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There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction

Children with cancer are frequently hospitalized. However, hospitalization and death by disease category are not well defined

6537 Background: Emerging evidence suggests mortality among children with cancer differs based on socioeconomic factors. The effects of residential location in relation to these factors are not well-characterized. We examined associations of rurality and neighborhood-level socioeconomic (SE) disadvantage with mortality in pediatric patients with cancer. Methods: We conducted a retrospective cohort study using Washington State (WA) Cancer Registry data (1992-2013) linked to state birth (1974-2013) and death records (1992-2013) to identify all children born in WA diagnosed with cancer < 20 years. We defined rural residence as patient addresses within 2010 census tract level rural-urban commuting area (RUCA) codes of ≥4.0 at diagnosis. Neighborhood-level socioeconomic disadvantage was determined using 2010 census block-group level Area Deprivation Index (ADI) quintiles normalized to WA. Patient addresses within the highest ADI quintile were categorized as having SE disadvantage. children in four mutually exclusive groups was compared using Kaplan-Meier analysis, pairwise log rank testing, and Cox proportional hazard ratios (HR): non-rural with SE disadvantage, rural without SE disadvantage, rural with SE disadvantage, and non-rural without SE disadvantage (). Models were adjusted for sex, race and ethnicity, age at diagnosis, birth year, and cancer type. Results: We identified 4,417 children for analysis. Median length of follow up among survivors was 5.0 years (inter-quartile range: 1.0-11.5). SE disadvantaged and 13% were rural. Pairwise log rank tests showed mortality differences among children living in rural, SE disadvantaged, or rural and SE disadvantaged neighborhoods when compared with children without either factor (individual p-values all < 0.005); no other differences were noted. Relative to children in non-rural areas without SE disadvantage, the mortality HR for those in non-rural areas with SE disadvantage was 1.68 (95% confidence intervals [CI] 1.37-2.07). The HR for children in rural areas without SE disadvantage was 1.59 (95% CI 1.19-2.12). The HR for children in rural areas with SE disadvantage was 1.56 (95% CI 1.20-2.03). In sub-analyses, associations for rurality and SE disadvantage remained significant for leukemia mortality, but CNS and solid tumor mortality was only associated with SE disadvantage (but not rural) status. Acute lymphoblastic leukemia mortality was associated with rural (but not SE disadvantage) status. Conclusions: Children with cancer living in socioeconomically disadvantaged and/or rural neighborhoods at diagnosis had higher mortality relative to those in non-rural areas with lower neighborhood deprivation. Associations varied by disease type. The individual effects of SE disadvantage and rurality suggest that interventions should be designed to target both factors.

BACKGROUND: Linked birth certificate–hospital discharge records are a valuable resource for examining pregnancy outcomes among women with disability conditions. Few studies relying on these data have been able to assess the accuracy of identification of pre-existing disability conditions. We assessed the accuracy of International Classification of Diseases version 9 (ICD9) codes for identifying selected physical, sensory, and intellectual conditions that may result in disability. As ICD9 codes were utilized until recently in most states, this information is useful to inform analyses with these records. METHODS: We reviewed 280 of 311 (90%) medical records of pregnant women with disabilities based on ICD9 codes and 390 of 8,337 (5%) records of pregnant women without disabilities who had deliveries at a large university medical center. We estimated sensitivity, specificity, and positive predictive values (PPV) using the medical record as gold standard. We adjusted for verification bias using inverse probability weighting and imputation. RESULTS: The estimated sensitivity of ICD9 codes to identify women with disabilities with deliveries 2009–2012 was 44%; PPV was 98%, improving over time. Although sensitivity was

We examined serious long-term outcomes among childhood cancer survivors using population-based data. We used 1982–2014 Washington State data to compare hospitalization and/or death (including cause-specific) during up to 27 years follow-up among all 5+ year childhood cancer survivors

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14years) 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 1-5years 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.

BACKGROUND: Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent. AIM: To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies. MATERIAL/METHODS: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants

Introduction Low birth weight has been associated with an increased risk of hypertension in children. Less clear is whether high birth weight is also associated with risk. We evaluated overall and age-specific risks of primary hypertension in children and young adults associated with birth weight and birth weight for gestational age. Methods We conducted a population-based case-control study using linked Washington State birth certificate and hospital discharge data from 1987 to 2003. Cases were persons hospitalized with primary hypertension at 8-24 years of age (n = 533). Controls were randomly selected among those born in the same years who were not hospitalized with hypertension (n = 25,966). Results Birth weight was not related to risk of primary hypertension overall, except for a suggestion of an increased risk associated with birth weight ≥4500 g relative to 3500-3999 g (odds ratio (OR) 1.55; 95 % confidence interval (CI) 0.96-2.49). Compared to children born appropriate weight for gestational age, those born small (SGA) (OR 1.32; 95 % CI 1.02-1.71) and large for gestational age (LGA) (OR 1.30; 95 % CI 1.00-1.71) had increased risks of primary hypertension. These overall associations were due to increased risks of hypertension at 15-24 years of age; no associations were observed with risk at 8-14 years of age. Discussion In this study, both SGA and LGA were associated with increased risks of primary hypertension. Our findings suggest a possible nonlinear (U-shaped) association between birth weight for gestational age and primary hypertension risk in children and young adults.

