Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Attitudes towards the mixing of COVID-19 vaccinated and unvaccinated patients in multi-bed hospital rooms.

AIM: To explore patient and staff views about the mixing of COVID-19 vaccinated and unvaccinated patients in multi-bed hospital rooms. METHODS: We conducted a mixed methods study with paper surveys and structured interviews. Self-administered surveys were undertaken with inpatients on the general medicine, general surgery, orthopaedic and respiratory wards in Dunedin Public Hospital. Face-to-face interviews were conducted with ward staff including consultants, registrars, charge nurses, registered nurses and nurse managers. The study was undertaken in February 2022, at the start of the first New Zealand wave of the Omicron variant. RESULTS: Of 118 eligible patients, 63 agreed to participate. Sixty (95%) of these patients were vaccinated for COVID-19. Most patients (59%) thought that vaccinated and unvaccinated people should be accommodated in separate hospital rooms. Vaccinated patients felt more comfortable sharing a multi-bed room with others of the same COVID-19 vaccination status as themselves than with unvaccinated patients. Participants who thought that they were at higher risk of severe illness from COVID-19 were more likely to support separation of patients based on vaccination status. Fifteen ward staff were interviewed: most would prefer the hospital to separate patients by vaccination status but were aware this would present practical and ethical problems and thought that current arrangements were adequate. CONCLUSION: While most vaccinated patients and staff wanted patients to be separated according to their COVID-19 vaccination status, the current precautionary measures for COVID-19 were viewed by most staff members as adequate.

Role of communication in successful outpatient attendance in a New Zealand hospital: a qualitative study.

BACKGROUND: There are significant implications for both patients and providers when patients do not attend outpatient specialist appointments. Nonattendance has an impact on the efficiency of health care, provider resources and patient health outcomes. AIMS: In this qualitative study we aimed to gather insights on how Dunedin Hospital notifies patients about their appointments, the implications for the hospital and for patients and how the system could be improved. METHODS: We interviewed 13 hospital staff members and nine patients who volunteered to participate because they had missed appointments as a result of communication problems. Interviews were transcribed and analysed thematically using NVivo software. RESULTS: Dunedin Hospital relies heavily on posted letters to inform people about their appointments, with some also receiving reminder texts closer to the time of the appointment. Frustration with the current system was a common theme among both patients and staff. Almost all patients had missed an appointment because of a letter not arriving. While most patients found that the text reminders were helpful, most said they were sent too late and did not allow enough time for arrangements to be made for their appointments. Almost all patients experienced treatment delays, which caused distress. Most patients believed a self-booking system would improve the ability to attend their appointments, and most of them wanted to be notified of appointments via email. CONCLUSIONS: We recommend that a patient-oriented approach to communication should be implemented, and alternative methods of communication should be explored.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Investigating attitudes and insights into the global warming impact of inhalers.

INTRODUCTION: Inhalers are commonly used in the management of respiratory diseases. The propellants used in pressurised metered dose inhalers (pMDIs) are potent greenhouse gases and carry a substantial global warming potential. Dry powder inhalers (DPIs) are propellant-free alternatives that have fewer consequences on the environment, while being equally effective. In this study, we assessed patients' and clinicians' attitudes towards choosing inhalers that have a lesser environmental impact. METHODS: Surveys of patients and practitioners were undertaken in primary and secondary care settings in Dunedin and Invercargill. Fifty-three patient and 16 practitioner responses were obtained. RESULTS: Sixty-four percent of patients were using pMDIs, while 53% were using DPIs. Sixty-nine percent of patients believed that the environment is an important consideration when switching inhalers. Sixty-three percent of practitioners were aware of the global warming potential of inhalers. Despite this, 56% of practitioners predominantly prescribe or recommend pMDIs. The 44% of practitioners who mostly prescribe DPIs were more comfortable doing so based on environmental impact alone. CONCLUSION: Most respondents believe global warming is an important issue and would consider changing their inhaler to a more environmentally friendly type. Many people were not aware that pressurised metered dose inhalers have a substantial carbon footprint. Greater awareness of their environmental impacts may encourage the use of inhalers with lower global warming potential.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

Impact of the 2020 New Zealand COVID-19 lockdown on participants in a community-based, peer-led fall prevention program.

