Background
Worldwide, tuberculosis remains a major health concern, with an estimated 9.6 million people infected in the year 2014, of which one-third were women. Tuberculosis is estimated to be even more prevalent in pregnant women than the general population. To date there has been conflicting evidence on the maternal and neonatal complications of tuberculosis in pregnancy.
Objective
We sought to determine trends in the incidence of tuberculosis in pregnancy and to examine the associations between tuberculosis in pregnancy and maternal and fetal complications.
Study Design
We conducted a retrospective cohort study using the 2003 through 2011 Healthcare Cost and Utilization Project Nationwide Inpatient Sample. We identified hospital admissions during which women with and without tuberculosis delivered. The temporal patterns in incidence of tuberculosis were estimated, as were the rates of pulmonary and nonpulmonary tuberculosis. Multivariate logistic regression was used to examine the adjusted effects of tuberculosis on maternal and neonatal outcomes.
Results
During the study period, there were 7,772,999 births, of which 2064 were to women with tuberculosis, for an overall incidence of 26.6 per 100,000 births. From 2003 through 2011, there was an upward trend in the incidence of tuberculosis from 1.92-4.06 per 10,000 births ( P < .0001), mostly due to increasing numbers of nonpulmonary tuberculosis. Compared with noncases, tuberculosis occurred with greater frequency in women who were 25-34 years of age and of Hispanic ethnicity. Significantly more women with tuberculosis had concurrent HIV. In addition, delivery hospitalizations with tuberculosis compared with those without tuberculosis were more likely to experience chorioamnionitis, preterm labor, postpartum anemia, blood transfusion, pneumonia, acute respiratory distress syndrome, and mechanical ventilation. Maternal mortality was significantly increased in women with tuberculosis. Congenital anomalies were higher among babies delivered to women with tuberculosis.
Conclusion
The rate of tuberculosis in pregnancy is rising in the United States. Although this increase appears to be mostly due to nonpulmonary disease, there was also a high incidence of maternal respiratory complications, mortality, and postpartum obstetric morbidity.
Introduction
Worldwide, tuberculosis (TB) remains a major health concern, with an estimated 9.6 million people infected worldwide in the year 2014, with the majority of these cases occurring in Asia (58%) and Africa (28%). In addition, one third of the cases are believed to occur in women. TB is the leading infectious cause of death in women, and now ranks alongside HIV as the leading cause of death worldwide.
Although the incidence of TB cases is lowest in developed countries at <10 cases per 100,00 population per year, foreign-born persons from endemic countries account for the majority of cases in the United States. About 75% of TB-infected individuals are within the reproductive age group of 15-45 years, and the prevalence of TB is estimated to be higher in pregnant women than the general population, although reports are conflicting. There is currently insufficient evidence on the epidemiology of TB in pregnancy, with conflicting rates of maternal and neonatal complications. As such, our objective is to determine the incidence of TB in pregnancy and to assess the effects of TB on maternal and fetal outcomes.
Materials and Methods
The Healthcare Cost and Utilization Project (HCUP)-Nationwide Inpatient Sample (NIS) databases from 2003 through 2011 were used to address the study objective. HCUP-NIS is the largest inpatient care database set in the United States. It is a 20% stratified sample of all discharges from US community hospitals, with the exception of long-term care and rehabilitation hospitals, and consists of data from an estimated 7 million hospital admissions from >1000 hospitals.
There have been numerous studies addressing the reliability of coding systems. Upon discharge, the patient’s medical record and all associated documentation are transferred to the medical record or health information management department. Concurrently, technicians check to ensure that all medical record information is accurate and complete. Coders then begin the process of classifying documentation, including diagnoses and procedures, using rigid International Classification of Diseases coding guidelines and conventions.
