrin alone in the puerperium. There does not appear to be any risk attached to treating the pregnant woman with chemotherapy throughout long periods of her pregnancy, and all the infants have appeared unaffected. As regards the use of cestrin, this very large dose is well tolerated by the puerperal woman. One patient in her forties developed menorrhagia after withdrawal of oestrin, and we would perhaps avoid cestrin again in elderly gravida. Summary We have treated a group of pregnant tuberculous women with chemotherapy and cestrogens. A rdgime of antenatal and post-natal chemotherapy, and cestrogens for a m i n i m u m of six weeks post-partum, has given a very low relapse rate in the puerperium. We should particularly like to thank our Consultant Obstetrician and Gynaecologist, Mrs. J. Karnicki, whose advice and encouragement made this study possible. It is also a pleasure to thank Miss Euniee Maddock, the unit Sister, for all her help. REFERENCES BEVEN,G. (1952): Tubercle, 32, I, t 3. B~OVCNE,J. S. L. et al. (I939): Amer. 07. Obst.Gyn~., 38, 927. COHEN,R. C. (I946): Brit. 07. Tuber. Dis. Chest, 40, xo. C~oMIp,J. B. (1954)" Brit. 07. Tuberc. Dis Chest, 48, 97LuRm, M. B. et al. (1949) : Amer. 07. Tuberc., 59, x69, x86. STEWART,C.J. and SI~MONns,F. A. H. (I947) : Brit. med. o7, 2, 706. TURNER,H. M. (I95o): Lancet, 1, 697.
T H E B R I T I S H J O U R N A L OF T U B E R C U L O S I S
TUBERCULOSIS AND THE P U E R P E R I U M A T R I A L OF C H E M O T H E R A P Y AND (ESTROGENS BY MARY FAR~UHARSON AND BERYL TURNER From the Pregnancy Unit, Grove Park Hospital, London
INTRODUCTION
STUDI~S on tuberculous women in the pucrpcrlum still show disturbing relapse rates, although medical opinion varies on this subject. In this unit intensive chemotherapy and, more recently, the addition of cestrogen therapy in the pucrperium have shown very encouraging results. For the last decade pregnancy in the tuberculous has been regarded as an incident carrying no increased risk. The views of such authors as Cohen (I946), Stewart and Simmonds (I947), and Midgley Turner (I95o), that childbearing has no influence on the progress of active and quiescent cases, are based on long-term follow-up studies. In spite of this the first trimester and the puerperium are still quoted as times of peculiar hazard for the tuberculous. Beven (i952) produced a very detailed paper confirming the grave influence of the puerperium; among his active cases there was a relapse rate of 43 per cent. during the first two months after delivery. Cromie (I954) , in a report from Northern Ireland, found that half his patients with active disease deteriorated either during pregnancy or in the subsquent six months. Beven's paper came from the unit at Grove Park Hospital which deals entirely with antenatal and post-natal patients with pulmonary tuberculosis. This report comes from the same unit, and we have tried to assess the present risks and the results of current treatment. O u r attention has been directed particularly to the possible influence of endocrine factors on the tuberculous process. Browne et al. (I939) estimated the varying blood levels of ~estrogen and chorionic gonadotropin during pregnancy and the puerperium. A notable rise of gonadotropin occurs in early pregnancy and is followed by a fall to near normal levels by the fifth month. The cestrogen level rises steadily from the fourth month, and falls abruptly at parturition. Lurie et al. (I949) found that in mature rabbits ~estrogens retarded the tuberculous process at the site of inoculation into the skin, while gonadotropins increased it: the cestrogens appeared to have a protective effect. It has been suggested that the deterioration in early pregnancy may be related to the high level ofgonadotropin in the blood, and that the puerperal deterioration may be partly attributed to the fall in cestrogens at parturition. Beven's paper was written in the early years of chemotherapy when the drugs were not so freely used as they are to-day. Few of his patients were receiving chemotherapy at the time of delivery nor in the puerperium. It was (Receivedfor publication May ~4, 1956.)
