Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review

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Porter" }, { "@type": "Person", "name": "Sebastian Hoffmann" }, { "@type": "Person", "name": "Matthew P. Longnecker" }, { "@type": "Person", "name": "Farhad Shokraneh" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-1595/v2", "name": "Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl..." } } ] } Home Browse Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Aali G, Porter AK, Hoffmann S et al. Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.12688/f1000research.144376.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Revised Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] Ghazaleh Aali 1 , Anna K. Porter https://orcid.org/0000-0002-4353-5422 2 , Sebastian Hoffmann 3 , Matthew P. Longnecker 2 , Farhad Shokraneh https://orcid.org/0000-0001-9687-8560 1 Ghazaleh Aali 1 , Anna K. Porter https://orcid.org/0000-0002-4353-5422 2 , [...] Sebastian Hoffmann 3 , Matthew P. Longnecker 2 , Farhad Shokraneh https://orcid.org/0000-0001-9687-8560 1 PUBLISHED 09 Oct 2024 Author details Author details 1 Department of Evidence Synthesis, Systematic Review Consultants LTD, Oxford, UK 2 Ramboll U.S. Consulting, Inc., Raleigh, NC, USA 3 seh consulting + services, Paderborn, Germany Ghazaleh Aali Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Anna K. Porter Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Sebastian Hoffmann Roles: Conceptualization, Data Curation, Formal Analysis, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Matthew P. Longnecker Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Farhad Shokraneh Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background Per- and polyfluoroalkyl substances (PFAS) were used or are being used in the manufacturing of products, including consumer-use products. The resulting environmental contamination has led to widespread human exposure. This review aimed to scope the characteristics of evidence covered and applied methodology of evidence to understand -- regardless of any results on the association of gestational diabetes mellitus (GDM) and PFAS -- if a new systematic review would be justified. Methods We systematically identified reports investigating associations of PFAS with GDM following a pre-specified and pre-registered PECO framework and protocol. Results The previous systematic reviews included 8-11 reports and either conducted meta-analyses stratified by comparator, analyzed results based on only high and low exposure categories, or pooled results across comparators. Included 20 reports presented data on 24 PFAS with PFOA, PFOS, PFHxS, PFNA, and PFDA being examined in almost all. The comparators employed were heterogeneous across the reports. Conclusions Because data from at least one new report on GDM is available since the previous systematic reviews and heterogeneous comparators, an updated systematic review using SWiM could add value to the literature. READ ALL READ LESS Keywords Perfluoroalkyl, Polyfluoroalkyl, Gestational Diabetes Mellitus, Glucose, Environmental Epidemiology, Exposure Corresponding Author(s) Farhad Shokraneh ( [email protected] ) Close Corresponding author: Farhad Shokraneh Competing interests: Support sources: This work was supported by 3M. 3M previously used PFOA, PFHxS, and precursors to PFOS in manufacturing, and has more recently used perfluorobutanesulfonyl fluoride (PBSF), which can degrade to perfluorobutanesulfonate (PFBS). Role of sponsor or funder: 3M requested a scoping review of gestational diabetes mellitus and PFAS but was not involved in the preparation of the manuscript. The authors retained sole control of the manuscript content and the findings, and statements in this paper are those of the authors and not those of the funder, the author’s employer, or the sponsors. No authors were directly compensated by 3M. This project was funded through a contract between 3M and Ramboll U.S. Consulting, Inc., an international science and engineering company that provided compensation to the authors. None of the authors are currently engaged to testify as experts in litigation related to the compounds discussed in this manuscript, nor have they done so in the past. Authors’ conflicts of interest: GA, SH and FS declared they have no conflicts of interest. AKP and MPL work for Ramboll U.S. Consulting, Inc., which has a contract with 3M. See sections on support sources and role of sponsor or funder for more information. Grant information: Financial support for the project was from 3M (to Ramboll U.S. Consulting), and 3M suggested the broad review question. Ramboll U.S. Consulting commissioned Systematic Review Consultants LTD to conduct this scoping review in collaboration with Ramboll scientists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Copyright: © 2024 Aali G et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Aali G, Porter AK, Hoffmann S et al. Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.12688/f1000research.144376.2 ) First published: 14 Dec 2023, 12 :1595 ( https://doi.org/10.12688/f1000research.144376.1 ) Latest published: 09 Oct 2024, 12 :1595 ( https://doi.org/10.12688/f1000research.144376.2 ) Revised Amendments from Version 1 Based on peer-review comments, we moved search strategies to the Extended data and revised the first paragraph in Results to report a more organized assessment of previous systematic reviews. Based on peer-review comments, we moved search strategies to the Extended data and revised the first paragraph in Results to report a more organized assessment of previous systematic reviews. See the authors' detailed response to the review by Brice Nouthé and Evrard Kepgang See the authors' detailed response to the review by Raju Kanukula READ REVIEWER RESPONSES Introduction Per- and polyfluoroalkyl substances (PFAS) were used or have ongoing use in the manufacturing of a variety of products, including consumer-use products. 1 , 2 Almost everyone in developed countries has a detectable amount of PFAS in their blood serum due to exposure via contaminated food and other sources, and the unreactivity of these chemicals. 3 Despite some being phased out of production, 4 PFAS are widespread and have been detected in different continents irrespective of the level of industrialization, indicating long-range atmospheric transport as an important pathway of PFAS distribution. 5 Serum or plasma concentrations of PFAS have been associated with several health outcomes, including gestational diabetes mellitus (GDM). 6 – 11 GDM increases risk among offspring of preterm birth and macrosomia, 12 and, among mothers, of type 2 diabetes mellitus. 13 In the U.S., the proportion of pregnant women who develop GDM has increased over the past ten years, possibly due to trends in risk factors such as obesity, but environmental factors could be contributing. 14 Our recent experience in evaluating systematic reviews of the relation of health outcomes to PFAS serum concentrations has made us aware of the variety of comparators used in original reports. 15 This variety poses challenges in summarizing data that have not been adequately addressed in the GDM-PFAS systematic review literature. Thus, in addition to identifying relevant original reports in this scoping review, we addressed our special interest in the methods used in previous meta-analyses – but not in their findings. Motivation and rationale Funding for this scoping review was provided by 3M. 3M previously used perfluorooctyl and perfluorohexyl chemistries in manufacturing and has more recently used precursors of PFBS. 3M has publicly communicated that they will exit all PFAS manufacturing by the end of 2025. 