Journal Articles

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    Antibiotic Use In Utero and Early Life and Risk of Chronic Childhood Conditions in New Zealand: Protocol for a Data Linkage Retrospective Cohort Study
    (JMIR Publications, 2025-02-28) Ram S; Corbin M; 't Mannetje A; Eng A; Kvalsig A; Baker M; Douwes J
    Background: The incidence of many common chronic childhood conditions has increased globally in the past few decades, which has been suggested to be potentially attributed to antibiotic overuse leading to dysbiosis in the gut microbiome. Objective: This linkage study will assess the role of antibiotic use in utero and in early life in the development of type 1 diabetes (T1D), attention-deficit/hyperactive disorder (ADHD), and inflammatory bowel disease. Methods: The study design involves several retrospective cohort studies using linked administrative health and social data from Statistics New Zealand’s Integrated Data Infrastructure. It uses data from all children who were born in New Zealand between October 2005 and December 2010 (N=334,204) and their mothers. Children’s antibiotic use is identified for 4 time periods (at pregnancy, at ≤1 year, at ≤2 years, and at ≤5 years), and the development of T1D, ADHD, and inflammatory bowel disease is measured from the end of the antibiotic use periods until death, emigration, or the end of the follow-up period (2021), whichever came first. Children who emigrated or died before the end of the antibiotic use period are excluded. Cox proportional hazards regression models are used while adjusting for a range of potential confounders. Results: As of September 2024, data linkage has been completed, involving the integration of antibiotic exposure and outcome variables for 315,789 children. Preliminary analyses show that both prenatal and early life antibiotic consumption is associated with T1D. Full analyses for all 3 outcomes will be completed by the end of 2025. Conclusions: This series of linked cohort studies using detailed, complete, and systematically collected antibiotic prescription data will provide critical new knowledge regarding the role of antibiotics in the development of common chronic childhood conditions. Thus, this study has the potential to contribute to the development of primary prevention strategies through, for example, targeted changes in antibiotic use.
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    Lung cancer risk in painters: results from the SYNERGY pooled case-control study consortium
    (BMJ Publishing Group Ltd, 2021-04) Guha N; Bouaoun L; Kromhout H; Vermeulen R; Brüning T; Behrens T; Peters S; Luzon V; Siemiatycki J; Xu M; Kendzia B; Guenel P; Luce D; Karrasch S; Wichmann H-E; Consonni D; Landi MT; Caporaso NE; Gustavsson P; Plato N; Merletti F; Mirabelli D; Richiardi L; Jöckel K-H; Ahrens W; Pohlabeln H; TSE LA; Yu IT-S; Tardón A; Boffetta P; Zaridze D; 't Mannetje A; Pearce N; Davies MPA; Lissowska J; Świątkowska B; McLaughlin J; Demers PA; Bencko V; Foretova L; Janout V; Pándics T; Fabianova E; Mates D; Forastiere F; Bueno-de-Mesquita B; Schüz J; Straif K; Olsson A
    OBJECTIVES: We evaluated the risk of lung cancer associated with ever working as a painter, duration of employment and type of painter by histological subtype as well as joint effects with smoking, within the SYNERGY project. METHODS: Data were pooled from 16 participating case-control studies conducted internationally. Detailed individual occupational and smoking histories were available for 19 369 lung cancer cases (684 ever employed as painters) and 23 674 age-matched and sex-matched controls (532 painters). Multivariable unconditional logistic regression models were adjusted for age, sex, centre, cigarette pack-years, time-since-smoking cessation and lifetime work in other jobs that entailed exposure to lung carcinogens. RESULTS: Ever having worked as a painter was associated with an increased risk of lung cancer in men (OR 1.30; 95% CI 1.13 to 1.50). The association was strongest for construction and repair painters and the risk was elevated for all histological subtypes, although more evident for small cell and squamous cell lung cancer than for adenocarcinoma and large cell carcinoma. There was evidence of interaction on the additive scale between smoking and employment as a painter (relative excess risk due to interaction >0). CONCLUSIONS: Our results by type/industry of painter may aid future identification of causative agents or exposure scenarios to develop evidence-based practices for reducing harmful exposures in painters.
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    Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study
    (Nordic Association of Occupational Safety and Health, 2021-01-01) Cocco P; Satta G; Meloni F; Pilia I; Ahmed F; Becker N; Casabonne D; de Sanjosé S; Foretova L; Maynadié M; Nieters A; Staines A; 't Mannetje A; Zucca M; Ennas MG; Campagna M; De Matteis S; Benavente Y
    Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.
