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Background The prevalence of tuberculosis, especially extrapulmonary tuberculosis, is increasing worldwide. Because information on the outcome of pregnancy among women with extrapulmonary tuberculosis is limited, we studied the course of pregnancy and labor and the perinatal outcome in these women and their infants.
Methods From 1983 to 1993, we followed 33 pregnant women who had extrapulmonary tuberculosis (12 with tuberculous lymphadenitis and 9 with intestinal, 7 with skeletal, 2 with renal, 2 with meningeal, and 1 with endometrial tuberculosis) through their deliveries. Of the 33, 29 received antituberculosis treatment during pregnancy. The antenatal complications, intrapartum events, and perinatal outcomes were compared with those among 132 healthy pregnant women without tuberculosis who were matched for age, parity, and socioeconomic status.
Results Tuberculous lymphadenitis did not affect the course of pregnancy or labor or the perinatal outcome. However, as compared with the control women, the 21 women with tubercular involvement of other extrapulmonary sites had higher rates of antenatal hospitalization (24 percent vs. 2 percent, P< 0.001), infants with low Apgar scores (
Conclusions Extrapulmonary tuberculosis that is confined to the lymph nodes has no effect on obstetrical outcomes, but tuberculosis at other extrapulmonary sites does adversely affect the outcome of pregnancy.
6) soon after birth (19 percent vs. 3 percent, P=0.01), and low-birth-weight (<2500 g) infants (33 percent vs. 11 percent, P=0.01).
Active pulmonary tuberculosis in pregnant women has been associated with increased risks to their infants, including prematurity, fetal-growth retardation, low birth weight, and perinatal mortality, as compared with the infants of healthy pregnant women who do not have tuberculosis.8 However, information on the obstetrical outcome among women with extrapulmonary tuberculosis is scanty and is usually in the form of case reports9,10,11,12 or case series.13 Therefore, we compared the course of pregnancy and labor and the perinatal outcome among women with extrapulmonary tuberculosis and matched control women without tuberculosis.
Methods
We studied 33 pregnant women with extrapulmonary tuberculosis (Table 1). These women were identified from among 178 pregnant women with tuberculosis who attended the Obstetric Medical Disorder Clinic at the Postgraduate Institute of Medical Education and Research, Chandigarh, India, from 1983 to 1993. Three other women (two with intestinal and one with skeletal tuberculosis) were excluded from the study because of inadequate information. The diagnosis of extrapulmonary tuberculosis was established by clinical findings combined with bacteriologic, histologic, and radiologic studies, and all patients fulfilled the diagnostic criteria of the World Health Organization.14 Twenty-nine women had active disease requiring antituberculosis treatment during pregnancy, and four women (three with intestinal and one with spinal [skeletal] tuberculosis) had completed such treatment before conception. Two women with tuberculous lymphadenitis also had pulmonary tuberculosis, but the remaining 31 women had no evidence of pulmonary tuberculosis.
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For each woman, we selected 4 healthy pregnant women without tuberculosis (total, 132) as controls. Each control was matched for age and parity with a woman with tuberculosis and had given birth in the hospital within 48 hours before or after the matching woman had given birth. The institute is a referral center for neighboring states of northern India; therefore, both the study and control groups were from the same area and had similar socioeconomic backgrounds. The results in the two groups were compared with the use of Student's t-tests and chi-square tests with Yates' correction.
Results
During the study period, for every 1043 women who delivered infants at our hospital, 1 had extrapulmonary tuberculosis, and the 36 women identified for the study (including the 3 who were excluded) accounted for 20 percent of all cases of tuberculosis among pregnant women. A preliminary analysis revealed no significant differences in the overall perinatal outcome between the women with tuberculosis and the control women. However, the 21 women who had extrapulmonary tuberculosis at sites other than lymph nodes had an increased incidence of perinatal complications and were therefore analyzed as a separate subgroup.
