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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2022)

Protecting and improving the health outcomes of children is of fundamental importance. The first two studies of this dissertation focus on prenatal risk factors for childhood cancers. The first study includes cancer cases identified from the Danish Cancer Registry and diagnosed under 19 between 1977 and 2016. Controls were selected from Central Population Registry and matched to cases on sex and birth year. We also included cases ascertained from the Taiwanese Cancer Registry and all children born in Taiwan between 2004 and 2014 that are listed in the Maternal and Child Health database. With access to population-based registries in Denmark and Taiwan, we examined the association between maternal diabetes and childhood cancer risk. In Denmark, the risks of central nervous system tumors among children prenatally exposed to maternal type I diabetes were increased, particularly for glioma. In Taiwan, the risks of glioma were elevated among children whose mothers had gestational diabetes. There was a two-fold increased risk for hepatoblastoma.Our second study includes cancer cases identified from the Danish Cancer Registry and diagnosed under 19 between 1968 and 2016 to investigate the effect of maternal occupational physical activity and childhood cancer risk. Overall, high levels of maternal occupational physical activity during pregnancy were associated with a higher risk of medulloblastoma with an indication of a dose-response pattern. Among health care professionals, maternal occupational physical activity exposures increased the risk of melanoma in offspring. The distribution of adverse pregnancy, birth and subsequent child developmental outcomes in the U.S. is characterized by pronounced racial-ethnic disparities and maternal immigrant status. In the third study, we compared metabolic profiles generated by the liquid chromatography-high resolution mass spectrometry platform of newborns of foreign-born and US-born Hispanic women in California (1983-2011) in an untargeted manner. Dried blood spots of eligible healthy children were collected by the California Genetic Disease Screening Program. We found that differences in metabolic profiles exist between newborns of US-born and foreign-born Hispanic mothers with an indication of alterations in inflammatory and oxidative stress pathways which could not be explained by the measured demographic, health behaviors, gestational and environmental factors.

    Cover page: Prenatal risk factors for childhood cancer and health: maternal diabetes, occupational physical activity and nativity
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2020)
      Cover page: Phototherapy and childhood cancer: Shared risk factors
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2022)
        Cover page: Exposure to nitrosatable drugs during pregnancy and childhood cancer: A matched case-control study in Denmark, 1996-2016.
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2022)

        Purpose: Prior studies examining the risk of retinoblastoma with maternal smoking were inconclusive, likely due in part to the reliance on self-reported maternal smoking. This study uses biomarkers of tobacco smoking in neonatal dried blood spots to investigate associations between maternal smoking and retinoblastoma in offspring.

         

        Methods: We randomly selected 498 retinoblastoma cases and 895 controls born between 1983-2011 from a population-based case-control study in California. Maternal pregnancy-related smoking was measured using the following 3 metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. We employed multivariable logistic regression to estimate the effects of maternal tobacco smoking on retinoblastoma.

         

        Results: Using all metrics (biomarkers or self-report), maternal smoking late in pregnancy or early postpartum was related to retinoblastoma [all types; Odds Ratio (OR)=1.44, 95% Confidence Interval (CI) 1.00, 2.09]. Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (OR=1.66, 95% CI 1.08, 2.57).

        Conclusion: The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.

          Cover page: Biomarkers of Maternal Smoking and the Risk of Retinoblastoma in Offspring
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2024)

          Background

          Systematically recorded smoking data are not always available in vital statistics records, and even when available it can underestimate true smoking rates.

          Objective

          To develop a prediction model for maternal tobacco smoking in late pregnancy based on birth certificate information using a combination of self- or provider-reported smoking and biomarkers (smoking metabolites) in neonatal blood spots as the alloyed gold standard.

          Methods

          We designed a case-control study where childhood cancer cases were identified from the California Cancer Registry and controls were from the California birth rolls between 1983 and 2011 who were cancer-free by the age of six. In this analysis, we included 894 control participants and performed high-resolution metabolomics analyses in their neonatal dried blood spots, where we extracted cotinine [mass-to-charge ratio (m/z) = 177.1023] and hydroxycotinine (m/z = 193.0973). Potential predictors of smoking were selected from California birth certificates. Logistic regression with stepwise backward selection was used to build a prediction model. Model performance was evaluated in a training sample, a bootstrapped sample, and an external validation sample.

          Results

          Out of seven predictor variables entered into the logistic model, five were selected by the stepwise procedure: maternal race/ethnicity, maternal education, child's birth year, parity, and child's birth weight. We calculated an overall discrimination accuracy of 0.72 and an area under the receiver operating characteristic curve (AUC) of 0.81 (95% confidence interval [CI] 0.77, 0.84) in the training set. Similar accuracies were achieved in the internal (AUC 0.81, 95% CI 0.77, 0.84) and external (AUC 0.69, 95% CI 0.64, 0.74) validation sets.

