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

Abstract

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. 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. 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. 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. 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/).