Prenatal Exposure to EDCs and Obesity

By the Collaborative on Health and the Environment

The incidence of childhood obesity has reached epidemic proportions globally and there is an urgent need to better understand the impact of early life exposure to chemical obesogens on the development of obesity.

The incidence of childhood obesity has reached epidemic proportions globally and there is an urgent need to better understand the impact of early life exposure to chemical obesogens on the development of obesity. The European OBELIX (Obesogenic endocrine disrupting chemicals: linking prenatal exposure to the development of obesity later in life) project examined the hypothesis that prenatal exposure to endocrine disrupting compounds (EDCs) plays a role in the development of obesity later in life using a multidisciplinary approach that combined various approaches, including epidemiology and toxicology.

The project focused on assessing prenatal exposure to major classes of EDCs including dioxins and dioxin-like polychlorinated biphenyls, non-dioxin-like PCBs, brominated flame retardants, organochlorine pesticides, phthalates, and perfluorinated alkyl acids. Toxicological studies in OBELIX demonstrated that perinatal dietary exposure to representatives of these EDC classes resulted in metabolic changes that persisted into adulthood, long after termination of exposure at weaning, and that effects were compound- and sex-specific. The observed effects were not consistently towards an obese phenotype; a lean phenotype was also observed in animal studies for some compounds. Epidemiological studies in birth cohorts throughout Europe indicated associations between pre- and postnatal exposure to EDCs and early growth trajectories and body mass index in children up to 7 years.

This call reviewed the main findings of the largest project up to now to examine the obesogen hypothesis.

Sources:

Additional resources of interest:
  • The OBELIX project website.
  • The OBELIX project: early life exposure to endocrine disruptors and obesity, PDF, 2011 May 4.
  • An Integrated Approach to Assess the Role of Chemical Exposure in ObesityPDF, 26 JUL 2013.
  • Birth Weight and Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Dichlorodiphenyldichloroethylene (DDE): A Meta-analysis within 12 European Birth Cohorts, PDF, Oct 13, 2011.
  • Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47, PDF2014 Apr 1.
  • Programming of metabolic effects in C57BL/6JxFVB mice by exposure to bisphenol A during gestation and lactation, PDF, 3 July 2014.

Conseils Juridiques aux Victimes du Distilbène DES

Interview de Maitre Karim Felissi, avocat et conseiller de la FNATH

Fin 2013, Maitre Karim Felissi, avocat et conseiller de la FNATH, nous avait expliqué quels éléments sont vraiment nécessaires pour qu’un dossier soit suffisamment étayé. Maintenant que les conclusions de l’étude 2013-2014 Réseau DES France 3 Génération Distilbène viennent d’être publiées, il nous explique quels impacts nous pouvons imaginer sur le plan judiciaire. Vidéo publiée le 18.12.2014 par Réseau DES FRANCE DISTILBENE.

Le Distilbène DES, en savoir plus

Fertility Treatment in 2013-2016 HFEA Trends and Figures Report

Lots of useful information brought together all in one place

The Human Fertilisation and Embryology Authority is the UK’s independent regulator overseeing the use of gametes and embryos in fertility treatment and research. The HFEA has released new figures and trends on fertility treatment in 2013.

Download the fertility trends report for 2014 – 2016.

HFEA 2013 fertility trends report image
If you’re exploring fertility treatment, the HFEA is the first place to go for reliable information.

Report Overview:

  • More treatment cycles than ever before; success rates remain constant
  • Multiple birth rate falls again
  • Number of women over 45 using donor eggs outnumbers those using their own
  • Number of IVF cycles using donated eggs and donated sperm more than doubles in five years
  • Number of same-sex female couples receiving treatment increases
  • New figures on fertility treatment released today by the Human Fertilisation and Embryology Authority (HFEA) reveal a continuing rise in the overall number of IVF cycles in the UK, with more undertaken in 2013 than ever before.

The report, “Fertility treatment 2013: trends and figures“, contains key statistics on fertility trends in the UK. It covers treatment cycles and outcomes for treatments started in 2012 and 2013 and how these coincide with short and long term trends. It is the fourth of its kind to be published by the HFEA.

In 2013, 49,636 women had a total of 64,600 cycles of IVF and 2,379 women had a total of 4,611 cycles of donor insemination (DI), representing an increase in both categories from the previous year. Overall, success rates have remained constant at around 25%.

