Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California.

BACKGROUND: Maternal 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. METHODS: The 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. RESULTS: 1,1,1-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). CONCLUSIONS: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Exposure to outdoor ambient air toxics and risk of breast cancer: The multiethnic cohort.

BACKGROUND: A growing literature has reported associations between traffic-related air pollution and breast cancer, however there are fewer investigations into specific ambient agents and any putative risk of breast cancer development, particularly studies occurring in populations residing in higher pollution areas such as Los Angeles. OBJECTIVES: To estimate breast cancer risks related to ambient air toxics exposure at residential addresses. METHODS: We examined the relationships between ambient air toxics and breast cancer risk in the Multiethnic Cohort among 48,665 California female participants followed for cancer from 2003 through 2013. We obtained exposure data on chemicals acting as endocrine disruptors or mammary gland carcinogens from the National-Scale Air Toxics Assessment. Cox proportional hazards models were used to estimate breast cancer risk per one interquartile range (IQR) increase in air toxics exposure lagged by 5-years. Stratified analyses were conducted by race, ethnicity, and hormone receptor types. RESULTS: Among all women, increased risks of invasive breast cancer were observed with toxicants related to industries [1,1,2,2-tetrachloroethane (hazard ratio [HR] = 4.22, 95% confidence interval [95% CI] 3.18-5.60), ethylene dichloride (HR = 2.81, 95% CI 2.20-3.59), and vinyl chloride (HR = 2.27, 95% CI 1.81, 2.85); these 3 agents were correlated (r2 = 0.45-0.77)]. Agents related to gasoline production or combustion were related to increased breast cancer risk [benzene (HR = 1.32, 95% CI 1.24, 1.41), ethylbenzene (HR = 1.20, 95% CI 1.13-1.28), toluene (HR = 1.29, 95% CI 1.20-1.38), naphthalene (HR = 1.11, 95% CI 1.02-2.22), acrolein (HR = 2.26, 95% CI 1.92, 2.65)]. Higher hazard ratios were observed in African Americans and Whites compared to other racial and ethnic groups (p-heterogeneity <0.05 for traffic-related air toxics, acrolein, and vinyl acetate). CONCLUSIONS: Our findings suggest that specific toxic air pollutants may be associated with increase breast cancer risk.

Effects of hypertension and use of antihypertensive drugs in pregnancy on the risks of childhood cancers in Taiwan.

BACKGROUND: Childhood 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. OBJECTIVE: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. METHODS: Data 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. RESULTS: Offspring 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. CONCLUSIONS: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Maternal autoimmune disease and its association with childhood cancer: A population-based case-control study in Denmark.

Background: Autoimmune 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. Methods: We linked data from several national registries in Denmark to identify childhood cancer cases in children <20 years diagnosed between 1977 to 2016. Controls were selected from the Central Population Register and matched to cases by birth year and sex (25:1). Mothers with autoimmune disease diagnosed in pregnancy or prior were identified from the National Patient Register. Multivariable conditional logistic regression analyses were used to estimate associations between maternal autoimmune diseases and childhood cancer in offspring. Results: Autoimmune diseases (all types) were positively associated with all childhood cancers combined (Odds Ratio (OR) = 1.25, 95% CI 1.06, 1.47), acute lymphoblastic leukemia (OR =1.52, 95% CI 1.09, 2.13), Burkitt lymphoma (OR = 2.69, 95% CI 1.04, 6.97), and central nervous system tumors (OR = 1.45, 95% CI 1.06, 1.99), especially astrocytoma (OR = 2.27, 95% CI 1.36, 3.77) and glioma (OR = 1.75, 95% CI 1.13, 2.73). When we examined mothers with rheumatoid arthritis, we observed an increased association for all cancers (OR = 2.15, 95% CI 1.40, 3.30), acute lymphoblastic leukemia (OR = 3.55, 95% CI 1.69, 7.47), and central nervous system tumors (OR = 2.91, 95% CI 1.46, 5.82), especially glioma (OR = 3.58, 95% CI 1.40, 9.18) in offspring. Conclusion: There is a positive association between maternal autoimmune disease and childhood cancer. This association is especially prominent in the offspring of women with rheumatoid arthritis.

Alpha-1 antitrypsin deficiency and pregnancy complications and birth outcomes: A population-based cohort study in Denmark.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is related to developing lung and liver disease, but no large-scale studies examine its association with birth outcomes. OBJECTIVE: We investigated the risk of pregnancy complications and adverse birth outcomes in mothers and children with AATD. METHODS: Using a large cohort data of Danish mothers and children with AATD from 1973 to 2013 (n = 2,027,229), with 559 cases (305 mothers and 254 children). We conducted Poisson regression to examine associations between alpha-1 antitrypsin deficiency, adverse birth outcomes, and pregnancy complications in mothers and children. RESULTS: AATD was related to term low birth weight [<2500g; Risk Ratio(RR) = 2.04, 95% confidence interval (CI): 1.50-2.79], lowest quartile of abdominal circumference at birth in children of non-smoking mothers (RR = 1.55, 95% CI: 1.14-2.11), delivery via Cesarean-section (RR = 1.59, 95% CI: 1.05-2.40), preterm birth (RR = 1.54, 95% CI: 1.19-2.00) and preeclampsia (RR = 2.64, 95% CI: 1.76-3.94). CONCLUSIONS: This emphasizes the need for mothers with AATD to be monitored closely during pregnancy to reduce the risk of adverse birth outcomes. Routine screening for alpha-1 antitrypsin in pregnancy may be considered among mothers with a pulmonary and liver disease history.

