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Background: Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms., Methods: We retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 μm) during first-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) to select metabolic features associated with air pollution exposure. Pathway analyses were employed to identify biologic pathways related to air pollution exposure. As potential confounders we included maternal age, maternal race/ethnicity, and maternal education., Results: In total we extracted 4038 and 4957 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for confounding factors, PLS-DA (Variable Importance in Projection (VIP) ≥2) yielded 181 and 251 metabolic features (HILIC and C18, respectively) that discriminated between the high (n = 98) and low exposed (n = 62). Pathway enrichment analysis for discriminatory features associated with air pollution indicated that in maternal serum oxidative stress and inflammation related pathways were altered, including linoleate, leukotriene, and prostaglandin pathways., Conclusion: The metabolomic features and pathways we found to be associated with air pollution exposure suggest that maternal exposure during pregnancy induces oxidative stress and inflammation pathways previously implicated in pregnancy complications and adverse outcomes., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BackgroundChildhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers.ResultsOffspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

BackgroundAutoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring.MethodsWe linked data from several national registries in Denmark to identify childhood cancer cases in children

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

BackgroundSystematically recorded smoking data are not always available in vital statistics records, and even when available it can underestimate true smoking rates.ObjectiveTo 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.MethodsWe 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.ResultsOut 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.ConclusionsThis 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.

ObjectiveOnly a few studies have reported on the association between hyperemesis gravidarum and the risk of childhood cancer. We examined possible associations in this population-based study in Denmark.MethodsPediatric cancer cases (n = 6420) were ascertained from the Denmark Cancer Registry among children born between 1977 and 2013. Twenty-five controls were matched to each case by sex and birth date from the Central Person Registry (n = 160500). Mothers with hyperemesis gravidarum were ascertained from the National Patient Register. The risk of childhood cancer was estimated using conditional logistic regression. In a separate analysis, we examined pregnancy prescription of antinauseant medications, ascertained from the National Pharmaceutical Register, to determine associations with childhood cancers.ResultsIn Denmark, hyperemesis gravidarum was associated with an increased risk of childhood cancer [all types combined; Odds Ratio (OR) = 1.43, 95% confidence interval (CI) 1.12, 1.81; n = 73 exposed cases). Hyperemesis gravidarum was also associated with an increased risk of neuroblastoma (OR = 2.52, 95% CI 1.00, 6.36; n = 5 exposed cases), acute lymphoblastic leukemia (OR = 1.63, 95% CI 0.98, 2.72; n = 16 exposed cases), and non-Hodgkin's lymphoma (OR = 2.41, 95% CI 0.95, 6.08; n = 5 exposed cases). We observed no childhood cancer risk increase from antinauseant prescriptions (OR = 1.05, 95% CI 0.84, 1.30; n = 91 exposed cases).ConclusionOur results are suggestive of an association between hyperemesis gravidarum and the overall cancer risk in offspring, particularly for neuroblastoma. Mothers with hyperemesis gravidarum should be closely monitored and receive appropriate treatment during pregnancy.

Epidemiologic studies of low-frequency exposures or outcomes using metabolomics analyses of neonatal dried blood spots (DBS) often require assembly of samples with substantial differences in duration of storage. Independent assessment of stability of metabolites in archived DBS will enable improved design and interpretation of epidemiologic research utilizing DBS. Neonatal DBS routinely collected and stored as part of the California Genetic Disease Screening Program between 1983 and 2011 were used. The study population included 899 children without cancer before age 6 years, born in California. High-resolution metabolomics with liquid-chromatography mass spectrometry was performed, and the relative ion intensities of common metabolites and selected xenobiotic metabolites of nicotine (cotinine and hydroxycotinine) were evaluated. In total, we detected 26,235 mass spectral features across 2 separate chromatography methods (C18 hydrophobic reversed-phase chromatography and hydrophilic-interaction liquid chromatography). For most of the 39 metabolites related to nutrition and health status, we found no statistically significant annual trends across the years of storage. Nicotine metabolites were captured in the DBS with relatively stable intensities. This study supports the usefulness of DBS stored long-term for epidemiologic studies of the metabolome. -Omics-based information gained from DBS may also provide a valuable tool for assessing prenatal environmental exposures in child health research.

While associations between maternal infections during pregnancy and childhood leukemia in offspring have been extensively studied, the evidence for other types of childhood cancers is limited. Additionally, antibiotic exposure during pregnancy could potentially increase the risk of childhood cancers. Our study investigates associations between maternal infections and antibiotic prescriptions during pregnancy and the risk of childhood cancer in Taiwan. We conducted a population-based cohort study using the Taiwan Maternal and Child Health Database (TMCHD), linked with national health and cancer registries. The study included 2 267 186 mother-child pairs, and the median follow-up time was 7.96 years. Cox proportional hazard models were utilized to estimate effects. Maternal infections during pregnancy were associated with a moderate increase in the risk of childhood hepatoblastoma (adjusted hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 0.90-1.98) and a weaker increase in the risk of childhood acute lymphoblastic leukemia (ALL) (adjusted HR = 1.15; 95% CI: 0.99-1.35). Antibiotic prescriptions during pregnancy were also associated with an elevated risk of childhood ALL (adjusted HR = 1.30; 95% CI: 1.04-1.63), particularly with tetracyclines (adjusted HR = 2.15; 95% CI: 1.34-3.45). Several specific antibiotics were also associated with an increased risk of hepatoblastoma and medulloblastoma. Children exposed in utero to antibiotic prescription or both infections and antibiotics during pregnancy were at higher risk of developing ALL. Our findings suggest that there are associations between maternal infections, antibiotic use during pregnancy and the risk of several childhood cancers in addition to ALL and highlight the importance of further research in this area.

