Related Experiment Videos
Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study
T Westergaard1, P K Andersen, J B Pedersen
1Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark.
Insights
Higher birth weight and having siblings are linked to increased childhood leukemia risk. Birth order may influence acute lymphoblastic leukemia (ALL) risk in young children, suggesting potential environmental factors.
Area of Science:
- Pediatric Oncology
- Epidemiology
- Environmental Health
Background:
- Childhood leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), may be influenced by prenatal factors and infant infection patterns.
- Investigating birth characteristics and sibling patterns can offer insights into leukemia etiology.
Purpose of the Study:
- To examine the impact of sibling patterns (birth order) and birth characteristics (birth weight) on the risk of childhood ALL and AML.
- To explore potential associations between these factors and leukemia development.
Main Methods:
- A population-based cohort of approximately 2.0 million children born in Denmark (1935-1978) was established through record linkage.
- Children diagnosed with ALL or AML (1968-1992) were identified, with birth weights obtained for a subset (1973-1992).
Main Results:
- Increased birth weight was significantly associated with higher risks of both ALL (RR=1.46 per kg) and AML (RR=2.14 per kg).
- Children born second or later had an increased risk of AML (RR=1.53).
- Having siblings was associated with a higher risk of AML in 2-3 year olds.
Conclusions:
- The strong association between birth weight and childhood leukemia highlights the importance of intrauterine factors, possibly related to cell proliferation.
- The findings suggest that birth order and sibship size may play a role in childhood AML risk, warranting further investigation into environmental influences.
Background:
The occurrence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) during childhood may be influenced by factors operating in fetal life. Furthermore, childhood ALL has been suggested to be linked to patterns of infection during infancy.
Purpose:
To explore these hypotheses and other associations, we studied the impact of sibling patterns (e.g., birth order) and birth characteristics (e.g., birth weight) on the risk of childhood ALL and AML.
Methods:
By linkage of records of population-based registries, a cohort of all children whose mothers were born in Denmark from April 1935 through March 1978 was established. Children who developed ALL or AML during the period from April 1968 through December 1992 were identified by linkage with the Danish Cancer Registry. Birth weights were obtained for children born during the period from January 1973 through December 1992 by linkage with the Medical Birth Registry.
Results:
The cohort of approximately 2.0 million children was followed for the diagnosis of ALL or AML for 20.9 million person-years. A total of 704 cases of childhood ALL were identified. Among 0-4 year olds, the relative risks (RRs) of ALL for birth order positions 1, 2, 3, and 4+ were 1.00 (reference), 0.85 (95% confidence interval [CI] = 0.68-1.07), 0.91 (95% CI = 0.66-1.25), and 0.57 (95% CI = 0.30-1.06), respectively (P for trend = .09). A decreasing trend was not observed among 5-14 year olds. A significant log-linear association between birth weight and the risk of ALL was observed for both age groups. Overall, the RR of ALL increased by a factor of 1.46 (95% CI = 1.18-1.81) (P = .0005) for each kilogram of increase in birth weight. A total of 114 cases of childhood AML were identified. Children born second or later in the birth order had an increased risk of AML (RR = 1.53; 95% CI = 1.01-2.32) compared with firstborns. A particularly high risk of AML at ages 2 (RR = 2.53; 95% CI = 1.46-4.40) and 3 years was associated with having siblings compared with being an only child at those ages. Similar to the findings for ALL risk, there was a significant association between birth weight and AML risk. The relative increase in AML risk per 1-kg increase in birth weight was 2.14 (95% CI = 1.19-3.85; P = .009).
Conclusion And Implications:
The association between birth weight and childhood leukemia suggests the importance of intrauterine factors. A plausible explanation may be that increasing birth weight is associated with a higher rate of cell proliferation and/or a larger number of precursor cells being at risk of malignant transformation. The inverse association between birth order and ALL risk among 0-4 year olds was weak, but it was compatible with the hypothesis that delayed exposure to infection may increase the risk of ALL in this age group. The association of childhood AML with birth order and sibship size at young ages deserves further attention in the search for environmental factors that affect childhood AML risk.