PURPOSE: Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. METHODS: We conducted a retrospective cohort study of singleton live births from 2001–2014 to women enrolled in Kaiser Permanente Washington, an integrated healthcare delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as “continuers” (n=1634); those without a fill were “discontinuers” (n=1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. RESULTS: Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10, 95% confidence interval [CI]: 0.84–1.44) and screening blood glucose levels (mean difference: 2.3 mg/dL, 95% CI: −1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30, 95% CI: 0.90–1.88) and venlafaxine (RR: 1.52, 95% CI: 0.87–2.68), but neither association was statistically significant. CONCLUSIONS: Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

One in 1,000 pregnancies is complicated by malignancies. Prevalence is greater for benign neoplasms. Adverse outcomes among women with malignancies have been reported. Less is known of postpartum outcomes for infants, or outcomes among women with benign neoplasms. We conducted a population-based cohort study using Washington State-linked vital-hospital discharge records. Women with neoplasms (707 malignant; 13,156 benign) with deliveries in 1987–2012 were identified, and a randomly selected comparison cohort. Obstetrical/infant outcomes and rehospitalization

Background Male sex is associated with an increased risk of childhood cancer as is high birthweight. Given that sex determination precedes birthweight we conducted a mediation analysis to estimate the direct effect of sex in association with childhood cancer tumor type with birthweight as the mediator. Methods Cases (n = 12,632) and controls (n = 64,439) (ages 0–14 years) were identified from population-based cancer and birth registries in Minnesota, New York, and Washington states (1970–2014). An inverse odds weighting (IOW) mediation analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) as the measure of association between sex and cancer. Results A significant indirect effect was observed for sex and lymphoid leukemia, mediated by birthweight (indirectOR: 1.03; 95% CI: 1.02–1.04). We observed significant direct effects for male sex and lymphoid leukemia (directOR: 1.16; 95% CI: 1.08–1.25), Hodgkin lymphoma (directOR: 1.48; 95% CI: 1.22–1.81), Burkitt lymphoma (directOR: 5.02; 95% CI: 3.40–7.42), other non-Hodgkin lymphoma (directOR: 1.42; 95% CI: 1.18–1.70), intracranial embryonal tumors (directOR: 1.49; 95% CI: 1.26–1.76), hepatoblastoma (directOR: 1.90; 95% CI: 1.40–2.59), and rhabdomyosarcoma (directOR: 1.47; 95% CI: 1.19–1.81). There were also inverse associations for extracranial GCTs (directOR: 0.41; 95% CI: 0.26–0.63) and thyroid carcinoma (directOR: 0.35; 95% CI: 0.25–0.50). Conclusion Significant direct effects for sex and numerous childhood cancer types suggests sex-specific factors such as differences in gene expression from the autosomes or the X chromosome, rather than birthweight, may underlie sex differences in tumor risk.

Background High birthweight is an established risk factor for childhood leukaemia. Its association with other childhood cancers is less clear, with studies hampered by low case numbers. Methods We used two large independent datasets to explore risk associations between birthweight and all subtypes of childhood cancer. Data for 16 554 cases and 53 716 controls were obtained by linkage of birth to cancer registration records across five US states, and 23 772 cases and 33 206 controls were obtained from the UK National Registry of Childhood Tumours. US, but not UK, data were adjusted for gestational age, birth order, plurality, and maternal age and race/ethnicity. Results Risk associations were found between birthweight and several childhood cancers, with strikingly similar results between datasets. Total cancer risk increased linearly with each 0.5 kg increase in birthweight in both the US [odds ratio 1.06 (95% confidence interval 1.04, 1.08)] and UK [1.06 (1.05, 1.08)] datasets. Risk was strongest for leukaemia [USA: 1.10 (1.06, 1.13), UK: 1.07 (1.04, 1.10)], tumours of the central nervous system [USA: 1.05 (1.01, 1.08), UK: 1.07 (1.04, 1.10)], renal tumours [USA: 1.17 (1.10, 1.24), UK: 1.12 (1.06, 1.19)] and soft tissue sarcomas [USA: 1.12 (1.05, 1.20), UK: 1.07 (1.00, 1.13)]. In contrast, increasing birthweight decreased the risk of hepatic tumours [USA: 0.77 (0.69, 0.85), UK: 0.79 (0.71, 0.89) per 0.5 kg increase]. Associations were also observed between high birthweight and risk of neuroblastoma, lymphomas, germ cell tumours and malignant melanomas. For some cancer subtypes, risk associations with birthweight were non-linear. We observed no association between birthweight and risk of retinoblastoma or bone tumours. Conclusions Approximately half of all childhood cancers exhibit associations with birthweight. The apparent independence from other factors indicates the importance of intrauterine growth regulation in the aetiology of these diseases.

Background Increased risk of adverse birth outcomes is well described in women with systemic lupus erythematosus (SLE), but risk of maternal or infant infection in the peripartum period has not been well studied. We conducted a population-based cohort study of infection risk in women with and without SLE and their infants. Methods Linked birth-hospital discharge data identified 1297 deliveries to women with SLE and a 4:1 comparison cohort of deliveries to women without SLE in Washington State, 1987-2013. Maternal and infant infections during the first 30 days after delivery were identified. Relative risks (RR) and 95% confidence intervals (CI) were estimated. Results Women with SLE were 1.7 times more likely (95% CI 1.4, 2.0) to have an infection during the birth hospitalisation and more likely to receive antibiotics during labour (RR 1.3, 95% CI 1.1, 1.5), though there was no increased risk of chorioamnionitis in women with SLE. Infants of women with SLE had an increased risk for an infection during the birth hospitalisation (RR 2.2, 95% CI 1.3, 3.5), although the size of the difference was smaller when adjusted for gestational age (RR 1.4, 95% CI 0.9, 2.1). Risks of neonatal infection, sepsis, receipt of antibiotics, and admission to neonatal intensive care were also increased, and were also attenuated after adjustment for gestational age. Conclusions Women with SLE have an increased risk of peripartum infections and antibiotic exposure. Their neonates have a greater likelihood of infection, much of which is attributable to preterm birth.

