Birth weight and other perinatal characteristics and childhood leukemia in California
Introduction
Childhood leukemia is the most common malignant disease in children worldwide and in the United States [1]. The incidence of childhood leukemia in California is 5.2 and 4.3 per 100,000 for males and females, respectively. Incidence is highest among the youngest age group (0–4 years), with 8.2 and 6.8 cases per 100,000 for males and females, respectively, then incidence declines with age until late adolescence [2].
The etiology of childhood leukemia remains largely unknown. Several perinatal characteristics have been linked to childhood leukemia but the relation of others to leukemia and particularly to its subtypes remains to be elucidated. Birth weight is one of a few perinatal factors that has been consistently reported to be related to childhood leukemia risk [3], with over 30 studies examining the association. Most reported positive association between birth weight and ALL; less consistent associations have been reported for AML [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. Few studies have taken into account gestational age in the analysis of birth weight. Of those that did, most showed that large-for-gestational age babies were at increased risk of childhood leukemia [12], [15].
Birth order is another perinatal factor that has been examined with regard to childhood leukemia risk. Most studies have found that high birth order was associated with decreased risk of ALL compared with first-born babies (OR varied from 0.57 to 0.95) [10], [16]. A few studies reported increased risk of ALL with increasing birth [3], [13]. For AML, studies have detected either positive association or no association with birth order [3], [10], [11], [12], [16], [17].
The majority of studies that looked at the relationships of maternal and paternal age to childhood leukemia detected an increased risk for older paternal age [5], [13], [17], [18], [19]. Some of these also reported an increased risk for older maternal age [18], [19].
Conflicting results have been reported for the association between childhood leukemia and several perinatal and reproductive factors such as history of fetal loss, preeclampsia, polyhydramnios, anemia and genital herpes [7]. The majority of studies found no association but a few reported positive associations [11], [20].
In a large case-control study linking data from the California Cancer Registry (1988–2008) and Birth Registry (1986–2007), we examined the association of childhood leukemia with perinatal factors, including birth weight, birth order and history of pregnancy terminations; maternal and paternal age as well as the difference between them; and complications during pregnancy. The large size of the sample allowed for detailed analysis by two major subtypes of leukemia, ALL and AML, which was not possible in most previous studies.
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Materials and methods
The California Cancer Registry (CCR), a population-based statewide cancer registry, was used to obtain information on all childhood leukemia cases diagnosed between 1988 and 2008 in children younger than 16 years who were born in California and resided in California at the time of diagnosis. The CCR is recognized as one of the leading cancer registries in the world with almost complete registration (99%). It routinely records age, race/ethnicity, sex, and residence at the time of diagnosis as
Results
A total of 6645 childhood leukemia cases were identified from the California cancer registry. Linkage to birth records was successful for 87.1% (5788/6645) of cases. Of the 5788 cases (55.8% males and 44.2% females) included in this analysis, 4721 were ALL cases (56.2% males and 43.8% females), 852 were AML cases (53.3% males and 46.7% females), and 215 were other childhood leukemia types. The mean age at diagnosis was 4.9 years with a range of 0–15.6 years. Table 1 shows additional
Discussion
Consistent with other studies, we observed an increased risk of childhood leukemia for high birth weight babies. We observed an 11% increase in risk of total childhood leukemia and acute lymphocytic leukemia per 1-kg increase in birth weight. For acute myeloid leukemia, no such risk increase was observed. In analyses with birth weight as a categorical variable with a reference category <2500 g, increased risk was present for all babies above 2500 g. The highest increase in risk for all types of
Conflict of interest
The authors declare that there is no conflict of interest.
Acknowledgements
This project was supported by a research contract from the Electric Power Research Institute (EPRI) to the UCLA and by UCLA Faculty Grants Program. Crespi was also partially supported by National Institutes of Health grant P30 CA16042.
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