BACKGROUND: Little is known about risk factors for childhood rhabdomyosarcoma (RMS) and the histology-specific details are rare.\n\nMETHODS: 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 (<10th percentile) size for gestational age were calculated based on birth weight distributions in controls and were similarly examined.\n\nRESULTS: High birth weight increased the risk of embryonal RMS and RMS overall. Each 500 g increase in birth weight increased the risk of embryonal RMS (odds ratio (OR)=1.27, 95% confidence interval (CI)=1.14-1.42) and RMS overall (OR=1.18, 95% CI=1.09-1.29). Large size for gestational age also significantly increased the risk of embryonal RMS (OR=1.42, 95% CI=1.03-1.96).\n\nCONCLUSIONS: These data suggest a positive association between accelerated in utero growth and embryonal RMS, but not alveolar RMS. These results warrant cautious interpretation owing to the small number of alveolar RMS cases.

Maternal diet and nutrition have been thought to play a role in many childhood conditions. Studies using food frequency questionnaires (FFQ) have reported associations with maternal diet, but these findings are difficult to interpret because the reliability and validity of the FFQs for diet during a past pregnancy are not known. We determined the reproducibility of reported diet and supplement use during a past pregnancy in a subset of mothers interviewed for a case-control study of maternal diet in relation to the risk of childhood brain tumours. Cases were Children's Oncology Group patients, diagnosed at age <6 with medulloblastoma or primitive neuroectodermal tumour from 1991 to 1997. Area code, race/ethnicity, and birth date matched controls were selected by random-digit-dialling. Case and control mothers completed a modified Willett FFQ a mean of 5 years after the index child's birth. A mean of 3.6 months later, a subset of mothers consisting of 52 case and 51 control mothers repeated the interview; these comprise the reproducibility study population. The mean intra-class correlation was 0.59 (range 0.41, 0.69) for energy-adjusted nutrients from dietary sources only; it was 0.41 (range 0.06, 0.70) when supplements were included. Agreement for reporting multivitamin use during pregnancy by time period and pattern was good to very good (kappa = 0.66-0.85). Overall, the reproducibility of nutrient estimates and supplement use in pregnancy was good and similar to that reported for adult diet.

Family history of testicular cancer is an established risk factor for adult testicular germ cell tumors (GCT). We evaluated the association between family history of cancer and pediatric GCT in a Children's Oncology Group case-control study that included 274 GCT cases (195 female and 79 male) diagnosed < age 15 years and 418 controls frequency matched to cases on sex and age. Family history data were collected through telephone interviews with biological mothers and fathers and unconditional logistic regression was used to evaluate associations with GCT adjusting for potential confounders. A family history of cancer with onset < age 40 years was associated with a reduced risk of GCT among female cases (Odds Ratio (OR) = 0.50, 95% Confidence Interval (CI) 0.28-0.89) and an increased risk among male cases (OR = 2.56, 95% CI 1.02-6.44). Male cases were more likely to report family history of melanoma compared with male controls (OR = 4.65, 95% CI 1.40-15.4). There was an inverse association between family history of ovarian or uterine cancers and GCT in girls (OR = 0.46, 95% CI 0.22-0.96). These sex and cancer site specific associations should be confirmed in additional studies as they may provide clues to the etiology of pediatric GCT.

Nearly 12,400 children and adolescents under the age of twenty years will be newly diagnosed with cancer each year in the United States. This means that a newborn has an approximately 1 in 315 chance of developing cancer in the first two decades of life. This chapter reviews the epidemiology of cancer in children. Topics covered include overall incidence, mortality and morbidity, acute lymphoblastic leukemia and acute myeloid leukemia, brain/central nervous system cancers, lymphomas, sympathetic nervous system tumors, soft tissue sarcoma, renal cancers, bone tumors, germ cell tumors, retinoblastoma, and hepatic tumors. © 2006 by Oxford University Press, Inc. All rights reserved.

