American Journal of Obstetrics and Gynecology (2006) 194, 4516

www.ajog.org

Tuberculosis prevention for nonUS-born pregnant women

Judith E. Sackoff, PhD,a,* Melissa R. Pfeiffer, MPH,a Cynthia R. Driver, DrPH,b Lynda S. Streett, MD,c Sonal S. Munsiff, MD,b Jack A. DeHovitz, MDa
Department of Medicine/Preventive Medicine and Community Health,a State University of New York (SUNY) Downstate Medical Center, Brooklyn, NY; New York City Department of Health and Mental Hygiene,b Bureau of Tuberculosis Control; Department of Medicine,c Columbia University, New York, NY
Received for publication April 24, 2005; revised June 21, 2005; accepted July 13, 2005

KEY WORDS
Tuberculosis Prevention Pregnancy

Objective: The purpose of this study was to evaluate whether nonUS-born pregnant women receiving prenatal care are targeted for treatment of latent tuberculosis (TB) infection (LTBI) with isoniazid (INH) to prevent active TB. Study design: This was a retrospective chart review study of 730 nonUS-born pregnant women receiving care at 5 New York City prenatal clinics from 1999 to 2000. Results: Among 678 women with known tuberculin skin test (TST) status, 341 (50.3%) had a TST-positive result, including 200 who were newly diagnosed. Of 291 TST-positive women with no previous LTBI treatment or history of TB, 27 (9.3%) completed R6 months of INH. In a subset with detailed follow-up, the most important reasons for not completing treatment were nonreferral for evaluation of a TST-positive result (30.9%), not keeping the appointment (17.9%), and nonadherence with prescribed treatment (34.6%). Conclusion: The prenatal setting represents a missed opportunity to link TST-positive nonUSborn women with LTBI treatment and support for treatment completion. 2006 Mosby, Inc. All rights reserved.

Increasingly, the elimination of tuberculosis (TB) in the United States (US) depends on control of the epidemic in the nonUS-born population.1,2 In 2003, 53.1% of TB cases in the US were diagnosed among nonUS-born, compared with 29.1% a decade earlier.3 In New York City (NYC), the TB case rate in nonUS-born in 2003 was almost 4 times higher than in US-born (26.5 vs 6.9 per 100,0000), and accounted for 68.1% of cases.4

Funded through grants from the Starr Foundation and the New York Community Trust. * Reprint requests: Judith E. Sacko, PhD, New York City Department of Health and Mental Hygiene, 346 Broadway, Room 706, New York, NY 10013. E-mail: jes20@columbia.edu 0002-9378/$ - see front matter 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.07.054

The majority of cases in nonUS-born are caused by reactivation of latent TB infection (LTBI) and not recent transmission.5 In addition to standard TB control practices,6 eorts to control the epidemic in nonUS-born have focused on treating LTBI with 6 to 9 months of isoniazid (INH).1 The Centers for Disease Control and Prevention (CDC) guidelines for LTBI treatment target recent entrants to the US (!5 years) from TB endemic countries because their TB risk is signicantly higher than longerterm residents.7,8 The Institute of Medicine (IOM) estimates that targeting recent immigrants from endemic countries for treatment of LTBI could prevent at least 1300 cases of TB annually in the 5 years after immigration.2 Implementation of the IOM recommendation remains a challenge. In most settings INH completion rates are

452 low to modest.4,9 One approach to improving completion rates has been to integrate tuberculosis skin testing and LTBI treatment with services routinely accessed by clients, such as methadone maintenance programs.10 Prenatal care is potentially another such setting. Tuberculin skin testing during prenatal care is recommended for women from TB endemic countries,1,11 and for recent immigrants,12 although treatment of LTBI during pregnancy is controversial because of the risk of INHassociated hepatitis.13-16 Both the American College of Obstetricians and Gynecologists and the CDC recommend deferring LTBI treatment until postpartum except for women with conditions that promote hematogenous spread of organisms to the placenta, such as human immunodeciency virus (HIV) infection or recent infection with TB.1,12 In this retrospective chart review study of nonUSborn pregnant women receiving prenatal care, we report on TST testing rates, completion rates for LTBI treatment, and a more detailed analysis of loss to follow-up in a subsample of patients.

Sackoff et al record. To allow time for patients to initiate INH postpartum and complete at least 6 months of treatment, the TB registry and individual patient records were reviewed a minimum of 12 months after delivery (range 1363).

