Birth weight and other risk factors for acute leukemia in the Jerusalem Perinatal Study cohort

Objectives: To assess the effect of birth weight of children and their siblings and other perinatal/parental factors on the risk of acute leukemia. Methods: We linked data from the Jerusalem Perinatal Study, a population-based research cohort (n = 88,829) of offspring born 1964 to 1976, with Israel's Cancer Registry. Risk factors for acute leukemia were assessed using univariate and multivariate proportional hazards models. Results: Leukemias developed in 65 individuals [24 acute myeloid leukemias (AML) and 41 acute lymphoblastic leukemias (ALL)]. A positive linear relation was found between gender-adjusted birth weight and all leukemias [hazard ratio (HR) 1.85, 95% confidence interval (95% CI) 1.1-3.0] and AML (HR 2.9, 95% CI 1.3-6.4). The association between birth weight and AML was especially notable among infants (HR 8.14, 95% CI 1.8-38.9 for age 0 to 1 year) but was also observed among subjects ages >14 years at diagnosis. The relation was particularly strong among females (P = 0.001). Other risk factors for AML risk on univariate analysis were maternal origin, socioeconomic status, birth weight of sibling > 3,500 g, and family size. On multivariate analysis, only birth weight retained borderline significance (adjusted HR 2.38 per kg, 95% CI 1.0-5.7). Significant predictors for ALL in both univariate and multivariate analyses were male sex (adjusted HR 1.92, 95% CI 1.0-3.7) and birth weight categories ≥ 3,000 g introduced into the model as nonlinear terms. Conclusion: Birth weight is associated with an increased risk of acute leukemia in infants, children, and young adults. Perinatal factors play a role in the development of childhood leukemias, but the patterns of association vary by leukemia type.