16 3M would like to gain insights as to the strengths and weaknesses of the collective epidemiologic research on gestational diabetes mellitus in relation to PFAS. 3M requested a highly rigorous scoping review to better understand the nature of the existing data and evaluate the need for a new systematic review. The sponsor will not be involved in the conduct of the work at any stage and will not see our work products until they are published in a peer-reviewed journal. Ramboll provides updates regarding progress toward publication and required resources. If PFAS are a risk factor for GDM, this might affect regulations on allowable amounts of PFAS in water or food. GDM was not considered a critical endpoint in a recent U.S. government evaluation, but a more recent European government evaluation indicated that it could be. 4 , 17 Our objective was to collect and summarize the research on the relationship between serum per- and polyfluoroalkyl substances and gestational diabetes mellitus with the aim to inform the necessity of systematically reviewing the topic, potentially including a meta-analysis, and to estimate the required investment of resources needed for such a review. Methods We followed Joanna Briggs Institute’s guidance for designing and conducting this scoping review 18 and followed PRISMA-P, 19 PRISMA-ScR, 20 PRISMA-Abstract, 21 and PRISMA-Search 22 in reporting the protocol and the final report of this review. The indications for a scoping review were: a) to examine how research is conducted on a certain topic or field, and b) as a precursor to a systematic review. 23 We used the PECO framework (Population, Exposure, Comparator, and Outcomes) 24 for formulating the problem to be addressed. The PECO also guided setting the eligibility criteria ( Table 1 ). The population used was pregnant women. The exposure was the concentration of any specific PFAS in serum or plasma during pregnancy. The measure of exposure was obtained from a blood specimen or, for populations in which a validated pharmacokinetic model of serum concentration was available, estimated on an individual basis. Estimated serum or plasma PFAS for an individual from a population for which a validated pharmacokinetic model of serum concentration was available is acceptable because in the absence of a serum or plasma measurement, pharmacokinetic models can be useful for imputation when a population water supply had unusual high PFAS concentrations. 25 The comparator was a contrast in serum PFAS concentration that was either per arithmetic unit of PFAS (e.g., ng/ml), per log unit increase, or categorical. The primary outcome was GDM, and the secondary outcome was serum glucose. Table 1. Eligibility and exclusion criteria of this scoping review according to the PECO framework. Eligibility criteria Exclusion criteria a Population Pregnant women regardless of age, health status, ethnicity, occupation, and socioeconomic status Any study not including pregnant women Exposure Concentrations of any specific PFAS in serum or plasma during pregnancy; measured or estimated PFAS may include PFAS measured outside of pregnancy in consideration of the long half-life of many PFAS Externally measured or estimated PFAS exposure concentrations, such as food, water, or air that are not translated to PFAS serum or plasma concentrations for specific people; mixture analyses Comparator An incremental increase in concentration of a specific PFAS compared with a lower concentration, across the entire range of exposure; systematic reviews with high:low exposure comparators will be included None b Outcomes • Gestational Diabetes Mellitus (primary) Gestational Diabetes Mellitus as defined by original authors None b • Serum glucose (secondary) Measured glucose None b Study type Case-control, cross-sectional, or cohort designs Ecologic studies, case studies, reviews, laboratory reports, letters a See Methods for an elaboration on the exclusion criteria. b Other than those implied by the eligibility criteria. Observational studies such as case-control, longitudinal (cohort, prospective, retrospective), or cross-sectional studies were included in this review. Full reports about original epidemiologic research or meta-analyses had to be published online or in print. Pre-clinical studies (cells or genetic material) and studies with non-human subjects were excluded. If the data were for a non-pregnant population only or a mixed population where separate data on the pregnant population was unavailable, we excluded the report. If a measured or estimated serum or plasma concentration of PFAS in the person was not examined in relation to the occurrence of GDM or blood glucose in the person the report was excluded. Mixture analyses where there were no single exposure analyses for PFAS reported in that paper were excluded. 26 We excluded narrative and systematic narrative reviews; however, before the exclusion, we checked for any relevant unique included reports in the systematic narrative reviews. To identify relevant ongoing or published systematic reviews to examine their methods, we conducted a rapid search in PROSPERO and PubMed . On 11 th December 2022, we systematically searched the latest available version of the following sources to identify original reports without date, time, document type, or language limitations 27 : CINAHL via EBSCOhost (1937 – search date); Embase via Ovid SP (1974 – 9 th December 2022); Emerging Sources Citation Index via Web of Science (2015 – search date); MEDLINE via Ovid SP (1946 – 9 th December 2022); PubMed (excluding MEDLINE; 1946 – search date); and Science Citation Index Expanded via Web of Science (1900 – search date). An information scientist designed the search strategies using the terms collected from the experts, literature, and controlled vocabularies (CINAHL Headings, Medical Subject Headings=MeSH, and Emtree). The search strategy for MEDLINE was shared with two experts on the topic for commenting and revisions and peer-reviewed by another information specialist based on PRESS guidance 28 before being translated into the syntax of other databases. The search strategies (See the Extended data ) were tested and tuned based on a randomly selected half of the studies included in the previous systematic reviews. The final search was tested against the remaining half of the included studies from previous reviews to ensure the comprehensiveness of the retrieval. Results were imported to the reference management software, EndNote X9, for de-duplication. The de-duplicated search results were imported into Rayyan 29 and two reviewers screened the search results independently after turning the blinding mode on. We followed the same procedure for screening the full reports of the studies. For any disagreement, the two reviewers discussed and agreed on a final decision to include or exclude the report. Data extraction was designed, piloted, and revised to include the following data points: study name (first author’s last name and publication year), study design, study period, country of origin, participants’ age, number of participants per group, duration of the pregnancy at the baseline of the study, time of glucose measure, name of the glucose test, diagnostic criteria for GDM, sample type for exposure measurement, time of measuring PFAS, ethnicity, setting (rural, urban), source of exposure, length of exposure, name of substances, summary statistic for PFAS and glucose concentrations per group, exposure data type, chemical analysis methods, measures of association, exposure metric (comparator), potentially relevant references for identifying more relevant studies, the lead author’s name and email address, and any relevant notes. When we could not find the required data in the report, we contacted the authors to request it. We summarized the findings narratively or in tables. Because this was a scoping review, we did not run any data analysis or risk of bias appraisal for the included studies. Results We identified three previously published systematic reviews that explored the GDM-PFAS association ( Table 2 ). 30 – 32 In one systematic review (Yan et al. , 2022), 32 the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al. , 2021), 30 results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al. , 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored. The most recent of the systematic reviews had a literature search end date of November 2021. None of the previous systematic reviews employed synthesis without meta-analysis (SWiM). 