A N D DISEASES O F T H E
CHEST
321
decided, therefore, to attempt to assess and compare the effects of two r6gimes of treatment: 1. Chemotherapy before and after delivery. II. Chemotherapy before delivery, and chemotherapy and eestrin after. MATERIAL The total hospital material comprises 13o cases, treated between J u n e 1953 and December 1955. There were 68 primigravida and 62 multigravida. Fiftyseven patients were under 26 years, and 73 over that age. One hundred and four patients had active disease and a more detailed classification of them is given below: Tuberculosis diagnosed during this pregnancy . . . . . . Chronic active tuberculosis . . . . . . . . . . . . Tuberculosis reactivated during this pregnancy . . . . . .
57 27 2o
O f the newly diagnosed cases 22 (38 per cent.) were found on routine antenatal X-ray. The large majority of the new cases were diagnosed in the first six months of pregnancy. T h e significance of the first trimester in the reactivation of tubercle is shown b y the fact that, of the 20 patients who were admitted because of reactivation of their lesions, this had occurred in the first trimester in IO. There were also 26 patients whose disease was considered by us to be quiescent. It should be noted, however, that all patients entering this unit a r e admitted at least six weeks before the expected date of delivery and remain in for at least six weeks afterwards, so that even quiescent cases m a y be expected to have some disquieting feature warranting this period of care. For our investigation we took two series of active cases, the first consisting of 46 patients treated between J u n e 1953 and September 1954: the second comprising 58 patients treated since October 1954. The two series are comparable as regards age and parity, and their Ministry of Health classification is shown in Table 1, and it m a y be well at this point to compare our type of case with that in Beven's paper. TABLE I.~CLASSIFICATION Of* DISEASE
At
Ai
Bt
Bs
Bs
Series I
. . . . . .
2
15
o
x9
xo
Series II
. . . . . .
S
14
x
34
6
5
29
I
53
16
12
20
'7
60
x8
TOTAL
.
.
.
.
.
.
Beven (x952) . . . . . .
.
.
As might bc expected, Bevcn's cases collected five years ago were more advanced than ours. However, our own series are reasonably comparable with each other. There is also close similarity between the two series in the type of disease--e.g., newly diagnosed, chronic active, or reactivated.
322
THE BRITISH JOURNAL
OF TUBERCULOSIS
TREATMENT
The patients in both series were given a minimum period of one month of a suitable combination of antituberculous drugs--e.g., streptomycin, PAS, or I N A H before delivery; these drugs were continued after delivery for a minim u m of six weeks. (In most cases much longer courses of drugs were used both before and after the confinement.) In addition the cases in Series II had a minimum of six weeks of an oestrin preparation, either Stilboestrol 5 rag. t.d.s., or ethinyl oestradiol o'2 rag. t.d.s, from the day of the confinement. The full course of cestrin therapy lasted for three months, and the majority of the patients had this. (On this unit previously an ~estrin preparation was given routinely for ten days post-partum to suppress lactation.) Each patient was X-rayed monthly and had tomograms on admission and six weeks post-partum. Three sputum cultures were set up on admission, and repeated at intervals. Six consecutive sputum cultures were set up post-partum, and three direct examinations made at six weeks after delivery. RESULTS
Active Cases
The relapses in the first two months of the puerperium in our two series and in Beven's cases are given in Table 2. TABLE 2.~Pu~RPERAL
RELAPSE RATES ON DIFFERENT TREATMENT I~GLMES
No. of cases
Beven
Series I
Series I I
Iz4
46
58
49 43%
IO
4 7%
..
No relapsing wlthi two monthg of delivery . . . . . . . . . . % relapse . . . . . . . . . .
Details regarding the 14 relapses in the present trial are given in Tables 3 and 4. TABLE 3.--TYPE
OF RELAPSE
Spread of disease . . . . Cavity enlargement . Positive sputum culture . Breakdown of solid focus . TABLE 4.~TIME Within ,,
,, ,,
.