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    Airborne Fumigants and Residual Chemicals in Shipping Containers Arriving in New Zealand
    (Oxford University Press on behalf of the British Occupational Hygiene Society, 2022-05) Hinz R; 't Mannetje A; Glass B; McLean D; Douwes J
    BACKGROUND: Airborne fumigants and other hazardous chemicals inside unopened shipping containers may pose a risk to workers handling containers. METHODS: Grab air samples from 490 sealed containers arriving in New Zealand were analysed for fumigants and other hazardous chemicals. We also collected grab air samples of 46 containers immediately upon opening and measured the total concentration of volatile organic compounds in real-time during ventilation. Additive Mixture Values (AMV) were calculated using the New Zealand Workplace Exposure standard (WES) and ACGIH Threshold Limit Values (TLV) of the 8-h, time-weighted average (TWA) exposure limit. Regression analyses assessed associations with container characteristics. RESULTS: Fumigants were detectable in 11.4% of sealed containers, with ethylene oxide detected most frequently (4.7%), followed by methyl bromide (3.5%). Other chemicals, mainly formaldehyde, were detected more frequently (84.7%). Fumigants and other chemicals exceeded the WES/TLV in 6.7%/7.8%, and 7.8%/20.0% of all containers, respectively. Correspondingly, they more frequently exceeded '1' for the AMV-TLV compared to the AMV-WES (25.7% versus 7.8%). In samples taken upon opening of doors, fumigants were detected in both fumigated and non-fumigated containers, but detection frequencies and exceedances of the WES, TLV, and AMVs were generally higher in fumigated containers. Detection frequencies for other chemicals were similar in fumigated and non-fumigated containers, and only formaldehyde exceeded both the WES and TLV in both container groups. Volatile compounds in container air reduced rapidly during ventilation. Some cargo types (tyres; personal hygiene, beauty and medical products; stone and ceramics; metal and glass; and pet food) and countries of origin (China) were associated with elevated airborne chemical and fumigant concentrations. CONCLUSION: Airborne chemicals in sealed containers frequently exceed exposure limits, both in fumigated and non-fumigated containers, and may contribute to short-term peak exposures of workers unloading or inspecting containers.
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    Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study
    (Elsevier Ltd, 2022-02) Castaño-Vinyals G; Sadetzki S; Vermeulen R; Momoli F; Kundi M; Merletti F; Maslanyj M; Calderon C; Wiart J; Lee A-K; Taki M; Sim M; Armstrong B; Benke G; Schattner R; Hutter H-P; Krewski D; Mohipp C; Ritvo P; Spinelli J; Lacour B; Remen T; Radon K; Weinmann T; Petridou ET; Moschovi M; Pourtsidis A; Oikonomou K; Kanavidis P; Bouka E; Dikshit R; Nagrani R; Chetrit A; Bruchim R; Maule M; Migliore E; Filippini G; Miligi L; Mattioli S; Kojimahara N; Yamaguchi N; Ha M; Choi K; Kromhout H; Goedhart G; 't Mannetje A; Eng A; Langer CE; Alguacil J; Aragonés N; Morales-Suárez-Varela M; Badia F; Albert A; Carretero G; Cardis E
    In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.
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    Exposure to drinking water trihalomethanes and nitrate and the risk of brain tumours in young people
    (Elsevier Inc, 2021-09) Zumel-Marne A; Castaño-Vinyals G; Alguacil J; Villanueva CM; Maule M; Gracia-Lavedan E; Momoli F; Krewski D; Mohipp C; Petridou E; Bouka E; Merletti F; Migliore E; Piro S; Ha M; 't Mannetje A; Eng A; Aragones N; Cardis E
    Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10-24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010-2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08-1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91-3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations.
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    Nitrate in drinking water and cancer risk: the biological mechanism, epidemiological evidence and future research
    (Elsevier BV on behalf of the Public Health Association of Australia, 2022-04) Chambers T; Douwes J; 't Mannetje A; Woodward A; Baker M; Wilson N; Hales S
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    Pesticide exposure in New Zealand school-aged children: Urinary concentrations of biomarkers and assessment of determinants
    (Elsevier Ltd, 2022-05) Li Y; Wang X; Feary McKenzie J; 't Mannetje A; Cheng S; He C; Leathem J; Pearce N; Sunyer J; Eskenazi B; Yeh R; Aylward LL; Donovan G; Mueller JF; Douwes J
    This study aimed to assess pesticide exposure and its determinants in children aged 5-14 years. Urine samples (n = 953) were collected from 501 participating children living in urban areas (participant n = 300), rural areas but not on a farm (n = 76), and living on a farm (n = 125). The majority provided two samples, one in the high and one in the low spraying season. Information on diet, lifestyle, and demographic factors was collected by questionnaire. Urine was analysed for 20 pesticide biomarkers by GC-MS/MS and LC-MS/MS. Nine analytes were detected in > 80% of samples, including six organophosphate insecticide metabolites (DMP, DMTP, DEP, DETP, TCPy, PNP), two pyrethroid insecticide metabolites (3-PBA, trans-DCCA), and one herbicide (2,4-D). The highest concentration was measured for TCPy (median 13 μg/g creatinine), a metabolite of chlorpyrifos and triclopyr, followed by DMP (11 μg/g) and DMTP (3.7 μg/g). Urine metabolite levels were generally similar or low compared to those reported for other countries, while relatively high for TCPy and pyrethroid metabolites. Living on a farm was associated with higher TCPy levels during the high spray season. Living in rural areas, dog ownership and in-home pest control were associated with higher levels of pyrethroid metabolites. Urinary concentrations of several pesticide metabolites were higher during the low spraying season, possibly due to consumption of imported fruits and vegetables. Organic fruit consumption was not associated with lower urine concentrations, but consumption of organic food other than fruit or vegetables was associated with lower concentrations of TCPy in the high spray season. In conclusion, compared to other countries such as the U.S., New Zealand children had relatively high exposures to chlorpyrifos/triclopyr and pyrethroids. Factors associated with exposure included age, season, area of residence, diet, in-home pest control, and pets.
