UCLA

It is hypothesized that about half of all childhood cancers have prenatal origins. The first two studies of this dissertation focus on prenatal risk factors for childhood cancers. The first study includes cancer cases identified from the California Cancer Registry and diagnosed under six years of age between 1988 and 2013. Controls were selected from California birth records and matched to cases on birth year. Using birth certificate information, we assessed the association between pre-pregnancy diabetes, gestational diabetes, pre-pregnancy body mass index, gestational weight gain, and childhood cancer risk. We found an increased risk of acute lymphoblastic leukemia in offspring of mothers with pre-pregnancy diabetes.

Our second study includes the same sample of children, but limited to children of Hispanic mothers. Census tract data from the US decennial census (1990, 2000) and the American Community Survey (2007-2011) was used to create an index measure of Hispanic enclaves. Overall, offspring of mothers residing outside of Hispanic enclaves during pregnancy were at reduced risk of acute myeloid leukemia, hepatoblastoma, and retinoblastoma.

The effect of prenatal exposures can also be assessed using measures of placental vascular resistance, which have been shown to be predictive of adverse pregnancy outcomes. In the third study, we examined whether prenatal exposure to air pollution and smoking increases placental vascular resistance. Our sample includes pregnant women recruited between 1993 and 1996 in Los Angeles, California. We found that air pollution exposure increased uterine artery resistance in late pregnancy. Additionally, being a former smoker increases umbilical resistance in late pregnancy while smoking during pregnancy increases umbilical resistance, and uterine resistance and notching in mid-pregnancy.

In conclusion, our findings underline the importance of management of diabetes during pregnancy in childhood cancer prevention. Our results also suggest that Hispanic women living in densely populated Hispanic neighborhoods may be more vulnerable to certain risk factors as offspring of mothers living outside of these enclaves had a reduced risk of some cancers. Lastly, our results for prenatal air pollution and smoking support that both influence placental vascular resistance, providing insight on a potential mechanistic link between these exposures and adverse pregnancy outcomes.