BACKGROUND Infant leukaemia (IL) is extremely rare with fewer than 150 cases occurring each year in the United States. Little is known about its causes. However, recent evidence supports a role of de novo mutations in IL aetiology. Parental age has been associated with several adverse outcomes in offspring, including childhood cancers. Given the role of older parental age in de novo mutations in offspring, we carried out an analysis of parental age and IL. METHODS We evaluated the relationship between parental age and IL in a case-control study using registry data from New York, Minnesota, California, Texas, and Washington. Records from 402 cases [219 acute lymphoblastic leukaemia (ALL), 131 acute myeloid leukaemia (AML), and 52 other] and 45 392 controls born during 1981-2004 were analysed. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Estimates were adjusted for infant sex, birth year category, maternal race, state, and mutually adjusted for paternal or maternal age, respectively. RESULTS Infants with mothers' age ≥40 years had an increased risk of developing AML (OR 4.80, 95% CI 1.80, 12.76). In contrast, paternal age

Background : Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives : The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods : By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31000 cases and 50000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions : CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic groups.

Background Prenatal exposure to tobacco is associated with adverse health outcomes for the mother and child, and has been associated with an increased risk of tobacco smoking and nicotine dependence in offspring. The objective of this study was to examine the risk of prenatal smoking, among daughters, associated with maternal prenatal smoking. Methods We used a population-based cohort study design, with linked vital records data of mothers and daughters delivering 1984–96 and 1996–2013, respectively, in Washington State. The exposure of interest was mothers’ prenatal smoking (any vs. no smoking at any time during pregnancy), while the outcome was daughters’ prenatal smoking (similarly assessed). We used multivariable log-binomial regression to obtain estimates of the relative risk (RR) and 95% confidence interval (CI). Results Daughters exposed to maternal prenatal smoking were more likely to smoke during their pregnancy, compared to unexposed daughters (RR 1.78, 95% CI 1.72, 1.84, adjusted for the year the daughter delivered, her marital status and educational attainment, and the mothers’ race/ethnicity). Conclusions In this relatively young population, we found that daughters exposed to maternal prenatal smoking have an increased risk of smoking later on during their own pregnancy, emphasizing the importance of exposures during the prenatal period. The mechanisms leading to prenatal smoking are multifactorial and likely include behavioural, genetic, epigenetic and environmental factors. An understanding of this risk factor for prenatal smoking may guide health care providers to better target smoking cessation interventions to at-risk populations.

Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003–2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06–1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95–1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI.

Background: Some epidemiologic studies suggest that maternal consumption of cured meat during pregnancy may increase risk of brain tumors in offspring. We explored whether this possible association was modified by fetal genetic polymorphisms in genes coding for glutathione S-transferases (GSTs) that may inactivate nitroso compounds. Methods: We assessed six GST variants: GSTM1 null, GSTT1 null, GSTP1I105V (rs1695), GSTP1A114V (rs1138272), GSTM3*B (3-bp deletion), and GSTM3A-63C (rs1332018) within a population-based case-control study with data on maternal prenatal cured meat consumption (202 cases and 286 controls born in California or Washington, 1978–1990). Results: Risk of childhood brain tumor increased with increasing cured meat intake by the mother during pregnancy among children without GSTT1 [OR = 1.29; 95% confidence interval (95% CI), 1.07–1.57 for each increase in the frequency of consumption per week] or with potentially reduced GSTM3 (any −63C allele; OR = 1.14; 95% CI, 1.03–1.26), whereas no increased risk was observed among those with GSTT1 or presumably normal GSTM3 levels (interaction P = 0.01 for each). Conclusions: Fetal ability to deactivate nitrosoureas may modify the association between childhood brain tumors and maternal prenatal consumption of cured meats. Impact: These results support the hypothesis that maternal avoidance during pregnancy of sources of some nitroso compounds or their precursors may reduce risk of brain tumors in some children. Cancer Epidemiol Biomarkers Prev; 20(11); 2413–9. ©2011 AACR.

Background: Carcinomas in children are rare and have not been well studied. Methods: We conducted a population-based case–control study and examined associations between birth characteristics and childhood carcinomas diagnosed from 28 days to 14 years during 1980–2004 using pooled data from five states (NY, WA, MN, TX, and CA) that linked their birth and cancer registries. The pooled data set contained 57 966 controls and 475 carcinoma cases, including 159 thyroid and 126 malignant melanoma cases. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results: White compared with ‘other' race was positively associated with melanoma (OR=3.22, 95% CI 1.33–8.33). Older maternal age increased the risk for melanoma (ORper 5-year age increase=1.20, 95% CI 1.00–1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10per 5-year age increase, 95% CI 1.01–1.20) and thyroid carcinoma (ORper 5-year age increase=1.16, 95% CI 1.01–1.33). Gestational age

The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect.

Background: Little has been reported on socioeconomic (SES) patterns of risk for most forms of childhood cancer. Methods: Population-based case–control data from epidemiological studies of childhood cancer conducted in five US states were pooled and associations of maternal, paternal and household educational attainment with childhood cancers were analysed. Odds ratios (ORs) and 95% confidence intervals were estimated using logistic regression, controlling for confounders. Results: Although there was no association with parental education for the majority of cancers evaluated, there was an indication of a positive association with lower education for Hodgkin's and Burkitt's lymphoma and Wilm's tumour, with the ORs ranging from 1.5 to >3.0 times that of more educated parents. A possible protective effect was seen for lower parental education and astrocytoma and hepatoblastoma, with ORs reduced by 30 to 40%. Conclusions: These study results should be viewed as exploratory because of the broad nature of the SES assessment, but they give some indication that childhood cancer studies might benefit from a more thorough assessment of SES.

