{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:29:46Z","timestamp":1792466986261,"version":"4.5.0"},"update-to":[{"DOI":"10.12688\/f1000research.27874.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}},{"DOI":"10.12688\/f1000research.27874.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}},{"DOI":"10.12688\/f1000research.27874.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}},{"DOI":"10.12688\/f1000research.27874.4","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000}}],"reference-count":41,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004944","name":"Naresuan University","doi-asserted-by":"publisher","award":["R2563N003"],"award-info":[{"award-number":["R2563N003"]}],"id":[{"id":"10.13039\/501100004944","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background<\/ns3:bold>\n                    : Developmental delay among children under 5 years of age is a serious global public health problem and much research has been carried out to find potential causes. Pesticides - especially organophosphates - are suspected to be one of the main causes of the problem.\u00a0 This study aimed to investigate the association between pesticide use by the mother during pregnancy and preschool children development using a case-control study.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods<\/ns3:bold>\n                    : Data on prenatal and postnatal pesticide exposure of 442 children with suspected developmental delay, and 413 controls with normal development were included for analysis. The children were matched for gender, age, and residency. Data on pesticide exposure were collected via interview with the mother, and data on pregnancy outcomes abstracted from hospital records. \u00a0\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Results<\/ns3:bold>\n                    : Chlorpyrifos exposure significantly increased the risk of developmental delay with an odds ratio (OR) of 3.71 (95% CI 1.03-13.36) for ever use of the pesticide, and an OR of 5.92 (95% CI 1.01-34.68) for postnatal exposure (p &lt;0.05). Some other pesticides also had a positive association with developmental delay but none were statistically significant (p &lt;0.05). Those pesticides were insecticide, fungicide, herbicide, and molluscicide. Individual pesticides with a positive association were glyphosate, paraquat, butachlor, methyl parathion (pholidon), savin, methomyl, endosulfan, carbosulfan, methamidophos, monochrotofos, mancozeb, and bordeaumixture.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Conclusions<\/ns3:bold>\n                    : This case-control study found that chlorpyrifos and some other pesticides exposure during pregnancy were positively associated with developmental delay in children aged under 5 years. Further research should be conducted to better understand this potential effects of pesticides on child neurodevelopment, and the public - especially those who plan to have families - should be informed.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.27874.5","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T11:28:18Z","timestamp":1629804498000},"page":"1501","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Chlorpyrifos and other pesticide exposure and suspected developmental delay in children aged under 5 years: a case-control study in Phitsanulok, Thailand"],"prefix":"10.12688","volume":"9","author":[{"given":"Yuwayong","family":"Juntarawijit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uraiwan","family":"Chaichanawirote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paphada","family":"Rakmeesri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punaphop","family":"Chairattanasakda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9977-5388","authenticated-orcid":false,"given":"Varintorn","family":"Pumyim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-5325","authenticated-orcid":false,"given":"Chudchawal","family":"Juntarawijit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"e1002034","DOI":"10.1371\/journal.pmed.1002034","article-title":"Early 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Neves","year":"2020","journal-title":"Sci Rep."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T18:46:40Z","timestamp":1673117200000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":41,"URL":"https:\/\/doi.org\/10.12688\/f1000research.27874.5","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.76814.r92747","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.76814.r92747","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.54363.r79508, Zhijun Zhou, School of Public Health, Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China, 26 Feb 2021, version 2, 1 approved, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/9-1501\/v2#referee-response-79508","order":0,"name":"referee-response-79508","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.54363.r79509, Ru-Lan Hsieh, Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, Taipei Medical University, Taipei, Taiwan, 06 Apr 2021, version 2, 1 approved, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/9-1501\/v2#referee-response-79509","order":1,"name":"referee-response-79509","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Chudchawal Juntarawijit<\/b>; <i>Posted: 05 May 2021<\/i>; <i>I have some comments for this revised paper, as listed below: 1. It is surprising that the ages of mother ranged from 13-42 in controls and 13-46 in cases. Please provide the numbers of ages less than 18 in both groups, respectively, in Table 1.<\/i> <b>Response<\/b>: First, we would like to thank you for your time and efforts provide valuable comments and suggestions. As suggested, the numbers of participants aged less than 18 in each group have been added to Table 1. It can be noticed that the proportion of participants with &lt;18 years in each group was similar to and there was no significant difference between the age group and developmental delay (p = 0.305). <i>2. Please provide the legal age for marriage in Thailand, and re-analyze the data by age less than 18 and &gt;=18, in addition to the continuous data as analyzed.