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性白血病(ALL)的风险，ALL是儿童最常见的血液系统恶性肿瘤。我们建议进行一项配对的病例对照研究，以调查ALL与3种围产期干预措施的关系：母体氧气疗法、新生儿氧气疗法和新生儿黄疸的光疗法。对于每一种暴露，都有一个合理的生物学基础支持这样的假设，即它们可能有助于白血病的形成过程，其中两种--新生儿氧气和光疗--流行病学研究表明，它们与儿童白血病有关。尚未对母体接触氧气与ALL的关系进行研究。组织学确诊的所有在10岁之前确诊并在1985年至2002年期间在密歇根州13家最大医院之一出生的儿童(n=200)将在密歇根州癌症登记中心进行确诊。在第一阶段，所有病例的记录将由密歇根州社区卫生部门与他们的出生证明和密歇根州住院患者数据库(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(两周)的对照儿童。从出生证明中，我们将检查父母的年龄和教育，农村和城市的居住情况，母亲的生育史，病例和对照中的妊娠和分娩并发症。我们将从MIDB获得住院时间、主要诊断和主要干预措施。这项研究的第二阶段扩大了对围产期暴露信息的搜索，前往分娩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，以寻找感兴趣的暴露的证据，包括母亲和婴儿使用氧气的范围和持续时间的详细测量，以及婴儿的光疗。我们还将提取易于使用氧气和光疗的条件的信息，如胎儿窘迫和延长分娩(母体氧气)、阿普加评分、呼吸状况(新生儿氧气)和不同年龄测量的血清胆红素水平(光疗)。到目前为止的研究表明，其中相当一部分可能归因于可以修改的围产期保健干预措施。如果是这样的话，我们就有可能减轻所有人的负担。我们提出的这项研究结合了详细的母亲和新生儿病历信息，并采用基于人群的大型方法来确定病例并仔细匹配对照儿童，这将是美国对这一主题的第一项病例对照研究，并将提供比目前更可靠的围产期氧气和光疗使用与所有风险之间的关联的估计。这项研究将试图找出给分娩中的母亲和出生后的婴儿吸氧是否会增加儿童后期患急性淋巴细胞白血病的风险。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患白血病的风险，应该有可能找到处理新生儿问题的替代方法，将暴露于这些治疗的风险降至最低。

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