Helen D. Bailey

Maternal folate and other vitamin supplementation during pregnancy and risk of acute lymphoblastic leukemia in the offspring

The Australian Study of Causes of Acute Lymphoblastic Leukemia in Children (Aus‐ALL) was designed to test the hypothesis, raised by a previous Western Australian study, that maternal folic acid supplementation during pregnancy might reduce the risk of childhood acute lymphoblastic leukemia (ALL). Aus‐ALL was a national, population‐based, multicenter case–control study that prospectively recruited 416 cases and 1,361 controls between 2003 and 2007. Detailed information was collected about maternal use of folic acid and other vitamin supplements before and during the index pregnancy. Data were analyzed using logistic regression, adjusting for matching factors and potential confounders. A meta‐analysis with the results of previous studies of folic acid supplementation was also conducted. We found weak evidence of a protective effect of maternal folate supplementation before pregnancy against risk of childhood ALL, but no evidence for a protective effect of its use during pregnancy. A meta‐analysis including this and 2 other studies, but not the study that raised the hypothesis, also found little evidence that folate supplementation during pregnancy protects against ALL: the summary odds ratios (ORs) for folate supplementation were 1.06 [95% confidence interval (CI): 0.77–1.48] with reference to no folate supplementation and 1.02 (95% CI: 0.86–1.20) with reference to no vitamin supplementation. For vitamin supplementation in general, the summary OR from a meta‐analysis of 5 studies—including Aus‐ALL—was 0.83 (95% CI: 0.73–0.94). Vitamin supplementation in pregnancy may protect against childhood ALL, but this effect is unlikely to be large or, if real, specifically due to folate.

Representativeness of child controls recruited by random digit dialling

Recruiting control subjects who are representative of the population from which the cases are drawn is a challenge in case-control studies. This paper examines the performance of random digit dialling (RDD) in obtaining a control sample, and the samples representativeness of the population with respect to socio-economic status. The study subjects were recruited from 2003 to 2006 for a national, population-based case-control study investigating causes of acute lymphoblastic leukaemia (ALL) in children <15 years of age in Australia. Control families addresses were linked to Australian Bureau of Statistics Census 2006 Collection Districts and thus to Socio-Economic Indexes for Area scores, which are area-based measures of socio-economic status. These scores were compared with those of all collection districts where families lived. We estimate that 55% of eligible families in the RDD sample agreed to participate in the study. Participation was directly related to socio-economic status with those of highest economic status most likely to participate. Completeness of participation in the components of data collection was similarly related to socio-economic status. This evidence of selection according to socio-economic status indicates that there may also be selection with respect to other factors potentially important in the aetiology of ALL.

Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia

Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency‐matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta‐analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the childs birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre‐B than T cell ALL and for t(12;21) (ETV6‐Runx‐1) than other cytogenetic sub‐types. The pooled OR from a meta‐analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta‐analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the childs early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations.

Maternal Dietary Intake of Folate and Vitamins B6 and B12 During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia

Our aim was to address the hypothesis that maternal dietary intake of folate during pregnancy is inversely associated with risk of acute lymphoblastic leukemia (ALL) in the offspring. Dietary intake of folate, vitamins B6 and B12 in the last 6 mo of pregnancy from 333 cases and 695 frequency-matched controls were assessed using a food frequency questionnaire. Data were analyzed using unconditional logistic regression, adjusting for study matching variables, total energy, and potentially confounding variables. Higher levels of dietary folate and B12 appeared to be associated with a decreased risk of ALL. Higher levels of vitamin B6 were associated with an increased risk. The strongest associations of ALL with these variables were seen when mothers consumed alcohol in pregnancy. Our findings are consistent with a modest protective effect of higher dietary intake of folate and vitamin B12 against ALL in the offspring, more particularly among women who drank alcohol during pregnancy. These findings are consistent with previous reports of the protective effects of a maternal diet high in fruit, vegetables, and nondairy protein sources. The vitamin B6 findings are not consistent with evidence that it is a protective factor against other cancers, and may be a chance finding.

