Childhood acute lymphoblastic leukaemia and birthweight: insights from a pooled analysis of case-control data from Germany, the United Kingdom and the United States.

BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and > 4500 g), we pooled data from three of the largest childhood cancer case-control studies ever conducted.
METHODS: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated using the UK study which accessed birth registrations of participants and non-participants. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models.
RESULTS: Children with ALL were, on average, heavier than controls at all gestations, the disparity being driven by a deficit of low-birthweight at all gestations and an excess of high-birthweight at ≥ 40 weeks. Overall, a 1.2 (95% CI 1.1-1.3) increase in ALL risk per kg increase in birthweight was observed; the ORs rising from 0.2 (0.1-0.7) at ≤ 1500 g through to 1.2 (0.9-1.6) at ≥ 4500 g; and 0.8 (0.7-0.9) <10th centile through to 1.3 (1.1-1.4) ≥ 90th centile.
CONCLUSION: Our findings demonstrate the importance of looking across the full birthweight spectrum when examining associations with disease risk. The new observation of a deficit of very-low-birthweight cases at all gestations has aetiological and study design implications for future work examining not only the in utero origins of ALL, but also other childhood and adult cancers.