Oxygen and Phototherapy in perinatal period: Risk of Acute Lymphoctyic Leukemia

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DESCRIPTION (provided by applicant): A growing body of evidence suggests that perinatal factors may increase the risk of acute lymphoblastic leukemia (ALL), the most common hematological malignancy in children. We propose to conduct a matched case-control study to investigate the relationship of ALL to 3 perinatal interventions: maternal O2 therapy, neonatal O2 therapy, and neonatal phototherapy for jaundice. For each of these exposures, a plausible biological rationale supports the hypothesis that they may contribute to the leukemogenic process, and for two of them - neonatal O2 and phototherapy - epidemiologic studies have shown associations with childhood leukemia. Maternal O2 exposures have not yet been studied in relation to ALL. Children with histologically- confirmed ALL diagnosed before age 10 and born in one of the 13 largest hospitals in Michigan from 1985- 2002 (n = 200) will be ascertained in the Michigan Cancer Registry. In Phase 1, records of ALL cases will be linked by the Michigan Department of Community Health to their birth certificates and to hospital discharge abstracts from the Michigan Inpatient Database (MIDB). From the birth certificate file, we will match 2 control surviving children of the same gender, ethnicity, birth weight ( 250 grams) and gestational age ( two weeks) born within 2 weeks of the case in the same hospital. From birth certificates we will examine parental age and education, rural vs. urban residence, mother's reproductive history, pregnancy and delivery complications in cases and controls. From MIDB we will obtain length of hospital stay, major diagnoses and major interventions. Phase II of this study expands the search for perinatal exposure information by going to hospitals of birth and care of cases and controls, and reviewing maternal and neonatal hospital (and NICU) medical records for evidence of the exposures of interest, including detailed measures of extent and duration of oxygen use in mothers and infants, and of phototherapy in infants. We will also abstract information on conditions that predispose to oxygen and phototherapy use such as fetal distress and prolonged labor (maternal O2), Apgar score, respiratory conditions (neonatal O2) and serum bilirubin levels measured at different ages (phototherapy). Studies thus far suggest that a considerable fraction of ALL might be attributable to perinatal health care interventions that could be modified. If this is so, we have a possible way to reduce the burden of ALL in the population. The study we propose, which incorporates detailed maternal and neonatal medical record information with a large, population-based approach to case ascertainment and careful matching of control children would be the first case-control study of this topic in the US, and will provide a more robust estimate of the association of perinatal oxygen and phototherapy use to ALL risk than is available now. This study will try to find out whether giving oxygen to mothers in labor, and to their babies after birth, increases the risk of acute lymphocytic leukemia later in childhood. We will also study whether phototherapy, which is used to treat jaundice in babies, might increase the risk of leukemia. If these treatments increase the risk of leukemia, it should be possible to find alternative ways to manage newborn problems that minimize exposure to these treatments