33 Although our focus was not on the results of the previous systematic reviews, a summary of their results was as follows: a) no significant association was found between PFAS and GDM 30 ; b) PFOA was significantly associated with higher risk of GDM 31 ; and c) PFOA and PFBS increase risk of GDM. 32 Table 2. Characteristics of previous systematic reviews of GDM and PFAS. 1 st author, year N of studies a Literature review end date Results combined across comparators b Results stratified by comparator Results based on single comparator Used synthesis without meta-analysis Gao 2021 9 Feb 21 N Y N N Wang 2022 8 Sep 20 N N Y c N Yan 2022 11 Nov 21 Y N N N a All eight studies included in Wang et al . (2022) are in Gao et al . (2021), and all nine studies included in Gao et al . (2021) are included in Yan et al . (2022). b Meta-analysis done across results based on different types of comparators. c Wang et al . (2022) conducted a meta-analysis based on a high:low exposure category comparator. Four protocols registered in PROSPERO either explicitly addressed GDM and PFAS or might have included it in a broader definition of outcome or exposure ( Table 3 ). Two of the protocols were old enough that it was likely the effort had been abandoned; of the more recent protocols, one did not specifically mention the inclusion of pregnant women or gestational diabetes. The remaining study described the use of a high:low exposure category comparator, which is statistically inefficient because it does not include all available results from a report and has other limitations (see Discussion). None of the studies mentioned use of SWiM. 33 Table 3. Protocols for systematic reviews registered in PROSPERO (updated on 14 th June 2023). Reg. Number Title End date Use of SWiM Corresponding publication * Notes CRD42020192570 Investigating the relationship between maternal exposure to persistent organic pollutants (POPs) during pregnancy and gestational diabetes 3-30-21 Not mentioned No CRD42021233141 Association of Per-polyfluoroalkyl substances with gestational diabetes mellitus and diabetes-related metabolic traits in pregnant women: a systematic review and meta-analysis 5-30-21 Not mentioned No CRD42022332561 Association of Perpolyfluoroalkyl exposure with diabetes mellitus prevalence and its related complications: a systematic review and meta-analysis [sic] 9-30-23 Not mentioned No No mention of pregnancy or gestation in protocol CRD42022369711 Exposure to Per- and Polyfluoroalkyl Substances (PFAS) and Diabetes Mellitus: A Systematic Review and Meta-Analysis 1-1-23 Not mentioned No Will use high:low exposure categories as comparator * Per PubMed search 6-16-23. The search for original data reports found 4938 records. After removing the duplicates, we screened the unique records and identified 82 possibly relevant records based on their titles and abstracts. When the full-text reports were obtained for these 82 records, we excluded 62 after documenting the reason for exclusion and included 20 reports in this review. 6 – 11 , 34 – 47 The process of selection of reports is shown in Figure 1 . Figure 1. The PRISMA diagram for the process of selecting the studies. Two reports used the data from the Shanghai Birth Cohort 11 , 45 with the possibility of duplicate and overlapping data. The source and length of exposure were not reported in any of the reports, presumably indicating that all were of populations with background exposure. Characteristics of the reports are presented in Table 4 . Based on these data, the prospective cohort (12 reports) was the most used study design followed by case-control (5). The studies were conducted between 1997 and 2021 in China (10 reports), North America (US (6) & Canada (1)), Denmark (2), and Spain (1). The 10 studies from China all had Chinese participants, the ethnicity of participants from all seven North American studies was diverse, one of the studies from Denmark included only participants of Danish ethnicity, while the other did not report participant ethnicity, and the one study from Spain had participants of primarily Spanish origin. Table 4. Characteristics of included reports. Study Design Period Country Age Participants Controls Pregnancy duration a Ethnicity Setting Zhang 2015 Prospective Cohort (With Control Group) 2005-2009 US 29.7 ± 3.7 258 pregnant women (28 GDM) 230 Non-GDM NA b White, Non-White NA Shapiro 2016 Prospective Cohort (With Control Group) 2008-2011 Canada 33.0 ± 4.9 1274 pregnant women (59 GDM) 1167 Normal Glucose 6 to < 14 GW White, Non-White Urban Matilla-Santander 2017 Prospective Cohort (No Control Group) 2003-2008 Spain 31.9 ± 4 1240 pregnant women (53 GDM) NA 1st Trimester Spanish Urban/mixed Starling 2017 Prospective Cohort (No Control Group) 2009-2014 US 27.8 ± 6:2 Age at Delivery 652 pregnant women (628 with fasting glucose) NA <24 GW Black/Non-Hispanic, Hispanic, White/Non-Hispanic, Others Urban/mixed Valvi 2017 Cohort (Retrospective Data, With Control Group) 1997-2000 Denmark 29.2 ± 5.2 Age at Delivery 604 pregnant women (49 GDM) 555 Non-GDM 34 GW Faroese Mixed Jensen 2018 Prospective Cohort (With Control Group) 2011 (Sep) - 2013 (Sep) Denmark 29.9 ± 4.4 158 pregnant women with high GDM risk (all with OGTT c ) 160 Low GDM Risk 8-16 GW Danish Urban/mixed Wang 2018a Prospective Cohort (Repeat Measurement-Based; No Control Group) 2013 (Sep) - 2014 (Dec) China 20-40 560 pregnant women (35 GDM) NA 5-15 GW Chinese Urban Wang 2018b Case-Control 2013 (Jan) - 2013 (Mar) China 29.5 (28.0 - 32.0) GDM 29.0 (28.0-31.0) Non-GDM 252 pregnant women (84 GDM) 168 Healthy NA Chinese Urban Liu 2019 Case-Control (Nested) 2013 (Aug) - 2015 (Jun) China 29.3 ± 2.9 439 pregnant women (63 GDM) 126 Healthy 1st Trimester Chinese Urban Rahman 2019 Prospective Cohort (No Control Group) 2009 (Jul) - 2013 (Jan) US 28.2 ± 5.5 2334 pregnant women (74 GDM) NA 8-13 GW Asian, Black/Non-Hispanic, Hispanic, White/Non-Hispanic NA Li 2020 Prospective Cohort (No Control Group) 2013 (Oct) - 2014 (Aug) China 28.3 ± 3.2 874 pregnant women (59 GDM) NA 24-28 GW Chinese Urban Preston 2020b Prospective Cohort (No Control Group) 1999-2002 US 31.9 ± 5.1 1540 pregnant women (85 GDM) NA 22 ≥ GW Asian, Black, Hispanic, White, Other Urban Ren 2020 Cohort (Retrospective Data, No Control Group) 2012 (Apr) - 2012 (Dec) China 27.8 ± 3.3 981 pregnant women (PFAS); 856 (FG); 705 (1hG) NA 12-16 GW Chinese Urban Xu 2020 Case-Control (Nested in Prospective Cohort) 2017 (Jul 1) - 2019 (Jan 31) China 29.7 ± 3.1 2460 pregnant women (165 GDM) 330 Healthy 24-28 GW Chinese Urban Mehta 2021 Prospective Cohort (No Control Group) 2011-2015 US ≤27 95 overweight and obese pregnant women (all with fasting glucose) NA <14 GW Black/Non-Hispanic, Latina, White/Non-Hispanic Urban Vuong 2021 Cohort (Retrospective Data, No Control Group) 2003 (Mar) - 2006 (Feb) US <25: 93 25-34: 229 ≥35: 61 388 pregnant women (234 with non-fasting glucose) NA 16 ± 3 GW Black/Non-Hispanic, White/Non-Hispanic, Others Urban Yu 2021 Prospective Cohort (With Control Group) 2013-2016 China 29.1 ± 3.7 2747 pregnant women (325 GDM) 2422 Non-GDM 15 (13-17) GW Median (IQR) Chinese Urban Xu 2022 Case-Control 2020 (Oct) - 2021 (Sep) China 31.5 ± 4.38 340 pregnant women (171 GDM) 169 Healthy 271 ± 7.22 (Days) Chinese Urban Wang 2023a Prospective Cohort (No Control Group) 2013-2016 China 29.4 ± 3.8 1405 pregnant women (270 GDM) NA 39.1 ± 1.4 GW Chinese Urban Zhang 2023 Case-Control 2011 (Jul) - 2012 (Nov) China 34.4 ± 4.6 (GDM) 30.9 ± 4.6 (Non-GDM) 204 pregnant women (135 GDM) 69 Healthy 38.3 ± 1.6 GW (GDM) 38.2 ± 1.8 GW (Non-GDM) Chinese Urban a At study baseline. b NA: Not available. c OGTT: Oral Glucose Tolerance Test. The 20 reports included a total of 18,805 participants. Among the 15 reports that presented the number of participants with GDM, the proportion with GDM was 10% (1,655/16,513); the other five reports presented results on serum glucose only and not GDM. The number of participants across the reports ranged between 95 and 2747. The participants’ age was between 20 and 40 with the most frequent mean age reported being between 28 and 32. Participants’ duration of pregnancy at study baseline varied between 5 and 38 weeks making it one of the most heterogenous items of data extracted. Table 5 summarizes the list of 24 PFAS (not counting isomers) for which a measure of association was reported in the included studies with results for PFOA, PFOS, PFHxS, PFNA, and PFDA being reported in almost all the studies. Table 5. PFAS in included reports for which a measure of association with an outcome was presented. Acronyms for Specific PFAS a CAS Number b No. Carbons c Jensen 2018 Li 2020 Liu 2019 Matilla-Santander 2017 Mehta 2021 Preston 2020b Rahman 2019 Ren 2020 Shapiro 2016 Starling 2017 Valvi 2017 Vuong 2021 Wang 2018a Wang 2018b Wang 2023a Xu 2020 Xu 2022 Yu 2021 Zhang 