Developmental Impacts - HH-RA.org

Bibliography Tag: developmental impacts

Kang et al., 2019

Kang, D. W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R.; “Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota;” Scientific Reports, 2019, 9(1), 5821; DOI: 10.1038/s41598-019-42183-0.

ABSTRACT:

Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future. FULL TEXT

Shah and Kingdom, 2011

Shah, Prakesh, & Kingdom, John; “Long-term neurocognitive outcomes of SGA/IUGR infants;” Obstetrics, Gynaecology & Reproductive Medicine, 2011, 21(5), 142-146; DOI: 10.1016/j.ogrm.2011.02.004.

ABSTRACT:

With advances in the management of preterm neonates, the chances of survival have increased even among those who are intrauterine growth restricted (IUGR) or who are born small for gestational age (SGA). However, infants who are IUGR/SGA are considered at higher risk of physical and neurodevelopmental abnormalities, although the reported impacts of IUGR and SGA status at birth on neurodevelopmental outcomes in long-term outcomes studies have varied. In particular, some reports have indicated gradual improvement in neurodevelopmental functions over time in these infants. We have therefore reviewed all the available reports describing neurodevelopmental outcomes of preterm and term SGA infants beyond 5 years of age. Preterm SGA infants are at increased risk of impairment in neuromotor, cognitive, behavioural and scholastic attainments compared with preterm non-SGA infants. On the other hand, term SGA infants had problems in scholastic/vocational attainments compared with term non SGA infants, while adverse neuromotor, cognitive and behavioural outcomes were not consistently observed at higher rates. Limitations regarding the validity of studies of long-term outcomes of SGA infants are discussed and a potential approach is suggested. FULL TEXT

Zhang et al., 2018

Zhang, M., Ma, W., Zhang, J., He, Y., & Wang, J.; “Analysis of gut microbiota profiles and microbe-disease associations in children with autism spectrum disorders in China;” Scientific Reports, 2018, 8(1), 13981; DOI: 10.1038/s41598-018-32219-2.

ABSTRACT:

Autism spectrum disorder (ASD) is a set of complex neurodevelopmental disorders. Recent studies reported that children with ASD have altered gut microbiota profiles compared with typical development (TD) children. However, few studies on gut bacteria of children with ASD have been conducted in China. Here, in order to elucidate changes of fecal microbiota in children with ASD, 16S rRNA sequencing was conducted and the 16S rRNA (V3-V4) gene tags were amplified. We investigated differences in fecal microbiota between 35 children with ASD and 6 TD children. At the phylum level, the fecal microbiota of ASD group indicated a significant increase of the Bacteroidetes/Firmicutes ratio. At the genus level, we found that the relative abundance of Sutterella, Odoribacter and Butyricimonas was much more abundant in the ASD group whereas the abundance of Veillonella and Streptococcus was decreased significantly compared to the control group. Functional analysis demonstrated that butyrate and lactate producers were less abundant in the ASD group. In addition, we downloaded the association data set of microbe-disease from human microbe-disease association database and constructed a human disease network including ASD using our gut microbiome results. In this microbe-disease network based on microbe similarity of diseases, we found that ASD is positively correlated with periodontal, negatively related to type 1 diabetes. Therefore, these results suggest that microbe-based disease analysis is able to predict novel connection between ASD and other diseases and may play a role in revealing the pathogenesis of ASD. FULL TEXT

Zhang et al., 2020

Zhang, M., Chu, Y., Meng, Q., Ding, R., Shi, X., Wang, Z., He, Y., Zhang, J., Liu, J., Zhang, J., Yu, J., Kang, Y., & Wang, J.; “A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children;” Science Advances, 2020, 6(43); DOI: 10.1126/sciadv.aba3760.

ABSTRACT:

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy-quasi-paired cohort-and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD. FULL TEXT

Ruden and Grandjean, 2018

Mie, A., Ruden, C., & Grandjean, P.; “Safety of Safety Evaluation of Pesticides: developmental neurotoxicity of chlorpyrifos and chlorpyrifos-methyl;” Environmental Health, 2018, 17(1), 77; DOI: 10.1186/s12940-018-0421-y.