4 6 8
•.
.
. . . . . . . . . . . . . . .
9 3 I x
OF RELAPSE POST-PARTUM
2 weeks ,, ,. ,~
. . . .
.
.
. .
. .
.
. .
. .
. .
.
.
.
. . . . . .
.
3 ••
. ..
5 2
Relapses occurred in 5 primigravida and 9 multigravida. There were 8 in 46 patients under 26 years, and 6 in 58 patients over 26 years. The younger patient therefore seems to run a slightly greater risk, as one might expect with tuberculosis in women. Their Ministry of Health classification was: 3 A~ cases, IO Bs cases, and I B 3 case.
AND DISEASES O F T H E
CHEST
323
Relapses occurred in both the newly diagnosed cases (8 in 57 cases) and in chronic active cases (5 in 27). There was only one relapse among the 20 patients who reactivated during pregnancy; this would seem to be related to the fact that the disease was probably treated and under control again before delivery. O n the whole, however, mor e prolonged treatment before delivery did not appear to be a safeguard. O f 48 patients treated for more than three months before delivery, 6 relapsed: of 32 treated for two months, 3 relapsed: and of 50 treated for one month, 5 relapsed. It should be mentioned that all the relapses we observed were minimal and the final outcome was probably not affected by them. Possibly the fact that the patients were on treatment minimised such deterioration as occurred. In addition to treatment with chemotherapy, a pneumoperitoneum was induced in 4 cases. Fifteen patients proceeded to excisional surgery, a n d 7 had thoracoplasties. In no case was it found necessary to operate during pregnancy, and surgery was carried out at a suitable time after the second month post-partum.
Quiescent Cases There were in addition 26 patients with quiescent disease, who were treated with the same rdgime as Series I I - - t h a t is, with antenatal and post-natal drugs and oestrin. Among this group there was only one relapse. As a control group for comparison with our hospital figures, we studied a series of Ioo tuberculous women attending Lewisham Chest Clinic, and delivered between I95O and i955. Their disease was considered stable, and they received no special care or treatment over their confinements, beyond the fact that many did not breast feed. Nine of these patients deteriorated within two months of delivery, and details in each year are given in Table 5. TABLE 5.~RELAPSES IN QUIESCENT CLINIG CASES
Tear 195o x95I x95~ x953 x954 x955
. . . . . . . . .
.
.
.
. . . . . . . . . . . .
Wo. ofeas~
Relapsesinpuerperium
7 8 i6 i8 20 ~9
o 2 2 o I 4
In such a study as this, it is desirable to have figures of the average relapse rates for tubercle treated with modern antibiotic and chemotherapeutic drugs. Such figures are difficult to obtain and it is for this reason that we have included for comparison a short series of non-pregnant women in the same age group, treated at the same hospital, and observed by one of us (B.T.). All were active cases, and various r6gimes of treatment were used. The results in Table 6 show relapses that occurred in the second to the fourth months of hospital treatment, this being a period comparable in time with the first two months of the puerperjure in our cases. There were 5 ° cases, with 2 relapses, giving a relapse rate of 4 per cent.
324
T H E B R I T I S H J O U R N A L OF T U B E R C U L O S I S TABLE
6.~RELAPSES
Deterioration o n ,, ,, ,, ,, TOTAL RELAPSES R e l a p s e rate .
IN N O N - P R E G N A N T
ACTIVE
CASES
b e d rest only . . . . . . . . single c h e m o t h e r a p y .... combined chemotherapy .... . . . . . . . . . . . . . . . . . . . . . . . . .