BackgroundMaternal migraine has been linked to adverse birth outcomes including low birth weight and preterm birth, as well as congenital anomalies in offspring. It has been speculated that this may be due to the use of medications in pregnancy, but lifestyle, genetic, hormonal, and neurochemical factors could also play a role. There is evidence for varying cancer incidences among adults with migraine. Here, we utilized data from national registries in Denmark to examine associations between maternal diagnoses of migraine and risk for cancer in offspring.MethodsWe linked several national registries in Denmark to identify cases from the Cancer Registry among children less than 20 years (diagnoses 1996–2016) and controls from the Central Population Register, matched to cases by birth year and sex (25:1 matching rate). Migraine diagnoses were identified from the National Patient Register using International Classification of Diseases, versions 8 and 10 codes and migraine-specific acute or prophylactic treatment recorded in the National Pharmaceutical Register. We used logistic regression to estimate the risk of childhood cancers associated with maternal migraine.ResultsMaternal migraine was positively associated with risk for non-Hodgkin lymphoma (odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.01–2.86), central nervous system tumors ([OR = 1.31, 95% CI: 1.02–1.68], particularly glioma [OR = 1.64, 95% CI: 1.12–2.40]), neuroblastoma (OR = 1.75, 95% CI: 1.00–3.08), and osteosarcoma (OR = 2.60, 95% CI: 1.18–5.76).ConclusionsAssociations with maternal migraine were observed for several childhood cancers, including neuronal tumors. Our findings raise questions about the role of lifestyle factors, sex hormones, genetic, and neurochemical factors in the relationship between migraine and childhood cancers.

Background:    Childhood cancer may be related to maternal health in pregnancy. Maternal anemia is a common condition in pregnancy, especially in low-income countries, but the association between maternal anemia and childhood cancer has not been studied using a nationally representative population. Objective:        To examine the potential relation between maternal anemia during pregnancy and childhood cancers in a population-based cohort study in Taiwan. Methods:         We examined the relationship between maternal anemia and childhood cancer in Taiwan (N= 2160 cancer cases, 2,076,877 non-cases). Cases were taken from the National Cancer Registry, and non-cases were selected from national records. Using national health registries, we obtained maternal anemia diagnoses. We estimated the risks for childhood cancers using Cox proportional hazard analysis. Results:           There was an increased risk of cancers in children born to mothers with nutritional anemia (Hazard Ratio (HR): 1.32, 95% CI 0.99, 1.76). Iron deficiency anemia (HR: 1.30, 95% CI 0.97-1.75) carried an increased risk, while non-nutritional anemias were not associated with childhood cancer risk. Conclusion:     Our results provide additional support for screening for anemia during pregnancy. Adequate nutrition and vitamin supplementation may help to prevent some childhood cancer cases.

BackgroundThe effect of maternal diabetes on childhood cancer has not been widely studied.MethodsWe 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.ResultsGestational 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).ConclusionsOur 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.

Retinoblastoma is a rare tumor of the retina, most commonly found in young children. Due to the rarity of this childhood cancer, few studies have been able to examine prenatal pesticide exposure as a risk factor.To examine the relationship between childhood retinoblastoma and prenatal exposure to pesticides through residential proximity to agricultural pesticide applications.We conducted a population-based case-control study using cases aged 5 and younger identified from the California Cancer Registry, and controls randomly selected from California birth certificates. Frequency matching cases to controls by age resulted in 221 cases of unilateral retinoblastoma and 114 cases of bilateral retinoblastoma, totaling 335 cases and 123,166 controls. Based on addresses from birth certificates we employed Pesticide Use Reports and land use information within a geographic information system approach to individually assess exposures to specific pesticides within 4000 m of the residence reported on birth certificates. The associations between retinoblastoma (all types combined and stratified by laterality) and individual pesticides were expressed as odds ratios estimates obtained from unconditional logistic regression models including a single pesticide, and from a hierarchical logistic regression model including all pesticides.We found that exposures to acephate (OR: 1.70, 95% CI: 1.20, 2.41) and bromacil (OR: 1.87, 95% CI: 1.07, 3.26) were associated with increased risk for unilateral retinoblastoma. In addition to acephate, we found that pymetrozine (OR: 1.45, 95% CI: 1.00, 2.08) and kresoxim-methyl (OR: 1.60, 95% CI: 1.00, 2.56) were associated with retinoblastoma (all types combined).Our findings suggest that certain types of prenatal ambient pesticide exposure from residing near agricultural fields may play a role in the development of childhood retinoblastoma.

BackgroundAlthough 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.MethodsWe 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).ResultsIn 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.ConclusionsParental 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.

BackgroundMaternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and childhood disorders. High-resolution metabolomics (HRM) has previously been employed to identify metabolic responses to traffic-related air pollution in adults, including pregnant women. Thus far, no studies have examined metabolic effects of air pollution exposure in utero on neonates.MethodsWe retrieved stored neonatal blood spots for 241 children born in California between 1998 and 2007. These children were randomly selected from all California birth rolls to serve as birth-year matched controls for children with retinoblastoma identified from the California cancer registry for a case control study of childhood cancer. We estimated prenatal traffic-related air pollution exposure (particulate matter less than 2.5 μm (PM2.5)) during the third-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We employed untargeted HRM to obtain metabolic profiles, and metabolites associated with air pollution exposure were identified using partial least squares (PLS) regression and linear regressions. Biological effects were characterized using pathway enrichment analyses adjusting for potential confounders including maternal age, race/ethnicity, and education.ResultsIn total we extracted 4038 and 4957 metabolite features from neonatal blood spots in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 reverse phase columns (negative ion mode), respectively. After controlling for confounding factors, partial least square regression (Variable Importance in Projection (VIP) ≥ 2) selected 402 HILIC positive and 182 C18 negative features as statistically significantly associated with increasing third trimester PM2.5 exposure. Using pathway enrichment analysis, we identified metabolites in oxidative stress and inflammation pathways as being altered, primarily involving lipid metabolism.ConclusionThe metabolite features and pathways associated with air pollution exposure in neonates suggest that maternal exposure during late pregnancy contributes to oxidative stress and inflammation in newborn children.

