Navigation Guide Systematic Review Methodology Research Articles

Effects of high temperatures and heatwaves on dengue fever: a systematic review and meta-analysis

Studies have shown that dengue virus transmission increases in association with ambient temperature. We performed a systematic review and meta-analysis to assess the effect of both high temperatures and heatwave events on dengue transmission in different climate zones globally. A systematic literature search was conducted in PubMed, Scopus, Embase, and Web of Science from January 1990 to September 20, 2022. We included peer reviewed original observational studies using ecological time series, case crossover, or case series study designs reporting the association of high temperatures and heatwave with dengue and comparing risks over different exposures or time periods. Studies classified as case reports, clinical trials, non-human studies, conference abstracts, editorials, reviews, books, posters, commentaries; and studies that examined only seasonal effects were excluded. Effect estimates were extracted from published literature. A random effects meta-analysis was performed to pool the relative risks (RRs) of dengue infection per 1°C increase in temperature, and further subgroup analyses were also conducted. The quality and strength of evidence were evaluated following the Navigation Guide systematic review methodology framework. The review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). The study selection process yielded 6367 studies. A total of 106 studies covering more than four million dengue cases fulfilled the inclusion criteria; of these, 54 studies were eligible for meta-analysis. The overall pooled estimate showed a 13% increase in risk of dengue infection (RR=1.13; 95% confidence interval (CI): 1.11-1.16, I2=98.0%) for each 1°C increase in high temperatures. Subgroup analyses by climate zones suggested greater effects of temperature in tropical monsoon climate zone (RR=1.29, 95% CI: 1.11-1.51) and humid subtropical climate zone (RR=1.20, 95% CI: 1.15-1.25). Heatwave events showed association with an increased risk of dengue infection (RR=1.08; 95% CI: 0.95-1.23, I2=88.9%), despite a wide confidence interval. The overall strength of evidence was found to be "sufficient" for high temperatures but "limited" for heatwaves. Our results showed that high temperatures increased the risk of dengue infection, albeit with varying risks across climate zones and different levels of national income. High temperatures increased the relative risk of dengue infection. Future studies on the association between temperature and dengue infection should consider local and regional climate, socio-demographic and environmental characteristics to explore vulnerability at local and regional levels for tailored prevention. Australian Research Council Discovery Program.

Vitamin D-Related Risk Factors for Maternal Morbidity and Mortality during Pregnancy: Systematic Review and Meta-Analysis.

Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL in serum) is a common health condition among pregnant women, especially in high-risk groups. Evidence has connected vitamin D levels with many health-related problems during pregnancy, including gestational diabetes and preeclampsia. Because of vitamin D’s effect on both mother and fetus, we systematically review the association between 25(OH)D level and its health effects. From a total of 143 studies, 43 came from PubMed, 4 from Cochrane, and 96 from EMBASE. After screening, we identified 38 studies as candidates for inclusion. Ultimately, we limited this review to 23 articles originating from 12 countries, written in English or Spanish, and conducted between 2010 and 2022. We conducted this review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and evaluated the quality and strength of the evidence by using the Navigation Guide Systematic Review Methodology (SING). These systematic reviews summarize findings that support vitamin D’s role in reducing risks of multiple outcomes and the possible contribution of adequate vitamin D levels to a healthy pregnancy.

Exposure to nature during the COVID-19 pandemic and the associated effect on mental health: a systematic review with meta-analysis