Exposure to house painting and the use of floor treatments and the risk of childhood acute lymphoblastic leukemia

Painting in the home has been identified as a potential risk factor for childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether exposure to house painting or floor treatments before birth or during childhood increased the risk of childhood ALL. Data from 389 cases and 876 frequency‐matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders. Overall, there was little evidence of an increased risk with painting inside the house in the year before the pregnancy, during the pregnancy, or after the childs birth; however, the risk appeared to be increased in certain circumstances. The odds ratio (OR) for more than three rooms being painted during pregnancy was 1.68 [95% confidence interval (CI) 1.01, 2.80]. The OR for someone other than the parents painting inside the house in the year before the pregnancy was 2.37 (95% CI 1.30, 4.30) and 3.07 (95% CI 1.46, 6.46) when more than three rooms were painted. The OR for the mother painting the outside of the house with oil‐based paint in the year before the pregnancy was 2.97 (95% CI 1.06, 8.33). No association was found with having floor treatments in any time period. We found some evidence of an increased risk of ALL associated with house painting. An apparently increased risk associated with someone other than the parents painting inside the house may be related to the amount of paint used and the intensity of the dose received.

Participation in population-based case-control studies: Does the observed decline vary by socio-economic status?

An Australian study of childhood leukaemia (Aus-ALL) previously reported that control participation was positively associated with socio-economic status (SES). A similar study of childhood brain tumours (Aus-CBT) was carried out 4 years later, and this paper compares control participation and its relationship with SES in the two studies. To assess the representativeness of controls in terms of SES, the addresses of controls were linked to Australian Bureau of Statistics Census 2006 Collection Districts (CDs), and hence to area-based indices of SES. Independent sample t-tests and chi-squared tests were used to compare the SES indices of CDs where Aus-CBT controls lived with those where Aus-ALL controls lived and with those of all CDs where Australian families lived. The overall percentage of eligible families who agreed to participate was lower in Aus-CBT (53.9%) than in Aus-ALL (70.3%). Control families in both studies were of higher SES than the general population, while the distribution of SES among recruited controls was similar in both studies. These findings provide some reassurance that the observed decline in research participation over time may not be associated with an increasingly unrepresentative participant population.

Barriers to immunisation in general practice

Objective: To identify barriers to immunisation in general practice.

Risk of childhood acute lymphoblastic leukaemia following parental occupational exposure to pesticides

Objective To ascertain whether there was an association between parental occupational exposure to pesticides and increased risk of acute lymphoblastic leukaemia (ALL) in the offspring. Method A population-based case–control study of childhood ALL was conducted in Australia. Information about the occupational pesticide exposure of mothers and fathers was collected using job-specific modules. Information on the types and extent of pesticide exposure was collected for mothers and fathers before and around the time of conception, and also for mothers during pregnancy for the index case or control and for 1u2005year after birth. Results Paternal occupational exposure to pesticides before or around conception was not related to increased risk of childhood ALL. There was a low prevalence of occupational exposure to pesticides among women that reduced after birth. Conclusions Paternal occupational exposure to pesticides was not found to be associated with an increased risk of acute lymphoblastic leukaemia in the offspring. The study was underpowered with respect to maternal exposure to pesticides.

Refuelling of vehicles, the use of wood burners and the risk of acute lymphoblastic leukaemia in childhood

It is plausible that exposure of the parents before birth or of the child to sources of benzene increases the risk of childhood acute lymphoblastic leukaemia (ALL). The aim of this analysis was to investigate whether refuelling a vehicle with petrol before birth or burning wood to heat the home before or after the childs birth increased the risk of childhood ALL. Data from 389 cases and 876 frequency-matched controls were analysed using unconditional logistic regression, adjusting for study matching factors and potential confounders. The odds ratio (OR) for the mother ever refuelling a vehicle with petrol for non-occupational purposes before or during the pregnancy was 0.97 [95% confidence interval (CI) 0.69, 1.38]. The OR for the father for this exposure in the year before conception was 0.88 [95% CI 0.52, 1.48]. The OR for use of a closed wood burner to heat the home in the year before or during pregnancy was 1.41 [95% CI 1.02, 1.94] and 1.25 [95% CI 0.92, 1.70] after birth. We found no evidence that non-occupational refuelling a vehicle with petrol in the year before or during pregnancy increased the risk of ALL in the offspring. There was weak evidence that burning wood in a closed burner to heat the home increased the risk, but there was no dose-response relationship and chance could explain the finding.

Risk of neuroblastoma, birth‐related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE)

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population‐based case‐control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency‐matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life‐style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0‐2.0) or large (OR 1.5 95% CI 1.1–2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3–8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5–1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3–0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.