Birth Weight and Risk for Childhood Leukemia in Denmark, Sweden, Norway, and Iceland

Authors: Lisa Lyngsie Hjalgrim1; Klaus Rostgaard2; Henrik Hjalgrim2; Tine Westergaard2; Harald Thomassen2; Erik Forestier2; Göran Gustafsson1; Jon Kristinsson2; Mads Melbye2; Kjeld Schmiegelow1

Source: Journal of the National Cancer Institute, Volume 96, Number 20, 20 October 2004 , pp. 1549-1556(8)

Publisher: Oxford University Press

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Abstract:

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. Conclusion: Our results are compatible with the hypothesis that a high birth weight is associated with an increased risk of ALL.

Document Type: Research article

DOI: 10.1093/jnci/djh287

Affiliations: 1: Affiliations of authors: Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark (LLH, KR, HH, TW, MM); Department of Pediatrics, Haukeland University Hospital, Bergen, Norway (HT); Department of Clinical Science, Pediatrics, University of Umeaa, Umeaa, Sweden (EF); Astrid Lindgren’s Children’s Hospital, Paediatric Cancer Research Unit, Stockholm, Sweden (GG); Children’s Hospital, University Hospital, Reykjavik, Iceland (JK); Department of Pediatrics, University Hospital, H:S. Rigshospitalet, Copenhagen (KS) 2: Affiliations of authors: Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark (LLH, KR, HH, TW, MM); Department of Pediatrics, Haukeland University Hospital, Bergen, Norway (HT); Department of Clinical Science, Pediatrics, University of Umeaa, Umeaa, Sweden (EF); Astrid Lindgren’s Children’s Hospital, Paediatric Cancer Research Unit, Stockholm, Sweden (GG); Children’s Hospital, University Hospital, Reykjavik, Iceland (JK); Department of Pediatrics, University Hospital, H:S. Rigshospitalet, Copenhagen (KS)

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