A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.

Validation of DNA methylation biomarkers for diagnosis of acute lymphoblastic leukemia

DNA methylation biomarkers capable of diagnosis and subtyping have been found for many cancers. Fifteen such markers have previously been identified for pediatric acute lymphoblastic leukemia (ALL). Validation of these markers is necessary to assess their clinical utility for molecular diagnostics. Substantial efficiencies could be achieved with these DNA methylation markers for disease tracking with potential to replace patient-specific genetic testing.

Birthweight and childhood cancer : preliminary findings from the International Childhood Cancer Cohort Consortium (I4C)

BACKGROUND: Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.

METHODS: We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥4.0 vs. <4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.

RESULTS: A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].

CONCLUSION: Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored.

The development of a screening questionnaire for childhood cruelty to animals

Childhood cruelty to animals may be a marker of poor prognosis amongst conduct disordered children. However, other than semistructured interviews with parents or children, there are no screening instruments for this behavior. The aim of this study was to develop such an instrument. In the first phase of the study, a parent-report questionnaire, Children's Attitudes and Behaviors Towards Animals (CABTA) was designed and piloted on 360 elementary school children, enabling community norms and a factor structure for the instrument to be derived. In the second phase, the questionnaire was completed by the parents of a small sample of children (N= 17) to establish its test-retest reliability. In the third phase of the study, the CABTA was completed by the parents of 19 children who had been diagnosed with either a Disruptive Behavioral Disorder or Attention Deficit Hyperactivity Disorder, and the results were compared with the outcome of a semistructured interview with parents regarding their child's behavior toward animals. The results of the various phases of the study indicated that the CABTA consists of two factors, Typical and Malicious Cruelty to animals, and is a reliable and valid tool for detecting childhood cruelty to animals. Possible use and adaptations of the CABTA as a screening instrument in clinical and community samples are discussed.

Building equitable staff-parent communication in early childhood settings : an Australian case study

International research has consistently found that good staff-parent relationships in early childhood centers benefit children, staff, and parents. Given these findings, the Australian federal government's Quality Improvement and Accreditation Scheme (QIAS) requires centers to involve parents in their programs. However, international research has also found that early childhood staff are anxious about their relationships with parents. This article describes a study in which early childhood staff in Australia were asked about their experiences with parent involvement. It draws on those interviews to consider communication strategies to create equitable relationships between staff and parents.

Gay men from heterosexual marriages : attitudes, behaviors, childhood experiences and reasons for marriage

In the current study, the attitudes, behaviors and experiences of 26 gay or bisexual men who were married to a woman are examined. Data are provided on childhood family background and experiences, sexual practices with men, reasons for entering marriage, and the “coming out” process. The frequency of childhood sexual experiences was associated with unsafe sexual practices with other men in adulthood. Attitudes toward lesbians and gay men were more negative now than at the time of marriage. The two most frequent reasons for marriage were that it seemed natural, and a desire for children and family life. The results support the hypothesis that internalised homophobia is a factor that leads men into mixed-orientation marriages. Cognitive consistency theory is used to explain the eventual marriage breakdown.

Preparing early childhood professionals to work with parents: the challenges of diversity and dissensus

This article examines how early childhood staff in diverse circumstances negotiate relationships with parents. It draws on interviews with staff in two rural and three urban communities in Australia, who were asked about their parent communication practices, their experiences of these practices, and their preferences within these practices. Their responses were analysed in the light of international research showing the importance of creating strong interpretive communities between staff and parents but consistent staff anxiety about their relationships with parents. The paper explores the extent to which staff's different approaches to communicating with parents can create sustainable interpretive communities between them, and it highlights some implications for staff training and development around parent involvement.

Maltreatment and family dysfunction in childhood and the subsequent adjustment of children and adults

The adjustment problems associated with sexual abuse, physical abuse, psychological maltreatment, neglect, and witnessing family violence during childhood were examined in three studies. Study 1 demonstrated significant overlap between maltreatment types in parent reports (N = 50) of maltreatment experiences of their child aged 5–12 years. Parental sexual punitiveness, traditionality, family adaptability and family cohesion significantly predicted scores on 4 maltreatment scales and children's externalizing behavior problems. Level of maltreatment predicted internalizing, externalizing, and sexual behavior problems. In Study 2, significant overlap was found between adults' retrospective reports (N = 138) of all 5 types of maltreating behaviors. Parental sexual punitiveness, traditionality, family adaptability, and family cohesion during childhood predicted the level of maltreatment and current psychopathology. Although child maltreatment scores predicted psychopathology, childhood family variables were better predictors of adjustment. Study 3 demonstrated that child maltreatment scores predicted positive aspects of adult adaptive functioning (N = 95).

The Relationship of Childhood Family Characteristics and Current Attachment Styles to Depression and Depressive Vulnerability

The role of adult romantic attachment style in the relationship between childhood experiences and current depression was examined. Childhood maltreatment, parental separation/divorce, family adaptability and cohesion during childhood, current attachment style in romantic relationships, vulnerability to depression, and current depressive symptoms were measured in a self-selected sample of adults (N = 133). A large degree of overlap was found in the experience of different types of maltreatment during childhood. Depressive symptoms were uniquely predicted by the sexual abuse and neglect scales, with significant additional variance explained after entering the degree to which respondents' current romantic attachment style was “secure”. Maltreatment and family dysfunction in childhood were significant predictors of depression and vulnerability to depression. Although maltreatment scores did not differentiate between different attachment styles, the degree to which respondents were securely attached may explain -in part -the association between early childhood environment and depressive symptoms in adulthood.

Perceptions of local neighbourhood environments and their relationship to childhood overweight and obesity

OBJECTIVES: To examine associations between parent and child perceptions of the local neighbourhood and overweight/obesity among children aged 5–6 and 10–12 y. DESIGN: Cross-sectional survey. SUBJECTS: In total, 291 families of 5–6-y-old and 919 families of 10–12-y-old children. MEASURES: Parent's perceptions of local neighbourhood and perceived child access to eight local destinations within walking distance of home; 10–12-y-old children's perception of local neighbourhood; socio-demographic characteristics (survey). Children's height and weight (measured). RESULTS: No perceptions of the local neighbourhood were associated with weight status among 5–6-y-old children. Among 10–12-y-old children, those whose parents agreed that there was heavy traffic in their local streets were more likely to be overweight or obese (OR=1.4, 95% CI=1.0–1.8), and those whose parents agreed that road safety was a concern were more likely to be obese (OR=3.9, 95% CI=1.0–15.2), compared to those whose parents disagreed with these statements. CONCLUSIONS: This study suggests that parental perceptions of heavy traffic on local streets and concern about road safety may be indirect influences on overweight and obesity among 10–12-y-old children. Future work should also consider perceptions of the neighbourhood related to food choice.

Generalising the Cinderella Effect to unintentional childhood fatalities

We investigated whether the repeatedly demonstrated increase in risk of child abuse and infanticide associated with living with a step parent generalized to cases of unintentional childhood fatal injury, the most common cause of death in children across the developed world. Reports were drawn from the Australian National Coroners' Information System (NCIS) on all cases of intentionally (n=32) and unintentionally (n=319) produced fatal injury in children aged under 5 years between 2000 and 2003. Even when using the most conservative possible analytic approach, in which all cases in which family type was unclear were classified as being from an ‘intact biological family’, step children under 5 years of age were found to be at significantly increased risk of unintentional fatal injury of any type, and of drowning in particular. Children from single-parented families were generally not found to be at significantly increased risk of intentional or unintentional fatal injury, while children who lived with neither of their biological parents were at greatest risk overall for fatal injury of any type.