2015 Zhang 2023 Total Carboxylic Acids PFBA d 375-22-4 4 - - - - - - - - - - - - - - - - - - - ✓ 1 PFPeA e 2706-90-3 5 - - - - - - - - - - - - - - - - - - - ✓ 1 PFHxA f 307-24-4 6 - - - - - - - - - - - - - - - - - - - ✓ 1 PFHpA g 375-85-9 7 - ✓ - - - - ✓ - - - - - - - - - ✓ ✓ - ✓ 5 ADONA h 919005-14-4 7 - - - - - - - - - - - - - - - - ✓ - - - 1 PFOA (sum) i 355-67-1 8 ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ 18 n-PFOA j 355-67-1 - - ✓ - - - - - - - - - - ✓ - - - - - - 2 6m-PFOA k 15166-06-0 - - ✓ - - - - - - - - - - - - - - - - - 1 PFNA l 375-95-1 9 ✓ ✓ - ✓ ✓ ✓ ✓ ✓ - ✓ ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ ✓ 17 PFDA (PFDeA) m 335-76-2 10 ✓ ✓ - - ✓ - ✓ ✓ - ✓ ✓ - - ✓ ✓ ✓ ✓ ✓ ✓ ✓ 14 PFUnDA n 2058-94-8 11 - ✓ - - - - ✓ ✓ - - - - - ✓ ✓ ✓ ✓ ✓ - - 8 PFDoA (PFDoDA) o 307-55-1 12 - ✓ - - - - ✓ ✓ - - - - - - - ✓ ✓ ✓ - ✓ 7 PFTrDA (PFTriDA) p 72629-94-8 13 - ✓ - - - - - ✓ - - - - - - - - ✓ - - ✓ 4 PFTeDA q 376-06-7 14 - ✓ - - - - - - - - - - - - - - - - - ✓ 2 Sulfonic Acids PFBS r 375-73-5 4 - ✓ - - - - - - - - - - - - - ✓ - ✓ - ✓ 4 PFHxS s 355-46-4 6 ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ - ✓ ✓ ✓ ✓ ✓ - ✓ 17 4:2FTS t 757124-72-4 6 - - - - - - - - - - - - - - - - ✓ - - - 1 PFHpS u 375-92-8 7 - - - - - - - - - - - - - - - ✓ - - - - 1 PFOS (sum) v 1763-23-1 8 ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ - ✓ ✓ ✓ ✓ ✓ ✓ 18 n-PFOS w 1763-23-1 - - ✓ - - - - - - - - - - ✓ - - - - - - 2 1m-PFOS x 1763-23-1 - - - - - - - - - - - - - ✓ - - - - - - 1 3m+4m-PFOSc aa 1763-23-1 - - - - - - - - - - - - - ✓ - - - - - - 1 5m-PFOS bb 1763-23-1 - - - - - - - - - - - - - ✓ - - - - - - 1 6m-PFOS cc 1763-23-1 - - - - - - - - - - - - - ✓ - - - - - - 1 6:2 Cl-PFESA dd 73606-19-6 8 - ✓ - - - - - - - - - - - - - - ✓ - - ✓ 3 6:2FTS ee 27619-97-2 8 - - - - - - - - - - - - - - - - ✓ - - - 1 8:2 Cl-PFESA ff 83329-89-9 10 - ✓ - - - - - - - - - - - - - - - - - ✓ 2 PFDS gg 335-77-3 10 - - - - - - - - - - - - - - - - ✓ - - - 1 Sulfonamides and Sulfonamidoacedic Acids PFOSA hh 754-91-6 8 - - - - - - - - - - - - - - - - - - ✓ ✓ 2 MeFOSAA (Me-PFOSA-AcOH) ii 2355-31-9 11 - - - - - ✓ ✓ - - - - - - - - - - - ✓ - 3 EtFOSAA (Et-PFOSA-AcOH) jj 2991-50-6 12 - - - - - ✓ - - - - - - - - - - - - ✓ - 2 a Frequently used alternative acronyms are in parentheses. b For PFOA and PFOS, isomer-specific CAS#s were not available at this time this manuscript was prepared (except for 6m-PFOS); we followed CDC’s example of using the same CAS# for the isomers of PFOA (sum) and PFOS (sum) ( https://www.cdc.gov/nceh/dls/oatb_capacity_14.html ). c Number of carbons not given for isomers. d PFBA (PFBA (C4)): Perfluorobutanoic Acid. e PFPeA (PFPeA (C5)): Perfluoropentanoic Acid. f PFHxA (PFHxA (C6)): Perfluorohexanoic Acid. g PFHpA (PFHpA (C7)): Perfluoroheptanoic Acid. h ADONA: 4,8-Dioxa-3H-Perfluorononanoic Acid. i PFOA (PFOA (C8)): Perfluorooctanoic Acid. j n-PFOA: N-Perfluorooctanoic Acid. k 6m-PFOA: Perfluoro-6-Methylpheptanoic Acid. l PFNA (PFNA (C9)): Perfluorononanoic Acid. m PFDA (PFDeA or PFDA (C10)): Perfluorodecanoic Acid. n PFUnDA (PFUnDA (C11)): Perfluoroundecanoate. o PFDoA (PFDoDA or PFDoDA (C12)): Perfluorododecanoic Acid. p PFTrDA (PFTriDA (C13) or PFTrDA (C13)): Perfluorotridecanoate. q PFTeDA (C14): Perflurotetradecanoate. r PFBS (PFBS (C4)): Perfluorobutanesulfonic Acid. s PFHxS (PFHxS (C6)): Perfluorohexanesulfonic Acid. t 4:2FTS: 4:2 Fluorotelomer Sulfonic Acid. u PFHpS: Perfluoroheptane Sulfonic Acid. v PFOS (PFOS (C8)): Perfluorooctanesulfonic Acid. w n-PFOS: N-Perfluorooctane Sulfonate. x 1m-PFOS: Perfluoro-1-Methylheptanesulfonate. y 3m-PFOS: Perfluoro-3-Methylheptanesulfonate. z 4m-PFOS: Perfluoro-4-Methylheptanesulfonate. aa 3m+4m-PFOSc: Perfluoro-3-Methylheptanesulfonate + Perfluoro-4-Methylheptanesulfonate. bb 5m-PFOS: Perfluoro-5-Methylheptanesulfonate. cc 6m-PFOS: Perfluoro-6-Methylheptanesulfonate. dd 6:2 Cl-PFESA: 6:2 Chlorinated Polyfluorinated Ether Sulfonate. ee 6:2FTS: 6:2 Fluorotelomer Sulfonic Acid. ff 8:2 Cl-PFESA: 8:2 Chlorinated Polyfluorinated Ether Sulfonic Acid. gg PFDS: Perfluorodecane Sulfonate. hh PFOSA: Perfluorooctanesulfonamide. ii MeFOSAA (Me-PFOSA-AcOH): Methylperfluorooctanesulfonamidoacetic Acid. jj EtFOSAA (Et-PFOSA-AcOH): Ethylperfluorooctane Sulfonamidoacetic Acid. Table 6 presents the data regarding the measurement and reporting of PFAS concentration, glucose, and GDM. An oral glucose tolerance test (OGTT) was used in 16 reports as the glucose test and seven reports followed the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosing GDM. Among 12 reports that reported type of glucose measure, 10 reported fasting glucose (FG), six reported one hour glucose (1hG), and five reported two hour glucose (2hG), most of which reported mean ± standard deviation (nine reports). While the time for measuring glucose levels varied between 14 weeks of gestation and 1-2 days pre-delivery, measurement of PFAS was in a wider time range from 8 weeks of gestation to delivery. HPLC LC-MS/MS was the most-used chemical analysis method for PFAS. A summary statistic for PFAS concentrations was presented for 19 reports with the geometric mean being the most frequently reported (10) followed by the median (seven reports). Standard deviation was presented in only four reports with geometric means and interquartile range (IQR) for six reports with median. Table 6. Measures of glucose and PFAS in the included reports. Study Glucose measure time Glucose test GDM Diagnostic criteria Chemical measure Time PFAS statistic Exposure categories Chemical analysis method Glucose measures Glucose statistic Measures of association Exposure metric (Comparator) Zhang 2015 NA NA Self-Report (Physician Diagnosis) NA Geometric Mean (95% CI) NA HPLC LC-MS/MS NA NA Crude and adjusted OR (GDM) Per SD ln-unit difference in PFAS concentration Shapiro 2016 NA OGTT Canadian Diabetes Association and the Society of Obstetricians and Gynaecologists of Canada 1st Trimester Geometric Mean (SD) Quartiles UPLC/MS-MS NA NA Crude and adjusted OR (IGT and GDM) By quartile of PFAS concentration Matilla-Santander 2017 24-28 GW OGTT Spanish Group of Diabetes and Pregnancy 13 GW (13:1 ± 1:4) Geometric Mean (SD) Quartiles HPLC LC-MS/MS NA NA Minimally adjusted a and fully adjusted OR (IGT and GDM) By quartile & per log10-unit difference in PFAS concentration Starling 2017 27 (20-34) GW Median (Range) NA NA 27 (20-34) GW Median (Range) Geometric Mean (95% CI) Tertiles Online Solid Phase Extraction-PLC-Isotope Dilution-Tandem MS (Modified) FG Mean ± SD Crude and adjusted β (FG) By terile & per ln-unit difference in PFAS concentration Valvi 2017 24-28 GW OGTT SOGC Clinical Practice Guidelines on Screening for Gestational Diabetes Mellitus 34 GW Median (IQR) Tertiles LC with Tandem MS NA NA Crude and adjusted OR (GDM) By tertile & per log2-unit difference in PFAS concentration Jensen 2018 28 GW OGTT European Association for the Study of Diabetes (Lind and Phillips, 1991) 11.3 (9.9; 14.3) GW (Median IQR) Median (5th - 95th Percentile) NA Online Solid Phase Extraction followed by LC-MS/MS FG 1hG 2hG Median (IQR) Crude and adjusted percent difference (FG, 1hG, 2hG) Per log2-unit difference in PFAS concentration Wang 2018a 21-26 GW; 26.8 ± 2.2 (26) Mean ± SD (Median) OGTT (n=385) IADPSG Middle Term of Pregnancy Range Tertiles UPLC-Q/TOF MS FG (Average) OGTT (Average) Mean ± SD Crude and adjusted β (FG, OGTT) and HR (GDM) By terile (GDM) & per log-unit difference in PFAS concentration (FG, OGTT) Wang 2018b 1-2 Days Pre-Delivery OGTT Ministry of Health China Criteria (WS311-2011), based on IADPSG 1-2 Days Pre-Delivery Median (IQR) Dichotomized NA NA NA Crude and adjusted OR (FG and GDM) Dichotomized (FG) & per 1 ng/mL difference in PFAS concentration (GDM) Liu 2019 24-28 GW OGTT Ministry of Health China Criteria (WS311-2011), based on IADPSG 1st Trimester Median (IQR) Tertiles HPLC LC-MS/MS FG 1hG 2hG Mean ± SD Conditioned b and adjusted OR (GDM) and adjusted β (FG, 1hG, 2hG) By tertile (GDM) & per ln-unit difference in PFAS concentration (GDM, FG, 1hG, 2hG) Rahman 2019 27.5 ± 4.3 GW OGTT Carpenter and Coustan 8-13 GW Geometric Mean (95% CI) NA LC-SPE-LC-MS/MS NA NA Adjusted RR (GDM) Per 1 SD-unit difference in PFAS concentration Li 2020 24-28 GW OGTT IADPSG Delivery Geometric Mean Dichotomized HPLC FG 1hOGTT 2hOGTT NA Crude and adjusted β (FG, 1hG, 2hG) and OR (GDM) Per log2-unit