The HCUP-NIS does not allow for individuals to be followed up for multiple hospital admissions; hence, the hospitalization during which individuals delivered was the focus of our analysis. We first identified all hospital discharge records associated with a delivery in the HCUP-NIS databases from 2003 through 2011 using the following delivery codes based on International Classification of Diseases, Ninth Revision ( ICD-9 ) codes for cesarean delivery (diagnosis codes: 669.7, 763.4; or procedure codes: 74.0, 74.1, 74.2, 74.4, 74.9) and general delivery (diagnosis codes: 650.x or 677.x or 651.xx-676.xx [with fifth digit as 0 or 1 or 2], excluding 63x.x; or procedure codes: 72.x, 73.x, 74.0, 74.1, 74.2, 74.4, 74.99). Then we used International Classification of Diseases, Ninth Revision, Clinical Modification codes to identify delivery hospitalizations associated with TB by combining the general delivery codes listed above with the pulmonary TB diagnosis codes (018.x, 010.x, 011.x, 012.x, 647.3) or nonpulmonary TB diagnosis codes (013.x, 014.x, 015.x, 016.x, 017.x, 137.x, V12.01).
Morbidities we considered in our study, identified by ICD-9 codes, included the following: in-hospital mortality, mechanical ventilation, pneumonia, acute respiratory distress syndrome (ARDS), and venous thromboembolism. Obstetrical outcomes assessed were preeclampsia, eclampsia, gestational diabetes, preterm premature rupture of membranes, chorioamnionitis, abruption, previa, threatened preterm labor, induction of labor, cesarean delivery, instrumental delivery, postpartum anemia, postpartum transfusion, postpartum infections, and wound complications. Fetal outcomes included congenital anomalies, prematurity, stillbirth, and growth restriction.
We ascertained the number of delivery hospitalizations with TB and the number without TB annually from 2003 through 2011 and then the rates of pulmonary and nonpulmonary TB were determined per 10,000 delivery hospitalizations. The existence of a linear change in TB incidence at delivery during the study period was examined using linear regression.
A prior study conducted in the United States found an increasing burden of severe maternal morbidities for delivery hospitalizations over time. As such, we examined maternal risks of severe respiratory complications, and other adverse medical and obstetric outcomes among hospitalizations affected by TB compared with those unaffected by TB. Further, the baseline demographic and clinical characteristics of these 2 groups were compared. Unconditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for medical and obstetric complications present during delivery hospitalizations with TB compared with those without TB. Analyses were adjusted for maternal demographic and clinical characteristics listed in Table 1 . P values <.05 were deemed statistically significant. SAS Enterprise Guide 6.1 (SAS Institute Inc, Cary, North Carolina) was used for all statistical analyses. This study used exclusively publicly available data; hence, according to the Tri-Council Policy Statement (2010), institutional review board approval was not required.
| Characteristics | No TB, % N = 7,770,935 | TB, % N = 2064 |
|---|---|---|
| Age, y | ||
| <25 | 34.4 | 25.4 |
| 25–34 | 51.0 | 54.5 |
| ≥35 | 14.6 | 20.1 |
| Race | ||
| Caucasian | 40.9 | 14.7 |
| African American | 10.7 | 13.4 |
| Hispanic | 19.1 | 34.6 |
| Other | 8.3 | 21.3 |
| Income quartile, US$ | ||
| 1–38,999 | 27.0 | 30.3 |
| 39,000–47,999 | 25.1 | 23.6 |
| 48,000–63,999 | 24.5 | 21.9 |
| ≥64,000 | 23.3 | 24.2 |
| Hospital type | ||
| Rural | 11.1 | 4.8 |
| Urban nonteaching | 43.1 | 26.6 |
| Urban teaching | 45.2 | 67.7 |
| Insurance type | ||
| Medicare | 0.6 | 0.5 |
| Medicaid | 42.0 | 54.6 |
| Private insurance | 51.2 | 36.9 |
| Other | 6.1 | 7.9 |
| HIV | 0.1 | 1.8 |
Results
A total of 7,772,999 births occurred during the 9-year study period, of which 2064 were to women with TB, resulting in an incidence of 26.6 per 100,000 births. As shown in Figure 1 , the incidence of TB increased linearly from 1.92-4.06 per 10,000 births ( P < .0001) during the study period. This increase may be largely attributed to nonpulmonary TB ( Figure 2 ). There was no temporal trend in the incidence of pulmonary TB over the 9-year study period.