Variable denitions
Women were classied as TST-positive if they either reported a previous positive test result or, if tested in the clinic, the TST induration measured R10 mm or the provider noted in the chart that the test was positive. A history of active TB was determined by self-report or provider documentation. Women with a previous TSTpositive result were classied as previously diagnosed, and all others as newly diagnosed. A complete regimen of LTBI treatment was dened as R6 of INH by self-report, physician documentation, or a note that the regimen had been completed without specifying duration.

Outcomes
The primary outcome was the proportion of TSTpositive women who completed R6 months of LTBI treatment during the prenatal or postpartum period. Women who had previously completed R6 months of INH or had a history of TB were excluded from this calculation. In the subsample receiving prenatal care at facilities that referred to a hospital medical service, information was available on whether the women were referred for evaluation, and among those referred, whether they kept the appointment, initiated LTBI treatment, and completed treatment.

Material and methods

Sample
We selected a convenience sample of 5 prenatal clinics in NYC at which R50% of the women were born in TB endemic countries.17 Two of the clinics were hospitalbased and 3 were free-standing. Medical records were reviewed if the woman initiated prenatal care in 1999 or 2000. At 1 clinic the sample was further limited to women who were TST-positive. Consecutive patients were sampled to a minimum of 175 per site, more if resources were available. In 3 clinics, the sample was stratied by calendar month of rst prenatal visit. Of 1029 patients identied, 299 were excluded: 121 were USborn or the country was unknown; 66 made fewer than 3 prenatal visits; 2 had incomplete information; 1 had active TB; and for 109 the medical record could not be located. The nal sample was 730.

Analysis
Descriptive statistics were calculated for the demographic and prenatal care characteristics of the sample. For each outcome, we reported the overall proportion achieving the outcome and the results of bivariate analyses between the outcome and demographic characteristics, prenatal clinic, and TST status (newly diagnosed vs previously diagnosed TST-positive). P values ! .05 were considered statistically signicant. The research was approved by the Institutional Review Board of the NYC DOHMH and each clinic.

Data sources
Prenatal medical records were reviewed for information on sociodemographic characteristics, prenatal care, TB history, and TB workup during the prenatal period. Three prenatal clinics referred patients to NYC Department of Health and Mental Hygiene (DOHMH) chest clinics for evaluation of a TST-positive result, and 2 referred to the medical service within their hospital. For women referred to DOHMH chest clinics, we obtained information on LTBI treatment completion from their registry. The registry does not include individuals who refused LTBI treatment or were not recommended to start. For women referred to a hospital medical service, detailed information was available from the medical

Results
Characteristics of sample
The median age of the 730 women was 26 years, 50.0% had completed high school, and 89.6% were from TB endemic countries (Table I). The largest proportions were from the Caribbean (36%), Central America (31%), Asia (18%), and South America (13%). Almost two thirds initiated prenatal care in the rst trimester, and the median number of prenatal visits was 11.

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Table I Characteristics of nonUS-born women attending 5 prenatal clinics in New York City, 1999 to 2000 Characteristic Age, median (IQR) Completed high school or greater Born in TB endemic country Number prenatal visits, median (IQR) Number weeks pregnant at rst PNV, median (IQR) Previous TB TB risk factors Recent arrival (!5 years) in US from TB endemic country Othery n/N (%) 26 years (2231) 365/730 (50.0%) 654/730 (89.6%) 11 visits (913) 12 (917) 5 (0.7%) 95/144 (66.0%)* 18/730 (2.5%)

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Table II Tuberculin skin testing and referral for evaluation of TST-positive result, among nonUS-born women attending 5 prenatal care clinics in New York City, 1999 to 2000 n/N Documented TST status Tested in clinic Previously diagnosed TST-positive* Tested TST-negative within previous year TST-positivey Timing of TST-positive result Newly diagnosed TST-positive Previously diagnosed TST-positive Previous LTBI treatment (R6 months) Referred for evaluation of positive TSTx Newly diagnosed TST-positive Previously diagnosed TST-positive 678/730 521/678 141/678 16/678 341/678 200/341 141/341 48/141z 202/291 161/199 41/92 % 92.9 76.8 20.8 2.4 50.3z 58.7 41.4 34.0 69.4 80.9 44.6

* Year of arrival in US was reported for 144/730 (19.7%) nonUSborn women; 118 were from 1 clinic. y Other risk factors include recent contact with TB patient (5), recent TST conversion %2 years (11), and diabetes (2).

