Elsevier

Cancer Epidemiology

Volume 36, Issue 6, December 2012, Pages e359-e365
Cancer Epidemiology

Birth weight and other perinatal characteristics and childhood leukemia in California

https://doi.org/10.1016/j.canep.2012.08.002Get rights and content

Abstract

Aims. We conducted a large registry-based study in California to investigate the association of perinatal factors and childhood leukemia with analysis of two major subtypes, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). Methods. We linked California cancer and birth registries to obtain information on 5788 cases and 5788 controls matched on age and sex (1:1). We examined the association of birth weight, gestational age, birth and pregnancy order, parental ages, and specific conditions during pregnancy and risk of total leukemia, ALL and AML using conditional logistic regression, with adjustment for potential confounders. Results. The odds ratio (OR) per 1000 g increase in birth weight was 1.11 for both total leukemia and ALL. The OR were highest for babies weighing ≥4500 g with reference <2500 g: 1.59 (95% CI: 1.05–2.40) and 1.70 (95% CI: 1.08–2.68) for total leukemia and ALL, respectively. For AML, increase in risk was also observed but the estimate was imprecise due to small numbers. Compared to average-for-gestational age (AGA), large-for-gestational age (LGA) babies were at slightly increased risk of total childhood leukemia (OR = 1.10) and both ALL and AML (OR = 1.07 and OR = 1.13, respectively) but estimates were imprecise. Being small-for-gestational age (SGA) was associated with reduced risk of childhood leukemia (OR = 0.81, 95% CI: 0.67–0.97) and ALL (OR = 0.77, 95% CI: 0.63–0.94), but not AML. Being first-born was associated with decreased risk of AML only (OR = 0.70; 95% CI: 0.53–0.93). Compared to children with paternal age <25 years, children with paternal age between 35 and 45 years were at increased risk of total childhood leukemia (OR = 1.12; 95% CI: 1.04–1.40) and ALL (OR = 1.23; 95% CI: 1.04–1.47). None of conditions during pregnancy examined or maternal age were associated with increased risk of childhood leukemia or its subtypes. Conclusions. Our results suggest that high birth weight and LGA were associated with increased risk and SGA with decreased risk of total childhood leukemia and ALL, being first-born was associated with decreased risk of AML, and advanced paternal age was associated with increased risk of ALL. These findings suggest that associations of childhood leukemia and perinatal factors depend highly on subtype of leukemia.

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.

Section snippets

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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