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    Neuropsychological symptoms in workers handling cargo from shipping containers and export logs
    (Springer-Verlag GmbH, 2022-10) Hinz R; 't Mannetje A; Glass B; McLean D; Douwes J
    PURPOSE: Acute poisonings of workers handling shipping containers by fumigants and other harmful chemicals off-gassed from cargo have been reported but (sub)-chronic neuropsychological effects have not been well studied. METHODS: This cross-sectional study assessed, using standardised questionnaires, current (past 3-months) neuropsychological symptoms in 274 container handlers, 38 retail workers, 35 fumigators, and 18 log workers, all potentially exposed to fumigants and off-gassed chemicals, and a reference group of 206 construction workers. Prevalence odds ratios (OR), adjusted for age, ethnicity, smoking, alcohol consumption, education, personality traits and BMI, were calculated to assess associations with the total number of symptoms (≥ 3, ≥ 5 or ≥ 10) and specific symptom domains (neurological, psychosomatic, mood, memory/concentration, fatigue, and sleep). RESULTS: Compared to the reference group, exposed workers were more likely to report ≥ 10 symptoms, statistically significant only for retail workers (OR 6.8, 95% CI 1.9-24.3) who also reported more fatigue (OR 10.7, 95% CI 2.7-42.7). Container handlers with the highest exposure-duration were more likely to report ≥ 10 symptoms, both when compared with reference workers (OR 4.0, 95% CI 1.4-11.7) and with container handlers with shorter exposure duration (OR 7.5, 95% CI 1.7-32.8). The duration of container handling was particularly associated with symptoms in the memory/concentration domain, again both when compared to reference workers (OR 8.8, 95% CI 2.5-31.4) and workers with the lowest exposure-duration (OR 6.8, 95% CI 1.5-30.3). CONCLUSION: Container handlers may have an increased risk of neuropsychological symptoms, especially in the memory/concentration domain. Retail workers may also be at risk, but this requires confirmation in a larger study.
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    A longitudinal linkage study of occupation and ischaemic heart disease in the general and Māori populations of New Zealand
    (PLOS, 21/01/2022) Barnes LA; Eng A; Corbin M; Denison HJ; 't Mannetje A; Haslett S; McLean D; Ellison-Loschmann L; Jackson R; Douwes J
    OBJECTIVES: Occupation is a poorly characterised risk factor for cardiovascular disease (CVD) with females and indigenous populations under-represented in most research. This study assessed associations between occupation and ischaemic heart disease (IHD) in males and females of the general and Māori (indigenous people of NZ) populations of New Zealand (NZ). METHODS: Two surveys of the NZ adult population (NZ Workforce Survey (NZWS); 2004-2006; n = 3003) and of the Māori population (NZWS Māori; 2009-2010; n = 2107) with detailed occupational histories were linked with routinely collected health data and followed-up until December 2018. Cox regression was used to calculate hazard ratios (HR) for IHD and "ever-worked" in any of the nine major occupational groups or 17 industries. Analyses were controlled for age, deprivation and smoking, and stratified by sex and survey. RESULTS: 'Plant/machine operators and assemblers' and 'elementary occupations' were positively associated with IHD in female Māori (HR 2.2, 95%CI 1.2-4.1 and HR 2.0, 1.1-3.8, respectively) and among NZWS males who had been employed as 'plant/machine operators and assemblers' for 10+ years (HR 1.7, 1.2-2.8). Working in the 'manufacturing' industry was also associated with IHD in NZWS females (HR 1.9, 1.1-3.7), whilst inverse associations were observed for 'technicians and associate professionals' (HR 0.5, 0.3-0.8) in NZWS males. For 'clerks', a positive association was found for NZWS males (HR 1.8, 1.2-2.7), whilst an inverse association was observed for Māori females (HR 0.4, 0.2-0.8). CONCLUSION: Associations with IHD differed significantly across occupational groups and were not consistent across males and females or for Māori and the general population, even within the same occupational groups, suggesting that current knowledge regarding the association between occupation and IHD may not be generalisable across different population groups.