Table 1 shows demographic and clinical characteristics of study subjects stratified by TB status. Relative to women without TB, those with TB were more likely to be Hispanic, be 25-34 years of age, have lower income, have Medicaid insurance, and be seen in an urban teaching hospital. Significantly more women with TB had concurrent HIV than women without TB.
The maternal outcomes of TB are displayed in Table 2 . Compared with women without TB, women with TB were more likely to have chorioamnionitis (OR, 1.35; 95% CI, 1.04–1.74), preterm labor (OR, 2.28; 95% CI, 1.43–3.63), postpartum anemia (OR, 1.51; 95% CI, 1.22–1.87), blood transfusion (OR, 1.49; 95% CI, 1.07–2.09), pneumonia (OR, 8.42; 95% CI, 5.77–12.29), and ARDS (OR, 2.85; 95% CI, 1.35–6.10), and to require mechanical ventilation (OR, 3.33; 95% CI, 1.66–6.68). Overall maternal mortality was increased among women with TB in pregnancy (OR, 6.27; 95% CI, 2.01–19.58).
| No TB, % N = 7,770,935 | TB, % N = 2064 | Crude OR (95% CI) | Adjusted OR (95% CI) a | P value | |
|---|---|---|---|---|---|
| Preeclampsia | 3.5 | 3.8 | 1.11 (0.89–1.39) | 1.06 (0.85–1.33) | NS |
| Eclampsia | 0.6 | 0.7 | 1.24 (0.73–2.10) | 0.88 (0.51–1.53) | NS |
| Gestational diabetes | 5.3 | 7.3 | 1.41 (1.19–1.66) | 1.08 (0.91–1.27) | NS |
| PPROM | 3.7 | 3.8 | 1.02 (0.81–1.28) | 0.95 (0.75–1.19) | NS |
| Chorioamnionitis | 1.8 | 3.0 | 1.71 (1.32–2.20) | 1.35 (1.04–1.74) | <.05 |
| Abruption | 1.1 | 0.9 | 0.81 (0.51–1.28) | 0.78 (0.49–1.24) | NS |
| Previa | 0.6 | 0.7 | 1.34 (0.80–2.22) | 1.09 (0.66–1.82) | NS |
| Threatened PTL | 0.3 | 0.9 | 2.70 (1.70–4.29) | 2.28 (1.43–3.63) | <.001 |
| Cesarean delivery | 31.4 | 31.4 | 1.00 (0.91–1.10) | 0.95 (0.86–1.04) | NS |
| IOL | 16.7 | 13.5 | 0.78 (0.69–0.88) | 0.93 (0.82–1.06) | NS |
| Instrumental delivery | 5.7 | 5.1 | 0.90 (0.74–1.09) | 1.01 (0.83–1.22) | NS |
| Postpartum anemia | 2.7 | 4.4 | 1.67 (1.35–2.06) | 1.51 (1.22–1.87) | <.001 |
| Blood transfusion | 0.9 | 1.7 | 1.90 (1.37–2.64) | 1.49 (1.07–2.09) | <.05 |
| Postpartum infection | 0.4 | 0.8 | 1.83 (1.12–2.90) | 1.31 (0.76–2.26) | NS |
| Wound complications | 0.1 | 0.2 | 2.77 (1.15–6.67) | 2.25 (0.93–5.41) | NS |
| VTE | 0.1 | 0.2 | 2.47 (0.93–6.56) | 2.27 (0.85–6.05) | NS |
| Pneumonia | 0.1 | 1.4 | 10.71 (7.37–15.56) | 8.42 (5.77–12.29) | <.001 |
| ARDS | 0.1 | 0.3 | 3.73 (1.78–7.84) | 2.85 (1.35–6.00) | <.01 |
| Mechanical ventilation | 0.1 | 0.4 | 4.50 (2.25–9.01) | 3.33 (1.66–6.68) | <.001 |
| Maternal mortality | 0.0 | 0.2 | 10.10 (3.26–31.34) | 6.27 (2.01–19.58) | <.01 |
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