A prediction model for classifying maternal pregnancy smoking using California state birth certificate information.

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.

Preeclampsia, antihypertensive medication use in pregnancy and risk of childhood cancer in offspring.

PURPOSE: Preeclampsia is a serious pregnancy complication that presents a significant risk to both the mother and the fetus. Preeclampsia and medications associated with its treatment are potentially linked to increased childhood cancer risk. Therefore, we examined the association between preeclampsia, antihypertensive medications, and childhood cancer in offspring. METHODS: Cases (n = 6,420) and controls (n = 160,484) were obtained from Danish national registries. We performed conditional logistic regression analyses to estimate the association between preeclampsia and childhood cancer risk, and examined the effects of antihypertensive medication use in pregnancy in relation to childhood cancer risk in the offspring with adjustment for relevant covariates. RESULTS: We observed an increased risk of acute lymphoblastic leukemia (ALL) among those whose mothers had preeclampsia (OR = 1.36, 95% CI 1.03, 1.79), especially for severe preeclampsia (OR = 2.36, 95% CI 1.37, 4.08). We also estimated an increased cancer risk in children born to mothers who were prescribed diuretics during pregnancy [OR = 2.09, 95% confidence interval (CI) 1.39, 3.14]. Intake of other antihypertensive medications was not associated with childhood cancer (OR = 0.78, 95% CI 0.50, 1.23). Among women who did not take diuretics in pregnancy, preeclampsia was associated with neuroblastoma (OR = 2.22, 95% CI 1.08, 4.55). CONCLUSION: Our findings suggested an increased risk for certain types of cancer in the offspring of mothers with preeclampsia and an increased risk of cancer with diuretic intake during pregnancy.

Maternal medically diagnosed infection and antibiotic prescription during pregnancy and risk of childhood cancer: A population-based cohort study in Taiwan, 2004 to 2015.

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.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Neonatal per- and polyfluoroalkyl substance exposure in relation to retinoblastoma.

BACKGROUND: Neonatal per- and polyfluoroalkyl substance (PFAS) exposure can disrupt hormonal homeostasis and induce neuro- and immunotoxicity in children. In this exploratory study, we investigated associations between PFAS levels in neonatal dried blood spots and retinoblastoma risk. MATERIALS AND METHODS: This study included 501 retinoblastoma cases born from 1983 to 2011 and 899 controls frequency-matched by birth year (20:1 matching ratio), born to 755 US-born and 366 Mexico-born mothers in California. Perfluorooctanesulfonic acid (PFOS), perflurooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) feature intensities were identified from neonatal blood spots from California newborn Genetic Disease Screening Program. Using logistic regression, we assessed whether an interquartile range (IQR) increase of PFAS levels or having above-mean levels of PFAS in blood affects retinoblastoma risk overall or its subtypes (i.e., unilateral, bilateral). We assessed children of US-born and Mexico-born mothers, separately. RESULTS AND DISCUSSION: Among all children, above-mean PFOS levels at birth increased the odds of retinoblastoma overall by 29% (95% Confidence Interval (CI): 1.00, 1.67) and unilateral retinoblastoma by 42% (95% CI: 1.03, 1.97). For children of Mexico-born mothers, we estimated the highest odds of retinoblastoma overall (adjusted odds ratio (aOR): 1.67; 95% CI: 1.06, 2.66) and bilateral retinoblastoma (aOR: 2.06; 95% CI: 1.12, 3.92) with above-mean PFOS levels. Among children of US-born mothers, higher PFOS levels increased the odds of unilateral retinoblastoma by 15% (95% CI: 0.99, 1.35) for each IQR increase and by 71% among children with above-mean PFOS levels (95% CI: 1.04, 2.90). In addition, for children of US-born mothers, PFOA increased the odds of retinoblastoma overall (aOR: 1.41; 95% CI: 1.00, 2.02 for above-mean levels, aOR: 1.06; 95% CI: 0.98, 1.16 per IQR increase). PFNA was not associated with retinoblastoma risk. CONCLUSIONS: Our results suggested that PFOS and PFOA might contribute to retinoblastoma risk in children born in California.

The neonatal blood spot metabolome in retinoblastoma.

