Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis
Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing....
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| Published in: | Environmental pollution (1987) Vol. 285; p. 117376 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier Ltd
15.09.2021
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| ISSN: | 0269-7491, 1873-6424, 1873-6424 |
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| Abstract | Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15–3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39–4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00–1.99) and insecticide (OR: 1.60, 95%CI: 1.11–2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12–0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44–3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98–5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08–2.85; ORpaternal: 1.20, 95%CI: 1.07–1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.
[Display omitted]
•Evidence on pesticide exposures and childhood leukemia risk remains inconsistent.•Environmental exposure to pesticides increases the risk of childhood leukemia.•The association is stronger for exposure during pregnancy, and for infant leukemia.•Insecticides and herbicides are both associated with higher risk of childhood ALL. |
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| AbstractList | Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08-2.85; ORpaternal: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08-2.85; ORpaternal: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure. Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15–3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39–4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00–1.99) and insecticide (OR: 1.60, 95%CI: 1.11–2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12–0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44–3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98–5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08–2.85; ORpaternal: 1.20, 95%CI: 1.07–1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure. [Display omitted] •Evidence on pesticide exposures and childhood leukemia risk remains inconsistent.•Environmental exposure to pesticides increases the risk of childhood leukemia.•The association is stronger for exposure during pregnancy, and for infant leukemia.•Insecticides and herbicides are both associated with higher risk of childhood ALL. Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (OR : 1.75, 95%CI: 1.08-2.85; OR : 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure. Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15–3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39–4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00–1.99) and insecticide (OR: 1.60, 95%CI: 1.11–2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12–0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44–3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98–5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORₚₐᵣₑₙₜₐₗ: 1.75, 95%CI: 1.08–2.85; ORₚₐₜₑᵣₙₐₗ: 1.20, 95%CI: 1.07–1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure. |
| ArticleNumber | 117376 |
| Author | Petridou, Eleni Th Karalexi, Maria A. Tagkas, Christos F. Tzoulaki, Ioanna Hernández, Antonio F. Psaltopoulou, Theodora Tseretopoulou, Xanthippi Halldorsson, Thorhallur I. Ntzani, Evangelia E. Markozannes, Georgios Schüz, Joachim |
| Author_xml | – sequence: 1 givenname: Maria A. surname: Karalexi fullname: Karalexi, Maria A. organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece – sequence: 2 givenname: Christos F. orcidid: 0000-0002-8600-4146 surname: Tagkas fullname: Tagkas, Christos F. organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece – sequence: 3 givenname: Georgios surname: Markozannes fullname: Markozannes, Georgios organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece – sequence: 4 givenname: Xanthippi orcidid: 0000-0002-3608-8695 surname: Tseretopoulou fullname: Tseretopoulou, Xanthippi organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece – sequence: 5 givenname: Antonio F. surname: Hernández fullname: Hernández, Antonio F. organization: Department of Legal Medicine and Toxicology, School of Medicine, University of Granada, Avenida de La Investigación 11, 18016, Granada, Spain – sequence: 6 givenname: Joachim surname: Schüz fullname: Schüz, Joachim organization: Section of Environment and Radiation, International Agency for Research on Cancer (IARC), Lyon, France – sequence: 7 givenname: Thorhallur I. surname: Halldorsson fullname: Halldorsson, Thorhallur I. organization: Unit for Nutrition Research, Landspitali, The National University Hospital of Iceland and Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland, Eiriksgata 29, 101, Reykjavik, Iceland – sequence: 8 givenname: Theodora surname: Psaltopoulou fullname: Psaltopoulou, Theodora organization: Department of Hygiene, Epidemiology, and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece – sequence: 9 givenname: Eleni Th surname: Petridou fullname: Petridou, Eleni Th organization: Department of Hygiene, Epidemiology, and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece – sequence: 10 givenname: Ioanna surname: Tzoulaki fullname: Tzoulaki, Ioanna organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece – sequence: 11 givenname: Evangelia E. orcidid: 0000-0003-3712-4181 surname: Ntzani fullname: Ntzani, Evangelia E. email: entzani@uoi.gr organization: Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, 45110, Greece |
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| Keywords | Childhood leukemia meta-Analysis Infants Risk of bias Pesticides Window of exposure |
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| ParticipantIDs | proquest_miscellaneous_2560835935 proquest_miscellaneous_2551938213 pubmed_primary_34380208 crossref_primary_10_1016_j_envpol_2021_117376 crossref_citationtrail_10_1016_j_envpol_2021_117376 elsevier_sciencedirect_doi_10_1016_j_envpol_2021_117376 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-09-15 |
| PublicationDateYYYYMMDD | 2021-09-15 |
| PublicationDate_xml | – month: 09 year: 2021 text: 2021-09-15 day: 15 |
| PublicationDecade | 2020 |
| PublicationPlace | England |
| PublicationPlace_xml | – name: England |
| PublicationTitle | Environmental pollution (1987) |
| PublicationTitleAlternate | Environ Pollut |
| PublicationYear | 2021 |
| Publisher | Elsevier Ltd |
| Publisher_xml | – name: Elsevier Ltd |
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| Title | Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis |
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