Year of entry to the US was available for only 144 women; of these, 95 (66.0%) had arrived within 5 years of the prenatal evaluation. Other TB risk factors were reported for 18 women. Of 698 women tested for HIV, none was positive.

* Women with a previous TST-positive test result, with or without documentation. y R10 mm induration or self-report. z Excluding women from 1 clinic where only TST-positive women were sampled, the prevalence of a TST-positive result was 39.6% (221/558). x Excludes women with contraindication for INH, previous or current active TB, or completion of R6 months LTBI treatment.

Tuberculin skin testing and referral

TST status was known for 678 (92.9%) women: 521 (76.8%) were tested in the prenatal clinic, 141 (20.8%) reported a previous TST-positive result and 16 (2.4%) reported a TST-negative result in the previous year (Table II, Figure 1). Of 678 women with a known status, 341 (50.3%) were TST-positive, including 200 (58.7%) newly diagnosed and 141 (41.4%) previously diagnosed. Excluding women from the clinic where only TSTpositive women were sampled, the prevalence of positive TSTs was 36.9% (221/558). The prevalence was highest in women from Haiti (57%), El Salvador (47%), Ecuador (44%), Dominican Republic (41%), and Jamaica (33%). The prevalence in Chinese patients could not be determined because they came from the clinic where only TST-positive patients were sampled. Of the 341 TST-positive women, 2 had previously been diagnosed with TB, and 48 had previously completed LTBI treatment. The remaining 291 were potentially eligible for LTBI treatment. Of this group, 202 (69.4%) were referred for medical evaluation to a DOHMH chest clinic or hospital medical service, and of those referred, 187 (92.6%) were advised to be evaluated postpartum and 15 (7.4%) prenatally. Referral was more likely in women newly diagnosed TSTpositive than previously diagnosed (80.9% vs 44.6%, P ! .0001). The proportion referred for evaluation diered signicantly by clinic (range 43%81%) but not by maternal age, whether the woman came from a TB

endemic country, or whether the clinic referred to a hospital medical service or DOHMH chest clinic.

LTBI treatment completion

Among the 291 women potentially eligible for LTBI treatment, 27 (9.3%) completed treatment. The proportion completing treatment did not dier signicantly by prenatal clinic (P = .81), or whether the women were referred to a hospital medical service or DOHMH chest clinic (P = .69). Women newly diagnosed TST-positive were more likely to complete LTBI treatment than women previously diagnosed (13% vs 2%, P =.005). The completion rate did not dier signicantly between women referred for evaluation during the prenatal period and those referred postpartum (20% vs 15%, P = .58). Information on loss to follow-up was available for a subsample of 162 women from 2 prenatal clinics (Figure 2): 50 of 162 (30.9%) TST-positive women potentially eligible for LTBI treatment were not referred for evaluation; 29 of 112 (25.9%) were referred but did not keep the appointment; and 11 of 83 (13.3%) who kept the appointment were not recommended to start LTBI treatment or refused. Of the 72 women in this subsample who initiated LTBI treatment (8 prenatally and 64 postpartum), 16 (22.2%) completed treatment. Among the 112 women referred for evaluation, those who kept the appointment did not dier signicantly from those who did not keep the appointment by age, education, or birth in a TB endemic country. However, women newly diagnosed

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Figure 1 Evaluation of 730 nonUS-born pregnant women for latent TB infection from 5 prenatal clinics in New York City from 1999 to 2000.

TST-positive were signicantly more likely to keep the referral appointment than those previously diagnosed TST-positive (78% vs 57%, P = .049). Women who completed LTBI treatment did not dier signicantly from those who did not on age, education, birth in a TB endemic country, or TST status.

Comment
We evaluated whether nonUS-born pregnant women, mostly from TB endemic countries, are targeted for tuberculin skin testing and linked to LTBI treatment. A TST result was documented for more than 90% of women,