OBJECTIVE: The risk of hepatoblastoma is strongly increased among children with very low birth weight (<1500 g). Because data on very low birth weight and other childhood cancers are sparse, we examined the risk of malignancy with very low birth weight in a large data set. METHODS: We combined case-control data sets created by linking the cancer and birth registries of California, Minnesota, New York, Texas, and Washington states, which included 17672 children diagnosed as having cancer at 0 to 14 years of age and 57966 randomly selected control subjects. Unconditional logistic regression analysis was used to examine the association of cancer with very low birth weight and moderately low birth weight (1500-1999 g and 2000-2499 g, respectively), compared with moderate/high birth weight (>or=2500 g), with adjustment for gender, gestational age, birth order, plurality, maternal age, maternal race, state, and year of birth. RESULTS: Most childhood cancers were not associated with low birth weights. However, retinoblastomas and gliomas other than astrocytomas and ependymomas were possibly associated with very low birth weight. The risk of other gliomas was also increased among children weighing 1500 to 1999 g at birth. CONCLUSIONS: These data suggested no association between most cancers and very low birth weight, with the exception of the known association of hepatoblastoma and possibly moderately increased risks of other gliomas and retinoblastoma, which may warrant confirmation.

BACKGROUND: Children with Down syndrome (DS) have about a 20-fold increased risk of developing leukemia. Early childhood infections may protect against acute lymphoid leukemia (ALL) in children with and without DS. We examined whether maternal infections and health conditions during pregnancy were associated with acute leukemia in children with DS.\n\nPROCEDURE: We conducted a case-control study of 158 children with DS and leukemia (including 97 cases with acute lymphoblastic leukemia (ALL) and 61 cases with acute myeloid leukemia (AML)) and 173 children with DS during the period 1997-2002. Maternal interview included information about 14 maternal conditions during gestation that are likely to induce an inflammatory response. We evaluated their prevalence in cases and controls. Five of these were common enough to allow analyses by leukemia subtype.\n\nRESULTS: Vaginal bleeding was the most frequent (18% cases, 25% controls) and was associated with a reduced risk (odds ratio (OR) = 0.57; 95% confidence interval (CI) = 0.33-0.99) for all cases combined. Other variables, while showing a potential trend toward reduced risk had effect estimates, which were imprecise and not statistically significant. In contrast, amniocentesis was marginally associated with an increased risk of AML (OR = 2.06, 95% CI = 0.90-4.69).\n\nCONCLUSIONS: Data from this exploratory investigation suggest that some health conditions during pregnancy may be relevant in childhood leukemogenesis. Larger epidemiological studies and other model systems (animal, clinical studies) may provide a clearer picture of the potential association and mechanisms.

BACKGROUND Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. METHODS We assessed the relationship between parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0-14 years during 1980-2004 and 57,966 controls born during 1970-2004. Individuals with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. RESULTS Positive linear trends per 5-year maternal age increase were observed for childhood cancers overall (odds ratio = 1.08 [95% confidence interval = 1.06-1.10]) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 [1.05-1.11]), lymphoma (1.06 [1.01-1.12]), central nervous system tumors (1.07 [1.03-1.10]), neuroblastoma (1.09 [1.04-1.15]), Wilms' tumor (1.16 [1.09-1.22]), bone tumors (1.10 [1.00-1.20]), and soft tissue sarcomas (1.10 [1.04-1.17]). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. CONCLUSIONS Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.

Traditionally, controls in US pediatric cancer studies were selected through random digit dialing. With declining participation and lack of nonparticipant information, random digit dialing (RDD) controls may be substandard. Birth certificate (BC) controls are an alternative, because they are population based and include data from nonparticipants. The authors examined controls collected by random digit dialing and birth certificates for a Children's Oncology Group case-control study of infant leukemia in 1995-2006. Demographic variables were used to assess differences in RDD and BC controls and their representativeness. RDD and BC controls did not differ significantly with regard to maternal variables (age, race, education, marital status, alcohol during pregnancy) or child variables (sex, gestational age, birth weight), but they varied in smoking during pregnancy (22% RDD controls, 12% BC controls) (P = 0.05). The study's combined control group differed significantly from US births: Mothers of controls were more likely to be older (29.8 vs. 27.2 years), white (84% vs. 59%), and married (85% vs. 67%) and to have >16 years of education (37% vs. 25%). Control children were more often full term (88% vs. 81%) and heavier (3,436 vs. 3,317 g). Finally, participating BC mothers were likely to be older and to have more education than nonparticipants. Thus, the study's control groups were comparable but differed from the population of interest.

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 <or=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 <2 y of age there was a reduced risk of Wilms' tumor (OR, 0.27; 95% CI, 0.09-0.86) and neuroblastoma (OR, 0.46; 95% CI, 0.25-0.84) and an increased risk of fibrosarcoma (OR, 5.81; 95% CI, 1.53-22.11). Higher-order multiple birth (triplets or higher) was not associated with childhood cancer. Our analysis suggests that mechanisms other than birth weight and gestational age may influence the lower risk of Wilms' tumor and neuroblastoma in multiple births.