Clinical Presentation
The clinical presentations and the methods of diagnosis of extrapulmonary tuberculosis in the 33 women are summarized in Table 1. Age, parity, literacy rate, weight, and hemoglobin concentrations were similar among the two groups of women with tuberculosis and the control group (Table 2). Twenty-two women (67 percent) had started treatment with antituberculosis drugs before the index pregnancy. Among the remaining 11 women, all of whom were given a diagnosis during the index pregnancy, 4 (12 percent) started treatment in the first trimester, 4 (12 percent) in the second trimester, and 3 (9 percent) in the third trimester.
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Of the 29 women who had active tuberculosis during the index pregnancy, 18 (62 percent) received isoniazid, rifampin, and ethambutol for nine months. Five women (17 percent) received isoniazid and ethambutol for 12 to 18 months (four had also received streptomycin before conception). All of the remaining six women (21 percent), four of whom were in an advanced stage of pregnancy and two of whom had tuberculous meningitis, received isoniazid, rifampin, and pyrazinamide. Treatment with pyrazinamide was stopped after two months, and all therapy was stopped after nine months. No adverse effects were observed.
Antenatal Events
Six women were hospitalized in the antenatal period; the reason for hospitalization was effusion of the left ankle in one woman with skeletal tuberculosis, deep venous thrombosis in one woman with spinal tuberculosis without paraplegia, severe pregnancy-induced hypertension in one woman with tuberculous lymphadenitis, prolonged fever in one woman with renal tuberculosis, and tuberculous meningitis in two women. The rate of admission among the women with extranodal tuberculosis was 24 percent (5 of 21), as compared with a rate of 2 percent in the control group (P<0.001) (Table 3). However, none had progression of tuberculosis or a relapse during the pregnancy or puerperium. The frequency of complications of pregnancy was similar among the two groups of women with tuberculosis and the control group (Table 3).
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Labor was induced in eight of the women with tuberculosis (24 percent). Two women with spinal tuberculosis and paraplegia had spontaneous vaginal deliveries. Cesarean sections were performed only for obstetrical indications. One woman with tuberculous kyphoscoliosis required cesarean section for pelvic contraction, and in another woman, cesarean section was complicated by the presence of extensive intraabdominal adhesions resulting from intestinal tuberculosis.
Perinatal Outcome
The mean (±SD) birth weight (2894±430 g) of the infants of the 12 women with tuberculous lymphadenitis was appropriate given the mean gestation of 38.9±1.5 weeks and was similar to the institute's reference values and to the value in the infants of the women in the control group (Table 4). However, the mean birth weight of the infants of the 21 women with tuberculosis at other extrapulmonary sites was 251 g lower than that of the infants of the women in the control group (2617 g vs. 2868 g, P=0.04); these infants also had a significantly higher incidence of low birth weight (33 percent vs. 11 percent, P=0.01) and an Apgar score of 6 or less one minute after birth (19 percent vs. 3 percent, P=0.01).
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Discussion
Extrapulmonary tuberculosis, which is present in 10 to 27 percent of all patients with tuberculosis,5,6,15,16 is rare among pregnant women.10,11,12,13 The diagnosis of this condition is often delayed because of its protean manifestations,5,15,16 and this type is less easy than pulmonary tuberculosis to identify with the use of radiologic evaluation and bacteriologic confirmation.16 Biopsy and surgical intervention during pregnancy may not be possible because of the risk of preterm labor, poor accessibility of the lesions, and anesthetic risk to the fetus.12 Since our institute is a referral center, the prevalence of extrapulmonary tuberculosis among pregnant women — 1 in 1043 deliveries — does not reflect the prevalence among pregnant women in the community.