OBJECTIVES: To explore the impacts of the 2020 New Zealand COVID-19 lockdown on peer-led Steady as You Go (SAYGO) fall prevention exercise classes and members, and to develop recommendations for mitigating impacts during future lockdowns. METHODS: Semi-structured phone interviews were conducted with 20 SAYGO program participants and managers following the first COVID-19 lockdown in New Zealand. Interviews were audio-recorded, transcribed verbatim and analysed using the General Inductive Approach. RESULTS: Participants were between 67 and 88 years of age, predominantly female (90%) and NZ European (80%), with one participant identifying as NZ Maori. Three themes were constructed from the analysis: Personal Function and Well-Being, Class Functioning and Logistics, and Future Strategies for Classes During Prospective Lockdowns. Participants used a range of strategies to stay connected with each other and continue the SAYGO exercises at home. Most participants and peer-leaders reported that they maintained physical function during lockdown, although some had feelings of psychological distress and social isolation. Contact systems and resource distribution varied substantially between groups. Classes resumed post-lockdown with only minor modifications and slightly decreased attendance. CONCLUSIONS: Overall, members of this peer-led model of fall prevention classes demonstrated resilience during the COVID-19 lockdown, despite some challenges. We propose three recommendations to address the challenges of maintaining existing peer-led exercise classes in the context of prospective lockdowns: (1) develop a comprehensive contact detail register and plans for each group; (2) delivery of modified exercise classes remotely over lockdown; and (3) implementation of a nationwide IT education and resource program for older adults.

Attitudes towards and use of cannabis in New Zealand patients with inflammatory bowel disease: an exploratory study.

AIMS: We aimed to assess the use of and attitudes towards cannabis use (medicinal and recreational) by people with IBD in New Zealand. METHODS: People with IBD were invited to complete an anonymous online questionnaire. Participants were recruited via postal mail using a hospital database of patients with IBD (developed by the Gas-troenterology Department at Dunedin Public Hospital) and via online recruitment (advertised on the Crohn's and Colitis New Zealand website, Facebook page and e-mail list). Inclusion criteria were ages 18+ and self-reported confirmed IBD diagnosis. RESULTS: In total, 378 participants completed the questionnaire, with 334 eligible responses. Partici-pants were predominantly New Zealand European (84%) and female (71%). Sixty-one percent of re-spondents had CD and 34% UC. Overall, 51% of respondents reported having ever used cannabis. Of those, 63% reported use as recreational and 31% for reduction of IBD symptoms. Users were more likely to be younger (on average by 6.4 years), with on-going symptoms, unemployed or self-employed and current or ex-smokers. There were no differences by disease status or severity. Symp-toms most reported as improved by cannabis use were abdominal pain/cramping, nausea/vomiting and loss of appetite. Fifty-four percent of participants reported that if cannabis were legal, they would request it for medicinal use to help manage their symptoms. CONCLUSIONS: Overall, our research aligns with previous observational research that reports im-provements in symptoms of IBD with cannabis use. Studies of a higher evidence level (eg, RCTs) would be needed to guide prescribing. In the meantime, this research provides useful background to clini-cians about patients' views and experiences.

Emergency department presentations in the Southern District of New Zealand during the 2020 COVID-19 pandemic lockdown.

OBJECTIVE: To assess changes in presentations to EDs during the COVID-19 pandemic lockdown in the Southern Region of New Zealand. METHODS: We conducted a retrospective audit of patients attending EDs in the Southern District Health Board (SDHB), from 1 March to 13 May 2020. We made comparisons with attendances during the same period in 2019. The 2020 study period included 'pre-lockdown' (1 March-25 March), 'level 4 (strict) lockdown' (26 March-27 April) and 'level 3 (eased) lockdown' (28 April-13 May). RESULTS: Patient volumes reduced in all SDHB EDs during levels 4 and 3, mostly representing a loss of low acuity patients (Australasian Triage Scale 3, 4 and 5), although high-acuity presentations also declined. Average patient age increased by 5 years; however, the proportions of sexes and ethnicities did not change. Presentations of cerebrovascular accidents and appendicitis did not change significantly. Trauma, mental health, acute coronary syndrome and infectious respiratory presentations decreased significantly during level 4, and infectious respiratory presentations decreased further in level 3. CONCLUSIONS: Within the SDHB, patient volumes reduced during levels 4 and 3 of our lockdown, with reduced low-acuity presentations. High-acuity patient numbers also declined. Trauma, mental health, alcohol-related, infectious respiratory and acute coronary syndrome presentations declined while cerebrovascular accident and appendicitis numbers showed little to no change.