BackgroundThe COVID-19 pandemic and measures such as lockdowns to control its transmission generated unique effects on psychological health and well-being. In these circumstances, access to nature and outdoor spaces became a potentially important coping strategy, but the evidence exploring the mental health benefits of nature exposure during different stages of the pandemic is mixed and poorly understood. We systematically synthesised the evidence to examine larger trends in associations between nature exposure and mental health during the COVID-19 pandemic. MethodsWe did a comprehensive keyword search in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo for articles published between Jan 1, 2020 and April 30, 2022. We followed the PRISMA guidelines to synthesise and report results. Using the Navigation Guide systematic review methodology, we established the risk of bias in studies at the individual level and throughout the body of evidence for each outcome of interest. FindingsA total of 2004 relevant articles were initially identified and after screening for relevancy, 72 were included in the review. Studies found associations between green space visit frequency, green space accessibility, and type of green space (eg, indoor vs outdoor) with mental health outcomes (eg, depression and anxiety) during the pandemic. However, evidence for links between satellite image-driven measures of greenness (eg, normalised difference vegetation index) and mental health was scarce. Meta-analysis shows that access to gardens was associated with lower odds of depression (odds ratio 0·71, 95% CI 0·61–0·82, I2=0%) and anxiety (0·73, 0·63–0·84, I2=0%). Similarly, higher frequency of visits to green space was associated with improved mental wellbeing (0·10, 95% CI 0·07–0·14, I2=0%) and general mental health (0·11, 95% CI 0·03–0·38, I2=82%). InterpretationInterventions that prioritise nature-based infrastructure and emphasise exposure to nearby nature (eg, indoor plants or gardens), and visits to green spaces such as parks, could create more psychologically resilient communities in the face of future public health crises. FundingNone.

Vitamin D-Related Risk Factors for Maternal Morbidity during Pregnancy: A Systematic Review.

Vitamin D has well-defined classical functions related to metabolism and bone health but also has non-classical effects that may influence pregnancy. Maternal morbidity remains a significant health care concern worldwide, despite efforts to improve maternal health. Nutritional deficiencies of vitamin D during pregnancy are related to adverse pregnancy outcomes, but the evidence base is difficult to navigate. The primary purpose of this review is to map the evidence on the effects of deficiencies of vitamin D on pregnancy outcome and the dosage used in such studies. A systematic search was performed for studies on vitamin D status during pregnancy and maternal outcomes. A total of 50 studies came from PubMed, 15 studies came from Cochrane, and 150 studies came from Embase, for a total of 215 articles. After screening, 34 were identified as candidate studies for inclusion. Finally, 28 articles met the inclusion criteria, which originated from 15 countries. The studies included 14 original research studies and 13 review studies conducted between 2012 and 2021. This review was finally limited to the 14 original studies. This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the quality and strength of the evidence was evaluated using the Navigation Guide Systematic Review Methodology (SING). We found evidence that supports the idea that supplementary vitamin D for pregnant women is important for reducing the risk of gestational diabetes, hypertension, preeclampsia, early labor, and other complications. The data retrieved from this review are consistent with the hypothesis that adequate vitamin D levels might contribute to a healthy pregnancy.

Application of the Navigation Guide systematic review methodology and meta-analysis to evaluate the association between prenatal particulate matter air pollution exposure and birth weight

TPS 642: Environmental justice and impacts, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Background: Case-control and cohort studies have demonstrated a positive association between prenatal exposure to particulate matter (PM) air pollution and low birth weight (LBW). Previous systematic reviews and meta-analyses report varying effect sizes and significant heterogeneity between studies. The considerable variation in study outcomes reflects methodological differences employed across studies. Objective: The objective of this study was to determine how developmental exposure to ambient particulate air pollution affects birth weight using the Navigation Guide systematic review methodology. Methods: We developed a study protocol and established a criteria to identify the relevant studies. Further, we determined the risk of bias for each study, conducted a quality of evidence and strength of evidence assessment, as well as a meta-analysis across all studies. Results: Forty-three studies met our inclusion criteria. We rated studies generally with low to probably-low risk of bias; however, several studies we judged as high or probably-high risk in the confounding and exposure characterization domains. Based on the meta-analysis, for every 10 µg/m3 increase in particulate matter, a decrease in birth weight was almost always negative. The strength of evidence assessment, for PM2.5, revealed “limited evidence of toxicity” for reducing birth weight when exposure is in the third trimester; for other exposure windows, the evidence is inadequate. For PM10, there is “limited evidence of toxicity” for reducing birth weight when exposure is in the third trimester and during the entire pregnancy; however, the evidence is “inadequate” for other exposure windows. For coarse PM (PM2.5-10), there is “inadequate evidence of toxicity” for reducing birth weight for all exposure windows. Conclusion: While sufficient evidence supports an association between prenatal exposure to ambient particulate matter and low birth weight, the estimated effect depends significantly on study design. Standardizing exposure characterization techniques could help reduce the variation in outcomes.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of occupational exposure to solar ultraviolet radiation and of the effect of occupational exposure to solar ultraviolet radiation on melanoma and non-melanoma skin cancer

