Results

Thirteen patients with tuberculosis during pregnancy were documented. Details of each case including presenting features and the basis on which the diagnosis was made are given in tables 1 and2.

Discussion

This is the first British series of patients developing tuberculosis in pregnancy to be reported since 1961. Unlike the earlier UK studies in which the patients were predominantly of white European descent, all our patients were recent immigrants to Britain. Most recent publications come from the developed world where the risk factors for patients developing tuberculosis were HIV co-infection or social deprivation. A few reports are from immigrant non-white populations3 ,7 ,8 but, in general, clinical data on tuberculosis in pregnancy in immigrants are lacking. This is a significant deficiency in our understanding of tuberculosis since immigration status is the major epidemiological factor in the UK. The 1993 national survey of tuberculosis in England and Wales produced incidence estimates for different ethnic groups of 4.3/100 000 for whites compared with 114.7/100 000 and 135.2/100 000, respectively, for subjects of Indian or black African origin.12Furthermore, there is a strong association with duration of residence in the UK. Data from the same 1993 survey show that, for adults aged 15–34 years born outside the UK, the incidence of tuberculosis after 15 years in residence was 53/100 000 compared with 440/100 000 for immigrants resident for less than five years.12

It is of interest to consider whether the very high incidence of tuberculosis in our study reflects the background incidence in this group, or whether pregnancy is an independent risk factor for developing tuberculosis. The question of pregnancy as a risk factor for tuberculosis has been debated since the earliest days of medicine. Hippocrates believed that pregnancy had a beneficial effect on the outcome of tuberculosis and this was the view generally held until the middle of the last century. In 1850 Grissole reported a series of patients whose tuberculosis worsened during the course of their confinement.13 This view then held sway until the large case series of the 1940/50s, prior to the advent of effective antituberculosis drugs. These studies failed to show either a beneficial or detrimental effect of pregnancy on tuberculosis.9 ,10 ,14 ,15 With these data the argument appeared to be settled, at least among women in developed countries. These data may not necessarily be applicable to different racial groups and studies both in the developing world and larger studies within immigrant populations such as ours are clearly indicated.

That a group of patients who, because they are pregnant, are under regular medical review can have symptoms of tuberculosis for a median of seven weeks before a diagnosis is made is clearly a cause for concern. We identified a variety of reasons for this delay. Firstly, symptoms were often non-specific—for example, lethargy, alteration in bowel habit, or failure to gain weight appropriately—and these were interpreted as usual symptoms commonly occurring in pregnancy. Secondly, the tuberculosis in these patients was commonly extrapulmonary; cough was often absent. Finally, there was an understandable tendency to defer radiological investigations during pregnancy. Useful data for comparison on duration of symptoms before diagnosis of tuberculosis are lacking in the literature. Previous studies have focused on hospitalised patients with pulmonary disease.16 ,17 A recent study of 203 patients in Missouri found a median time lapse of only six days between admission and onset of treatment but information on duration of symptoms was not given. Interestingly, the delay was less for patients from ethnic minorities in this study, probably reflecting a higher index of suspicion in the attending physician.18

The lack of specific symptoms when tuberculosis occurs in pregnancy is in keeping with previous studies. Up to 20% of pregnant women with tuberculosis have been found to be asymptomatic.5 In one study a group of pregnant patients with pulmonary tuberculosis were matched to non-pregnant women with pulmonary tuberculosis and found to be significantly more likely to be asymptomatic at time of diagnosis.3 In another, pregnant patients with tuberculosis were significantly more likely to have non-specific symptoms and also to experience a delay in obtaining a chest radiograph than non-pregnant women with tuberculosis.7 Infant and maternal mortality from untreated active tuberculosis are between 30% and 40%.10 A recent study15 comparing outcomes in patients who started treatment early and late in pregnancy found a significant increase in obstetric morbidity and perinatal mortality in patients whose treatment was started late in pregnancy.

The high proportion of extrapulmonary tuberculosis in this series is intriguing and also partly explains the delay in diagnosis. Previous series of tuberculosis in pregnancy showed no excess of extrapulmonary disease. Ten of 16 patients in a New York study had pulmonary tuberculosis4 despite the known link between HIV infection and extrapulmonary disease.19 Nine of 10 patients in Kentucky had pulmonary tuberculosis,20 and all 27 patients whose tuberculosis occurred during pregnancy or up to one year after delivery in Denver during the late 1970s had pulmonary tuberculosis.5 Twenty five patients collected over 66 months in Mexico City during the early 1990s included 12 patients with extrapulmonary disease, most of which were renal.8 In the UK, however, there is a well established link between extrapulmonary tuberculosis and immigrants. The MRC 1983 survey found 66% of immigrants from India and 63% of immigrants from Bangladesh/Pakistan to have extrapulmonary disease.21 The bias of our population towards recent immigrants may partly explain the frequency of extrapulmonary disease seen. It is interesting to note that, in the three series published from places where patients were predominantly recent immigrants or non-whites, all reported frequent extrapulmonary disease. In these reports the ratio of extrapulmonary to pulmonary cases was 2:5, 3:1, and 12:13, respectively.3 ,7 ,8

In New York, where the resurgence of tuberculosis was linked to HIV co-infection, the development of tuberculosis in pregnancy was similarly related to HIV. Among a total of 16 patients with tuberculosis in pregnancy over seven years, the incidence of tuberculosis increased from 12.4/100 000 deliveries between 1985 and 1990 to 94.8/100 000 deliveries between 1990 and 1992.4Eleven of the patients were tested for HIV and seven were seropositive. The overall tuberculosis notification rate in New York in 1992 was 50.2/100 000.22 Although both the tuberculosis notification rate among UK immigrants and our estimates of the incidence among pregnant immigrants are much higher than the New York rates, a significant impact from HIV on tuberculosis in the UK has not been found.23

The most recent guidelines from the British Thoracic Society on control and prevention of tuberculosis make no specific recommendations regarding pregnancy.24 From our experience it is likely that pregnant women from ethnic minority groups in the UK are at an especially high risk of developing tuberculosis. Furthermore, because of the predominance of extrapulmonary disease and the non-specific symptomatology in these patients, a high index of suspicion for tuberculosis is needed when such patients develop symptoms.