Background Children of different racial/ethnic backgrounds have varying risks of cancer. However, few studies have examined cancer occurrence in mixed ancestry children.

Background: Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare. Methods: Case–control studies formed by linking cancer and birth registries of California, Minnesota, New York, Texas and Washington, which included 583 RMS cases (363 embryonal and 85 alveolar RMS) and 57 966 randomly selected control subjects, were analysed using logistic regression. The associations of RMS (overall, and based on embryonal or alveolar histology) with birth weight across five 500 g categories (from 2000 to 4500 g) were examined using normal birth weight (2500–3999 g) as a reference. Large (>90th percentile) and small (

Although several studies have found no change or a decreased risk of childhood cancer in twins, few have controlled for potential confounders such as birth weight. We examined the association of birth plurality and childhood cancer in pooled data from five U.S. states (California, Minnesota, New York, Texas, and Washington) using linked birth-cancer registry data. The data, excluding children with Down syndrome or who died before 28 days of life, included 17,672 cases diagnosed from 1980 to 2004 at ages 28 days to 14 years and 57,966 controls with all cases and controls born from 1970 to 2004. Analyses were restricted to children weighing ≤4,000 g at birth. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression adjusting for sex, gestational age, birth weight, birth order, maternal age, maternal race, state of birth, and birth year. Children who were multiples had no difference in risk of cancer overall (OR, 0.93; 95% CI, 0.82-1.07), but a borderline reduced risk of Wilms' tumor (OR, 0.65; 95% CI, 0.39-1.09). For children diagnosed

International audience; OBJECTIVE: To examine whether childhood brain tumors (CBTs) are associated with a family history of brain tumors or other cancers in an international case-control study. METHODS: Cancers in children's first- and second-degree relatives were ascertained by interview with parents of 620 children with astroglial tumors, 255 with primitive neuroectodermal tumors, 324 with other CBTs, and 2,218 controls from Australia, Canada, France, Israel, Italy, Spain, and the US. These were used with histories of neurofibromatosis or tuberous sclerosis to exclude in subanalyses children with Li-Fraumeni or other hereditary syndromes predisposing to brain tumors. RESULTS: A first- or second-degree relative of 4% of children with astroglial tumors, 6% with PNET, 5% with other CBTs, and 5% of controls had had a brain tumor. Any potential differences were statistically non-significant, including when focusing on relatives diagnosed in childhood. In the US, where anatomical sites of relatives' other cancers were known, CBT occurrence was not associated with any other specific site. Results were not markedly altered by exclusion of children with hereditary syndromes. CONCLUSION: Consistent with most prior studies using these methods, we observed no strong relationship between CBT occurrence and cancers in family members.

Purpose To evaluate the feasibility of obtaining dried blood spots (DBS) from newborn screening archives for subjects in epidemiologic studies and using these specimens for genotyping, and to evaluate the potential for bias in their use. Methods We attempted to locate DBS at Washington State's archives for 230 participants in a previous case-control study of childhood cancer, who were born 1978–1990. We compared characteristics of children for whom we did and did not locate specimens and attempted genetic polymorphism analyses (11 polymorphisms, 82–480 bp amplicons). Results We retrieved specimens for 203 (88%) children, including 199 (94%) born in months when a DBS catalog was available. Among the latter, the proportion with specimens located varied by birth place (e.g., hospital, home), maternal education, and prenatal smoking, but did not vary significantly by race/ethnicity. All genotyping assays were completed for all specimens, and among controls genotype distributions were in Hardy-Weinberg equilibrium and similar to previous reports. Conclusions Newborn screening archives have potential to provide specimens for epidemiologic studies conducting genotyping and perhaps other assays, but the possibility that reliance on these resources could bias risk estimates must be considered.

Consumption of nitrate and nitrite is associated with a variety of health outcomes. Commercially available test strips that allow semi-quantitative estimation of these contaminants in drinking water are inexpensive relative to laboratory testing, and are simple to use. To examine the accuracy of a nitrate/nitrite test strip, we recruited Washington State residents to estimate levels of these contaminants in their tap water using these strips, and simultaneously provide a tap water sample for laboratory analysis. Paired results were available from 102 homes. On the basis of laboratory assay, nitrate levels as nitrogen ranged from no nitrate (27%) to 40.5 mg/l (median 0.4 mg/l). Spearman's correlation coefficient between test strip- and laboratory-measured nitrate indicated moderate precision overall (r=0.72). Correlation was similar for homes inside and outside city/town limits, but differed by primary source of water for the purveyor indicated by residents (r=0.72 for groundwater and r=0.34 for surface water). Seven (7%) participants reported difficulty in distinguishing colors (contaminant levels) when using the test strip; and among the samples with nitrate, the laboratory assay indicated higher nitrate levels than the test strip for 81%. Nitrite was not detected by laboratory assay; in comparison, five (5%) subjects reported any nitrite according to the test strip. Nitrate/nitrite test strips may be useful in some epidemiologic studies, but should be used with caution, preferably as a screening tool or when laboratory assays are not feasible.