Women over 40 represent the minority of all patients treated, with women aged over 45 accounting for just 2.% of all treatments. More than two-thirds of women undergoing treatment are aged 37 and under, while the average age for treatment remains static at 35. The report also shows that a majority of women over 45 are using donor eggs rather than their own when trying to conceive.

The number of IVF treatment cycles involving same-sex female couples has increased by nearly 20% year-on-year, rising from 766 treatments in 2011 to 902 in 2012. The number of donor insemination cycles involving same-sex couples (DI) rose by nearly 15%, from 1,271 in 2011 to 1,458 in 2012. These amount to a minority of overall treatments undertaken in the period covered.

Elsewhere, the HFEA’s “One at a Time” campaign to reduce multiple births is shown to have had good impact, with multiple births continuing to decrease. The report shows that multiple births occurred in 16.9% of treatment cycles in 2012, down from 18.8% in 2011.

The report also shows that the number of IVF treatment cycles using both donor eggs and donor sperm has doubled over the last five years, while the use of frozen embryos is now involved in more than 20% of all treatments.

Sally Cheshire, Chair of the HFEA welcomed the publication of the report:

At the HFEA we are committed to ensuring high quality care for everyone affected by assisted reproduction, and this report is key to that commitment. It offers unrivalled insight into one of the world’s most advanced IVF sectors, helping to inform the decisions of patients and clinicians alike.

We are very pleased to see that outcomes in most categories are improving each year, and are particularly heartened by the continuing downward trend in multiple births, something we’ve worked hard with professionals to achieve.

But as well as providing data, over time these reports offer us a unique insight into the changing nature of social norms, whether that is same-sex parenting or older mums. In that sense they have become a fascinating resource not just for patients and clinicians, but for everyone.”

Other findings include:

  • Pregnancy rate (per embryo transfer) rises for all age ranges
  • The live births rate is at highest-ever level
  • Number of IVF cycles using fresh donated eggs up more than 50% in five years
  • London and South East account for over a third of all treatments

Getting started : HFEA Sept 2017 Guide to Fertility Treatment

Lots of useful information brought together all in one place

The Human Fertilisation and Embryology Authority is the UK’s independent regulator overseeing the use of gametes and embryos in fertility treatment and research.
The HFEA has updated their free guide to fertility treatment which brings lots of useful information together all in one place.

image of the HFEA_Getting_Started_Guide_NOV_2014 cover
If you’re exploring fertility treatment, the HFEA is the first place to go for reliable information.

The HFEA expertise and years of experience mean they can provide you with authoritative, independent information. “Getting started” is their free guide to fertility treatment which brings lots of useful information together all in one place. It gives you an overall view of:

  • how and when to seek treatment
  • initial considerations (eg, NHS or private treatment)
  • how to choose a clinic and what to expect
  • treatment options
  • what to think about before starting treatment (including risks)
  • where to find support and advice.

If you’re exploring fertility treatment, the HFEA is the first place to go for reliable information. Making sure you have all the information you need means you can be confident that you’re making the right choices.

Pesticide Exposure and Depression among Farmers and Farm Residents

Pesticide poisoning and depression in farm residents

Farm image
The studies support a positive association between pesticide exposure and depression, including associations with several specific pesticides.

Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study

Background:
Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.

Objective:
We evaluated associations between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.

Methods:
We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993–1997 who completed a follow-up telephone interview in 2005–2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.

Results:
After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides—the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion—were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.

Conclusions:
Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.

Depression and pesticide exposures among private pesticide applicators enrolled in the Agricultural Health Study

Background:
We evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina.

Methods:
There were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226-752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression.

Results:
After adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74-3.79] than intermediate (OR = 1.07; 95% CI, 0.87-1.31) or high (OR = 1.11; 95% CI, 0.87-1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33-2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16-2.04).

Conclusions:
These findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning.

A cohort study of pesticide poisoning and depression in Colorado farm residents

Purpose:
Depressive symptoms have been associated with pesticide poisoning among farmers in cross-sectional studies, but no longitudinal studies have assessed the long-term influence of poisoning on depressive symptoms. The purpose of this study was to describe the associations between pesticide poisoning and depressive symptoms in a cohort of farm residents.