In this study, we assessed the obstetrical implications of extrapulmonary tuberculosis by matching two groups of pregnant women — one group with extrapulmonary tuberculosis and one without tuberculosis — with similar demographic characteristics. Tuberculous lymphadenitis, the most common form of extrapulmonary tuberculosis,5,15,17 had no adverse effect on maternal and fetal outcome. Because lymphadenitis is often diagnosed early, it rarely causes debility or systemic toxicity.17 However, women with extranodal tuberculosis had infants who weighed a mean of 251 g less at birth than the infants of the control women, although there was no significant difference between the groups in the mean gestational age at delivery or the rate of prematurity. These results suggest that like pulmonary tuberculosis,8 maternal extranodal tuberculosis increases the risk of fetal-growth retardation. There were also significant increases in the frequency of low-birth-weight infants and infants with low Apgar scores soon after birth in this subgroup. Furthermore, in our previous study, which did not include any of the women who were in the current study, we found that the infants of women with pulmonary tuberculosis were approximately twice as likely as the infants of healthy women without tuberculosis to be premature, to be small for gestational age, and to have a low birth weight. In both studies diagnosis late in pregnancy and advanced disease probably contributed to the perinatal problems, as did physical disability in the present study.
Intestinal tuberculosis is difficult to diagnose without the use of laparotomy.9,16 However, we found endoscopic or fine-needle aspiration biopsy to be useful in selected patients. In one woman with intestinal tuberculosis in our study, cesarean section was complicated by the presence of extensive abdominal and pelvic adhesions.
Spinal tuberculosis, although rare in pregnancy, is associated with serious morbidity.18,19 The absence of systemic symptoms and reluctance to perform spinal radiography in pregnant women often delayed the diagnosis in our study, resulting in early-onset paraplegia in two women. In women with paraplegia, pregnancy is associated with an increased risk of urinary tract infection, decubitus ulcers, preterm labor, and autonomic hyperreflexia — a potentially life-threatening complication.10 In our study, the condition of both women with paraplegia improved with antituberculosis-drug therapy, and both had vaginal deliveries, although one woman had a preterm delivery. In other reports, five women with tuberculous paraplegia who required spinal surgery during pregnancy or the puerperium had successful vaginal deliveries and normal infants.10,12 However, spinal deformity and reduced cardiopulmonary reserve associated with kyphoscoliosis can complicate the use of regional and general anesthesia during delivery.20
Tuberculous meningitis in pregnant women is associated with neurologic morbidity and an increased risk of death to both the women and their infants.11 Endometrial tuberculosis often leads to infertility, miscarriage, or ectopic pregnancy.21 In contrast, the patients who had tuberculous meningitis and endometritis in our study had good outcomes, probably as a result of early diagnosis and treatment.
Treatment with antituberculosis drugs poses special problems during pregnancy because of concern about potential teratogenic effects. Most of the women in our study received isoniazid, ethambutol, and rifampin, all of which are relatively safe to use during pregnancy,22 and none of their infants had any congenital anomalies. Little is known about the fetal effects of pyrazinamide. The six women who received pyrazinamide because of its bactericidal effects and penetration of cerebrospinal fluid had no adverse effects.11
In summary, the effects of extrapulmonary tuberculosis on pregnancy depend on the sites involved, the severity and duration of the disease, and the occurrence of pregnancy-associated complications. Tuberculous lymphadenitis had no significant effect on perinatal outcome. However, extrapulmonary tuberculosis at other sites was associated with an increased frequency of maternal disability, hospitalization during pregnancy, fetal-growth retardation, and infants with low Apgar scores soon after birth.
We are indebted to S. Barik, M.D., M.E. Covell, B.Tech., and P. Narang, M.D., for their helpful comments on the manuscript.
Source Information
From the Department of Obstetrics and Gynaecology, Memorial Hospital, Darlington, United Kingdom (N.J.); the Department of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India (K.V., S.C.S.); and the Department of Obstetrics and Gynaecology, West Middlesex University Hospital, Isleworth, Middlesex, United Kingdom (K.G.).
Address reprint requests to Dr. Vasishta at the Department of Obstetrics and Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
References
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