Our objective was to investigate the association of childhood leukaemia with selected maternal and birth characteristics by conducting a population-based case-control study using linked cancer registry and birth certificate records for Washington State. We compared maternal and infant characteristics of 595 Washington-born residents

International audience; N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.

Experimental evidence suggests that parental exposure to polycyclic aromatic hydrocarbons (PAH), which occurs primarily through tobacco smoke, occupational exposure, and air pollution, could increase the risk of cancer during childhood. Population-based case-control studies carried out in seven countries as part of the SEARCH Program compared data for 1,218 cases of childhood brain tumors and 2,223 controls (1976-1994). Parental occupational exposure to PAH during the 5-year period before birth was estimated with a job exposure matrix. Risk estimates were adjusted for child's age, sex, and study center. Paternal preconceptional occupational exposure to PAH was associated with increased risks of all childhood brain tumors (odds ratio (OR) = 1.3, 95% confidence interval: 1.1, 1.6) and astroglial tumors (OR = 1.4, 95% confidence interval: 1.1, 1.7). However, there was no trend of increasing risk with predicted level of exposure. Paternal smoking alone (OR = 1.4) was also associated with the risk of astroglial tumors in comparison with nonsmoking, non-occupationally-exposed fathers. Risks for paternal occupational exposure were higher, with (OR = 1.6) or without (OR = 1.7) smoking. Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. This large study supports the hypothesis that paternal preconceptional exposure to PAH increases the risk of brain tumors in humans.

The etiology of childhood brain tumors (CBTs) remains unknown. Tobacco smoke contains several known carcinogens and can induce DNA adducts in human placenta and hemoglobin adducts in fetuses. We present the results of an international case-control study to evaluate the association between CBTs and exposure of parents and children to cigarette smoke. The study was undertaken as part of the SEARCH program of the IARC. Nine centers in 7 countries were involved. The studies mainly covered the 1980s and early 1990s. Cases (1,218, ages 0-19 years) were children newly diagnosed with a primary brain tumor; there were 2,223 population-based controls. Most mothers who agreed to participate were interviewed in person at home. Odds ratios (ORs) were calculated by unconditional logistic regression, adjusted for age, sex and center, for all types of CBT combined, 4 CBT histotypes, 5 age groups and each center. There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life. These results did not change considering the child's age at diagnosis, the histologic type of tumor or center.

Objective: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT).

Data from a population-based case-control study in 19 counties in California and Washington State were used to investigate the association between parental employment and childhood brain tumors. Parents of 540 cases (including 308 astroglial and 109 primitive neuroectodermal tumors) and 801 controls diagnosed from 1984 to 1991 were interviewed. Analysis was completed for parents' self-reported industry of employment and job tasks during the five years preceding the birth of the child. Parents who worked in the chemical industry were at increased risk of having had children with astroglial tumors (fathers' odds ratio [OR] = 2.1; 95 % confidence interval [CI], 1.1-3.9); mothers' OR = 3.3; 95% CI, 1.4-7.7), but no trend by duration of employment was seen for mothers. Children of fathers employed as electrical workers were at increased risk of developing brain tumors of any histologic type (OR = 2.3; 95% CI, 1.3-4.0).

To evaluate the risk of childhood brain tumor occurrence in relation to epilepsy and anticonvulsant use.As part of a multicenter case-control study of pediatric brain tumors, maternal report on epilepsy occurrence before diagnosis of her child's brain tumor was collected for 540 cases and compared with 801 control children. Mothers also reported on any long-term (or = 2 weeks) use of medications by her child before the date of tumor diagnosis (or a comparable reference date for controls) and these medications were classified according to whether they contained barbiturates.As expected, because seizures are often an early brain tumor symptom, a strong association was observed between epilepsy and brain tumor occurrence (odds ratio, OR = 6.2; 95% confidence limit, CL = 2.9, 14). The association remained elevated even after aor = 10-year interval between diagnoses of epilepsy and brain tumor (OR = 4.7; CL = 0.8, 48). Elevated odds ratios were observed both for epileptic children who were treated with anticonvulsants containing barbiturates (OR = 5.8; CL = 2.2, 18) and for those not treated with barbiturates (OR = 7.9; CL = 1.7, 74), relative to nonepileptic children.Whereas most of the brain tumor risk associated with epilepsy may be due to occult tumors, the finding of an elevated risk many years after diagnosis of epilepsy is of interest.

A population-based study was conducted using maternally-linked birth certificate records from Washington State for 1980–93 to evaluate the risk of birth defect occurrence among infants with pre-viously affected siblings, relative to infants whose siblings did not have birth defects. The risks of recurrence of similar and dissimilar defects were estimated, and the effects of change in paternity and/or city of residence were evaluated as proxies of genetic and environmental effects. At the first birth on record, 3322 women were identified in the linked certificates as giving birth to a child with a birth defect; 6620 women whose first birth did not result in an infant with a defect were randomly selected for comparison. Women with a malformed infant had an in-creased risk of having a malformed infant at the subsequent birth (Relative Risk = 1.9, [95% Confidence Interval (CI) = 1.5–2.4]), which did not vary by intervening changes in partner or residence. The risk of recurrence of the same general type of defect [RR = 11.7, 95% CI = 9.7–19.50] was much greater than that of occurrence of a dissimilar defect [RR = 1.5, 95% CI = 1.1–1.9]. This was consistent for all defect categories, and did not vary markedly by changes in partner or residence.

