Birth characteristics and childhood carcinomas

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 (OR(per 5-year age increase)=1.20, 95% CI 1.00–1.44), whereas paternal age increased the risk for any carcinoma (OR=1.10(per 5-year age increase), 95% CI 1.01–1.20) and thyroid carcinoma (OR(per 5-year age increase)=1.16, 95% CI 1.01–1.33). Gestational age <37 vs 37–42 weeks increased the risk for thyroid carcinoma (OR=1.87, 95% CI 1.07–3.27). Plurality, birth weight, and birth order were not significantly associated with childhood carcinomas. CONCLUSION: This exploratory study indicates that some birth characteristics including older parental age and low gestational age may be related to childhood carcinoma aetiology

Similar DNA methylation levels in specific imprinting control regions in children conceived with and without assisted reproductive technology: a cross-sectional study

BACKGROUND: While a possible link between assisted reproductive technology (ART) and rare imprinting disorders has been found, it is not clear if this is indicative of subtler disruptions of epigenetic mechanisms. Results from previous studies have been mixed, but some methylation differences have been observed. METHODS: Children conceived through ART and children conceived spontaneously were recruited for this cross-sectional study. Information about reproductive history, demographic factors, birth characteristics, and infertility treatment was obtained from maternal interview and medical records. Peripheral blood lymphocytes and buccal cell samples were collected from participating children. Methylation analysis was performed on five loci using pyrosequencing. Statistical analysis of methylation differences was performed using linear regression with generalized estimating equations. Results are reported as differences with 95% confidence intervals (CI). RESULTS: A total of 67 ART children and 31 spontaneously conceived (SC) children participated. No significant difference in methylation in lymphocyte samples was observed between groups for any loci. Possible differences were found in buccal cell samples for IGF2 DMR0 (Difference: 2.07; 95% confidence interval (CI): -0.28, 4.42; p = 0.08) and IGF2R (Difference: -2.79; 95% CI: -5.74, 0.16; p = 0.06). Subgroup analysis indicated potential lower methylation in those whose parents used ART for unexplained infertility. CONCLUSIONS: Observed differences in methylation between the ART and SC groups were small for all loci in the two sample types examined and no statistical differences were observed. It is still unclear whether or not small differences observed in several studies represent a real difference between groups and if this difference is biologically meaningful. Larger studies with long term follow-up are needed to fully answer these questions

Infant birthweight and risk of childhood cancer: international population-based case control studies of 40 000 cases

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

Parental and infant characteristics and childhood leukemia in Minnesota

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML) diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR) and 95% confidence intervals (CIs).</p> <p>Results</p> <p>Male sex (HR = 1.41, 95% CI 1.16–1.70), white race (HR = 2.32, 95% CI 1.13–4.76), and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70) increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47). Higher birth weights (>3798 grams) (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65), and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60) increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education.</p> <p>Conclusion</p> <p>We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.</p

Antipsychotic Use at Adult Ambulatory Care Visits by Patients With Mental Health Disorders in the United States, 1996-2003: National Estimates and Associated Factors

Objectives: This retrospective analysis was conducted to derive national estimates of typical, atypical, and combination (typical-atypical) antipsychotic use and to examine factors associated with their use at adult (age ≫-18 years) ambulatory care visits by patients with mental health disorders in the United States. Methods: Data on adult visits with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for a mental health disorder were extracted from the office-based National Ambulatory Medical Care Survey and the outpatient facilitybased National Hospital Ambulatory Medical Care Survey from 1996 through 2003. The visits were categorized according to whether use of a typical, atypical, or combination antipsychotic was mentioned (either prescribed, supplied, administered, ordered, or continued at the visits). Total weighted visit estimates, weighted visit percentages, and 95% CIs were calculated across the 3 types of visit groups. Bivariate analysis was performed on the association between selected characteristics and the 3 visit groups. Multivariate logistic regression was performed on factors associated with atypical versus typical antipsychotic use. Results: During the 8-year period, there were an estimated 47.7 million adult ambulatory care visits involving a mental health disorder and mention of an antipsychotic (weighted percent: 0.83%; 95% CI, 0.73-0.93). From 1996/1997 to 2002/2003, visits involving atypical and combination antipsychotics increased by 195% and 149%, respectively, and visits involving typical antipsychotics decreased by 71%. Men, blacks, and those with public insurance made more visits in which combination antipsychotics rather than typical or atypical antipsychotics were mentioned. Relative to typical or combination antipsychotic visits, more atypical antipsychotic visits involved antide-pressants (weighted percent: 61.23% atypical, 37.29% typical, and 38.32% combination). Fewer atypical antipsychotic visits compared with typical or combination antipsychotic visits involved psychotic disorders (weighted percent: 32.94%, 51.23%, and 69.93%, respectively) and medications for extrapyramidal symptoms (weighted percent: 6.69%, 29.95%, and 36.64%). In multivariate analyses controlling for sex, race, diagnosis of schizophrenia, region, diagnosis of anxiety, and recent years, atypical versus typical antipsychotic use was significantly less likely at visits by those aged 41 to 64 years compared with those aged 18 to 40 years (adjusted odds ratio [OR] = 0.63; 95% CI, 0.47-0.84; P = 0.002); significantly less likely at visits by those with public compared with private insurance (Medicare OR = 0.59 [95% CI, 0.40-0.88], P = 0.010; Medicaid OR = 0.44 [95% CI, 0.28-0.69], P \u3c 0.001); and significantly more likely at visits associated with depression compared with those not associated with depression (OR = 1.92; 95% CI, 1.26-2.93; P = 0.003) and those associated with bipolar disorder compared with those not associated with bipolar disorder (OR = 2.10; 95% CI, 1.32-3.36; P = 0.002). Conclusions: This retrospective analysis found more atypical than typical or combination antipsychotic use at US ambulatory care visits by adults with mental health disorders other than schizophrenia or psychoses in the period studied. Atypical versus typical antipsychotic use was significantly less likely at visits by adults aged 41 to 64 years and those with public insurance, but significantly more likely at visits by those with depression or bipolar disorder

Epigenetics in Pediatrics

Epigenetic mechanisms are external modifications of DNA that cause changes in gene function and are involved in many diseases. Specific examples of pediatric diseases with a known or suspected epigenetic component include Beckwith-Wiedemann syndrome, childhood leukemia, allergies, asthma, fetal alcohol spectrum disorders, childhood obesity, and type 2 diabetes mellitus. Currently, epigenetically active treatments are being used to treat childhood leukemia. Potential epigenetically active treatments and preventive regimens are under study for other diseases. Pediatricians need to be aware of the epigenetic basis of disease to help inform clinical decision making in the future.</jats:p