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Prenatal and neonatal risk factors for childhood lymphatic leukemia
S Cnattingius1, M M Zack, A Ekbom
1Department of Social Medicine, University Hospital, Uppsala University, Sweden.
Insights
Maternal and perinatal factors like Down's syndrome and renal disease are linked to childhood lymphatic leukemia, but most causes remain unknown, especially in very young children.
Area of Science:
- Pediatric Oncology
- Epidemiology
- Genetics
Background:
- Childhood acute lymphatic leukemia incidence peaks between ages 2-4, suggesting prenatal/neonatal risk factors.
- Previous studies on perinatal risk factors yielded contradictory results due to limited scope.
- A nationwide study is needed to comprehensively investigate these factors.
Purpose of the Study:
- To identify maternal and perinatal risk factors for childhood lymphatic leukemia.
- To conduct a nationwide case-control study in Sweden.
- To analyze associations between various pregnancy and birth factors and leukemia risk.
Main Methods:
- A nationwide case-control study nested within Swedish birth cohorts (1973-1989).
- Utilized the Medical Birth Register for maternal and neonatal data.
- Matched 613 leukemia cases with 5 controls each using conditional logistic regression.
Main Results:
- Increased risk associated with Down's syndrome, maternal renal disease, supplementary oxygen, postpartum asphyxia, high birth weight (>4500g), and hypertensive pregnancy disease.
- Down's syndrome primarily affected younger children (<5 years), while other factors impacted older children (≥5 years).
- Multiple births increased risk in older children.
Conclusions:
- Identified several maternal and perinatal risk factors for childhood lymphatic leukemia with age-specific effects.
- These identified factors account for a small proportion of total cases.
- The majority of risk factors for childhood lymphatic leukemia, particularly in very young children, remain unidentified.
Background:
Because the incidence of childhood acute lymphatic leukemia peaks between 2 and 4 years of age, the risk factors may exert their influence during the prenatal and/or the neonatal periods. Results of previous studies of perinatal risk factors have been contradictory, perhaps because most studies either have been hospital based or have been restricted to limited geographical areas.
Purpose:
A nationwide case-control study was carried out to identify maternal and perinatal risk factors for this disease.
Methods:
The case-control study was nested in cohorts defined by all live births in Sweden recorded in the nationwide Medical Birth Register. Since 1973, this register has routinely collected information on all hospital births in regard to maternal demographic data, reproductive history, pregnancy, delivery, and the neonatal period. From the Swedish National Cancer Register, 613 case subjects were identified in successive birth cohorts from 1973 through 1989. Five control subjects per case subject were randomly selected from the pool of children matched by sex and month and year of birth. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for potential risk factors and to estimate their effects after adjustment for possible confounders.
Results:
Risk of childhood lymphatic leukemia at all ages increased with Down's syndrome (OR = 20.0; 95% CI = 4.2-94.2), maternal renal disease (OR = 4.4; 95% CI = 1.6-12.1), use of supplementary oxygen (OR = 2.3; 95% CI = 1.5-3.6), postpartum asphyxia (OR = 1.8; 95% CI = 1.2-2.6), birth weight of more than 4500 g (OR = 1.7; 95% CI = 1.1-2.7), and hypertensive disease during pregnancy (OR = 1.4; 95% CI = 1.0-1.9). Down's syndrome affected risk mostly in children younger than 5 years, whereas other factors affected those children 5 years old or older. Being one of a multiple birth also increased risk among older children (OR = 2.5; 95% CI = 1.0-6.0). Use of supplementary oxygen may act as a causal intermediate (surrogate) for postpartum asphyxia and its causes, as would high birth weight for its causes.
Conclusions:
Several maternal and perinatal risk factors were found to be associated with childhood lymphatic leukemia, but they showed age-specific differences. Overall, only a few risk factors were identified, and these accounted for a small proportion of cases. We concluded that most risk factors for childhood lymphatic leukemia remain unidentified in very young children.