Premature rupture of the amniotic membranes (PROM) occurs in up to 20% of all births. Although many studies have examined risk factors for PROM and, in particular, preterm PROM (PPROM, if less than 37 weeks' gestation), the aetiology of PROM recurrence has not been examined as closely. This study investigated factors that may increase the risk of PROM among women who have already experienced one PROM birth. Maternally linked Washington State birth certificates from 1984 to 1993 identified 208 women with consecutive PROM births. Controls were a random sample (n = 848) of women who had one birth on record complicated by PROM, but whose subsequent birth was not. Among women with a prior term PROM, increased risk for PROM recurrence (term PROM or PPROM) was associated with an intervening fetal death at less than 20 weeks' gestation (OR = 2.4, 1.3-4.5) and with parity of two or more (OR = 2.0, 1.3-3.4). None of the factors assessed significantly increased the risk of recurrence of PROM (term PROM or PPROM) among women with a prior PPROM. Other potential risk factors for PROM recurrence were evaluated within the two PROM groups (PPROM or term PROM at first birth) by stratifying among the cases according to gestational length at subsequent birth.

Purpose To assess the accuracy of smoking data in contemporary U.S. birth certificates. Methods We compared data on prenatal smoking as reported on Washington State birth certificates to cotinine measured in archived newborn screening dried blood spots for 200 infants born in 2007 (100 randomly selected from births to self-reported nonsmokers and 100 born to self-reported smokers). We estimated the sensitivity of the birth certificate data to identify prenatal smokers and the precision with which self-identified third trimester smokers report smoking levels. Results Infants born to two (2%) mothers who reported they did not smoke during the pregnancy had whole blood cotinine concentrations consistent with active smoking by the mother (sensitivity 85%). Sensitivity of the birth certificate to identify reported smokers who continued to smoke throughout pregnancy was similar (89%). Among self-identified third trimester smokers whose infants' specimens were collected shortly after delivery, Spearman rho between infant cotinine and maternal-reported cigarettes/day in the third trimester was 0.54. Conclusions Birth certificates may represent a viable option for assessing prenatal smoking status, and possibly smoking cessation and level among smokers, in epidemiologic studies sufficiently powered to overcome a moderate amount of exposure measurement error.

Background: Women who were younger at their first live birth have a reduced breast cancer risk. Other pregnancy characteristics, including complications, also may affect risk but because they are rare, require large datasets to study. Methods: The association of pregnancy history and breast cancer risk was assessed in a population-based study including 22,646 cases diagnosed in Washington State 1974 to 2009, and 224,721 controls, frequency matched on parity, age, calendar year of delivery, and race/ethnicity. Information on prediagnosis pregnancies derived from linked birth certificate and hospital discharge databases. Adjusted odd ratios (ORs) and 95% confidence intervals (CI) were calculated. Results: Multiple gestation pregnancies were associated with decreased breast cancer risk (OR, 0.65; 95% CI, 0.57–0.74) as was prepregnancy obesity (OR, 0.76; 95% CI, 0.65–0.90). Infant birth weight was positively associated (6% per 1,000 g; 95% CI, 3%–9%). The ORs for first trimester bleeding (OR, 3.35; 95% CI, 1.48–7.55) and placental abnormality/insufficiency (OR, 2.24; 95% CI, 1.08–4.67) were increased in women diagnosed at age 50+ years and 15+ years after the index pregnancy. Results were similar in analyses restricted to first pregnancies, those closest to diagnosis, and when excluding in situ disease. Conclusion: These data suggest that multiple gestation pregnancies are protective, whereas delivering larger infants increases risk for later development of maternal breast cancer. Placental abnormalities that result in bleeding in pregnancy also may reverse the long-term protection in postmenopausal women associated with parity. Impact: Certain pregnancy characteristics seem to be associated with later maternal breast cancer risk. Cancer Epidemiol Biomarkers Prev; 22(5); 835–47. ©2013 AACR.

Many cardiovascular drugs have been implicated as causes of depression. With the exception of beta-blockers, few have been studied in formal epidemiologic designs. I present a new approach to such analyses that effectively controls for confounders that are stable over time. I analyzed the exposure histories of 11,244 incident antidepressant users, using the Odense University PharmacoEpidemiologic Database. All persons starting both beta-blockers and antidepressants during a predefined period were identified. If beta-blockers do not cause depression, this particular population should show equal numbers of persons starting either drug first. A depression-provoking effect of beta-blockers would generate an excess of persons starting beta-blockers first, that is a nonsymmetrical distribution of prescription orders. Confounders causing the two drugs to be co-prescribed would rarely be expected to affect the symmetry. The initial screening showed nonsymmetrical prescription orders for a wide range of cardiovascular drugs. After adjustment for an increasing incidence of antidepressant prescribing, I found a depression-provoking effect only for angiotensin-converting enzyme (ACE) inhibitors (rate ratio = 1.29; 95% confidence interval = 1.08-1.56) and calcium channel blockers (rate ratio = 1.31; 95% confidence interval = 1.14-1.51). This prescription sequence symmetry analysis may be useful as a screening tool.

In reconstructing exposure histories needed to calculate cumulative exposures, gaps often occur. Our investigation was motivated by case-control studies of residential radon exposure and lung cancer, where half or more of the targeted homes may not be measurable. Investigators have adopted various schemes for imputing exposures for such gaps. We first undertook simulations to assess the performance of five such methods under an excess relative risk model, in the presence of random missingness and under assumed independence among the true exposure levels for different epochs of exposure (houses). Assuming no other source of measurement error, one of the methods performed without bias and with coverage of nominally 95% confidence intervals that was close to 95%. This method assigns to the missing residences the arithmetic mean across all measured control residences. We show that its good properties can be explained by the fact that this approach produces approximate "Berkson errors." To take advantage of predictive information that might exist about the missing epochs of exposure, one might prefer to carry out the imputations within strata. In further simulations, we asked whether the method would still perform well if imputations were carried out within many strata. It does, and much of the lost statistical power/precision can be recovered if the stratification system is moderately predictive of the missing exposures. Thus, observed control mean imputation provides a way to impute missing exposures without corrupting the study's validity; and stratifying the imputations can enhance precision. The technique is applicable in other settings where exposure histories contain gaps.