BackgroundThe World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from melanoma and non-melanoma skin cancer (or keratinocyte carcinoma) from occupational exposure to solar ultraviolet radiation, to inform the development of the WHO/ILO joint methodology. ObjectivesWe aim to systematically review studies on occupational exposure to solar ultraviolet radiation (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational exposure to solar ultraviolet radiation on melanoma and non-melanoma skin cancer (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework and conducting both systematic reviews in tandem and in a harmonized way. Data sourcesSeparately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and Web of Science. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference list of previous systematic reviews and included study records and consult additional experts. Study eligibility and criteriaWe will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (<15 years) and unpaid domestic workers. For Systematic Review 1, we will include quantitative studies on the prevalence of relevant levels of occupational exposure to solar ultraviolet radiation (i.e. <0.33 SED/d and ≥0.33 SED/d) and of the total working time spent outdoors, stratified by country, sex, age and industrial sector or occupation, in the years 1960 to 2018. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of any occupational exposure to solar ultraviolet radiation (i.e., ≥0.33 SED/d) on the prevalence of, incidence of or mortality due to melanoma and non-melanoma skin cancer, compared with the theoretical minimum risk exposure level (i.e. <0.33 SED/d). Study appraisal and synthesis methodsAt least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess the risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2. PROSPERO registration numberCRD42018094817.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to occupational noise and of the effect of exposure to occupational noise on cardiovascular disease

BackgroundThe World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of deaths and disability-adjusted life years from cardiovascular disease attributable to exposure to occupational noise, to inform the development of the WHO/ILO joint methodology. ObjectivesWe aim to systematically review studies on exposure to occupational noise (Systematic Review 1) and systematically review and meta-analyse estimates of the effect of occupational noise on cardiovascular diseases (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way. Data sourcesSeparately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand search reference list of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteriaWe will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (<15 years) and unpaid domestic workers. The eligible risk factor will be occupational noise. Eligible outcomes will be hypertensive heart disease, ischaemic heart disease, stroke, cardiomyopathy, myocarditis, endocarditis and other circulatory diseases. For Systematic Review 1, we will include quantitative prevalence studies of exposure to occupational noise (i.e., low: <85 dB(A) and high: ≥85 dB(A)) stratified by country, sex, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the relative effect of high exposure to occupational noise on the prevalence of, incidence of or mortality due to cardiovascular disease, compared with the theoretical minimum risk exposure level (i.e., low exposure). Study appraisal and synthesis methodsAt least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2.PROSPERO registration number: CRD42018092272.

WHO/ILO work-related burden of disease and injury: Protocol for systematic reviews of exposure to occupational ergonomic risk factors and of the effect of exposure to occupational ergonomic risk factors on osteoarthritis of hip or knee and selected other musculoskeletal diseases