difference in PFAS concentration Preston 2020b 28 GW OGTT Carpenter and Coustan 9.7 GW (Median) NA Quartiles NA GCT Blood Glucose Mean ± SD Adjusted OR (IGT and GDM) and β (1hG) By quartile (IGT, GDM, 1hG) & per ln-unit difference in PFAS concentration (IGT, GDM) Ren 2020 12-20 GW (FG); 20-28 GW (1hG) OGTT Medical Records at Birth 12-16 GW Geometric Mean (SD) Tertiles HPLC LC-MS/MS FG 1hG Mean ± SD Crude and adjusted OR (FG and 1hG) Per ln-unit difference in PFAS concentration Xu 2020 24-28 GW OGTT IADPSG 16-20 GW Median Quartiles UPLC-Q/TOF MS NA NA Crude and adjusted OR (GDM) By quartile & per log10-unit difference in PFAS concentration Mehta 2021 <14 GW OGTT NA 16 (10-24) GW Median (Range) Geometric Mean (SE) NA LC-SPE-LC-MS/MS FG Geometric Mean (SE) Adjusted percent difference (FG) Per log2-unit difference in PFAS concentration Vuong 2021 ≥ 26 GW (n=234) OGTT NA 16 or 26 GW Geometric Mean (SD) NA HPLC-Isotope Dilution-Tandem MS Glucose at ≥ 26 Mean ± SD Adjusted β (1hG) Per ln-unit difference in PFAS concentration Yu 2021 24-28 GW NA IADPSG 15 (13-17) GW Median (IQR) Median (IQR) Tertiles HPLC LC-MS/MS FG 1hG 2hG Mean ± SD Adjusted OR (GDM) Adjusted β (FG, 1hG and 2hG) Per ln-unit difference in PFAS concentration Xu 2022 271 ± 7.22 (Days) OGTT IADPSG 1-2 Days Pre-Delivery Median (IQR) Tertiles UPLC/MS-MS FG 1hG 2hG Mean ± SD Crude and adjusted OR (GDM) Adjusted β (FG, 1hG and 2hG) By tertile of PFAS concentration Wang 2023a 24-28 GW NA IADPSG 15 (9-16) GW Median (Range) Geometric Mean (Range) NA HPLC LC-MS/MS FG Mean ± SD Crude and adjusted β (FG) Per log2-unit difference in PFAS concentration Zhang 2023 24-28 GW OGTT IADPSG 1st Trimester Mean Tertiles HPLC LC-MS/MS NA NA Crude and adjusted OR (GDM) By tertile & per log10-unit difference in PFAS concentration a Adjusted for subcohort only. b Conditioned on matching factor, maternal age. To measure the association between PFAS concentration and glucose, the reports used associations between PFAS and one or more of the glucose measures: FG, 1hG, 2hG, OGTT (average of 1hG and 2hG), Impaired Glucose Tolerance (IGT), and GDM. Adjusted odds ratio (OR) (12 reports), crude OR (eight), adjusted regression coefficient (β) relating serum glucose to PFAS (nine), and crude β (three) were the main reported association measures. When a log exposure metric (comparator) was used, it was implemented heterogeneously with per one log-unit difference in PFAS concentration presented in nine studies, per log2 (doubling) difference in four, and per log10 difference in three. Eleven of the reports examined associations with exposure data categorized as either tertiles (six reports), quartiles (four), or dichotomized (one). The majority of these were in conjunction with exposure data examined as a continuous variable, but two reports displayed results with categorized PFAS concentration only, one as tertiles and one as quartiles of exposure. We summarized the type of data in the original reports identified by our literature review according to the comparator and outcome ( Table 7 ). Results from reports that reported an effect measure for GDM (e.g., odds ratio) with exposure categorized into more than two categories were counted in the table as being arithmetic comparators because the results can be re-expressed that way. 48 For GDM, we found that 12 reports could be combined in a SWiM analysis for the two major PFAS. For reports presenting effect measures for glucose during pregnancy (same two PFAS), we found 11 results that could potentially be combined using SWiM. If results for GDM and glucose were combined in a SWiM, results for 17 could be included – assuming the participants in Wang et al . 2023a were a subset of those in Yu et al . 2021. Table 7. Number of reports that could be included in a meta-analysis or SWiM by type of outcome and type of comparator. Type of outcome Type of comparator N of reports * PFOA PFOS Gestational Diabetes Mellitus Arithmetic (ng/ml) † 8 8 Log (ng/ml) ‡ 9 9 SWiM § 12 12 Glucose during pregnancy Arithmetic (ng/ml) † 3 3 Log (ng/ml) ‡ 8 8 SWiM § 11 11 * N of studies using total amount of PFOA or PFOS. † Includes studies with categorical results only that have more than two categories of exposure because these can be re-expressed as ng/ml. ‡ Regardless of the log of base used. For example, studies reporting difference in outcome per doubling of exposure (base log 2) are counted, as well as those using natural log or base 10 log. § Number of unique studies that could be included in a synthesis without meta-analysis. For example, if a study reported one set of results using an arithmetic comparator and another set of results using a log comparator, that study would be counted only once towards the number in the SWiM. Discussion This scoping review of the evidence and methods used in primary and secondary data on the relation of GDM with PFAS addressed the overall question of whether a new systematic review was needed. Because data from several new reports were available since previous systematic reviews were conducted and because SWiM 33 could make the best use of all available data, an updated systematic review using SWiM would be a valuable addition to the literature. The variety of comparators used in the original reports poses challenges to the use of meta-analysis to summarize data. If the original reports include a categorical exposure scale, a meta-analysis using a high:low exposure category comparator has been presented as an option. 24 The weaknesses of this approach, however, merit discussion. For PFAS, the exposure contrast corresponding to the high:low comparison is likely to vary substantially across studies. If a dose-response relation is operative, the magnitude of the meta-analytic summary would reflect the distribution of exposure in the studies, and the validity of the resulting meta-analytic statistics associated with such a summary is questionable. 49 Furthermore, categorical results within-study can be re-expressed to an arithmetic effect measure, which solves the above-mentioned problem and has the further benefit of using, rather than a portion, all the available data. Another issue is that if arithmetic and logged exposure measures were interchangeable after some type of re-expression, that would facilitate meta-analysis. But such re-expression does not work reliably. 50 An interesting example of the underlying problem can be found in a recent report by Padula et al . (2023). 51 They analyzed individual-level data on birth weight and serum PFOA first using log (exposure) and again using arithmetic exposure. The association was inverse in both analyses, but it was statistically significant when log (exposure) was used but not when arithmetic exposure was used. The SWiM is the only widely-accepted non-narrative approach to synthesizing the data from evidence streams based on different comparators. 33 The three previous systematic reviews each had methodologic elements yielding questionable results. Specifically, a) Gao et al . 30 did not provide an overall summary of results from different evidence streams, b) Wang et al ., 31 by using a high:low comparator, ignored part of the data and combined results in the face of varying exposure contrasts, and c) Yan et al ., 32 combined results across comparators, rendering nebulous the statistics associated with the results. Another potential improvement in a future systematic review of the GDM-PFAS association would be to integrate data from the GDM-PFAS and blood glucose-PFAS evidence streams. Among studies of blood glucose as the only outcome (no GDM analysis), four out of the five included participants with GDM. Because blood glucose is near to normally distributed, the odds ratio for GDM and the beta coefficient for blood glucose are, with re-expression, interchangeable metrics. 