Recent medication use of 3,394 members of the Group Health Cooperative of Puget Sound (GHC) diagnosed with an incident work-related injury was compared to that of two controls selected from the GHC membership and matched on age, gender, and Standard Industrial Classification Code of their employer. Medication use was determined from the GHC pharmacy data base. The injuries of the cases included 496 fractures or dislocations, 2,728 open wounds, crushing injuries, or superficial injuries, 176 burns, and 64 internal or intracranial injuries. The risk of injury was elevated among users of antihistamines [odds ratio (OR) = 1.5, 95% confidence interval (CI) = 1.1-1.9], antibiotics (OR = 1.2, 95% CI = 1.0-1.5), and diabetes medications (OR = 1.3, 95% CI = 0.9-1.9). The patterns of risk were similar for males and females, but varied by type of injury. No consistent associations between use of antidepressants, antianxiety medication, or narcotics and work-related injury were observed. The use of some medications, or conditions requiring medications, may contribute to the risk of a work-related injury.

To study maternal smoking during pregnancy and the risk of congenital urinary tract anomalies, we interviewed mothers of 118 affected infants born to residents of western Washington State during 1990 and 1991 and mothers of 369 control infants randomly selected from those without birth defects delivered during those years in five hospitals in King County, Washington. Maternal smoking was associated with an increased risk of congenital urinary tract anomalies in offspring (adjusted odds ratio [OR] = 2.3; 95% confidence interval [CI] = 1.2, 4.5). This risk was higher among light smokers (1-1000 cigarettes during the pregnancy) (OR = 3.7; 95% CI = 1.7, 8.6) than among heavy smokers (OR = 1.4; 95% CI = 0.6, 3.3). Our results corroborate previous findings and support the hypothesis of a causal relation.

To assess the relation between childhood brain tumor occurrence and exposure to potential sources of residential magnetic fields, a population-based case-control study of incident brain tumors was conducted in the Seattle, Washington, area at the Fred Hutchinson Cancer Research Center from 1989 to 1994 among children younger than age 20 years who were diagnosed from 1984 to 1990. The specific aims were to evaluate whether proximity to high-current residential power lines, as defined by the Wertheimer-Leeper code, or use of electric appliances or electric heating sources by the mother while pregnant or by the child before diagnosis were associated with increased risks of brain tumor occurrence. The mothers of 133 cases and 270 controls (recruited by random digit dialing) participated. Risk of brain tumor occurrence did not increase with increasing exposure, as indicated by the five-level Wertheimer-Leeper code. When exposure was dichotomized as high versus low, the odds ratio was 0.9 (95% confidence interval 0.5-1.5) and did not vary significantly by sex, age, or histology. No elevations in risk were found for ever versus never use of electric blankets, water beds, or electric heating sources. Odds ratios were slightly elevated for nine appliances and were at or below 1.0 for eight others. These data do not support the hypothesis that exposure to magnetic fields from high-current power lines, electric heating sources, or electric appliances is associated with the subsequent occurrence of brain tumors in children.

Summary. Prior studies suggest that diagnosis of gestational diabetes is associated with increased risk for development of gestational diabetes in future pregnancies, and with subsequent onset of established diabetes. The magnitudes of these risks have not been measured. Using linked birth certificate data from Washington State it is possible to identify all women with two or more births occurring during 1984-91. All women with gestational diabetes (n= 1375) or with established diabetes (n= 220), during their pregnancy for the second or greater birth were identified, and a control group consisting of women whose second or greater birth was not complicated by either condition was randomly selected (n = 6380). Data from the birth certificate, for the previous birth, were compared in order to estimate the risks of developing gestational or established diabetes in a subsequent pregnancy among women with prior gestational diabetes relative to women without gestational diabetes. The age-adjusted risk of developing gestational diabetes in the pregnancy for the subsequent birth associated with prior gestational diabetes was 23.2 (95% (confidence interval) CI = 17.2–31.2); the risk of having developed established diabetes by the time of the subsequent birth was 55.5 (95% CI = 34.4–89.4). Women who had a macrosomic infant (> 4000 gm) in the prior birth were also at increased risk for developing gestational diabetes (odds ratio OR = 3.3, 95% CI = 2.9-3.8) or established diabetes (OR = 5.8, 95% CI = 4.0–8.5). When data were restricted to patients with only one prior birth, to patients with early prenatal care, to delivery at facilities with long-established protocols for diagnosing gestational diabetes, or to more recent years, the risk estimates remained similarly elevated. The 23-fold increased risk of gestational diabetes associated with having gestational diabetes indicated on the birth certificate of a woman's previous baby, although not unexpected, is still remarkable and reinforces the importance of careful monitoring of women with this history. Although changes in how screening is conducted may account for some of the elevation in risk, our results stayed consistently elevated even when restrictions were made within the data to control for this. The fact that there was a 56-fold increased risk of having developed established diabetes by the time of the subsequent birth on record, associated with prior gestational diabetes, and a 6-fold increased risk associated with a macro-somic infant, supports the idea that these may be early steps in the development of established diabetes, and identifies a group that may benefit from close monitoring and possible intervention.