PurposeTo examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma).MethodsThis population-based case-control study included childhood GCT cases in Denmark diagnosed 1968-2015 (

BackgroundPreviously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring.ObjectivesTo identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD.MethodsWe obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter

Background:Pesticide exposures have been examined previously as risk factors for childhood brain cancers, but few studies were able to assess risk from specific agents.Objective:To evaluate risks for childhood central nervous system tumors associated with residential proximity to agricultural pesticide applications.Methods:Using the California Cancer Registry, we identified cancer cases less than 6 years of age and frequency matched them by year of birth to 20 cancer-free controls identified from birth certificates. We restricted analyses to mothers living in rural areas and births occurring between 1998 and 2011, resulting in 667 cases of childhood central nervous system tumors and 123,158 controls. Possible carcinogens were selected per the Environmental Protection Agency’s (US. EPA) classifications, and prenatal exposure was assessed according to pesticides reported by the California Department of Pesticide Regulation’s (CDPR) Pesticide Use Reporting (PUR) system as being applied within 4000m of the maternal residence at birth. We computed odds ratios for individual pesticide associations using unconditional logistic and hierarchical regression models.Results:We observed elevated risks in the hierarchical models for diffuse astrocytoma with exposure to bromacil (OR: 2.12, 95% CI: 1.13-3.97), thiophanate-methyl (OR: 1.64, 95% CI: 1.02-2.66), triforine (OR: 2.38, 95% CI: 1.44-3.92), and kresoxim methyl (OR: 2.09, 95% CI: 1.03-4.21); elevated risks for medulloblastoma with exposure to chlorothalonil (OR: 1.78, 95% CI: 1.15-2.76), propiconazole (OR: 1.60, 95% CI: 1.02, 2.53), dimethoate (OR: 1.60, 95% CI: 1.06, 2.43), and linuron (OR: 2.52, 95% CI: 1.25, 5.11); and elevated risk for ependymoma with exposure to thiophanate-methyl (OR: 1.72, 95% CI: 1.10-2.68).Conclusion:Our study suggests that exposure to certain pesticides through residential proximity to agricultural applications during pregnancy may increase the risk of childhood central nervous system tumors.

BackgroundA number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool.MethodsWe identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998-2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency's classifications and pesticide use was collected from the California Department of Pesticide Regulation's (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations.ResultsWe observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67-4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57-3.60), phosmet (OR: 2.10, 95% CI: 1.46-3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14-2.75), and propanil (OR: 2.58, 95% CI: 1.44-4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56-3.99), anilides (OR: 2.16, 95% CI: 1.38-3.36), and ureas (OR: 2.18, 95% CI: 1.42-3.34).ConclusionOur findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.

BackgroundParental occupational exposures are suggested as contributing causes of childhood cancer.MethodsChildren age< = 19, born in Denmark and diagnosed with leukemia, central nervous system (CNS) cancers and likely prenatally initiated cancers [hepatoblastoma, medulloblastoma, Wilms tumor (nephroblastoma), neuroblastoma, retinoblastoma and acute lymphoid leukemia] n = 4268 were identified using Danish registries. We randomly selected twenty-five controls per case matched on birth year and sex. Parents and their employment histories were extracted from nationwide registries. We examined occupational dust exposures perinatally and postnatally in both parents. Odds ratios (ORs) and 95 % confidence intervals (95 % CI) were estimated using conditional logistic regression.ResultsMaternal wood dust exposure from birth to diagnosis was associated with increased risks of leukemia (OR 1.44, 95 % CI 1.08-1.94) and acute myeloid leukemia (OR 2.14, 95 % CI 1.13-4.03); exposure to paper dust was associated with CNS cancer (OR 2.28, 95 % CI 1.22-4.2).. Paternal exposure to wood dust was associated with astrocytoma in both periods (OR 1.43, 95 % CI 1.05-1.96 and 1.42, 1.09-1.86, respectively) and CNS cancer (OR 1.24, 95 % CI 1.00-1.53) in the perinatal period. The increased risk observed for potentially prenatally-initiated cancers in relation to wood was driven by ORs for neuroblastoma (1.54, 95 % CI 1.03-2.29) and hepatoblastoma (2.41, 95 % CI 0.99-5.88). An OR of 2.58 (95 % CI 1.10-6.05) for CNS cancer was associated with both parents working in textile industries postnatally.ConclusionThe study suggests that parental exposure to wood dust may increase risk of specific childhood cancers.

Background:Pesticide exposures have been examined previously as risk factors for childhood brain cancers, but few studies were able to assess risk from specific agents.Objective:To evaluate risks for childhood central nervous system tumors associated with residential proximity to agricultural pesticide applications.Methods:Using the California Cancer Registry, we identified cancer cases less than 6 years of age and frequency matched them by year of birth to 20 cancer-free controls identified from birth certificates. We restricted analyses to mothers living in rural areas and births occurring between 1998 and 2011, resulting in 667 cases of childhood central nervous system tumors and 123,158 controls. Possible carcinogens were selected per the Environmental Protection Agency’s (US. EPA) classifications, and prenatal exposure was assessed according to pesticides reported by the California Department of Pesticide Regulation’s (CDPR) Pesticide Use Reporting (PUR) system as being applied within 4000m of the maternal residence at birth. We computed odds ratios for individual pesticide associations using unconditional logistic and hierarchical regression models.Results:We observed elevated risks in the hierarchical models for diffuse astrocytoma with exposure to bromacil (OR: 2.12, 95% CI: 1.13-3.97), thiophanate-methyl (OR: 1.64, 95% CI: 1.02-2.66), triforine (OR: 2.38, 95% CI: 1.44-3.92), and kresoxim methyl (OR: 2.09, 95% CI: 1.03-4.21); elevated risks for medulloblastoma with exposure to chlorothalonil (OR: 1.78, 95% CI: 1.15-2.76), propiconazole (OR: 1.60, 95% CI: 1.02, 2.53), dimethoate (OR: 1.60, 95% CI: 1.06, 2.43), and linuron (OR: 2.52, 95% CI: 1.25, 5.11); and elevated risk for ependymoma with exposure to thiophanate-methyl (OR: 1.72, 95% CI: 1.10-2.68).Conclusion:Our study suggests that exposure to certain pesticides through residential proximity to agricultural applications during pregnancy may increase the risk of childhood central nervous system tumors.

BackgroundMaternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms.MethodsWe retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter

ObjectivesOnly a small number of studies have reported on the association of parental occupational exposure to benzene and risk of childhood and adolescent leukaemias. We examined associations with acute lymphoblastic leukaemia (ALL) in this population-based study in Denmark.MethodsBenzene was largely banned from Danish workplaces after 1975, thus this case-control study focused on the immediately prior years. Paediatric cancer cases (ResultsWe identified 217 employed case fathers and 169 employed case mothers, of which 22 (10.1%) and 11 (6.5%), respectively, were exposed to benzene (vs 6.7% and 2.9% of control fathers and mothers). Most exposed parents worked as machine or engine mechanics, or in the shoe industry. Maternal occupational exposure to benzene in pregnancy was related to increased risk of ALL in offspring (adjusted OR=2.28, 95% CI 1.17 to 4.41), while paternal preconceptional benzene exposure was not as strongly associated (adjusted OR=1.40, 95% CI 0.88 to 2.22).ConclusionsOur study supports an increased risk for ALL with parental occupational benzene exposure.