BackgroundThe World Health Organization (WHO) and the International Labour Organization (ILO) are developing a joint methodology for estimating the national and global work-related burden of disease and injury (WHO/ILO joint methodology), with contributions from a large network of experts. In this paper, we present the protocol for two systematic reviews of parameters for estimating the number of disability-adjusted life years from osteoarthritis of hip or knee, and selected other musculoskeletal diseases respectively, attributable to exposure to occupational ergonomic risk factors to inform the development of the WHO/ILO joint methodology. ObjectivesWe aim to systematically review studies on exposure to occupational ergonomic risk factors (Systematic Review 1) and systematically review and meta-analyze estimates of the effect of exposure to occupational ergonomic risk factors on osteoarthritis of the hip or knee, and selected other musculoskeletal diseases respectively (Systematic Review 2), applying the Navigation Guide systematic review methodology as an organizing framework, conducting both systematic reviews in tandem and in a harmonized way. Data sourcesSeparately for Systematic Reviews 1 and 2, we will search electronic academic databases for potentially relevant records from published and unpublished studies, including Medline, EMBASE, Web of Science and CISDOC. We will also search electronic grey literature databases, Internet search engines and organizational websites; hand-search reference lists of previous systematic reviews and included study records; and consult additional experts. Study eligibility and criteriaWe will include working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State, but exclude children (<15 years) and unpaid domestic workers. The included occupational ergonomic risk factors will be any exposure to one or more of: force exertion; demanding posture; repetitiveness; hand-arm vibration; lifting; kneeling and/or squatting; and climbing. Included outcomes will be (i) osteoarthritis and (ii) other musculoskeletal diseases (i.e., one or more of: rotator cuff syndrome; bicipital tendinitis; calcific tendinitis; shoulder impingement; bursitis shoulder; epicondylitis medialis; epicondylitis lateralis; bursitis elbow; bursitis hip; chondromalacia patellae; meniscus disorders; and/or bursitis knee). For Systematic Review 1, we will include quantitative prevalence studies of any exposure to occupational ergonomic risk factors stratified by country, gender, age and industrial sector or occupation. For Systematic Review 2, we will include randomized controlled trials, cohort studies, case-control-studies and other non-randomized intervention studies with an estimate of the relative effect of any exposure with occupational ergonomic risk factors on the prevalence or incidence of osteoarthritis and/or selected musculoskeletal diseases, compared with the theoretical minimum risk exposure level (i.e., no exposure). Study appraisal and synthesis methodsAt least two review authors will independently screen titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. At least two review authors will assess risk of bias and the quality of evidence, using the most suited tools currently available. For Systematic Review 2, if feasible, we will combine relative risks using meta-analysis. We will report results using the guidelines for accurate and transparent health estimates reporting (GATHER) for Systematic Review 1 and the preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) for Systematic Review 2.PROSPERO registration number: CRD42018102631.

Endocrine Disruptors and Autism Spectrum Disorder in Pregnancy: A Review and Evaluation of the Quality of the Epidemiological Evidence.

Exposure to environmental contaminants during pregnancy has been linked to adverse health outcomes later in life. Notable among these pollutants are the endocrine disruptors chemicals (EDCs), which are ubiquitously present in the environment and they have been measured and quantified in the fetus. In this systematic review, our objective was to summarize the epidemiological research on the potential association between prenatal exposure to EDCs and Autism Spectrum Disorder (ASD) published from 2005 to 2016. The Navigation Guide Systematic Review Methodology was applied. A total of 17 studies met the inclusion criteria for this review, including: five cohorts and 12 case-control. According to the definitions specified in the Navigation Guide, we rated the quality of evidence for a relationship between prenatal exposure to EDCs and ASD as “moderate”. Although the studies generally showed a positive association between EDCs and ASD, after considering the strengths and limitations, we concluded that the overall strength of evidence supporting an association between prenatal exposure to EDCs and later ASD in humans remains “limited” and inconclusive. Further well-conducted prospective studies are warranted to clarify the role of EDCs on ASD development.

Breastfeeding as a Predictor of Serum Concentrations of Per- and Polyfluorinated Alkyl Substances in Reproductive-Aged Women and Young Children: A Rapid Systematic Review

Per- and polyfluorinated alkyl substances (PFASs) are synthetic chemicals widely detected in human serum, and at low levels in breast milk. We conducted a rapid systematic review on breastfeeding practices and serum concentrations of PFASs—specifically PFOS and PFOA—among reproductive-aged women and young children using the Navigation Guide systematic review methodology. We included 14 studies examining associations between breastfeeding and PFASs in infants/toddlers or pregnant/postnatal women. Breastfeeding was significantly associated with lower PFASs exposure among women and higher PFASs exposure among children. We concluded there was “sufficient” evidence supporting an association between breastfeeding and serum PFASs concentrations among women, and “limited” evidence of an association among children due to issues with sample size, confounding, and exposure assessment. These findings reinforce that lactation is an important excretion route of PFASs for women, and that breast milk may be an important exposure pathway for young children.

