Birth weight and risk for childhood leukemia in Denmark, Sweden, Norway, and Iceland.
BACKGROUND
Compelling evidence suggests that childhood leukemia often originates in utero. Birth weight is one of the few pregnancy-related risk factors that has been associated with leukemia risk, but the association has remained poorly characterized. We conducted a population-based case-control study in Denmark, Sweden, Norway, and Iceland to investigate the association between birth weight (and other birth characteristics) and the risk of childhood leukemia.


METHODS
Overall, 1905 children (aged 0-14 years) with acute lymphoblastic leukemia (ALL) and 299 children with acute myeloid leukemia (AML) diagnosed between January 1, 1984, and December 31, 1999, were identified in the Nordic Society of Paediatric Haematology and Oncology acute leukemia database. Each case patient was matched to five population control subjects (n = 10745) on nationality, age, and sex. All live-born siblings of case patients (n = 3812) and control subjects (n = 17,937) were also identified in population registers. Information on birth weight and gestational age at birth was ascertained from the national Medical Birth Registers. The association between various birth characteristics and leukemia risk was assessed by conditional logistic regression. All statistical tests were two-sided.


RESULTS
Risk of ALL overall was statistically significantly associated with birth weight (odds ratio [OR] = 1.26 per 1-kg increase in birth weight, 95% confidence interval [CI] = 1.13 to 1.41). The association was similar for B- and T-lineage ALL and across all diagnostic ages (0-14 years). However, children with ALL did not weigh more at birth than their siblings. Statistically significantly reduced risks of B-precursor ALL were observed with increasing position in the birth order (OR = 0.90 per position increase, 95% CI = 0.84 to 0.96) and increasing gestational age (OR = 0.87 per 2-week increase in gestational age, 95% CI = 0.81 to 0.94). Risk of AML did not vary monotonically with birth weight, and low birth weight (<1500 g [i.e., 3.3 pounds]) was associated with the highest risk.


CONCLUSIONS
Our results are compatible with the hypothesis that a high birth weight is associated with an increased risk of ALL.
Hjalgrim
Lisa Lyngsie
LL
Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. lih@ssi.dk
Rostgaard
Klaus
K
Hjalgrim
Henrik
H
Westergaard
Tine
T
Thomassen
Harald
H
Forestier
Erik
E
Gustafsson
Göran
G
Kristinsson
Jon
J
Melbye
Mads
M
Schmiegelow
Kjeld
K
D000293:Adolescent; D001722:Birth Order; D001724:Birth Weight; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D005865:Gestational Age; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007223:Infant; D007231:Infant, Newborn; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000209:etiology; D009664:Norway / Q000453:epidemiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology* / Q000209:etiology; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology