Understanding the causes of childhood leukemia—the most common cancer among children—remains a global research priority. Studies have identified abnormal chromosomes—extra, missing, or structurally rearranged—in cells at birth in most childhood leukemia cases, suggesting an initiation in utero. A second, postnatal mutation then triggers full-blown leukemia, likely because of a weakened immune system; it has been postulated that delayed exposure to infections could disrupt the development of the child’s immune system and increase leukemia risk.
Multiple hypotheses are being examined to explain this initiation in utero, including exposure to infection during pregnancy from the mother herself. To explore this link, CLIC’s researchers conducted a large meta-analysis of case-control studies collected in 17 centers across 11 countries (North Africa, North and South America, Europe, and Southwest Oceania). The study analyzed a total of 13,638 leukemia cases and 26,870 controls. Maternal infections during pregnancy, such as respiratory, urinary tract, genital, and viral infections, were examined. Data were obtained from maternal interviews or medical registries, with some studies reporting the trimester of infection.
Overall, the findings indicated a slightly increased risk among children whose mothers reported infections during pregnancy. Patterns suggested potential differences by infection type, timing, and frequency, with the largest effect size observed for exposure during the first trimester for example. Furthermore, White children generally had higher risks of childhood leukemia than Hispanic/Latino children, notably before the age of 2 years, yet differences were not conclusive. While these associations were modest, they align with previous reports indicating that maternal infections could, directly or indirectly, subtly alter fetal immune system maturation, setting the stage for leukemia during childhood. The mechanism may be due to actions of the infectious agent on fetal development and/or shared immune characteristics, increasing the risks for both infection and cancer.
CLIC’s global collaboration demonstrates the power of combining data from multiple regions to address complex questions about childhood cancer. Although maternal infections are common and most do not result in leukemia, these findings contribute valuable insight into how prenatal health may influence cancer risk later in life. CLIC scientists aim to deepen our understanding of preventable factors that could reduce the burden of childhood leukemia worldwide.
Citation:
Article Title: Maternal prenatal infection and childhood leukaemia: a Childhood Cancer and Leukemia International Consortium (CLIC) meta-analysis
Authors: Piedvache A, Rashed WM, Petridou ET, Mueller BA, Bonaventure A, Clavel J, et al.
Published In: Int J Epidemiol. 2025 Oct 1;54(5):dyaf167. https://doi.org/10.1093/ije/dyaf167