ObjectiveTo assess prenatal air toxics exposure and risk for childhood germ cell tumors (GCTs) by histological subtype (yolk sac tumor and teratoma).MethodsIn this case-control study, GCT cases less than 6 years (n = 243) identified from California Cancer Registry records were matched by birth year to cancer-free population controls (n = 147,100), 1984 to 2013. Routinely monitored air toxic exposures were linked to subjects' birth address. Logistic regression estimated GCT risks per interquartile range increase in exposure.ResultsPrenatal exposure to various highly-correlated, traffic-related air toxics during the second trimester increased GCT risk, particularly 1,3-butadiene (odds ratio [OR] = 1.51; 95% confidence interval [CI] = 1.01, 2.26) and meta/para-xylene (OR = 1.56; 95% CI = 1.10, 2.21). Analyses by subtype indicated elevated ORs for yolk sac tumors but not teratomas.ConclusionOur estimated ORs are consistent with positive associations between some prenatal traffic-related air toxics and GCT risk, notably yolk sac tumors.

Studies of environmental exposures and childhood cancers that rely on records often only use maternal address at birth or address at cancer diagnosis to assess exposures in early childhood, possibly leading to exposure misclassification and questionable validity due to residential mobility during early childhood. Our objective was to assess patterns and identify factors that may predict residential mobility in early childhood, and examine the impact of mobility on early childhood exposure assessment for agriculturally applied pesticides and childhood cancers in California. We obtained the addresses at diagnosis of all childhood cancer cases born in 1998-2011 and diagnosed at 0-5 years of age (n = 6478) from the California Cancer Registry (CCR), and their birth addresses from linked birth certificates. Controls were randomly selected from California birth records and frequency matched (20:1) to all cases by year of birth. We obtained residential histories from a public-record database LexisNexis for both case (n = 3877 with age at diagnosis 1-5 years) and control (n = 99,262) families. Logistic regression analyses were conducted to assess the socio-demographic factors in relation to residential mobility in early childhood. We employed a Geographic Information System (GIS)-based system to estimate children's first year of life exposures to agriculturally applied pesticides based on birth vs diagnosis address or residential histories based upon Lexis-Nexis Public Records and assessed agreement between exposure measures using Spearman correlations and kappa statistics. Over 20% of case and control children moved in their first year of life, and 55% of children with cancer moved between birth and diagnosis. Older age at diagnosis, younger maternal age, lower maternal education, not having a Hispanic ethnic background, use of public health insurance, and non-metropolitan residence at birth were predictors of higher residential mobility. There was moderate to strong correlation (Spearman correlation = 0.76-0.83) and good agreement (kappa = 0.75-0.81) between the first year of life exposure estimates for agricultural pesticides applied within 2 km of a residence relying on an address at birth or at diagnosis or LexisNexis addresses; this did not differ by outcome status, but agreement decreased with decreasing buffer size, and increasing distance moved or age at diagnosis. These findings suggest that residential addresses collected at one point in time may represent residential history in early childhood to a reasonable extent; nevertheless, they exposure misclassification in the first year of life remains an issue. Also, the highest proportion of women not captured by LexisNexis were Hispanic women born in Mexico and those living in the lowest SES neighborhoods, i.e. possibly those with the higher environmental exposures, as well as younger women and those with less than high school education. Though LexisNexis only captures a sub-population, its data may be useful for augmenting address information and assessing the extent of exposure misclassification when estimating environmental exposures in large record linkage studies. Future research should investigate how to correct for exposure misclassification introduced by residential mobility that is not being captured by records.

BackgroundThe "fetal programming" hypothesis has been evaluated in many adult diseases including cancer, but not for Wilms tumor. Wilms tumor has been related to high birthweight, but little is known about other growth metrics such as a baby's birth length, ponderal index, or placenta size, which can shed additional light on growth patterns.MethodsCases of Wilms tumor (N = 217) were taken from the Danish Cancer Registry, and controls (N = 4340) were randomly selected from the Population Register and matched to cases by sex and age. Linkage to the Medical Births Registry provided information on gestational factors and fetal growth measurements, while linkage to the Patient Register provided information on maternal and child health conditions.ResultsDespite having typically normal to higher birthweights, Wilms tumor cases had smaller placentas (≤540 g; odds ratio (OR) = 4.24; 95% confidence interval (CI), 1.84-9.78) and a lower placenta-to-birthweight ratio (OR = 1.81; 95% CI, 1.17-2.82, per 1 SD decrease). Small placentas were more common among Wilms cases without congenital anomalies (OR = 6.43; 95% CI, 1.95-21.21). Wilms tumor cases had a higher prevalence of high birthweight (>4000 g; OR = 1.57; 95% CI, 1.11-2.22), birth length 55 cm or longer (OR = 1.74; 95% CI, 1.09-2.78), and being large for gestational age (OR = 1.79; 95% CI, 1.08-2.96).ConclusionsOur study corroborates earlier studies showing associations with high birthweight and suggests associations between Wilms tumor and decreased placental size and low placenta-to-birthweight ratio.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I2 = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.

Findings from studies of prenatal exposure to pesticides and adverse birth outcomes have been equivocal so far. We examined prenatal exposure to agricultural pesticides in relation to preterm birth and term low birthweight, respectively, in children born between 1998 and 2010, randomly selected from California birth records. We estimated residential exposure to agriculturally applied pesticides within 2 km of residential addresses at birth by pregnancy trimester for 17 individual pesticides and three chemical classes (organophosphates, pyrethroids, and carbamates). Among maternal addresses located within 2 km of any agricultural pesticide application, we identified 24,693 preterm and 220,297 term births, and 4412 term low birthweight and 194,732 term normal birthweight infants. First or second trimester exposure to individual pesticides (e.g., glyphosates, paraquat, imidacloprid) or exposure to 2 or more pesticides in the three chemical classes were associated with a small increase (3⁻7%) in risk for preterm birth; associations were stronger for female offspring. We did not find associations between term low birthweight and exposure to pesticides other than myclobutanil (OR: 1.11; 95% CI: 1.04⁻1.20) and possibly the pyrethroids class. Our improved exposure assessment revealed that first and second trimester exposure to pesticides is associated with preterm delivery but is rarely linked with term low birthweight.

