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

描述（由申请人提供）： 越来越多的证据表明，围产期因素可能会增加急性淋巴细胞白血病（ALL）的风险，这是儿童最常见的血液恶性肿瘤。我们建议进行一项配对病例对照研究，以探讨急性淋巴细胞白血病与3种围产期干预措施的关系：母亲O2治疗，新生儿O2治疗和新生儿黄疸光疗。对于这些暴露中的每一种，一个合理的生物学原理支持这样的假设，即它们可能有助于白血病的发生过程，并且对于其中的两种-新生儿O2和光疗-流行病学研究表明与儿童白血病有关。尚未研究母体O2暴露与ALL的关系。1985- 2002年在密歇根州13家最大的医院之一出生的10岁之前诊断出组织学确诊的ALL儿童（n = 200）将在密歇根州癌症登记处确定。在第一阶段，密歇根州社区卫生部将把所有病例的记录与他们的出生证明和密歇根州住院病人数据库（MIDB）的出院摘要联系起来。从出生证明文件中，我们将匹配2名在同一医院出生的相同性别、种族、出生体重（250克）和胎龄（2周）的对照存活儿童。从出生证明，我们将检查父母的年龄和教育，农村与城市居住，母亲的生育史，怀孕和分娩并发症的情况下，控制。从MIDB，我们将获得住院时间，主要诊断和主要干预措施。本研究的第二阶段通过前往出生和护理病例和对照的医院，并审查孕产妇和新生儿医院（和NICU）的医疗记录，以获得感兴趣的暴露证据，包括母亲和婴儿使用氧气的程度和持续时间以及婴儿光疗的详细措施，扩大了对围产期暴露信息的搜索。我们还将提取有关易于使用氧气和光疗的条件的信息，例如胎儿窘迫和分娩时间延长（母体O2），Apgar评分，呼吸条件（新生儿O2）和在不同年龄测量的血清胆红素水平（光疗）。迄今为止的研究表明，ALL的相当一部分可能归因于围产期保健干预措施，可以修改。如果是这样的话，我们就有可能减轻人口中所有人的负担。我们提出的这项研究将详细的孕产妇和新生儿病历信息与大量基于人群的病例确定方法相结合，并仔细匹配对照儿童，这将是美国第一个关于这一主题的病例对照研究，并将提供比现在更可靠的估计围产期氧和光疗使用与ALL风险的关联。这项研究将试图找出是否给氧气的母亲在劳动，并在出生后，他们的婴儿，增加急性淋巴细胞白血病的风险以后在儿童。我们还将研究用于治疗婴儿黄疸的光疗是否会增加患白血病的风险。如果这些治疗增加了白血病的风险，那么应该有可能找到替代方法来管理新生儿问题，以尽量减少对这些治疗的暴露

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