          Conclusions

          This easy-to-apply model may benefit future birth registry-based studies when there is missing maternal smoking information; however, some smoking status misclassification remains a concern when only variables from the birth certificate are used to predict maternal smoking.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2022)

            Background

            The effect of maternal diabetes on childhood cancer has not been widely studied.

            Methods

            We examined this in two population-based studies in Denmark (N = 6420 cancer cases, 160,484 controls) and Taiwan (N = 2160 cancer cases, 2,076,877 non-cases) using logistic regression and Cox proportional hazard regression adjusted for birth year, child's sex, maternal age and birth order.

            Results

            Gestational diabetes in Denmark [odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.71-1.35] or type II and gestational diabetes in Taiwan (type II: hazard ratio (HR) = 0.81, 95% CI: 0.63-1.05; gestational diabetes: HR = 1.06, 95% CI: 0.92-1.22) were not associated with cancer (all types combined). In Denmark, maternal type I diabetes was associated with the risk of glioma (OR = 2.33, 95% CI: 1.04-5.22), while in Taiwan, the risks of glioma (HR = 1.59, 95% CI: 1.01-2.50) were elevated among children whose mothers had gestational diabetes. There was a twofold increased risk for hepatoblastoma with maternal type II diabetes (HR = 2.02, 95% CI: 1.02-4.00).

            Conclusions

            Our results suggest that maternal diabetes is an important risk factor for certain types of childhood cancers, emphasising the need for effective interventions targeting maternal diabetes to prevent serious health effects in offspring.
              Cover page: Maternal diabetes and childhood cancer risks in offspring: two population-based studiesCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)

              Childhood cancer risk is associated with maternal health during pregnancy. Anemia in pregnancy is a common condition, especially in low-income countries, but a possible association between maternal anemia and childhood cancer has not been widely studied.

              We examined the relation in a population-based study in Denmark (N = 6420 cancer cases, 160,485 controls). Cases were taken from the Danish Cancer Registry, and controls were selected from national records. We obtained maternal anemia diagnoses from the National Patient and Medical Births registries. In a separate analysis within the years available (births 1995-2014), we examined cancer risks among mothers taking prescribed vitamin supplements, using data from the National Prescription Register. We estimated the risks of childhood cancer using conditional logistic regression.

              The risks of neuroblastoma [odds ratio (OR= 1.83, 95% confidence interval (CI): 1.04, 3.22] and acute lymphoblastic leukemia (OR= 1.46, 95% CI 1.09, 1.97) were increased in children born to mothers with anemia in pregnancy. There was a two-fold increased risk for bone tumors (OR= 2.59, 95% CI: 1.42, 4.72), particularly osteosarcoma (OR= 3.54, 95% CI 1.60, 7.82). With regards to prescribed supplement use, mothers prescribed supplements for B12 and folate deficiency anemia (OR= 4.03, 95% CI 1.91, 8.50) had an increased risk for cancer in offspring.

              Our results suggest that screening for anemia in pregnancy and vitamin supplementation may be an actionable strategy to prevent some cases of childhood cancer.

                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2022)

                Background

                Although viral hepatitis causes paediatric hepatocellular carcinoma and hepatic and extrahepatic cancers in adults, there are few epidemiologic studies on paediatric-cancer risks from parental viral hepatitis. In a nationwide study in a viral hepatitis endemic region and with confirmation in another population-based sample, we examined associations between parental hepatitis B (HBV) and C (HCV) infections and risks of cancers in offspring.

                Methods

                We included all children born in Taiwan in 2004-2014 (N = 2 079 037) with 2160 cancer cases ascertained from the Cancer Registry. We estimated risks for paediatric cancers using Cox proportional-hazard regressions. We checked these associations in a nationwide case-control study in Denmark (6422 cases, 160 522 controls).

                Results

                In Taiwan, paternal HBV was related to child's hepatoblastoma [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05, 2.97] when identified at any time in the medical record, and when analyses were limited to hepatitis diagnoses occurring before the child's birth, risks increased (HR = 2.08, 95% CI = 1.13-3.80). Paternal HCV was related to child's non-Hodgkin lymphoma (HR = 2.06, 95% CI = 1.13-3.74). Maternal HCV was weakly related to increased risks of all childhood cancers [all types combined; HR = 1.45, 95% CI = 0.95-2.22]. The population-attributable fraction of hepatoblastoma for maternal, paternal and child HBV was 2.6%, 6.8% and 2.8%, respectively.

                Conclusions

                Parental HBV and HCV may be risk factors for hepatic and non-hepatic cancers in children. If associations are causal, then parental screening and treatment with antivirals may prevent some paediatric cancers.
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