52 Thus, data from the glucose-PFAS reports could be used to address the overall question. Even without such re-expression, SWiM could be used to combine the evidence streams. Results for five PFAS (PFOA, PFOS, PFHxS, PFNA, and PFDA) were reported in almost all the original data studies because these are the PFAS that have the highest median serum concentration in background-exposed populations. In the previous systematic reviews, Gao et al . (2021) reported results for all five 30 ; Wang et al . (2022) reported on four, 31 and Yan et al . (2022) reported on these five plus three additional PFAS. 32 PFAS with lower median concentrations could have been analyzed by the original authors with the comparator > LOD vs not, and such results have not, to date, been included in meta-analyses; however, they could be included in a SWiM. When conducting a meta-analysis of odds ratios for GDM, an assumption is that the log of the odds ratio per comparator unit (beta coefficient) does not vary by the prevalence of GDM in the underlying populations. The prevalence of GDM in the underlying populations is a function of the diagnostic criteria, the prevalence of obesity, and other study or population characteristics. 53 – 55 Whether these characteristics modify the beta coefficient could be evaluated in a meta-regression; such regression was not done in the previous meta-analyses. Time has passed since the date of the search for relevant original data reports. Our search for relevant systematic reviews, however, was much more recent, and it is this search that is most important for our conclusions to remain valid. The number of new reports available was not as important for our conclusions as the finding that the methods employed in previous systematic reviews could be substantially improved. Data availability All data underlying the results are available as part of the article and no additional source data are required. 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Obstet Med. 2012; 5 (2): 71–77. PubMed Abstract | Publisher Full Text | Free Full Text 55. Torloni MR, Betran AP, Horta BL, et al. : Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis. Obes. Rev. 2009; 10 (2): 194–203. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 14 Dec 2023 ADD YOUR COMMENT Comment Author details Author details 1 Department of Evidence Synthesis, Systematic Review Consultants LTD, Oxford, UK 2 Ramboll U.S. Consulting, Inc., Raleigh, NC, USA 3 seh consulting + services, Paderborn, Germany Ghazaleh Aali Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Anna K. Porter Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Sebastian Hoffmann Roles: Conceptualization, Data Curation, Formal Analysis, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Matthew P. Longnecker Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Farhad Shokraneh Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests Support sources: This work was supported by 3M. 3M previously used PFOA, PFHxS, and precursors to PFOS in manufacturing, and has more recently used perfluorobutanesulfonyl fluoride (PBSF), which can degrade to perfluorobutanesulfonate (PFBS). Role of sponsor or funder: 3M requested a scoping review of gestational diabetes mellitus and PFAS but was not involved in the preparation of the manuscript. The authors retained sole control of the manuscript content and the findings, and statements in this paper are those of the authors and not those of the funder, the author’s employer, or the sponsors. No authors were directly compensated by 3M. This project was funded through a contract between 3M and Ramboll U.S. Consulting, Inc., an international science and engineering company that provided compensation to the authors. None of the authors are currently engaged to testify as experts in litigation related to the compounds discussed in this manuscript, nor have they done so in the past. Authors’ conflicts of interest: GA, SH and FS declared they have no conflicts of interest. AKP and MPL work for Ramboll U.S. Consulting, Inc., which has a contract with 3M. See sections on support sources and role of sponsor or funder for more information. Grant information Financial support for the project was from 3M (to Ramboll U.S. Consulting), and 3M suggested the broad review question. Ramboll U.S. Consulting commissioned Systematic Review Consultants LTD to conduct this scoping review in collaboration with Ramboll scientists. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) version 2 Revised Published: 09 Oct 2024, 12:1595 https://doi.org/10.12688/f1000research.144376.2 version 1 Published: 14 Dec 2023, 12:1595 https://doi.org/10.12688/f1000research.144376.1 Copyright © 2024 Aali G et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Aali G, Porter AK, Hoffmann S et al. Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.12688/f1000research.144376.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 09 Oct 2024 Revised Views 0 Cite How to cite this report: Nouthé B and Kepgang E. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.172869.r330434 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v2#referee-response-330434 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Oct 2024 Brice Nouthé , Faculty of Medicine, The University of British Columbia, Vancouver, Canada Evrard Kepgang , Faculty of Medicine and Health Sciences, University of Antwerp, Flanders, Belgium Approved VIEWS 0 https://doi.org/10.5256/f1000research.172869.r330434 Great work done: Kudos! ... Continue reading READ ALL Great work done: Kudos! No further changes needed at this juncture. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Diabetes Mellitus We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Nouthé B and Kepgang E. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.172869.r330434 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v2#referee-response-330434 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 14 Dec 2023 Views 0 Cite How to cite this report: Kanukula R. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r324731 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-324731 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Sep 2024 Raju Kanukula , Monash University, Victoria, Australia Approved VIEWS 0 https://doi.org/10.5256/f1000research.158160.r324731 This scoping review was conducted very well without any issues, however I have the following concerns. 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. 2) What is the rationale ... Continue reading READ ALL This scoping review was conducted very well without any issues, however I have the following concerns. 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. 2) What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Methodologist and pharmacist. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kanukula R. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r324731 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-324731 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Oct 2024 Farhad Shokraneh 09 Oct 2024 Author Response Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review ... Continue reading Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review examined the studies that assess the ‘Association’ from the observational studies. Considering that confounding factors such as obesity—as mentioned in the introduction—can contribute to GDM, we are unable to discuss ‘Causation’ and have yet to see research suggesting such a mechanism. Comment : What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Response : We excluded the narrative review articles with no usable data or a list of included studies. We, however, studied the systematic reviews and meta-analyses to identify more relevant studies for a possible systematic review in the future, avoid duplicate work, and discuss the suitability of conducting meta-analysis in these reviews. Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review examined the studies that assess the ‘Association’ from the observational studies. Considering that confounding factors such as obesity—as mentioned in the introduction—can contribute to GDM, we are unable to discuss ‘Causation’ and have yet to see research suggesting such a mechanism. Comment : What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Response : We excluded the narrative review articles with no usable data or a list of included studies. We, however, studied the systematic reviews and meta-analyses to identify more relevant studies for a possible systematic review in the future, avoid duplicate work, and discuss the suitability of conducting meta-analysis in these reviews. Competing Interests: None known. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Oct 2024 Farhad Shokraneh 09 Oct 2024 Author Response Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review ... Continue reading Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review examined the studies that assess the ‘Association’ from the observational studies. Considering that confounding factors such as obesity—as mentioned in the introduction—can contribute to GDM, we are unable to discuss ‘Causation’ and have yet to see research suggesting such a mechanism. Comment : What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Response : We excluded the narrative review articles with no usable data or a list of included studies. We, however, studied the systematic reviews and meta-analyses to identify more relevant studies for a possible systematic review in the future, avoid duplicate work, and discuss the suitability of conducting meta-analysis in these reviews. Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review examined the studies that assess the ‘Association’ from the observational studies. Considering that confounding factors such as obesity—as mentioned in the introduction—can contribute to GDM, we are unable to discuss ‘Causation’ and have yet to see research suggesting such a mechanism. Comment : What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Response : We excluded the narrative review articles with no usable data or a list of included studies. We, however, studied the systematic reviews and meta-analyses to identify more relevant studies for a possible systematic review in the future, avoid duplicate work, and discuss the suitability of conducting meta-analysis in these reviews. Competing Interests: None known. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Nouthé B and Kepgang E. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r296883 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-296883 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Jul 2024 Brice Nouthé , Faculty of Medicine, The University of British Columbia, Vancouver, Canada Evrard Kepgang , Faculty of Medicine and Health Sciences, University of Antwerp, Flanders, Belgium Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.158160.r296883 The authors aimed to evaluate the evidence on a potential relationship between Gestational Diabetes Mellitus (GDM) and serum per-&polyfluoroalkyl substances (PFAS). This sponsored effort (by 3M) to evaluate the risk, caused by this group of synthetic carbon-fluorine compounds ensuring slow ... Continue reading READ ALL The authors aimed to evaluate the evidence on a potential relationship between Gestational Diabetes Mellitus (GDM) and serum per-&polyfluoroalkyl substances (PFAS). This sponsored effort (by 3M) to evaluate the risk, caused by this group of synthetic carbon-fluorine compounds ensuring slow degradation, is timely because of the important issues evolving around the demonstrated relationship of PFAS, known to have an extensive human exposure, and diabetes mellitus the different concerns about GDM across continents despite known lifelong consequences of GDM the potential conflictual results of previous meta-analysis. Suggestion1: The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Suggestion 2: In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material . Also, the procedure to solve disagreement does not need to be repeated. Suggestion 3: The flow in the Results' section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around he potential pitfalls like the use of meta-analyses with different comparators ( but without meta-regression) The combination of results form different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Diabetes Mellitus We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Nouthé B and Kepgang E. Reviewer Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r296883 ) The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-296883 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 09 Oct 2024 Farhad Shokraneh 09 Oct 2024 Author Response Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they ... Continue reading Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Response : Thank you for spending time reviewing this scoping review and for your suggestion not to expand the introduction. Suggestion 2 : In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material. Response : Thank you. We followed your recommendations and F1000Research’s guidelines and shared the search strategies on the Open Science Framework (OSF). Comment : The procedure to solve disagreement does not need to be repeated. Response : We agree with your decision and have revised the manuscript to reflect it. Suggestion 3 : The flow in the Results section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around the potential pitfalls like The use of meta-analyses with different comparators (but without meta-regression) The combination of results from different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Response : Thank you for your suggestion, based on which we changed the first section of results as follows: “In one systematic review (Yan et al., 2022), the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al., 2021), results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al., 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored.” Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Response : Thank you for spending time reviewing this scoping review and for your suggestion not to expand the introduction. Suggestion 2 : In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material. Response : Thank you. We followed your recommendations and F1000Research’s guidelines and shared the search strategies on the Open Science Framework (OSF). Comment : The procedure to solve disagreement does not need to be repeated. Response : We agree with your decision and have revised the manuscript to reflect it. Suggestion 3 : The flow in the Results section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around the potential pitfalls like The use of meta-analyses with different comparators (but without meta-regression) The combination of results from different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Response : Thank you for your suggestion, based on which we changed the first section of results as follows: “In one systematic review (Yan et al., 2022), the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al., 2021), results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al., 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored.” Competing Interests: None known. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 09 Oct 2024 Farhad Shokraneh 09 Oct 2024 Author Response Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they ... Continue reading Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Response : Thank you for spending time reviewing this scoping review and for your suggestion not to expand the introduction. Suggestion 2 : In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material. Response : Thank you. We followed your recommendations and F1000Research’s guidelines and shared the search strategies on the Open Science Framework (OSF). Comment : The procedure to solve disagreement does not need to be repeated. Response : We agree with your decision and have revised the manuscript to reflect it. Suggestion 3 : The flow in the Results section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around the potential pitfalls like The use of meta-analyses with different comparators (but without meta-regression) The combination of results from different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Response : Thank you for your suggestion, based on which we changed the first section of results as follows: “In one systematic review (Yan et al., 2022), the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al., 2021), results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al., 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored.” Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Response : Thank you for spending time reviewing this scoping review and for your suggestion not to expand the introduction. Suggestion 2 : In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material. Response : Thank you. We followed your recommendations and F1000Research’s guidelines and shared the search strategies on the Open Science Framework (OSF). Comment : The procedure to solve disagreement does not need to be repeated. Response : We agree with your decision and have revised the manuscript to reflect it. Suggestion 3 : The flow in the Results section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around the potential pitfalls like The use of meta-analyses with different comparators (but without meta-regression) The combination of results from different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Response : Thank you for your suggestion, based on which we changed the first section of results as follows: “In one systematic review (Yan et al., 2022), the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al., 2021), results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al., 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored.” Competing Interests: None known. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 14 Dec 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 Version 2 (revision) 09 Oct 24 read Version 1 14 Dec 23 read read Brice Nouthé , The University of British Columbia, Vancouver, Canada Evrard Kepgang , University of Antwerp, Flanders, Belgium Raju Kanukula , Monash University, Victoria, Australia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Nouthé B et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Oct 2024 | for Version 2 Brice Nouthé , Faculty of Medicine, The University of British Columbia, Vancouver, Canada Evrard Kepgang , Faculty of Medicine and Health Sciences, University of Antwerp, Flanders, Belgium 0 Views copyright © 2024 Nouthé B et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Great work done: Kudos! No further changes needed at this juncture. Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes Mellitus We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Nouthé B and Kepgang E. Peer Review Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.172869.r330434) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1595/v2#referee-response-330434 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Kanukula R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 Sep 2024 | for Version 1 Raju Kanukula , Monash University, Victoria, Australia 0 Views copyright © 2024 Kanukula R. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This scoping review was conducted very well without any issues, however I have the following concerns. 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. 2) What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Are the rationale for, and objectives of, the Systematic Review clearly stated? Partly Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No Competing Interests No competing interests were disclosed. Reviewer Expertise Methodologist and pharmacist. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 09 Oct 2024 Farhad Shokraneh Comment : 1) In the rationale, authors could have explained the causative pathway between PFAS and GDM. Response : Thank you for reading our review and for your comment. This scoping review examined the studies that assess the ‘Association’ from the observational studies. Considering that confounding factors such as obesity—as mentioned in the introduction—can contribute to GDM, we are unable to discuss ‘Causation’ and have yet to see research suggesting such a mechanism. Comment : What is the rationale behind excluding review articles on this topic, but included meta-analyses. Apart from these, I have no other concerns. Response : We excluded the narrative review articles with no usable data or a list of included studies. We, however, studied the systematic reviews and meta-analyses to identify more relevant studies for a possible systematic review in the future, avoid duplicate work, and discuss the suitability of conducting meta-analysis in these reviews. View more View less Competing Interests None known. reply Respond Report a concern Kanukula R. Peer Review Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r324731) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-324731 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Nouthé B et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Jul 2024 | for Version 1 Brice Nouthé , Faculty of Medicine, The University of British Columbia, Vancouver, Canada Evrard Kepgang , Faculty of Medicine and Health Sciences, University of Antwerp, Flanders, Belgium 0 Views copyright © 2024 Nouthé B et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The authors aimed to evaluate the evidence on a potential relationship between Gestational Diabetes Mellitus (GDM) and serum per-&polyfluoroalkyl substances (PFAS). This sponsored effort (by 3M) to evaluate the risk, caused by this group of synthetic carbon-fluorine compounds ensuring slow degradation, is timely because of the important issues evolving around the demonstrated relationship of PFAS, known to have an extensive human exposure, and diabetes mellitus the different concerns about GDM across continents despite known lifelong consequences of GDM the potential conflictual results of previous meta-analysis. Suggestion1: The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Suggestion 2: In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material . Also, the procedure to solve disagreement does not need to be repeated. Suggestion 3: The flow in the Results' section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around he potential pitfalls like the use of meta-analyses with different comparators ( but without meta-regression) The combination of results form different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Yes If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Diabetes Mellitus We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 09 Oct 2024 Farhad Shokraneh Suggestion 1 : The authors used studies publicly available & sought to present the need for an updated systematic review before even looking at new source of information. We believe they do not need to expand the Introduction section because it could just be around the motivation of the study. Response : Thank you for spending time reviewing this scoping review and for your suggestion not to expand the introduction. Suggestion 2 : In the Methods' section, the justification to use PECO & description the different strategies to retrieve the data could easily be included in a Supplemental Material. Response : Thank you. We followed your recommendations and F1000Research’s guidelines and shared the search strategies on the Open Science Framework (OSF). Comment : The procedure to solve disagreement does not need to be repeated. Response : We agree with your decision and have revised the manuscript to reflect it. Suggestion 3 : The flow in the Results section about the in-depth assessment of the 3 previous meta-analyses could be less of a narrative part but rather separated around the potential pitfalls like The use of meta-analyses with different comparators (but without meta-regression) The combination of results from different evidence streams without appropriate summary The variability of exposure contrasts also rendering the use of a high-low exposure category comparator much questionable. Response : Thank you for your suggestion, based on which we changed the first section of results as follows: “In one systematic review (Yan et al., 2022), the use of meta-analysis to combine results across comparators rendered the meaning of the summary OR obscure. In another systematic review (Gao et al., 2021), results from different evidence streams were not combined using an appropriate summary. In the third systematic review (Wang et al., 2022), the focus on only high:low exposure category comparators meant: a) informative data from each included study were ignored, b) the variability of the exposure contrasts made use of this comparator questionable, and c) reports using only models with exposure as a continuous variable were ignored.” View more View less Competing Interests None known. reply Respond Report a concern Nouthé B and Kepgang E. Peer Review Report For: Gestational diabetes mellitus in relation to serum per- and polyfluoroalkyl substances: A scoping review to evaluate the need for a new systematic review [version 2; peer review: 2 approved] . F1000Research 2024, 12 :1595 ( https://doi.org/10.5256/f1000research.158160.r296883) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-1595/v1#referee-response-296883 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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