ABSTRACT:

Authorization of pesticides for market release requires toxicity testing on animals, typically performed by test laboratories on contract with the pesticide producer. The latter provides the results and summary to the regulatory authorities. For the commonly used pesticide chlorpyrifos, an industry-funded toxicity study concludes that no selective effects on neurodevelopment occur even at high exposures. In contrast, the evidence from independent studies points to adverse effects of current exposures on cognitive development in children. We reviewed the industry-funded developmental neurotoxicity test data on chlorpyrifos and the related substance chlorpyrifos-methyl. We noted treatment-related changes in a brain dimension measure for chlorpyrifos at all dose levels tested, although not been reported in the original test summary. We further found issues which inappropriately decrease the ability of the studies to reveal true effects, including a dosage regimen that resulted in too low exposure of the nursing pups for chlorpyrifos and possibly for chlorpyrifos-methyl, and a failure to detect any neurobehavioral effects of lead nitrate used as positive control in the chlorpyrifos study. Our observations thus suggest that conclusions in test reports submitted by the producer may be misleading. This discrepancy affects the ability of regulatory authorities to perform a valid and safe evaluation of these pesticides. The difference between raw data and conclusions in the test reports indicates a potential existence of bias that would require regulatory attention and possible resolution. FULL TEXT

Gillezeau et al., 2020

Gillezeau, C., Lieberman-Cribbin, W., & Taioli, E.; “Update on human exposure to glyphosate, with a complete review of exposure in children;” Environmental Health, 2020, 19(1), 115; DOI: 10.1186/s12940-020-00673-z.

ABSTRACT:

BACKGROUND: Glyphosate, a commonly used pesticide, has been the topic of much debate. The effects of exposure to glyphosate remains a contentious topic. This paper provides an update to the existing literature regarding levels of glyphosate exposure in occupationally exposed individuals and focuses or reviewing all the available published literature regarding glyphosate exposure levels in children.

METHODS: A literature review was conducted and any articles reporting quantifiable exposure levels in humans published since January 2019 (the last published review on glyphosate exposure) were reviewed and data extracted and standardized.

RESULTS: A total of five new studies reporting exposure levels in humans were found including 578 subjects. Two of these studies focused on occupationally exposed individuals while three of them focused on glyphosate exposure levels in children. Given the sparse nature of the new data, previously identified studies on exposure to glyphosate in children were included in our analysis of children’s exposure. The lowest average level of glyphosate exposure reported was 0.28 μg/L and the highest average exposure levels reported was 4.04 μg/L.

CONCLUSION: The literature on glyphosate exposure levels, especially in children, remains limited. Without more data collected in a standardized way, parsing out the potential relationship between glyphosate exposure and disease will not be possible. FULL TEXT

Hantsoo et al., 2019

Hantsoo, L., Jasarevic, E., Criniti, S., McGeehan, B., Tanes, C., Sammel, M. D., Elovitz, M. A., Compher, C., Wu, G., & Epperson, C. N.; “Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy;” Brain, Behavior, and Immunity, 2019, 75, 240-250; DOI: 10.1016/j.bbi.2018.11.005.

ABSTRACT:

BACKGROUND: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women.

METHODS: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34weeks gestation; plasma interleukin-6 (IL-6), interleukin-1beta (IL-1beta), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-alpha), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated.

RESULTS: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q=5.7×10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-alpha and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p=0.03) and eicosapentaenoic acid (EPA) (p=0.05).

DISCUSSION: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of omega-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.

FULL TEXT

Pellizzari et al., 2019

Pellizzari, E. D., Woodruff, T. J., Boyles, R. R., Kannan, K., Beamer, P. I., Buckley, J. P., Wang, A., Zhu, Y., & Bennett, D. H.; “Identifying and Prioritizing Chemicals with Uncertain Burden of Exposure: Opportunities for Biomonitoring and Health-Related Research;” Environmental Health Perspectives, 2019, 127(12), 126001; DOI: 10.1289/EHP5133.

