Vitamin D concentrations in infancy and the risk of tuberculosis in childhood: A prospective birth cohort in Cape Town, South Africa

INTRODUCTION: Low vitamin D may increase the risk of tuberculosis; however, previous observational cohort studies have had variable results. We investigated the relationship between vitamin D levels in infancy and subsequent development of tuberculosis throughout childhood.

METHODS: We enrolled pregnant women between 20-28 weeks' gestation attending antenatal care in a peri-urban South African setting in the Drakenstein Child Health Study. Serum 25(OH)D concentrations were measured in newborn infants between 6-10 weeks of age. Children were followed prospectively for tuberculosis infection and disease using annual tuberculin skin testing, radiographic examinations, and microbiological diagnosis with GeneXpert, culture, and smear testing. Univariable and multivariable Cox regression was performed and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated.

RESULTS: Children were followed for tuberculosis for a median of 7.2 years (IQR, 6.2-7.9). Among 744 children (< 1% living with HIV, 21% HIV-exposed living without HIV), those who were vitamin D deficient in early infancy were not at increased risk of developing tuberculosis (AHR, 0.8; 95% CI, 0.4-1.6). Infants in the lowest vitamin D concentration tertile were at similar risk of tuberculosis compared to the highest tertile (AHR, 0.7; 95% CI, 0.4-1.4). Vitamin D deficiency was associated with tuberculin conversion ≤2 years of age at a <30nmol/l (AOR, 1.9; 95% CI, 1.2-3.2), but not <50nmol/l (AOR, 1.5; 95% CI, 0.8-2.9), cutoff.

CONCLUSION: In a setting with hyperendemic tuberculosis, vitamin D levels in infancy did not predict tuberculosis at any point in childhood. However, very low vitamin D levels were associated with tuberculin conversion in young children.