Development, Application and Evaluation of Risk of Bias Criteria for Case-Crossover and Time-Series Studies of Air Pollution and Health

Systematic review and meta-analysis methods are increasingly being applied to environmental health literature. However, these methods have not been routinely applied within the context of formal risk assessments, despite common aims and practices, including systematic identification, analysis and summary assessment of the weight of evidence linking exposures and outcomes. A particular gap in these practices is the availability of standardized criteria for assessing risk of bias in studies of environmental exposures, operationalized in a form that can be efficiently and reliably applied by reviewers / risk assessors to a potentially large number of primary studies. Building on the Navigation Guide systematic review methodology, we developed, applied and evaluated risk of bias criteria applicable to time series and case-crossover studies linking air pollution and cardiovascular and respiratory morbidity, operationalizing them in DistillerSR&amp;#8482; systematic review software in the context of a systematic review of health effects of nitrogen dioxide. Risk of bias domains comprised: selection bias and generalizability, exposure assessment, confounding, outcome assessment, completeness of outcome data, selective outcome reporting, conflict of interest and other sources of bias. Risk of bias criteria were developed through literature review and expert consultation and evaluated with respect to content and face validity, inter-rater agreement and completion time. Our findings address the feasibility and reliability of our risk of bias criteria for time series and case-crossover studies linking air pollution and cardiovascular and respiratory morbidity. These criteria may provide a promising tool in the context of both systematic review and risk assessment. PROSPERO registration number CRD42018084497.

Breastfeeding as a Predictor of Serum Concentrations of Per- and Polyfluorinated Alkyl Substances in Reproductive-Aged Women and Young Children: A Rapid Systematic Review.

Per- and polyfluorinated alkyl substances (PFASs) are synthetic chemicals widely detected in human serum, and at low levels in breast milk. We conducted a rapid systematic review on breastfeeding practices and serum concentrations of PFASs-specifically PFOS and PFOA-among reproductive-aged women and young children using the Navigation Guide systematic review methodology. We included 14 studies examining associations between breastfeeding and PFASs in infants/toddlers or pregnant/postnatal women. Breastfeeding was significantly associated with lower PFASs exposure among women and higher PFASs exposure among children. We concluded there was "sufficient" evidence supporting an association between breastfeeding and serum PFASs concentrations among women, and "limited" evidence of an association among children due to issues with sample size, confounding, and exposure assessment. These findings reinforce that lactation is an important excretion route of PFASs for women, and that breast milk may be an important exposure pathway for young children.

Developmental PBDE Exposure and IQ/ADHD in Childhood: A Systematic Review and Meta-analysis.

Background:In the United States, one in six children are affected by neurodevelopmental disorders, and polybrominated diphenyl ethers (PBDEs) in flame-retardant chemicals are measured ubiquitously in children.Objective:We conducted a systematic a systematic review regarding developmental exposure to PBDEs and intelligence or Attention Deficit/Hyperactivity Disorder (ADHD) and attention-related behavioral conditions in humans.Methods:We searched articles published up to 26 September 2016, and included original studies that quantified exposures to PBDEs incurred any time in proximity to conception or during in utero, perinatal, or childhood time periods. We evaluated the risk of bias of individual studies and the overall quality and strength of the evidence according to the Navigation Guide systematic review methodology. We established criteria in advance to identify studies that could be combined using random effects meta-analyses (DerSimonian-Laird method).Results:Fifteen studies met the inclusion criteria; 10 studies met the criteria for intelligence and nine for attention-related problems. We rated studies generally with “low” to “probably low” risk of bias and rated the overall body of evidence as “moderate” quality with “sufficient” evidence for an association between Intelligence Quotient (IQ) and PBDEs. Our meta-analysis of four studies estimated a 10-fold increase (in other words, times 10) in PBDE exposure associated with a decrement of 3.70 IQ points (95% confidence interval: 0.83, 6.56). We concluded the body of evidence was of “moderate” quality for ADHD with “limited” evidence for an association with PBDEs, based on the heterogeneity of association estimates reported by a small number of studies and the fact that chance, bias, and confounding could not be ruled out with reasonable confidence.Conclusion:We concluded there was sufficient evidence supporting an association between developmental PBDE exposure and reduced IQ. Preventing developmental exposure to PBDEs could help prevent loss of human intelligence. https://doi.org/10.1289/EHP1632