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455 keep their appointment. These provider and patient decisions may reect knowledge that the infection is long standing and that the womans TB risk is, therefore, not very high.18 We also observed that women generally agreed to start LTBI treatment, but that only 1 in 5 completed treatment and the median length of treatment was 1 month. This suggests that oering LTBI treatment can be a wasted gesture if not accompanied by actions to ensure adherence. The IOM has identied treatment of LTBI among nonUS-born as a central strategy for eliminating TB in the US.2 Against this background, the very low completion rates among women rst identied in the prenatal clinic is disappointing because the prenatal clinic can be an ecient setting for identifying high-risk women and linking them to LTBI treatment. At the prenatal clinics we surveyed, approximately one third of all women had untreated LTBI and were from a TB endemic country. An unknown proportion of them had entered the US within the previous 5 years. To reach nonUS-born women at highest risk, prenatal patients should be routinely asked about their immigration and travel history, and those who have arrived from a TB-endemic country within the previous 5 years should be referred for evaluation and possible LTBI treatment prenatally or postpartum. Another possible benet of screening in the prenatal setting is the option of oering LTBI treatment during pregnancy. A cost-eectiveness analysis concluded that it was preferable to treat TST-positive women during pregnancy than postpartum or not at all.16 Although perhaps theoretically advantageous, the acceptability of LTBI treatment during pregnancy is not known. In our study only 15 women were referred for LTBI treatment during pregnancy. The possible increased risk of hepatotoxic eects of INH in pregnancy and postpartum may be an underlying concern. The evidence for increased hepatotoxicity is from the 1970s and early 1980s, and includes case reports of possible INH-related deaths to postpartum women13,14 and a study of pregnant women prescribed INH prenatally who had a statistically nonsignciant increase in liver toxicity and death.15 Protocols for monitoring patients on INH are more conservative now than in these earlier reports, and include monthly monitoring of clinical symptoms for all women, and liver function for pregnant women12,19 These protocol changes have been associated with an approximately 6-fold decrease in the risk of heptatoxicity in the nonpregnant population.14,20 Prenatal care in NYC is provided by over 80 clinics and thousands of private doctors. Thus, we cannot generalize from our select sample to the universe of non US-born pregnant women and the providers that serve them. Further, this was a retrospective chart review study with its attendant limitations, namely dependence on patient self-report and provider documentation, and the absence of a standardized, well-documented

Figure 2 Detailed follow-up information on 162/291 TSTpositive nonUS-born pregnant women potentially eligible for LTBI treatment, from 2 prenatal clinics in New York City from 1999 to 2000.

but less than 10% of the potentially eligible cohort of TST-positive women completed LTBI treatment. The 3 important points of attrition were nonreferral for treatment evaluation (31%), failure to keep the referral appointment (18%), and nonadherence with treatment (35%). Our study was not designed to explain why appropriate linkages and follow-through did not occur. Nonetheless, we observed some patterns. Women previously diagnosed TST-positive were less likely to be referred for LTBI treatment evaluation and, if referred, less likely to

456 intervention. Nonetheless, our ndings of low LTBI treatment completion rates are consistent across the 5 clinics surveyed and with other reports of the limited acceptance of LTBI treatment.4,9 In NYC, considerable eort has been made to extend TB prevention programs into the nonUS-born community.4 The prenatal setting is potentially another avenue for reaching this large population, estimated at 9000 births annually to recent immigrants from TB-endemic countries.21 Our data suggest 2 areas in which TB prevention services to this high-risk population can be improved. First, strong linkages between the prenatal care setting and postpartum treatment must be built. Referral of TST-positive patients for clinical evaluation, not just a chest x-ray to exclude active TB, must be part of the clinic protocol, and patients must be followed to ensure that appointments are kept. Second, providers who prescribe LTBI treatment must take steps to ensure treatment completion. Although directly observed therapy has been highly successful in improving treatment completion for persons with active TB, because of limited resources, directly observed preventive therapy for persons receiving LTBI treatment is not oered routinely.19,22 One successful model for improving adherence to LTBI treatment among new immigrants is cultural case management.23 Completion rates of over 70% have been achieved by employing case managers as cultural mediators to serve patient-dened needs and monitor adherence to LTBI treatment. Bilingual and bicultural outreach sta work with immigrant communities and individuals to counter opposition to LTBI treatment based on cultural misunderstandings about its purpose and fears of stigmatization. The approach also puts the clients own health and social service priorities, often related to their new immigrant status, equal to the priorities of LTBI treatment. Interventions such as this have the potential to translate the identication of large numbers of nonUSborn women at high risk of TB into reduced TB case rates.

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Acknowledgments
We would like to thank Michelle Macaraig, MPH, and Shavvy Raj-Singh, MPH, for chart abstraction, and Anita LaSala, MD, Merle Cunningham, MD, Martina Frandina, MD, Miriam Cremer, MD, and Maria Uribellarea for facilitating the research at their institutions.

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