<\/i> <b>Response<\/b>: In Thailand, the law restricts marriage under the age of 17. In this study, we started with selected children with developmental delay and their controls. The information of the mother and pesticide exposure were collected later, without restriction on either the marital status or age of the mother. Further analysis using age as a categorical variable (&lt;18, and 18 or more) was conducted as a suggestion, and the results, OR (adjusted2 in table 1-1). However, not much difference was observed as compared to the previous result when age was treated as a continuous variable (Table 3). It was also found that there was no literature to support a higher risk of developmental delay and among mothers below 18 years of age. Under the circumstances, therefore, it is better to treat age as a continuous variable. <i>3. The only significant factor to suspected developmental delay is Chlorpyrifos exposure in the present study. After the correction of crude OR in Table 3, the crude OR of ever Chlorpyrifos exposure is 1.11, prenatal exposure is 1.03, and postnatal exposure is 1.88. After adjustment, the OR of ever Chlorpyrifos exposure is 3.71 (p&lt;0.05), prenatal exposure is 2.97, and postnatal exposure is 5.92 (p&lt;0.05). The ORs after adjustment were much higher than the crude OR. Please provide a detailed regression model and correlation coefficient of each variable.<\/i> <b>Response<\/b>: The difference between crude and adjusted OR might be explained by the fact that there are several factors that can affect child development. The results support that control of confounding factors is important. In this study, the adjusted variables were: mother\u2019s age when pregnant (continuous), education (no school, primary school, secondary school, college degree), occupation (farmer, own business, civil servant, employee [formal], employee [general work], housewife, retired, unemployed), income (&lt;5000 baht, 5000\u20139999, 10000\u201314999, 15000 or more), chronic disease (yes, no), alcohol consumption (yes, no), gestation (&lt;37 weeks, 37 or more weeks), birth order (1, 2, 3 or more), delivery method (vaginal delivery, cesarean section, assisted delivery), baby weight (&lt;2500 grams, 2500 grams or more), and breastfeeding (yes, no). This information had been already presented in the Method section and in the table. In Table 3-1, the output of regression analysis of chlorpyrifos exposure and the correlation coefficient (B) of each variable was presented. <i>4. The authors did not adjust the factor of pesticide environment exposure for OR, why?<\/i> <b>Response<\/b>: This is a good point and thanks to you for the question. Yes, we did not adjust for pesticide environment exposure for several reasons. One reason is that the model has already contained many adjusted variables whereas the sample size was rather small with only 47 control and 46 cases reported using pesticides. It was also found that all of the environmental exposure variables were not significantly associated with developmental delay (Table 1). In addition, further analysis shows that these variables were strongly associated with pesticide use (data was not presented). For example, chlorpyrifos use was strongly associated with having a family member working as a farmer (p&lt;0.001), year of residency in the area (p=0.010), frequency of farm entry (&lt;0.001), and keeping pesticides in a house (p=0.009). <i>5. How could the authors get the contents of the pesticide as detailed as 14 kinds (such as Glyphosate, Paraquat, Butachlor, methyl parathion, Savin, Chlorpyrifos, etc.) just by questionnaires?<\/i> <b>Response<\/b>: Yes, the data on the 14 pesticides were collected using a face-to-face interview questionnaire. During the interview, village health volunteers asked each participant whether or not he\/she ever used each individual pesticide, such as glyphosate, paraquat, butachlor, etc. This data collection method has been accepted and widely used in epidemiological studies. The method was suitable for a large study and studies that looked for the effects of long-term exposure because the blood or urine analyses are expensive and represent short-term exposure only.&nbsp; <i>6. In the discussion section, the authors mentioned that \u201cThis is consistent with the present study which also found an elevated risk of SDD among those exposed to mancozeb, with odds ratio of 1.87 for prenatal exposure, and OR of 3.97 for postnatal exposure (Table 3)\u201d. However, the OR did not reach statistically significant (p&lt;0.05) in the present study. Therefore, the authors should not give this comment.<\/i> <b>Response<\/b>: Yes, it was true that the OR was not significant. However, when considered an association or effect, it should not depend solely on p-value and use it as a magic number. The problem of p-value and its misuse was discussed quite frequently in the literature. For example, Wasserstein, Schirm, and Lazar (2019) said that \u201cDon\u2019t believe that an association or effect is absent just because it was not statistically significant.\u201d In the paper of Bonner <i>et al.<\/i> (2017) published in Environmental Health Perspective, many of the associations between pesticides and lung cancer were presented when the OR or HR did not reach statistically significant, p &lt;0.05 or confident interval included 1. For example, \u201cthe association between pendimethalin use and lung cancer (HR = 1.50; 95% CI: <u>0.98, 2.31<\/u>)\u201d. Table 1-1 and Table 3-1 was in Figshare: https:\/\/doi.org\/10.6084\/m9.figshare.14540154.v1 <b>Table 1-1<\/b>. Comparison of OR with two different adjustments of age, continuous (OR, adjusted) and categorical (OR, adjusted2) of some selected individual pesticides. Table 3-1. The output of regression analysis of chlorpyrifos exposure and the correlation coefficient (B) of each variable.","URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5#referee-comment-6644","order":2,"name":"referee-comment-6644","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.76814.r92747, Dana Boyd Barr, Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA, 14 Sep 2021, version 5, indexed","URL":"https:\/\/f1000research.com\/articles\/9-1501\/v5#referee-response-92747","order":3,"name":"referee-response-92747","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project received grant support from the Faculty of Nursing, Naresuan University, Thailand (grant number R2563N003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}