Exploring the Association between Developmental PBDE Exposure and IQ/ADHD Effects: Application of the Navigation Guide Systematic Review Methodology

Background: PBDEs are ubiquitous in the environment and people; a systematic review of the evidence evaluating PBDEs and brain development was lacking. Methods: We applied the Navigation Guide methodology to answer the question: Does developmental exposure to PBDEs in humans affect IQ or ADHD? We developed a protocol, searched the literature; identified relevant human studies using pre-specified criteria, evaluated potential risk of bias for each study, and rated the quality and strength of the overall body of evidence. Results: Twelve of 1,824 human studies identified met our inclusion criteria. IQ: Nine studies measured IQ, most were “low” or “probably low” risk of bias, and overall the evidence was of “moderate” quality. Studies consistently showed an inverse relationship between IQ and PBDE exposures; meta-analysis found decrements of 1.53 loss of IQ points (95% CI: -2.73, -0.33) per approximately 2-fold increase in PBDE exposure. The strength of the body of evidence met the definition of “sufficient.” ADHD: Seven studies measured ADHD, most were “low” or “probably low” risk of bias, and overall the evidence was of “moderate” quality. Studies showed inconsistent relationship and the data were not amenable to meta-analysis. The strength of the body of evidence was considered “insufficient.” Conclusion: Our study highlights the value of systematic review methods to transparently evaluate available scientific information. Our estimate of the effect of developmental PBDE exposure on IQ is approximately 5-6 points IQ reduction for every 10-fold increase in PBDE exposure (for comparison, lead is ~6 points of IQ reduction per 10-fold increase in child blood lead levels). We conclude that there is a need to pursue stronger policies, regulations, and market actions to limit chemical exposures that pose threats to neurodevelopment and other serious, chronic health effects.

Application of the Navigation Guide systematic review methodology to the evidence for developmental and reproductive toxicity of triclosan

BackgroundThere are reports of developmental and reproductive health effects associated with the widely used biocide triclosan. ObjectiveApply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction? MethodsWe applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data. ResultsWe found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: −0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: −0.38, −0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a “moderate/low” quality rating to the body of evidence for human thyroid hormone alterations and a “moderate” quality rating to the body of evidence for non-human thyroid hormone alterations. ConclusionBased on this application of the Navigation Guide systematic review methodology, we concluded that there was “sufficient” non-human evidence and “inadequate” human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is “possibly toxic” to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.

Fetal growth and maternal glomerular filtration rate: a systematic review

Objective: Glomerular filtration rate (GFR) may influence concentrations of biomarkers of exposure and their etiologic significance in observational studies of associations between environmental contaminants and fetal growth. It is unknown whether the size of a developing fetus affects maternal GFR such that a small fetus leads to reduced plasma volume expansion (PVE), reduced GFR and subsequent higher concentrations of biomarkers in maternal serum. Our objective was to answer the question: “Is there an association between fetal growth and maternal GFR in humans?”Methods: We adapted and applied the Navigation Guide systematic review methodology to assess the evidence of an association between fetal growth and GFR, either directly or indirectly via reduction in PVE.Results: We identified 35 relevant studies. We rated 31 human and two non-human observational studies as “low” quality and two experimental non-human studies as “very low” quality. We rated all three evidence streams as “inadequate”. The association between fetal growth and GFR was “not classifiable” according to pre-specified definitions.Conclusions: There is currently insufficient evidence to support the plausibility of a reverse causality hypothesis for associations between exposure to environmental chemicals during pregnancy and fetal growth. Further research would be needed to confirm or disprove this hypothesis.

