The Long-Term Impact of Early-Life Tuberculosis Disease on Child Health: A Prospective Birth Cohort Study

RATIONALE: There is growing concern that post–tuberculosis disease (TB) sequelae and morbidity are substantial, but no studies have controlled for preexisting factors before disease. Whether children have post-TB morbidity is not well characterized. OBJECTIVES: To assess the effect of a TB diagnosis on wheezing episodes, lung function, and anthropometric measurements among children enrolled in a prospective birth cohort study in South Africa. METHODS: We prospectively followed children from birth through 5 years for TB using diagnostic tests including chest radiography and repeated induced sputum sample testing with Xpert MTB/RIF and liquid culture. We longitudinally measured health outcomes including growth, wheezing, and lung function up to 5 years. Mixed-effects linear regression models were used to assess growth and lung function after TB. Poisson regression was used to assess risk of subsequent wheezing. MEASUREMENTS AND MAIN RESULTS: Among 1,068 participants, 96 TB cases occurred (1,228 cases per 100,000 person-years [95% confidence interval (CI), 1,006–1,500]) occurred over 7,815 child-years of follow-up. TB was associated with lower length-for-age (−0.40 [95% CI, −0.68 to −0.11]), weight-for-age (−0.30 [95% CI, −0.59 to −0.01]), and body mass index (−0.54 [95% CI, −0.83 to −0.25]) z-scores at 5 years. Children developing TB were consistently more likely to wheeze regardless of the timing of TB. Children with diagnoses of TB between 0 and 1 year of age had reduced time to peak tidal expiratory flow over total expiratory time (−2.35% [95% CI, −4.86% to −0.17%]) and higher fractional exhaled nitric oxide (2.88 ppb [95% CI, 0.57–5.19 ppb]) at 5 years. Children with diagnoses of TB between 1 and 4 years of age had impaired Vt (−9.32 ml [95% CI, −14.89 to −3.75 ml]) and time to peak tidal expiratory flow over total expiratory time (−2.73% [95% CI, −5.45% to −0.01%]) at 5 years. CONCLUSIONS: Prevention of TB disease in the first few years of life may have substantial long-term benefits through childhood.