Fetal growth and childhood acute lymphoblastic leukemia: Findings from the childhood leukemia international consortium

Abstract

Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors.

Radiation exposure from computerized tomography and risk of childhood leukemia: Finnish register-based case-control study of childhood leukemia (FRECCLE)

“…7,8 Furthermore, there is reasonably consistent evidence of a slightly increased risk associated with large birth weight relative to gestational time. 9 A higher risk has also been suggested for older parental age, delivery by Cesarean section, and paternal smoking. 10–13 However, daycare attendance, allergic diseases, maternal folic acid supplementation before birth, and early immune stimulation have been suggested to reduce the risk of leukemia.…”

Global characteristics of childhood acute promyelocytic leukemia

“…In utero exposure to ionizing radiation [43], 3 rd trimester air toxics exposures to chloroform, benzene, and two other traffic-related chemicals (meta/para-xylene and toluene) [45], and parental smoking [44], as well as childhood exposure to petroleum solvents [42] are potentially assosicated with development of childhood AML. Increased risk of childhood ALL has been associated with accelerated fetal growth [266], home exposure to herbicides (chlorthal, and possibly alachlor) [267] and paint [42], paternal ever smoking, particularly preconception [268]. Elevated ALL risks associated with use of paints in the home (ever) and indoor insecticides (pre-birth) were found to be limited to subjects carrying specific haplotypes of CYP2C8 and ABCB1 , respectively [269].…”

Genetic and Nongenetic Risk Factors for Childhood Cancer

“…Risk of ALL(36), central nervous system tumors(37), neuroblastoma(38), and Wilm's tumor(39), among others, rises as a linear function of birth weight, to varying degrees, and recent analyses that have used alternate measures of birth size (e.g. size for gestational age, percent of optimal birth weight) have found similar results (40). Risk of acute myeloid leukemia is elevated with both low and high birth weight(41), while risk of hepatoblastoma is inversely related to birth weight and strikingly elevated among the smallest infants (42).…”