IntroductionAlthough other studies have found evidence for perinatal health disparities among Pacific Islanders in other regions, no studies have evaluated racial/ethnic disparities in adverse perinatal health outcomes in the small US island territory of the Commonwealth of the Northern Mariana Islands (CNMI).MethodsWe used retrospective cohort data on 8,427 singleton births from 2007 to 2014 at the Commonwealth Healthcare Corporation (CHCC), the only hospital in the CNMI. We used multivariate logistic regression to estimate risk for preterm birth (4,000 g) among the racial/ethnic groups in the CNMI.ResultsIndigenous CNMI mothers (Chamorros and Carolinians, hereinafter Chamorro/Carolinian) and other Pacific Islander mothers were significantly more likely to have a preterm birth than Chinese mothers (adjusted odds ratio [AOR] = 2.7; 95% confidence interval [CI], 2.0-3.6 for Chamorro/Carolinians and AOR = 2.9; 95% CI, 2.1-4.1 for other Pacific Islanders). Additionally, Chamorro/Carolinian mothers and other Pacific Islander mothers were also significantly more likely to deliver babies with macrosomia (AOR = 2.4; 95% CI, 1.7-3.5 and 2.3; 95% CI 1.4-3.6 respectively) than Filipino mothers.ConclusionAlthough underlying causes for these disparities are still unknown, these findings add to the limited knowledge on maternal and neonatal health among Pacific Islanders and provide support for further research and intervention development to aid in reducing racial/ethnic disparities of perinatal health in the CNMI.

ObjectivesWe examined associations between parental occupational chemical exposures up to 10 years before conception and the risk of sporadic retinoblastoma among offspring.MethodsIn our multicentre study on non-familial retinoblastoma, parents of 187 unilateral and 95 bilateral cases and 155 friend controls were interviewed by telephone. Exposure information was collected retroactively through a detailed occupational questionnaire that asked fathers to report every job held in the 10 years before conception, and mothers 1 month before and during the index pregnancy. An industrial hygienist reviewed all occupational data and assigned an overall exposure score to each job indicating the presence of nine hazardous agents.ResultsWe estimated elevated ORs for unilateral and bilateral retinoblastoma among offspring of fathers who were exposed to polycyclic aromatic hydrocarbons or paints in the 10 years before conception. However, only for exposure to paints did confidence limits exclude the null for bilateral disease (OR: 8.76, 95% CI: 1.32 to 58.09). Maternal prenatal exposure to at least one of the nine agents was related to increased risk of unilateral disease in their children (OR: 5.25, 95% CI: 1.14 to 24.16). Fathers exposed to at least one of the nine agents and who were ≥30 years of age were at increased risk of having a child diagnosed with bilateral retinoblastoma (OR: 6.59, 95% CI: 1.34 to 32.42).ConclusionsOur results suggest a role for several hazardous occupational exposures in the development of childhood retinoblastoma.

BackgroundThe incidence of childhood cancers has been increasing and environmental exposure to air toxics has been suggested as a possible risk factor. This study aims to explore ambient exposure to dichloromethane (methylene chloride).MethodsWe frequency matched by birth year approximately 20 cancer-free controls identified from birth records to all childhood cancers ages 0-5 in the California Cancer Registry diagnosed from 1988 to 2012; i.e. 13,636 cases and a total of 270,673 controls. Information on industrial releases of dichloromethane within 3km of birth addresses was retrieved from mandatory industry reports to the EPA's Toxics Release Inventory (TRI). We derived exposure to dichloromethane within close vicinity of birth residences using several modeling techniques including unconditional logistic regression models with multiple buffer distances, inverse distance weighting, and quadratic decay models.ResultsWe observed elevated risks for germ cell tumors [Odds Ratio (OR): 1.52, 95% Confidence Interval (CI) 1.11, 2.08], particularly teratomas (OR: 2.08, 95% CI 1.38-3.13), and possible increased risk for acute myeloid leukemias (AML) (OR: 1.64, 95% CI 1.15-2.32 in the quadratic decay model). Risk estimates were similar in magnitude whether releases occurred in pregnancy or the child's first year of life.ConclusionOur findings suggest that exposure to industrial dichloromethane releases may be a risk factor for childhood germ cell tumors, teratomas, and possibly AML.

PurposeTo examine whether parental pesticide exposure contributes to the development of sporadic retinoblastoma.DesignCase-control study.MethodsData were collected by a large multicenter study of sporadic retinoblastoma in which parents of 99 unilateral and 56 bilateral age-matched case-control pairs were interviewed by telephone. Retrospective exposure information was collected on the type, location, timing, and frequency of residential pesticide use. We used conditional logistic regression analyses to estimate odds ratios for maternal pesticide exposure in the month before or during pregnancy and to assess whether the type of product, and the circumstances under which it was applied, were associated with risk of disease.ResultsUnilateral retinoblastoma was associated with parental insecticide use (odds ratio [OR], 2.8; confidence interval [CI], 1.1-6.7) and the use of professional lawn or landscape services (OR, 2.8; CI, 1.0-8.2). For bilateral disease we observed large point estimates for several exposures but the small number of cases rendered these results uninformative (ie, resulted in wide confidence intervals). Whether parents used the pesticide inside vs outside the home did not appear to modify risk estimates for unilateral retinoblastoma (OR, 2.5; CI, 0.9-7.0 vs OR, 2.5; CI, 1.0-6.5), nor did the type, frequency, timing related to pregnancy, or applicator of pesticide used influence estimates to an appreciable degree for disease.ConclusionsOur results suggest that parental pesticide exposure before or during pregnancy may play a role in the development of childhood retinoblastoma. Retrospectively collected exposure data introduces the possibility of recall bias; therefore, results should be interpreted cautiously until additional studies are conducted.

Smoking during pregnancy is a plausible risk factor for childhood cancer, yet previous studies have yielded conflicting results, and few prospective studies have been published. Data on maternal smoking were obtained from California birth certificates. We linked California birth certificates (births 2007-2011) with California Cancer Registry records for childhood cancer cases (diagnosed January 2007-September 2013) that were ages 5 or younger at diagnosis (N cases = 2,021). Controls (N = 40,356) were frequency-matched by birth year and randomly selected from birth certificate records. We used unconditional logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI) to assess the association between smoking during pregnancy and childhood cancer. We observed positive associations for gliomas (OR = 1.8, 95% CI: 1.0-3.4) and retinoblastoma (OR = 3.0, 95% CI: 1.4-6.6), particularly bilateral retinoblastoma (OR = 9.4, 95% CI 3.6-24.7) with maternal smoking in pregnancy. Maternal smoking during pregnancy may be a risk factor for retinoblastoma and certain types of childhood brain tumors.

BackgroundRetinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma.MethodsTwo large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma.FindingsMaternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption.ConclusionThe results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.

A few studies have suggested an association between maternal exposure to ambient air pollution from vehicular traffic and risk of congenital anomalies in the offspring, but epidemiologic evidence is neither strong nor entirely consistent. In a population-based case-control study in a Northern Italy community encompassing 228 cases of birth defects and 228 referent newborns, we investigated if maternal exposure to PM10 and benzene from vehicular traffic during early pregnancy, as estimated through a dispersion model, was associated with excess teratogenic risk. In conditional logistic regression analysis, and with adjustment for the other pollutant, we found that higher exposure to PM10 but not benzene was associated with increased risk of birth defects overall. Anomaly categories showing the strongest dose-response relation with PM10 exposure were musculoskeletal and chromosomal abnormalities but not cardiovascular defects, with Down syndrome being among the specific abnormalities showing the strongest association, though risk estimates particularly for the less frequent defects were statistically very unstable. Further adjustment in the regression model for potential confounders did not considerably alter the results. All the associations were stronger for average levels of PM10 than for their maximal level. Findings of this study give some support for an excess teratogenic risk following maternal exposure during pregnancy to PM10, but not benzene. Such association appears to be limited to some birth defect categories.

BackgroundThe early age at retinoblastoma occurrence, the most common eye malignancy in childhood, suggests that perinatal factors may contribute to its etiology.MethodsIn a large multicenter study of non-familial retinoblastoma, we conducted structured interviews with the parents of 280 cases and 146 controls to elicit information on health during the perinatal period. We used unconditional logistic regression to assess associations between retinoblastoma and parental fertility treatment, birth control use in the year prior to pregnancy, maternal health conditions and the use of prescription medications during pregnancy, and whether mothers breastfed the index child.ResultsBilateral retinoblastoma was related to maternal underweight (body mass index

We examined ambient exposure to specific air toxics in the perinatal period in relation to retinoblastoma development. Cases were ascertained from California Cancer Registry records of children diagnosed between 1990 and 2007 and matched to California birth certificates. Controls were randomly selected from state birth records for the same time period. We chose 27 air toxics for the present study that had been listed as possible, probable, or established human carcinogens by the International Agency for Research on Cancer. Children (103 cases and 30,601 controls) included in the study lived within 5 miles of an air pollution monitor. Using logistic regression analyses, we modeled the risk of retinoblastoma due to air toxic exposure, separately for exposures in pregnancy and the first year of life. With a per interquartile range increase in air toxic exposure, retinoblastoma risk was found to be increased with pregnancy exposure to benzene (OR=1.67, 95% CI: 1.06, 2.64) and other toxics which primarily arise from gasoline and diesel combustion: toluene, 1,3-butadiene, ethyl benzene, ortho-xylene, and meta/para-xylene; these six toxics were highly correlated. Retinoblastoma risk was also increased with pregnancy exposure to chloroform (OR=1.35, 95% CI: 1.07, 1.70), chromium (OR=1.29, 95% CI: 1.04, 1.60), para-dichlorobenzene (OR=1.24, 95% CI: 1.04, 1.49), nickel (OR=1.48, 95% CI: 1.08, 2.01), and in the first year of life, acetaldehyde (OR=1.62, 95% CI: 1.06, 2.48). Sources of these agents are discussed.

PurposePrevious studies have suggested a role for parental diet in childhood cancer prevention, but there are few studies of retinoblastoma. The aim of this study was to examine the relation between maternal diet and unilateral retinoblastoma.MethodsA case-control study of 163 unilateral RB cases and 136 controls ascertained information on maternal diet during pregnancy using a standardized food frequency questionnaire. Logistic regression was used to assess the relation between retinoblastoma and food groups and dietary patterns.ResultsWe observed a negative association between retinoblastoma and intake of fruit [odds ratio (OR) 0.38, 95 % confidence interval (CI) 0.14-1.02]. Positive associations were seen with intake of cured meats (OR 5.07, 95 % CI 1.63-15.70) and fried foods (OR 4.89, 95 % CI 1.72-13.89). A food pattern of high fruits and vegetables and low fried food and sweets was negatively associated with disease (OR 0.75, 95 % CI 0.61-0.92).ConclusionOur study provides preliminary evidence that mothers who consume diets higher in fruit and lower in fried foods and cured meats during pregnancy may reduce the risk of unilateral retinoblastoma in their offspring.

There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children

ObjectiveTo study prenatal air toxic exposure and Wilms' tumor in children.MethodsWe identified 337 Wilms' tumor cases among children younger than 6 years (1988 to 2008) from the California Cancer Registry, randomly selected 96,514 controls from California birth rolls in 20:1 ratio matched to all cancer cases, then linked birth addresses to air monitors within 15 miles to assess exposures. Multiple logistic regressions were applied to estimate effects.ResultsChildren prenatally exposed to formaldehyde, polycyclic aromatic hydrocarbons, perchloroethylene, or acetaldehyde in the third trimester had an increased odds of Wilms' tumor per interquartile increase in concentration (odds ratio [95% confidence interval]: 1.28 [1.12 to 1.45], 1.10 [0.99 to 1.22], 1.09 [1.00 to 1.18], 1.25 [1.07 to 1.45], respectively).ConclusionsWe found positive associations for four air toxics. This is the first study of this kind. Future studies are needed to confirm our findings.