Methods:
Farm operators and their spouses were recruited in 1993 from farm truck registrations using stratified probability sampling. The Center for Epidemiologic Studies-Depression scale was used to evaluate depression in participants using generalized estimating equations. Baseline self-reported pesticide poisoning was the exposure of interest in longitudinal analyses.

Results:
Pesticide poisoning was significantly associated with depression in three years of follow-up after adjusting for age, gender, and marital status (odds ratio [OR] 2.59; 95% confidence interval [CI] 1.20-5.58). Depression remained elevated after adjusting for health, decreased income, and increased debt (OR 2.00; CI 0.91-4.39) and was primarily due to significant associations with the symptoms being bothered by things (OR 3.29; CI 1.95-5.55) and feeling everything was an effort (OR 1.93; CI 1.14-3.27).

Conclusions:
Feeling bothered and that everything was an effort were persistently associated with a history of pesticide poisoning, supportive of the hypothesis that prolonged irritability may result from pesticide poisoning.

Sources and more information
  • Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study, ehp, 1 September 2014.
  • Depression and pesticide exposures among private pesticide applicators enrolled in the Agricultural Health Study, NCBI PMID: PubMed 19079725, 2008 Sept 9.
  • A cohort study of pesticide poisoning and depression in Colorado farm residents, NCBI PMID: PubMed 18693039, 2008 Aug 9.

Retha Newbold about CLARITY BPA

By the Collaborative on Health and the Environment

Retha Newbold discussed the program called The Consortium Linking Academic and Regulatory Insights on the Toxicity of Bisphenol A (CLARITY-BPA).

On this call Retha Newbold, MS, Researcher Emeritus, National Toxicology Program, National Institute of Environmental Health Sciences, discussed the program called “The Consortium Linking Academic and Regulatory Insights on the Toxicity of Bisphenol A (CLARITY-BPA)” which is an interagency agreement, conducted under the auspices of the National Toxicology Program (NTP), between The National Institute of Environmental Health Sciences (NIEHS) supported grantees, the staff of the Division of the National Toxicology Program (DNTP) at NIH/NIEHS, and the Food and Drug Administration at the National Center for Toxicological Research (FDA/NCTR). The goals of the consortium are to enhance the utility of a perinatal 2-year GLP chronic toxicity study on BPA for regulatory decision-making by incorporating a wide range of doses and some additional disease-related endpoints that are not usually covered.

To this end, 12 NIEHS grantees are studying hypothesis-driven mechanisms by investigating specific endpoints that maybe altered by BPA including behavioral/neuroendocrine, immune function, cardiac, reproductive tract, cancer, thyroid, and other organ systems. This consortium is unique in that it combines the knowledge and skills of the NTP staff with experts from the academic field who are covering more mechanistic studies. Although this program focuses on BPA, it may provide an example of how to better study effects of other endocrine disrupting chemicals especially since numerous organ systems may be involved.

Sources:

Additional resources of interest:
  • A new approach to synergize academic and guideline-compliant research: The CLARITY-BPA research program – PDF.
  • Bisphenol-A: Questions and Answers about BPA, NIEHS.
  • NIEHS-supported Bisphenol-A Research Articles, NIEHS.
  • Environmental Factor (Mar 2013): BPA Grantees Share Findings, NIEHS.
  • Environmental Health Perspectives: Consortium-Based Science: The NIEHS’s Multipronged, Collaborative Approach to Assessing the Health Effects of Bisphenol A, EHP.
  • Questions & Answers on Bisphenol A (BPA) Use in Food Contact ApplicationsFDA.
  • Bisphenol-A: Overview and UpdatesFDA.

Antibiotic Guardian Resources Toolkit for Healthcare Professionals

Held every 18 November, European Antibiotic Awareness Day (EAAD) is a day to encourage responsible use of antibiotics

Developed by Public Health England

Held every 18 November, European Antibiotic Awareness Day (EAAD) is a day to encourage responsible use of antibiotics.

The plan for EAAD2014 is to increase measurable engagement by healthcare professionals and the public. Public Health England main objective is that by 30th November we have a combined 10, 000 Antibiotic Guardian pledges from healthcare professionals and the public to at least one pledge for prudent use of antimicrobials.

