Exposure to isoniazid prevention therapy during the first trimester of pregnancy is associated with increased risk for fetal demise, according to study results published in Clinical Infectious Diseases.
Isoniazid prevention therapy is a key global strategy to reduce the risk for tuberculosis (TB) infection and TB-associated mortality in individuals with HIV infection. The World Health Organization (WHO) recommends isoniazid for TB prevention for all HIV-infected individuals, including during pregnancy.
Researchers conducted a prespecified secondary analysis of a multicountry, randomized trial (ClinicalTrials.gov Identifier: NCT01404312) in which standard isoniazid (300 mg daily for 36 weeks) was compared against isoniazid plus rifapentine in patients with HIV infection residing in TB-endemic areas. In this study, the researchers evaluated adverse pregnancy outcomes among women who had been randomly assigned to the standard treatment group and became pregnant during or after exposure to isoniazid.
Poisson regression models were used to evaluate the association between isoniazid exposure and adverse pregnancy outcomes, with adjustments for latent TB infection, maternal age, CD4+ count, and antiretroviral therapy (ART) use. Adverse pregnancy outcomes were evaluated in both mothers and infants and were defined as any event that resulted in nonlive birth, excluding induced abortion.
A total of 39 women were exposed and 89 were not exposed to isoniazid during the first trimester of pregnancy, of whom the median ages at the time of conception were 30.0 (IQR, 26.4-36.3) and 31.8 (IQR, 27.2-36.0) years, and the median CD4 counts were 527 (IQR, 432-735) and 538 (IQR, 432-678) cells/µL, respectively.
The analysis included only singleton pregnancies, and more women in the exposed cohort reported ART use at the time of conception (79% vs 96%; P =.007).
Overall, 35 (27%) pregnancies ended in nonlive birth outcomes, including 25 spontaneous abortions, 6 induced abortions, 2 stillbirths, and 2 ectopic pregnancies. Among women who were exposed to isoniazid, 49% completed treatment during pregnancy and 23% discontinued treatment early. Data captured from 19 live births indicated that the median duration of exposure during pregnancy 14.7 (IQR, 7.3-24.3) weeks.
Further analysis of individual live birth outcomes showed similar rates of preterm birth (20% vs 23%) and low birth weight (14% vs 13%) between exposed vs unexposed patients.
The occurrence of any adverse pregnancy outcome other than induced abortion was noted in 33% of isoniazid-exposed pregnancies and 18% of unexposed pregnancies. Antenatal receipt of isoniazid was significantly associated with adverse pregnancy outcomes, both in unadjusted (relative risk [RR], 1.85; 95% CI, 0.99-3.47; P =.05) and adjusted (aRR, 1.90; 95% CI, 1.01-3.54; P =.04) analyses.
However, the relationship between isoniazid and adverse pregnancy outcomes was attenuated in a separate analysis, primarily by increased ART use between baseline and outcome occurrence (aRR, 1.45; 95% CI, 0.75-2.89; P =.027).
Similar associations between isoniazid exposure and adverse pregnancy outcomes were found regardless of whether outcomes of induced abortions were included (RR, 1.94; 95% CI, 1.04-3.61; P =.04) or excluded (RR, 1.92; 95% CI, 1.11-3.33; P =.02) from the analysis.
Study limitations include the small sample size, the possibility of missed pregnancy losses, and the inability to assess the duration of isoniazid exposure for all pregnancies.
According to the researchers, “Efforts to scale up short course TB preventive therapy, where incident pregnancies are unlikely to occur, should be prioritized.”
Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Gupta A, Hughes MD, Cruz JL, et al. Adverse pregnancy outcomes among HIV-infected women taking isoniazid preventive therapy during the first trimester. Clin Infect Dis. Published online September 28, 2023. doi:10.1093/cid/ciad583
Source: Infectious Disease Advisor