Evidence for an effect of fetal growth on the risk of tuberculosis

We examined the risk of tuberculosis in relation to birth weight and ponderal index among 21,596 Swedish twins born from 1926 through 1958. Using a cohort design, tuberculosis risk was 11% lower for every 500 g of birth weight (P = .05) and 8% lower for every 0.2 of ponderal index, calculated as birth weight in grams multiplied by 100 and divided by the cube of birth length in centimeters (P = .08). The association between birth weight and tuberculosis was stronger in male individuals than in female individuals. In co-twin control analyses among disease-discordant monozygotic twins, tuberculosis risk was 46% lower for every 500 g of birth weight (P = .05). The association was stronger in male individuals (87% risk reduction; P = .02) than it was in female individuals (16% reduction; P = .62). A similarly stronger relation with male sex, compared with female sex, was found for ponderal index. Because associations among monozygotic twins are largely independent of shared genetic or environmental factors, we postulate that fetal growth may play a causal role in susceptibility to tuberculosis, possibly through early programming of immunity.