Application of the Navigation Guide Systematic Review Methodology to Assessing the Potential Developmental and Reproductive Hazards of Triclosan

Background: The Navigation Guide was developed by 22 clinicians and scientists to bring systematic review methodology from evidence-based medicine to environmental health risk assessment. We applied the Navigation Guide methodology to the question: Does exposure to the antimicrobial triclosan have adverse effects on human development or reproduction? Methods: We searched 5 databases for toxicological studies of triclosan. We screened abstracts and potentially relevant full texts according to a specified set of exclusion criteria. We extracted data from relevant studies into a structured database and compared data across all studies. We assessed risk of bias for individual studies and rated the quality and strength of an entire body of evidence for toxicity. Results: Our search resulted in 4282 unique references. We excluded 4034 abstracts according to pre-specified criteria, which took on average 18 hours of reviewer time. The remaining 248 full texts were screened in about 6 hours. We identified 12 relevant experimental mammal studies (reporting 133 separate outcomes) and 6 relevant human studies (reporting 21 outcomes involving 5156 individuals). Human studies were generally at low risk of bias whereas non-human studies were generally at high risk of bias, particularly for randomization, blinding and incomplete outcome data. The human and non-human evidence streams were each rated according to pre-specified strength of evidence definitions. Conclusion: The adoption of an efficient systematic and transparent method will speed the incorporation of research into decision-making to protect public health. Systematic review methodology has implications for conduct of environmental health research because the process emphasizes features of study design and reporting that may affect future requirements for publication in peer-reviewed literature.

The Navigation Guide - evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth.

Background: The Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method.Objective: We applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans.Methods: We applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence.Results: We identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a –18.9 g (95% CI: –29.8, –7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a “moderate” quality rating to the overall body of human evidence.Conclusion: On the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is “sufficient” human evidence that developmental exposure to PFOA reduces fetal growth.Citation: Johnson PI, Sutton P, Atchley DS, Koustas E, Lam J, Sen S, Robinson KA, Axelrad DA, Woodruff TJ. 2014. The Navigation Guide—evidence-based medicine meets environmental health: systematic review of human evidence for PFOA effects on fetal growth. Environ Health Perspect 122:1028–1039; http://dx.doi.org/10.1289/ehp.1307893

The Navigation Guide systematic review methodology: a rigorous and transparent method for translating environmental health science into better health outcomes.

Background: Synthesizing what is known about the environmental drivers of health is instrumental to taking prevention-oriented action. Methods of research synthesis commonly used in environmental health lag behind systematic review methods developed in the clinical sciences over the past 20 years.Objectives: We sought to develop a proof of concept of the “Navigation Guide,” a systematic and transparent method of research synthesis in environmental health.Discussion: The Navigation Guide methodology builds on best practices in research synthesis in evidence-based medicine and environmental health. Key points of departure from current methods of expert-based narrative review prevalent in environmental health include a prespecified protocol, standardized and transparent documentation including expert judgment, a comprehensive search strategy, assessment of “risk of bias,” and separation of the science from values and preferences. Key points of departure from evidence-based medicine include assigning a “moderate” quality rating to human observational studies and combining diverse evidence streams.Conclusions: The Navigation Guide methodology is a systematic and rigorous approach to research synthesis that has been developed to reduce bias and maximize transparency in the evaluation of environmental health information. Although novel aspects of the method will require further development and validation, our findings demonstrated that improved methods of research synthesis under development at the National Toxicology Program and under consideration by the U.S. Environmental Protection Agency are fully achievable. The institutionalization of robust methods of systematic and transparent review would provide a concrete mechanism for linking science to timely action to prevent harm.Citation: Woodruff TJ, Sutton P. 2014. The Navigation Guide systematic review methodology: a rigorous and transparent method for translating environmental health science into better health outcomes. Environ Health Perspect 122:1007–1014; http://dx.doi.org/10.1289/ehp.1307175

