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 pre-existing factors prior to 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.

RESULTS: Among 1,068 participants, 96 TB cases occurred (1,228 cases per 100,000 person-years, 95%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, -0.11), weight-for-age (-0.30; 95%CI, -0.59, -0.01), and BMI z-scores (-0.54; 95%CI, -0.83, -0.25) at 5 years. Children developing TB were consistently more likely to wheeze regardless of the timing of TB. Children diagnosed with TB between 0-1 year old had reduced tPTEF/tE (-2.35%; 95% CI, -4.86, -0.17) and higher fractional exhaled nitric oxide (2.88ppb; 95% CI, 0.57-5.19) at 5 years. Children diagnosed with TB between 1-4 years old had impaired tidal volume (-9.32 mL; 95% CI, -14.89, -3.75) and tPTEF/tE (-2.35%; 95%CI, -4.86, -0.17]) at 5 years.

CONCLUSIONS: Prevention of TB disease in the first few years of life may have substantial long-term benefits through childhood. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).