x x o 2 4°/o
Discussion The problem of a peculiar risk for the tuberculous during pregnancy is still unsolved. When approaching this subject on the basis of our results, there are two significant facts to bear in mind. Firstly, these relapses are occurring within the very short period of two months, and secondly, all the patients were on active treatment at the time. Papcrs such as those of Beven and Cromie suggest that there is a definite danger, whereas those of Stewart and Simmonds maintain that in the long run there is no significant effect. Possibly data obtained from in-patients where observation is closer will give higher relapse rates. It may be that discrepancies between the reports arise because the first two authors collected their data shortly after delivery, whereas Stewart and Simmonds' follow-up was carried out eighteen months later. This would suggest that the tendency to deteriorate may be self-limiting. This further report from the Grove Park Unit supports the view that the puerperium is an unfavourable period. Puerperal relapses may be duc to one (or both) of two main factors, mechanical and constitutional, including hormonal. Those occurring immediately after delivery (within hours or days) may have a mechanical basis, and such instances might be prcventcd by a large pneumoperitoneum. Earlier diagnosis and more effective treatment have wholly altered the prognosis in tuberculosis; hence comparison with previous findings are unreliable. The figures set out below can only be used to show current results. For active cases Beven found a puerperal relapse rate of 43 per cent., on Sanatorium rdgime. Our relapse rate was 22 per cent. on chcmotherapy (Scries I), and 7 per cent with the addition of cestrin in the puerperium (Series II). This latest figure is so low, and the character of the relapses so minor, that we have not considered termination justifiable on the grounds of pulmonary tuberculosis in any of our cases. The difference bctwecn the results of Series I and Series II is considerable and would strongly suggest that the administration of high doses of cestrin in the puerperium has a marked effect in reducing the numbcr of relapses. As regards the quiescent cases, the clinic figure of a 9 per cent. relapse rate compares unfavourably with that for quiescent cases treated with drugs and ccstrin (one relapse in 26 cases), especially when bearing in mind that the quiescent cases would not have been in our unit unless there was some cause for anxiety. The findings in this unit suggest that, as with the active cases, so with the quiescent cases, the best results may be achieved with antenatal and post-natal drugs and cestrin. Apart from the material used for this report there have bcen a few quiescent cases on the unit treated by variations of our standard r6gime; they are included in Table 7.
AND DISEASES OF THE CHEST
325
TABL]~ 7.'--RELAPSES IN O UIESG~NT CASES
Type of treatment
No. of cases
Relapses
No active treatment (clinic cases) . . . . . . No active treatment (hospital cases) . . . . . . Post-natal o~strinonly . . . . . . . . . . Post-natal chemotherapy and cestrin . . . . . . Ante-natal and post-natal chemotherapy and post-natal oestrin . . . . . . . . . . . . . .
IOO
9
8
5 6
I
3 I
06
There seems little justification for the use of cestrin alone in the puerperium. There does not appear to be any risk attached to treating the pregnant woman with chemotherapy throughout long periods of her pregnancy, and all the infants have appeared unaffected. As regards the use of cestrin, this very large dose is well tolerated by the puerperal woman. One patient in her forties developed menorrhagia after withdrawal of oestrin, and we would perhaps avoid cestrin again in elderly gravida. Summary We have treated a group of pregnant tuberculous women with chemotherapy and cestrogens. A rdgime of antenatal and post-natal chemotherapy, and cestrogens for a m i n i m u m of six weeks post-partum, has given a very low relapse rate in the puerperium. We should particularly like to thank our Consultant Obstetrician and Gynaecologist, Mrs. J. Karnicki, whose advice and encouragement made this study possible. It is also a pleasure to thank Miss Euniee Maddock, the unit Sister, for all her help. REFERENCES BEVEN,G. (1952): Tubercle, 32, I, t 3. B~OVCNE,J. S. L. et al. (I939): Amer. 07. Obst.Gyn~., 38, 927. COHEN,R. C. (I946): Brit. 07. Tuber. Dis. Chest, 40, xo. C~oMIp,J. B. (1954)" Brit. 07. Tuberc. Dis Chest, 48, 97LuRm, M. B. et al. (1949) : Amer. 07. Tuberc., 59, x69, x86. STEWART,C.J. and SI~MONns,F. A. H. (I947) : Brit. med. o7, 2, 706. TURNER,H. M. (I95o): Lancet, 1, 697.