Sources:
On Slideshare;

Dr. Philippe Grandjean on Chemical Brain Drain

By the Collaborative on Health and the Environment

How the Next Generation’s Brain Functions are Endangered by EDCs and Other Environmental Chemicals.

Dr. Philippe Grandjean suggests that new scientific insights reveal that the next generation’s brain functions are endangered by environmental chemicals. The fetus is not protected by the placenta and therefore shares the mother’s cumulated exposures to toxic chemicals. Infants and children are likewise exposed to a cocktail of foreign substances against which the body has no innate defense. Prenatal and early postnatal brain development is an extremely complex process that we now know is uniquely vulnerable. Lead, mercury and a few other substances have long been known to be toxic to brain development. Recent research suggests that many chemicals, perhaps thousands, may cause similar effects because they can gain access to the developing brain and exert their toxicity to brain cells. This new insight needs to be translated into public policy to protect the brain functions of the next generation. On this call Dr. Grandjean discussed what he terms “chemical brain drain” and how we might work to protect the brain health of future generations.

Sources:

Additional resources of interest:

The Influence of Prenatal DES Exposure on the Associations of Reproductive Factors and Osteoporosis

Prenatal DES exposure may reduce osteoporosis protection

DES Follow-up Study Summary

National Cancer Inst logo image
Lifetime cumulative exposure to estrogens is protective against osteoporosis ; prenatal exposure to estrogen appears to modify these associations.

Included in this study were 5,573 women who participated in the NCI DES Follow-up Study between 1994 and 2006. Data on reproductive history and medical conditions were collected on the first follow-up questionnaire in 1994 and subsequently on the 1997, 2001, and 2006 questionnaires.

The results of the study showed that women who had fewer than 25 years of menstruation (between the start of menstrual cycles and menopause) had a higher incidence of osteoporosis when compared with women who menstruated for 35 years or more. The association of years of menstruation with osteoporosis was shown observed in both DES-exposed and unexposed women, but was stronger among women who had not been prenatally exposed to DES.

The study’s results support the hypothesis that total lifetime exposure to estrogens that occur naturally through a woman’s reproductive years protects against the development of osteoporosis. Furthermore, prenatal exposure to estrogen, in the form of DES, may reduce this protection, although we do not yet know how.

2014 Study Abstract:

CONTEXT:
Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause.

OBJECTIVE:
The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations.

DESIGN, SETTING, AND PARTICIPANTS:
Participants were 5573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models.

MAIN OUTCOME MEASURE:
Osteoporosis was the main outcome measure.

RESULTS:
The IRRs for osteoporosis incidence with age at menarche less than 11 years and age at menopause of 50 years or younger were 0.82 (CI 0.59, 1.14) and 0.61 (CI 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR 1.80; CI 1.14, 2.86) compared with 35 years or more of menstruation. Associations were stronger among women who had not been prenatally exposed to DES.

CONCLUSIONS:
Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.

Sources:

  • Menarche, menopause, years of menstruation, and the incidence of osteoporosis: the influence of prenatal exposure to diethylstilbestrolNCBI, PMID: 24248183, 2014 Feb;99(2):594-601. doi: 10.1210/jc.2013-2954. Epub 2013 Nov 18. Full text link.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

Pesticide Levels on Food Unknown ; FDA and USDA Monitoring Programs must improve says U.S. GAO

GAO recommends that FDA improve its methodology and FDA and USDA disclose limitations in their monitoring and data collection efforts

The U.S. Food and Drug Administration does not perform enough pesticide residue tests — on either imported or domestic foods – to say whether the American food supply is safe, according to federal auditors.

The U.S. Government Accountability Office (GAO) report, which was released Thursday, said FDA is testing less than one-tenth of 1 percent of all imported fruits and vegetables and less than 1 percent of domestic fruits and vegetables.

GAO Highlights

U.S. GAO logo image
FDA and USDA monitor certain foods for pesticide residues. In 2012, FDA reported testing less than 0.1% of imported shipments. GAO recommends that FDA improve its methodology and FDA and USDA disclose limitations in their monitoring and data collection efforts.

