History of maternal fetal loss and increased risk of childhood acute leukemia at an early age. A report from the childrens cancer group

Abstract

Background. Maternal reproductive history of fetal loss previously has been reported to be associated with an increased risk of leukemia in subsequent offspring. Data from a Childrens Cancer Group (CCG) case‐control study were analyzed to test the hypothesis that this association was dependent on the number of previous fetal losses age at leukemia diagnosis. Methods. A case‐control study using a large Childrens Cancer Group database examined maternal history of fetal loss as a risk factor for childhood leukemia in subsequent offspring. One thousand seven hundred fifty‐three patients with childhood acute leukemia were compared with 839 community control subjects s and 2081 nonleukemia cancer control subjects. Results. A modest increase in risk was found to be associated with a history of fetal loss. Stratification by age at diagnosis of leukemia showed that this association was significant only for those patients diagnosed before 4 years of age and most significant in those patients diagnosed before 2 years of age. When comparing community controls with patients acute lymphocytic leukemia diagnosed before 2 years of age, one previous fetal loss was associated with a five‐fold increased risk (P < 0.001) whereas two or more fetal losses were associated with a relative risk of 24.8 (P < 0.001). Similarly, patients with acute myelocytic leukemia diagnosed before 2 years of age demonstrated 5‐fold and 12‐fold increased risks associated with the previous fetal loss and 2 or more previous fetal losses, respectively. Conclusions. Childhood acute leukemia occurring at younger ages may be associated with an underlying genetic abnormality or chronic environmental exposure, which can be either lethal to the developing fetus or mutagenic and result in the development of acute leukemia.

Maternal Factors and Risk of Childhood Leukemia

“…A history of fetal loss may reflect genetic predisposition, abnormal intrauterine environment, or the effect of a common environmental exposure (Ross et al, 1997). While some studies similar to this study did not show any significant associations (Kaye et al, 1991;OU et al, 2002) others suggest it as a possible risk factor (Yeazel et al, 1995;Podvin et al, 2006;Specter et al, 2007). These controversies may be explained as follows: First, the characteristics of leukemia cases in different studies varied.…”

Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome

“…It has been reported in a few studies that prior fetal loss significantly increased the risk of acute leukemia, 12,25 whereas most others reported no difference in risk. [15][16][17][20][21][22][23][24] One study demonstrated an inverse association.…”

“…Previous studies in children without DS have indicated no or little elevation in risk for advanced maternal age, [10][11][12][13][14][15][16][17][18][19] prior fetal loss, 12,[14][15][16][17][20][21][22][23][24][25] prior contraceptive use, 15,[26][27][28] time between births, 16,22 and birth order. 12,[14][15][16]20,21,[29][30][31] However, those factors may have a greater impact on the development of leukemia in children with DS, because trisomy 21 may represent a first genetic ''hit,'' and stronger associations may be expected than those reported in studies of children without DS.…”

Acute leukemia in early childhood

“…Since insulin-like growth factor-1 is important in blood formation and regulation and has been shown to stimulate the growth of both myeloid and lymphoid cells in culture, it was postulated that high levels of insulin-like growth factor-1 might produce large babies and contribute to the development of leukemia (46). A maternal history of fetal loss has also been associated with a five-to 12-fold increased risk of developing ALL or AML (47). However, Ross et al (48) later showed that the relationships between birth weight, prior fetal loss, and risk of infant leukemia appear to be complex, and that only highbirth weight was in fact a significant risk factor of developing childhood leukemia.…”