The New Zealand nuclear veteran and families study, exploring the options to assess heritable health outcomes.

AIMS: To describe health conditions in New Zealand nuclear veterans and their offspring, and examine the utility of tests to assess their heritability. METHOD: An online survey, open to all veterans and offspring, with questions on health conditions, the GHQ12 to measure psychological distress, the Euroquol-5D visual analogue scale (EQ5D VAS) to measure health state, and free text items on veteran support. RESULTS: Eighty-three responses (56%) were from veterans, 65 (44%) from offspring. Anxiety and depression were prevalent in both groups, with cancers (n=31, 37%) and joint conditions common in veterans (n=26, 31%). Few offspring reported cancer, rather problems with fertility (n=18, 40%). The free text themes fell into four domains, official commitment, health, emotional and information support; however, little support had been sought. CONCLUSION: Cancers have utility in assessing heritability, but a low prevalence and lack of diagnostic data rules this out. Psychological conditions may be heritable, but the techniques to assess this are still developing. Chromosomal damage in veterans and offspring can be detected, but with present knowledge cannot explain health outcomes. Future work should assemble a veteran and family register with linkage to routine data-sets. Veterans and offspring should be encouraged to seek support.

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

AIM: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. METHODS: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. RESULTS: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers. CONCLUSIONS: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring: findings from the Childhood Leukaemia International Consortium (CLIC).

OBJECTIVES: Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium. METHODS: We pooled 11 case-control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses. RESULTS: ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses. CONCLUSIONS: In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia.

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium.

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 <1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period. RESULTS: Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers ≥40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year. CONCLUSIONS: An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.

Association between maternal education and survival after childhood cancer.

BACKGROUND: Several nonbiological factors, including socioeconomic status indicators and other family characteristics, influence survival from childhood cancers. Our study explores the association between parental education and childhood cancer survival. METHODS: The specialized Childhood Cancer Registry of the Piedmont region in Italy provided data on all the cases (aged 0-14) diagnosed with cancer in the period 1976-2011 who resided in the city of Turin (capital of the Piedmont region) at least once since 1971. Information on parental education was extracted from the Turin Longitudinal Study by record linkage. The association between parental educational level and survival was estimated using Cox regression. RESULTS: The study included 949 children. We observed a disadvantage in the overall survival for children of less educated mothers. No such effect was observed for paternal education. The effect of maternal education was particularly strong for central nervous system tumors (hazard ratios, 2.9; 95% confidence interval, 1.1-8.0). A similar effect, though smaller in magnitude, was observed for leukemia and embryonal tumors, whereas the estimates for lymphoma were imprecise. CONCLUSIONS: Our study shows an association between maternal educational level and survival in children with central nervous system tumors, a diagnosis that often requires long-lasting treatment and special care. Giving support to the families of affected children to provide them the optimal care has the potential to improve children's cancer treatment outcomes.

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium.

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

Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium.

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis.

Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.

Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC).

BACKGROUND: Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. METHODS: We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. FINDINGS: The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1·06 (95% CI 0·99-1·13), and was significant for prelabour caesarean delivery and ALL (1·23 [1·04-1·47]; p=0·018). Emergency caesarean delivery was not associated with ALL (OR 1·02 [95% CI 0·81-1·30]). AML was not associated with caesarean delivery (all indications OR 0·99 [95% CI 0·84-1·17]; prelabour caesarean delivery 0·83 [0·54-1·26]; and emergency caesarean delivery 1·05 [0·63-1·77]). INTERPRETATION: Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism. FUNDING: National Cancer Institute.

Home paint exposures and risk of childhood acute lymphoblastic leukemia: findings from the Childhood Leukemia International Consortium.

PURPOSE: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL). METHODS: We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression. RESULTS: Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting. CONCLUSIONS: Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods.

Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.