What GAO Found:
The Food and Drug Administration’s (FDA) most recent data from 2008 through 2012 show that pesticide residue violation rates in 10 selected fruits and vegetables were low, but FDA’s approach to monitoring for violations, which targets commodities it has identified as high risk, has limitations. Among other things, GAO found that FDA tests relatively few targeted (i.e., non-generalizable) samples for pesticide residues. For example, in 2012, FDA tested less than one-tenth of 1 percent of imported shipments. Further, FDA does not disclose in its annual monitoring reports that it does not test for several commonly used pesticides with an Environmental Protection Agency (EPA) established tolerance (the maximum amount of a pesticide residue that is allowed to remain on or in a food)—including glyphosate, the most used agricultural pesticide. Although FDA is not required by law to select particular commodities for sampling or test for specific pesticides, disclosing this limitation would help meet Office of Management and Budget (OMB) best practices for conducting and reporting data collection and help users of the reports interpret the data. Also, FDA does not use statistically valid methods consistent with OMB standards to collect national information on the incidence and level of pesticide residues. FDA officials said that it would be costly to calculate national estimates for the foods it regulates because it would require a large number of samples for a wide array of products, but did not provide documentation on the cost of doing so or an assessment of the trade-offs of doing less targeting and more random sampling. Limitations in FDA’s methodology hamper its ability to determine the national incidence and level of pesticide residues in the foods it regulates, one of its stated objectives.
For domestic and imported meat, poultry, and processed egg products, the U.S. Department of Agriculture’s (USDA) Food Safety and Inspection Service’s (FSIS) most recent available data from 2000 through 2011 show the agency found a low rate of pesticide residue violations, but its data had limitations. Specifically, for this period, FSIS did not test meat, poultry, and processed egg products for all pesticides with established EPA tolerance levels. Like FDA, FSIS is not required by law to test the foods it samples for specific pesticides, but disclosing this limitation in annual reports would meet OMB reporting best practices. Since 2011, FSIS has increased the number of pesticides it has tested for and samples it has taken and engaged with EPA on changes to FSIS’s monitoring program to better provide EPA with data it needs to assess the risks of pesticides.
The most recent data from USDA’s Agricultural Marketing Service’s (AMS) annual survey of highly consumed commodities, including fruits and vegetables, show that, from 1998 through 2012, pesticide residue detections varied by commodity and were generally well below tolerance levels. EPA and others praise AMS’s data collection efforts as providing valuable information on the incidence and level of pesticide residues in foods. In addition, while the sampling methodology used by AMS in the Pesticide Data Program meets many of OMB’s best practices for conducting and releasing information to the public concerning a data collection effort, it does not meet several others, such as some principles of probability sampling that are important for ensuring that the data the agency collects are nationally representative. As AMS does not disclose these limitations in its annual monitoring reports, users of the data may misinterpret information in these reports and draw erroneous conclusions based on the data.

Why GAO Did This Study:
From 1970 to 2007, hundreds of millions of pounds of pesticides were applied annually to U.S. food crops to protect them from pests. To protect consumers, EPA sets standards—known as tolerances—for pesticide residues on foods. FSIS monitors meat, poultry, and processed egg products to ensure they do not violate EPA’s tolerances, and FDA monitors other foods, including fruits and vegetables. AMS gathers annual residue data for highly consumed foods, although not for enforcement purposes.
GAO was asked to review federal oversight of pesticide residues in food. This report examines (1) what FDA data show with respect to pesticide residue violations in the foods that it regulates; (2) what FSIS data show with respect to pesticide residue violations in the foods that it regulates; and (3) what AMS data show with respect to pesticide residue levels in fruits and vegetables. For each agency, GAO examined limitations, if any, in the agencies’ monitoring of foods for pesticide residues. GAO analyzed FDA, FSIS, and AMS pesticide residue data, including their reliability, reviewed agency methods for sampling foods for testing, and interviewed agency officials.

What GAO Recommends:
GAO recommends that FDA improve its methodology and FDA and USDA disclose limitations in their monitoring and data collection efforts. FDA said it will consider methodological changes and will disclose limitations. USDA agreed with GAO’s recommendations.

Sources and more information:

  • GAO Report to the Ranking Member, Subcommittee on Environment and the Economy, Committee on Energy and Commerce, House of Representatives, GAO-15-38, October 2014.
  • Pesticide levels on food unknown due to poor government testing, The Washington Post, November 7 2014.
  • FDA and USDA Should Strengthen Pesticide Residue Monitoring Programs and Further Disclose Monitoring Limitations,
    GAO press release, Nov 6, 2014.