To study the relation of maternal periconceptional vitamin use to the risk of a congenital urinary tract anomaly (CUTA), we conducted a case-control study using the Washington State Birth Defect Registry. We identified CUTA cases with no known chromosomal abnormality in seven counties in western Washington State occurring between January 1, 1990, and December 31, 1991. We randomly selected a sample, as controls, of all infants delivered in five large hospitals in King County who did not have a birth defect and who were born in the same year as the cases. About 55% of all infants in King County and a smaller proportion of infants in the other six counties are delivered in these five hospitals. We interviewed mothers of 118 cases and 369 controls to obtain information about their vitamin use during the pregnancy and during the year before the conception. After adjustment for maternal race, family income, county of maternal residence, and birth year, we found that women who used multivitamins during the first trimester had only 15% the risk of bearing a child with a CUTA compared with women who did not take vitamins [odds ratio (OR) = 0.15; 95% confidence interval (CI) = 0.05-0.43]. The reduction was smaller for use restricted to the second or third trimesters (OR = 0.31; 95% CI = 0.09-1.02). Among women who used vitamins during the first trimester, vitamin use before conception was not associated with any further reduction in the risk, nor did there appear to be an association with the amount or brand of vitamin used.(ABSTRACT TRUNCATED AT 250 WORDS)

Several case-control studies have reported positive associations between childhood cancer and proximity to high-current residential power lines as defined by the Wertheimer-Leeper code. We conducted a study to evaluate whether or not differential nonparticipation of controls as a function of socioeconomic status is likely to account for the observed associations. We assessed the relation of annual family income to the Wertheimer-Leeper code in a sample of 392 households in western Washington state, and we evaluated the magnitude of bias that could occur from differential participation of low- and high-income eligible controls. Very-high-current configurations were most frequently located among households with self-reported family income of less than +15,000 per year, and very-low-current configurations were most frequently located among those with self-reported family income of more than +45,000 per year. In a hypothetical case-control study in which: (1) it was assumed that there is no true etiologic relation between power line configurations and cancer occurrence, and (2) controls with very low income were less likely to participate than others, observed (biased) odds ratios ranged from 1.03 to 1.24. If these results are applicable to other areas where case-control studies of cancer in relation to power lines have been conducted, they suggest that relatively lower participation among exposed controls (as a function of very low income) is not likely to account for the elevated risks of 1.5- to 3-fold that have been observed in these previous studies.

Purpose To examine whether smoking during first pregnancy, a time of potential vulnerability to tobacco mutagens, is associated with breast cancer. Methods We conducted a nested case-control study within a cohort of Washington State residents with first deliveries during 1984–1999, identified in birth and fetal death records. Linkage to population-based cancer registry data identified 1,099 women in the cohort aged 65 years and younger diagnosed with breast cancer in 1985–2000. Controls (N=10,922) were matched by year and age of first delivery, race/ethnicity, and birth outcome. Maternal smoking and other variables characterizing the pregnancy were obtained from birth and fetal death records. Conditional logistic regression was used to analyze the data. Results The adjusted risk ratio for breast cancer was 0.8, 95% confidence interval 0.7–0.9, among women who smoked during their pregnancy compared with similar women who did not smoke. When the sample was restricted to known state residents at the time of the matched case's diagnosis, there was no association (risk ratio 1.0; 0.8–1.1). Conclusions Our results do not suggest that cigarette smoking during first pregnancy increases the risk of breast cancer.

Using the 1983 United States population of single live births, birthweight and gestational duration were compared for babies of these different parental racial groups: both parents White, mother White-father Black, mother Black-father White, both parents Black. The four groups differed significantly with respect to the usual sociodemographic variables. Mean birthweight and mean gestational duration decreased in that order from the White-White reference group, and conversely there were increasing trends for low birthweight and preterm delivery. Adjustment for the usual sociodemographic variables did not alter these trends appreciably. Group differences were more strongly related to the mother's race than to the father's, and the trends were related to the mother's race. Because the father's race was significant, genetic factors are probably of some importance. The evidence from this study, together with the often-demonstrated relationships between low birthweight and preterm delivery with sociodemographic variables, and the short-term downward secular trends in low birthweight, support the concept that non-genetic maternal factors are more important for these abnormal outcomes. But because neither the usually utilised sociodemographic variables nor genetic factors seem to explain much of the group differences, new approaches are necessary to understand why, irrespective of ethnic group, some women are at excess risk for suboptimal birth outcome.

Brain tumor research is unlike some other areas of cancer research, in which definite causes have been identified and prevention and treatment strategies may be developed. Primary brain tumors are heterogeneous with respect to several characteristics, and brain tumor research is hampered by this fact, as well as by the small numbers of cases, by the lack of a clearly established and consistently applied histopathologic classification scheme, and by geographical variations in diagnostic capabilities and mechanisms for case reporting. The current movement toward molecular epidemiology has resulted in several changes in the ways we will be able to investigate cancer etiologies in the future, and promises to be especially fruitful in the area of brain tumor research. The search is under way for biologic markers of risk exposures for various cancers, and for laboratory methods to identify those individuals who, because of their genetic qualities, are most likely to have brain tumors. There are probably multiple causes for brain tumors, incorporating both genetic and environmental pathways. Prior research has consistently identified few risk factors for brain tumors, such as ionizing radiation. Thus, collaborative efforts among clinicians, laboratory scientists, and epidemiologists, which make use of molecular epidemiologic methods, are perhaps of greater importance in this field than for cancers arising at other sites.