Implementing Systematic Review at the National Toxicology Program: Status and Next Steps

The National Toxicology Program (NTP), an interagency program headquartered at the National Institute of Environmental Health Sciences (NIEHS), carries out a broad range of toxicology research and testing and serves as a resource for identification of substances in our environment that are hazards for human health. One of the ways that the NTP identifies hazards is through carrying out literature-based health assessments. Approximately 2 years ago we began exploring systematic-review methodology as a means to enhance transparency and increase efficiency in summarizing and synthesizing findings from studies in our literature-based health assessments. A systematic review uses an explicit, prespecified approach to identify, select, assess, and appraise the data from studies that focus on addressing a specific scientific question (Institute of Medicine 2011). Although traditionally used to grade the quality of evidence and strength of scientific support for recommendations for clinical practice guidelines and healthcare interventions [Agency for Healthcare Research and Quality (AHRQ) 2012; Guyatt et al. 2011; Higgins and Green 2011], we—and others—were interested in how systematic review methodology might be applied to environmental health questions (Agency for Toxic Substances and Disease Registry 2012; National Research Council 2011; Silbergeld and Scherer 2013; U.S. Environmental Protection Agency 2013; Woodruff and Sutton 2011). With the establishment of the Office of Health Assessment and Translation (OHAT) in 2011, the NIEHS launched a new problem-solving resource for the NTP, particularly with respect to identification of noncancer hazards in our environment (Bucher et al. 2011). OHAT took the lead in investigating how systematic review methodology might be used by the NTP. We embraced systematic review methodology as a useful approach for providing thorough documentation of the steps, inputs, and decisions in a literature-based evaluation. However, we also recognized the necessity to extend existing systematic review methods to accommodate our need in environmental health to integrate data from multiple evidence streams (human, animal, in vitro) and focus on observational human studies rather than on the randomized clinical trials more commonly encountered in the field of health-care intervention (NTP 2012a, 2012b). In late February 2013, the NTP released the Draft OHAT Approach for Systematic Review and Evidence Integration for Literature-based Health Assessments – February 2013 [Draft OHAT Approach; Department of Health and Human Services (DHHS) 2013] for public comment; the deadline for receipt of comments is 11 June 2013. The Draft OHAT Approach adopts or adapts guidance from authoritative systematic review groups (AHRQ 2012; Guyatt et al. 2011; Higgins and Green 2011) to handle the breadth of data from human, animal, in vitro, and mechanistic studies relevant for addressing environmental health questions. In developing a draft approach, OHAT sought advice on systematic review through educational webinars and consultation with technical experts, the NTP Executive Committee, a working group of the NTP Board of Scientific Counselors, the NTP Board of Scientific Counselors, and the public. The draft approach involves a seven-step framework for incorporating systematic review methodology into OHAT literature-based health assessments. In early April of 2013, OHAT will release protocols for two case studies to illustrate application of this framework in specific evaluations. We will test our approach in these case studies to help determine whether additional refinement or revision to the Draft OHAT Approach might be needed. To help the public understand the draft approach and protocols, the NTP will hold a web-based informational meeting on 23 April 2013 to provide an overview of the framework, describe the contents of the case-study protocols, and respond to questions (DHHS 2013). Our intent is to carefully consider all public comments received on the draft approach and to present the Draft OHAT Approach to the NTP Board of Scientific Counselors at its meeting on 25–26 June 2013, with discussion by the NTP of any plans to update the document on the basis of the public’s input. Moving forward, our goal is to increase efficiency and provide greater transparency to the rigorous and objective approach that has been the hallmark of OHAT literature-based health assessments.