BackgroundLymphoma is the third most common childhood malignancy and comprises two types, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The etiology of pediatric lymphomas is largely unknown, but has been suggested to have prenatal origins.MethodsIn this population-based study, California birth certificates were identified for 478 lymphoma cases diagnosed in children 0-5 years of age between 1988 and 2007; 208,015 controls frequency-matched by birth year were randomly selected from California birth records.ResultsCompared to non-Hispanic whites, Hispanic children had an increased risk of HL (odds ratio (OR) and 95% confidence interval (CI) 2.43 [1.14, 5.17]), and in particular, were diagnosed more often with the mixed cellularity subtype. For all types of lymphoma, we observed an about twofold risk increase with indicators for high risk pregnancies including tocolysis, fetopelvic disproportion and previous preterm birth. NHL risk doubled with the complication premature rupture of membranes (OR and 95% CI 2.18 [1.12, 4.25]) and HL with meconium staining of amniotic fluids (OR and 95% CI 2.55 [1.01, 6.43]).ConclusionThese data support previously reported associations between Hispanic ethnicity and HL and suggest that pregnancy related factors, such as intra-uterine infections and factors associated with preterm labor, may be involved in lymphoma pathogenesis.

BackgroundThe literature on traffic-related air pollution and childhood cancers is inconclusive, and little is known on rarer cancer types.ObjectivesWe sought to examine associations between childhood cancers and traffic-related pollution exposure.MethodsThe present study included children < 6 years of age identified in the California Cancer Registry (born 1998-2007) who could be linked to a California birth certificate (n = 3,590). Controls were selected at random from California birthrolls (n = 80,224). CAlifornia LINE Source Dispersion Modeling, version 4 (CALINE4) was used to generate estimates of local traffic exposures for each trimester of pregnancy and in the first year of life at the address indicated on the birth certificate. We checked our findings by additionally examining associations with particulate matter (≤ 2.5 μm in aerodynamic diameter; PM2.5) pollution measured by community-based air pollution monitors, and with a simple measure of traffic density.ResultsWith unconditional logistic regression, a per interquartile range increase in exposure to traffic-related pollution during the first trimester (0.0538 ppm carbon monoxide, estimated using CALINE4) was associated with acute lymphoblastic leukemia [ALL; first trimester odds ratio (OR) = 1.05; 95% CI: 1.01, 1.10]; germ cell tumors (OR = 1.16; 95% CI: 1.04, 1.29), particularly teratomas (OR = 1.26; 95% CI: 1.12, 1.41); and retinoblastoma (OR = 1.11; 95% CI: 1.01, 1.21), particularly bilateral retinoblastoma (OR = 1.16; 95% CI: 1.02, 1.33). Retinoblastoma was also associated with average PM2.5 concentrations during pregnancy, and ALL and teratomas were associated with traffic density near the child's residence at birth.ConclusionsWe estimated weak associations between early exposure to traffic pollution and several childhood cancers. Because this is the first study to report on traffic pollution in relation to retinoblastoma or germ cell tumors, and both cancers are rare, these findings require replication in other studies.

Little is known about the etiology of neuroblastoma, the most common cancer in infancy. In this study, we examined maternal exposure to ambient air toxics in pregnancy in relation to neuroblastoma in the child. We ascertained all cases of neuroblastoma listed in the California Cancer Registry 1990-2007 that could be linked to a California birth certificate, and controls were selected at random from California birth records. Average air toxics exposures during pregnancy were determined based upon measures from community-based air pollution monitors. The study included 75 cases and 14,602 controls who lived with 5 km of an air pollution monitor, and we additionally examined results for those living within a smaller radius around the monitor (2.5 km). Logistic regression was used to determine the risk of neuroblastoma with one interquartile range increase in air toxic exposure. Neuroblastoma risk was increased with higher maternal exposure to carbon tetrachloride (OR=2.65, 95%CI 1.07, 6.53) and polycyclic aromatic hydrocarbons (OR=1.39, 95%CI 1.05, 1.84), particularly indeno(1,2,3-cd)pyrene and dibenz(a,h)anthracene. Hexavalent chromium was associated with neuroblastoma at the 5 km distance (OR=1.32, 95%CI 1.00, 1.74) but not at the 2.5 km distance. This is one of the first studies to report associations between neuroblastoma and these air toxics.

Exposure to air pollution during pregnancy has been linked to the risk of childhood cancer, but the evidence remains inconclusive. In the present study, we used land use regression modeling to estimate prenatal exposures to traffic exhaust and evaluate the associations with cancer risk in very young children. Participants in the Air Pollution and Childhood Cancers Study who were 5 years of age or younger and diagnosed with cancer between 1988 and 2008 were had their records linked to California birth certificates, and controls were selected from birth certificates. Land use regression-based estimates of exposures to nitric oxide, nitrogen dioxide, and nitrogen oxides were assigned based on birthplace residence and temporally adjusted using routine monitoring station data to evaluate air pollution exposures during specific pregnancy periods. Logistic regression models were adjusted for maternal age, race/ethnicity, educational level, parity, insurance type, and Census-based socioeconomic status, as well as child's sex and birth year. The odds of acute lymphoblastic leukemia increased by 9%, 23%, and 8% for each 25-ppb increase in average nitric oxide, nitrogen dioxide, and nitrogen oxide levels, respectively, over the entire pregnancy. Second- and third-trimester exposures increased the odds of bilateral retinoblastoma. No associations were found for annual average exposures without temporal components or for any other cancer type. These results lend support to a link between prenatal exposure to traffic exhaust and the risk of acute lymphoblastic leukemia and bilateral retinoblastoma.

BackgroundHepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology.MethodsWe matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n=218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates.ResultsWe observed increased risks for hepatoblastoma among children with low [1500-2499 g, Odds Ratio (OR)=2.02, 95% confidence interval (CI) 1.29-3.15] and very low birthweight (

BackgroundStudies have shown that higher solar UV radiation exposure (UVR) may be related to lower risk of some cancers in adults. Recently, an ecologic study reported lower risks of some cancers among children living in higher UVR cities and countries. In a large population-based case-control study in California, we tested the hypothesis that childhood cancers may be influenced by UVR.MethodsCancers in children ages 0 to 5 years were identified from California Cancer Registry records for 1988 to 2007 and linked to birth certificate data. Controls were sampled from the birth certificates at a ratio of 20:1. Based on birth address, we assigned UVR exposure in units of Watt-hours/m(2) using a geostatistical exposure model developed with data from the National Solar Radiation Database.ResultsFor cases with UVR exposure of 5,111 Watt-hours/m(2) or above, we estimated a reduction in odds of developing acute lymphoblastic leukemia (OR: 0.89, 95% CI: 0.81-0.99), hepatoblastoma (OR: 0.69, 95% CI: 0.48-1.00), and non-Hodgkin's lymphoma (OR: 0.71, 95% CI: 0.50-1.02) adjusting for mother's age, mother's race, and child's year of birth. We also observed a small increase in odds for intracranial/intraspinal embryonal tumors (OR: 1.29, 95% CI: 1.01-1.65).ConclusionsOur findings suggest that UVR during pregnancy may decrease the odds of some childhood cancers. Future studies should explore additional factors that may be correlated with UVR exposure and possibly include biomarkers of immune function and vitamin D.ImpactThis study shows protective associations of UVR with some childhood cancers.