BACKGROUND: Recent studies in childhood cancer suggest that maternal vitamin supplementation may reduce the risk of leukaemia, neuroblastoma and certain types of childhood brain tumours. For example, a previous study found a significantly reduced risk of acute lymphoblastic leukaemia (ALL) but not acute myeloid leukaemia (AML) in children with Down syndrome whose mothers reported any vitamin supplement use prior to knowledge of pregnancy (ALL OR adjusted for confounders 0.51, 95% confidence limits (CL): 0.30, 0.89; AML OR adjusted for confounders 0.92, 95% CL 0.48, 1.76). Recall of exposures, including maternal vitamin supplement use, however, may be difficult and subject to error. Epidemiologists are encouraged to quantitatively adjust for systematic error in study results, but often do not. METHODS: The impact that misclassification of maternal vitamin supplement use may have had on the observed ORs in this study was quantified. Uncertainty analysis was used to calculate ORs adjusted for inaccurate reporting of vitamin supplement use under assumed probability distributions for exposure misclassification parameters. RESULTS: Given our assumptions, adjustment for exposure misclassification yielded ORs that were predominantly more protective for ALL than the crude OR. CONCLUSIONS: Uncertainty analysis can give important insights into the magnitude and direction of error in study results due to exposure misclassification.

Objective: To determine whether the postnatal growth rate of infants with intrauterine growth restriction (IUGR) is associated with later cognitive function and body mass index (BMI). Study design: Infants with IUGR (<2211 g at ≥37 weeks' gestation) were identified in data from the Collaborative Perinatal Project, excluding those with diagnoses affecting cognition or growth. Wechsler Scale of Children's Intelligence (WISC) scores at age 7 years and data on postnatal growth at 16 weeks were available for 463 infants with IUGR. Linear regression relating postnatal growth and WISC score, adjusting for potential confounders, was performed for these infants. BMI at 7 years also was examined. Results: Weight gain at 16 postnatal weeks ranged from 1059 to 5119 g in the infants with IUGR, with lower achieved cognitive testing scores apparent at both extremes (ie, an inverted J-shape; P < .001). Infants gaining 1200 and 5000 g scored 15.5 and 2.4 fewer points, respectively, on the full scale compared with infants with score-maximizing growth. In contrast, BMI at 7 years was linearly related to postnatal weight gain (P < .001). Conclusions: Growth in the first 4 postnatal months is an independent risk factor for cognitive outcome at age 7 years, with both extremes associated with negative effects. © 2009 Mosby, Inc. All rights reserved.

Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL), few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology.

We confirmed the strong association of hepatoblastoma with very low birth weight (relative risk <1000 g vs >or=2000 g=25.6; 95% confidence interval: 7.70-85.0) and demonstrated independent associations with congenital abnormalities and maternal Asian race in a population-based Minnesota study that included 36 cases and 7788 controls.

More than 13,000 children are estimated to be newly diagnosed with cancer each year in the United States ([1][1]). Despite substantial improvements in survival over the last several decades, cancer is still the leading cause of death due to disease in children ages 1 to 14 years ([2][2]). The

Wilms tumor (WT) is a childhood kidney cancer with the highest rate of occurrence before the age of 2. Since it is rare, previous research has been limited and few risk factors have been established. We used a case-cohort design to examine the influence of birth characteristics on occurrence of WT in Minnesota. A total of 2,188 cases of cancer diagnosed in children aged 28 days to 14 years from 1988 to 2004 were identified using the Minnesota Cancer Surveillance System (MCSS). For each case, 4 children were randomly selected from Minnesota birth records during 1976-2004, frequency matched on birth year. Thus, a total of 8,752 children comprised the subcohort for the study, who in this analysis, served as comparison to the 138 cases of WT. Study variables included parental demographics, maternal pregnancy history and conditions and health and conditions of the child at birth. Associations with WT were assessed using hazard ratios (HR) and 95% confidence intervals (CI) calculated from stratified Cox regression models. We found an increased risk of WT for children who were large for gestational age compared to those average for gestational age and for children with congenital abnormalities. There was also an increased risk for children with a birth weight > 4,000 g compared to those with a birth weight between 2,500 and 4,000 g. All other factors examined showed no association with WT. This study contributes to the mounting evidence that children with large size at birth have an increased risk of WT.