ABSTRACT:

BACKGROUND: The National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) initiative aims to understand the impact of environmental factors on childhood disease. Over 40,000 chemicals are approved for commercial use. The challenge is to prioritize chemicals for biomonitoring that may present health risk concerns.

OBJECTIVES: Our aim was to prioritize chemicals that may elicit child health effects of interest to ECHO but that have not been biomonitored nationwide and to identify gaps needing additional research.

METHODS: We searched databases and the literature for chemicals in environmental media and in consumer products that were potentially toxic. We selected chemicals that were not measured in the National Health and Nutrition Examination Survey. From over 700 chemicals, we chose 155 chemicals and created eight chemical panels. For each chemical, we compiled biomonitoring and toxicity data, U.S. Environmental Protection Agency exposure predictions, and annual production usage. We also applied predictive modeling to estimate toxicity. Using these data, we recommended chemicals either for biomonitoring, to be deferred pending additional data, or as low priority for biomonitoring.

RESULTS: For the 155 chemicals, 97 were measured in food or water, 67 in air or house dust, and 52 in biospecimens. We found in vivo endocrine, developmental, reproductive, and neurotoxic effects for 61, 74, 47, and 32 chemicals, respectively. Eighty-six had data from high-throughput in vitro assays. Positive results for endocrine, developmental, neurotoxicity, and obesity were observed for 32, 11, 35, and 60 chemicals, respectively. Predictive modeling results suggested 90% are toxicants. Biomarkers were reported for 76 chemicals. Thirty-six were recommended for biomonitoring, 108 deferred pending additional research, and 11 as low priority for biomonitoring.

DISCUSSION: The 108 deferred chemicals included those lacking biomonitoring methods or toxicity data, representing an opportunity for future research. Our evaluation was, in general, limited by the large number of unmeasured or untested chemicals. FULL TEXT

Buckley et al., 2020

Buckley, J. P., Barrett, E. S., Beamer, P. I., Bennett, D. H., Bloom, M. S., Fennell, T. R., Fry, R. C., Funk, W. E., Hamra, G. B., Hecht, S. S., Kannan, K., Iyer, R., Karagas, M. R., Lyall, K., Parsons, P. J., Pellizzari, E. D., Signes-Pastor, A. J., Starling, A. P., Wang, A., Watkins, D. J., Zhang, M., Woodruff, T. J., & program collaborators for, Echo; “Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program;” Journal of exposure science & environmental epidemiology, 2020, 30(3), 397-419; DOI: 10.1038/s41370-020-0211-9.

ABSTRACT:

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children. FULL TEXT

Smith et al., 2020

Smith, Dylan B., Arce, Andres N., Ramos Rodrigues, Ana, Bischoff, Philipp H., Burris, Daisy, Ahmed, Farah, & Gill, Richard J.; “Insecticide exposure during brood or early-adult development reduces brain growth and impairs adult learning in bumblebees;” Proceedings of the Royal Society B: Biological Sciences, 2020, 287(1922); DOI: 10.1098/rspb.2019.2442.

ABSTRACT:

For social bees, an understudied step in evaluating pesticide risk is how contaminated food entering colonies affects residing offspring development and maturation. For instance, neurotoxic insecticide compounds in food could affect central nervous system development predisposing individuals to become poorer task performers later-in-life. Studying bumblebee colonies provisioned with neonicotinoid spiked nectar substitute, we measured brain volume and learning behaviour of 3 or 12-day old adults that had experienced in-hive exposure during brood and/or early-stage adult development. Micro-computed tomography scanning and segmentation of multiple brain neuropils showed exposure during either of the developmental stages caused reduced mushroom body calycal growth relative to unexposed workers. Associated with this was a lower probability of responding to a sucrose reward and lower learning performance in an olfactory conditioning test. While calycal volume of control workers positively correlated with learning score, this relationship was absent for exposed workers indicating neuropil functional impairment. Comparison of 3- and 12-day adults exposed during brood development showed a similar degree of reduced calycal volume and impaired behaviour highlighting lasting and irrecoverable effects from exposure despite no adult exposure. Our findings help explain how the onset of pesticide exposure to whole colonies can lead to lag-effects on growth and resultant dysfunction. FULL TEXT

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