BackgroundRhabdoid tumors are a rare and aggressive cancer subtype which is usually diagnosed in early childhood. Little is known about their etiology. The purpose of this study was to describe the epidemiology of rhabdoid tumors and examine their relation to perinatal characteristics.MethodsWe identified 44 atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS) and 61 rhabdoid sarcomas (renal and extra-renal non-CNS tumors) from California Cancer Registry records of diagnoses 1988-2007 among children 42 weeks, OR = 3.66, 95% CI 1.54, 8.71) also increased risk of rhabdoid sarcomas. Rhabdoid sarcoma cases (OR = 3.08, 95% CI 1.11, 8.55) and AT/RT cases (OR = 3.16, 95% CI 1.23, 8.13) also were more likely to be multiple births.ConclusionThe excess of twin pregnancies may suggest an association with infertility treatments. This is the first population-based epidemiologic study to examine these rare tumors.

PurposeThe etiology of retinoblastoma remains poorly understood. In the present study, we examined associations between perinatal factors and retinoblastoma risk in California children.MethodsWe identified 609 retinoblastoma cases (420 unilateral, 187 bilateral, and 2 with laterality unknown) from California Cancer Registry records of diagnoses 1988-2007 among children

While associations between maternal infections during pregnancy and childhood leukemia in offspring have been extensively studied, the evidence for other types of childhood cancers is limited. Additionally, antibiotic exposure during pregnancy could potentially increase the risk of childhood cancers. Our study investigates associations between maternal infections and antibiotic prescriptions during pregnancy and the risk of childhood cancer in Taiwan. We conducted a population‐based cohort study using the Taiwan Maternal and Child Health Database (TMCHD), linked with national health and cancer registries. The study included 2 267 186 mother‐child pairs, and the median follow‐up time was 7.96 years. Cox proportional hazard models were utilized to estimate effects. Maternal infections during pregnancy were associated with a moderate increase in the risk of childhood hepatoblastoma (adjusted hazard ratio [HR] = 1.34; 95% confidence interval [CI]: 0.90‐1.98) and a weaker increase in the risk of childhood acute lymphoblastic leukemia (ALL) (adjusted HR = 1.15; 95% CI: 0.99‐1.35). Antibiotic prescriptions during pregnancy were also associated with an elevated risk of childhood ALL (adjusted HR = 1.30; 95% CI: 1.04‐1.63), particularly with tetracyclines (adjusted HR = 2.15; 95% CI: 1.34‐3.45). Several specific antibiotics were also associated with an increased risk of hepatoblastoma and medulloblastoma. Children exposed in utero to antibiotic prescription or both infections and antibiotics during pregnancy were at higher risk of developing ALL. Our findings suggest that there are associations between maternal infections, antibiotic use during pregnancy and the risk of several childhood cancers in addition to ALL and highlight the importance of further research in this area. [ABSTRACT FROM AUTHOR]

Background: Nitrosatable drugs can be synthesized to N‐nitroso compounds in human stomach. In a pregnant woman, N‐nitroso compounds can be translocated to the fetus through the placenta. Maternal exposure of nitrosatable compounds during pregnancy has been associated with childhood brain tumors and leukemia. However, few studies have investigated an association between nitrosatable drug exposure during pregnancy and childhood cancer. We examined if maternal prescriptions of nitrosatable drugs received during pregnancy are associated with childhood cancer. Methods: A matched case‐control study was conducted using Danish nationwide registry data from 1995 to 2016. Each childhood cancer case was matched with twenty‐five controls. Maternal exposure of nitrosatable drugs during pregnancy was identified from the Danish National Prescription Register. A multivariable conditional logistic regression model was used to estimate adjusted odds ratios (adj.OR) with 95% confidence intervals (CI) for each childhood cancer type. Results: Maternal prescriptions of nitrosatable drugs positively associate with central nervous system tumors (adj.OR = 1.25; 95% CI = 1.04–1.51) and neuroblastoma (adj.OR = 1.96; 95% CI = 1.34–2.85) in offspring. We also observed a positive association between perinatal exposure of nitrosatable drugs and acute lymphoblastic leukemia (adj.OR = 1.31; 95% CI = 1.07–1.59), however, it appeared to be due to confounding by indication, i.e., maternal infections. Conclusion: Nitrosatable drug use during pregnancy potentially increased risk of central nervous system tumors and neuroblastoma. While a positive association between maternal prescriptions of nitrosatable drugs and acute lymphoblastic leukemia should be interpreted cautiously because of confounding by indication. [ABSTRACT FROM AUTHOR]

Objective: The study investigated maternal exposure to heavy metals from industrial sources during pregnancy as potential risk factors for childhood cancer. Methods: Cases ages 0-19 were identified from California Cancer Registry. Controls (20:1 ratio) were randomly selected from California Birth Registry, frequency-matched by birth year (1998-2016). We estimated maternal exposure to lead, nickel, and cobalt in ambient air from the Toxics Release Inventory. We examined "ever/never" and "high/low" exposures categorized by median exposure. Models were adjusted for maternal age, race/ethnicity, method of payment for prenatal care, neighborhood socioeconomic status, and urban/rural residence. Results: Among highly exposed persons, lead was associated with an increased teratoma risk (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 0.97, 2.37), whereas nickel was associated with an increased rhabdomyosarcoma risk (aOR: 1.45; 95% CI: 1.03, 2.04). Cobaltwas associated with an increased glioma risk (aOR: 2.25; 95% CI: 1.39, 3.65) among ever-exposed persons. Inverse associations were found between Wilms tumor and nickel among the ever exposed and highly exposed (ever: aOR: 0.75; 95% CI: 0.59, 0.96; high: aOR: 0.64; 95% CI: 0.45, 0.93). Conclusions: Findings suggest that air pollution from heavy metals released by industrial sources may elevate childhood cancer risk. [ABSTRACT FROM AUTHOR]