Background: A growing body of evidence suggests that a number of perinatal factors may increase the risk of acute lymphocytic leukemia (ALL), the most common childhood cancer. Objective: To better understand perinatal factors associated with ALL with particular attention to oxygen supplementation, phototherapy, and fetal growth ratio (FGR). Materials and Methods: In Phase I of this research, all children (n =1,021) with histologically-confirmed ALL diagnosed in Michigan between 1985 and 2003 were ascertained in the population-based Michigan Cancer Registry. Their records were linked by the Michigan Department of Community Health (MDCH) to their birth certificates. The MDCH randomly selected, from birth certificate files, two surviving (to age one year) children as controls for each case, matched on hospital of birth, gestational age (GA +/- two weeks), sex, month and year of birth. In Phase II, maternal and newborn records of a subset of cases (n=231) and matched controls (n=377) born in 12 large hospitals in Michigan were reviewed. Odds ratio (OR) and 95% confidence interval (CI) were estimated using conditional logistic regression. Results: In Phase I, 867 ALL cases were successfully matched with 1,416 controls. Mean birth weight (BW) was 3,459 g for cases and 3,399 g for controls (mean difference = 60 g). Significant ORs were obtained for white maternal race (2.4, CI 1.7-3.5; black as reference), white paternal race (2.5, CI 1.6-4.1), maternal age > 18 y (1.6, CI 1.0-2.4), and BW of ≥ 4,000 g (1.47, CI 1.06-2.03). Compared to infants with slow fetal growth (FGR below the 25th percentile), infants with rapid fetal growth (FGR > 75th percentile) had the odds of 1.52 (CI 1.1- 2.1) for developing ALL [OR 1.48 (CI 1.16-1.91) after adjusting for maternal race]. A significant excess risk (OR 2.58, CI 1.11-5.99) was found in high BW babies whose mothers smoked during pregnancy. Based on the data from Phase II, neonatal exposure to X-ray carried an OR of 1.73 (CI 0.99-3.04). Jaundice observed in the first 24 hours after birth was associated with an OR of 1.92 (CI 0.97-3.79). No excess risk of ALL with oxygen exposure in the delivery room was found (OR 0.8, CI 0.56-1.15). However, the OR for oxygen exposure post delivery room was 1.61 (CI 0.93-2.77). After adjustment for potential confounders (maternal age and race, X-ray exposure, early neonatal jaundice, and Apgar score at 5 minutes), this latter OR was reduced to 1.16 (CI 0.46-2.91). Maternal exposure to oxygen in labor was not associated with ALL. An OR of 0.88 (CI 0.44-1.74) was found for infant phototherapy and ALL. Conclusions: We did not confirm study hypotheses relating either oxygen exposure or phototherapy to ALL. We did confirm the finding that black children in the US are at lower risk of ALL than white children. We also extend the consistent finding of higher BW in ALL, adding the insight that this association is specific to fetal growth in the highest quartile. A condition often associated with oxygen exposure, X-ray exposure, which in these data was mainly chest X-rays for respiratory disease, was associated with a borderline significant 73% excess of ALL. While we expected that phototherapy might be associated with ALL, its treatment target, hyperbilirubinemia, was nearly significantly positively associated with ALL. Two unpredicted associations with ALL were a reduction of risk in mothers < 18 y, and an interaction of smoking and high fetal growth.
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