Background: Retinoblastoma is rare but nevertheless the most common pediatric eye cancer that occurs in children under age 5. High-resolution metabolomics (HRM) is a powerful analytical approach to profile metabolic features and pathways or identify metabolite biomarkers. To date, no studies have used pre-diagnosis blood samples from retinoblastoma cases and compared them to healthy controls to elucidate early perturbations in tumor pathways. Objectives: Here, we report on metabolic profiles of neonatal blood comparing cases later in childhood diagnosed with retinoblastoma and controls. Methods: We employed untargeted metabolomics analysis using neonatal dried blood spots for 1327 children (474 retinoblastoma cases and 853 healthy controls) born in California from 1983 to 2011. Cases were selected from the California Cancer Registry and controls, frequency matched to cases by birth year, from California birth rolls. We performed high-resolution metabolomics to extract metabolic features, partial least squares discriminant analysis (PLS-DA) and logistic regression to identify features associated with disease, and Mummichog pathway analysis to characterize enriched biological pathways. Results: PLS-DA identified 1917 discriminative features associated with retinoblastoma and Mummichog identified 14 retinoblastoma-related enriched pathways including linoleate metabolism, pentose phosphate pathway, pyrimidine metabolism, fructose and mannose metabolism, vitamin A metabolism, as well as fatty acid and lipid metabolism. Interpretation: Our findings linked a retinoblastoma diagnosis in early life to newborn blood metabolome perturbations indicating alterations in inflammatory pathways and energy metabolism. Neonatal blood spots may provide a venue for early detection for this or potentially other childhood cancers.

Hyperemesis gravidarum and the risk of childhood cancer - A case-control study in Denmark.

OBJECTIVE: Only 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. METHODS: Pediatric 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. RESULTS: In 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). CONCLUSION: Our 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.

Association between medically diagnosed postnatal infection and childhood cancers: A matched case-control study in Denmark, 1978 to 2016.

Although the association between infection and childhood cancer has been long investigated, there is limited information on rarer cancers. This article aimed to explore the association between postnatal infection and childhood cancers in the Danish population. A matched case-control study was conducted using Danish nationwide registries from 1978 to 2016. Each childhood cancer case was matched 1:25 with controls by birth date within a week and sex. Postnatal infections were identified from the Danish National Patient Registry, which lists diagnoses seen in hospital, specialist or emergency care services. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (adj.OR) and 95% confidence intervals (CI). Specific types of infections and the number of infection episodes were also considered. The study included 4125 childhood cancer cases and 103 526 matched controls with ages ranging from 0 to 19 years. Medically diagnosed postnatal infections were positively associated with many types of childhood cancer including acute lymphoblastic leukemia (adj.OR = 1.42; 95% CI: 1.23-1.63), acute myeloid leukemia (adj.OR = 1.80; 95% CI: 1.28-2.52), non-Hodgkin lymphoma (adj.OR = 1.53; 95% CI: 1.19-1.97) and central nervous system tumors (adj.OR = 1.57; 95% CI: 1.39-1.77). A higher number of infection episodes were also associated with an increased risk of these cancers. Specific infections such as viral, enteric and urinary tract infections were also strongly associated with specific types of cancer. In conclusion, children who later develop cancer appear to have adverse reactions to infections necessitating referral to specialized health care services, perhaps indicating dysregulated immune function.

Metabolite Stability in Archived Neonatal Dried Blood Spots Used for Epidemiologic Research.

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.

Danish Population Based Study of Familial Epilepsy and Childhood Cancer.

Objective: Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Methods: Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Results: Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95%CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.15, 95%CI = 1.01, 1.31), and central nervous system tumors (OR = 1.32, 95%CI = 1.03, 1.69) as well as neuroblastoma (OR = 2.05, 95%CI = 1.29, 3.28) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.78, 95%CI = 0.99, 3.21), however the confidence interval included the null. Significance: Maternal use of certain anticonvulsant medications may be a risk factor for cancer in offspring. Medical providers may need to consider what type of treatments to prescribe to pregnant mothers with epilepsy.

Maternal migraine and risk of pediatric cancers.

BACKGROUND: Maternal 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. METHODS: We 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. RESULTS: Maternal 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). CONCLUSIONS: Associations 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.

BIOMARKERS OF MATERNAL SMOKING AND THE RISK OF RETINOBLASTOMA IN OFFSPRING.

PURPOSE: Previous 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: The authors randomly selected 498 retinoblastoma cases and 895 control subjects born between 1983 and 2011 from a population-based case-control study in California. Maternal pregnancy-related smoking was measured using the following three metrics: provider or self-reported smoking during pregnancy, cotinine, and hydroxycotinine in neonatal blood. The authors used 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 = 1.44, 95% confidence interval: 1.00-2.09). Relying on cotinine or hydroxycotinine to ascertain smoking, maternal smoking was related to unilateral retinoblastoma (odds ratio = 1.66, 95% confidence interval: 1.08-2.57). CONCLUSION: The results indicate that maternal smoking during pregnancy may be a risk factor for retinoblastoma, particularly among unilateral cases.

Maternal anemia and the risk of childhood cancer: A population-based cohort study in Taiwan.

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 widely studied. 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 noncases). Cases were taken from the National Cancer Registry, and noncases were selected from birth 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.

Maternal anemia and childhood cancer: a population-based case-control study in Denmark.

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