The Endocrine Society calls for improved guidance to identify endocrine-disrupting chemicals

Changes needed to ensure implementation of EU EDC criteria will protect public health

WASHINGTONThe Endocrine Society called for European regulators to ensure that endocrine-disrupting chemicals (EDCs) can be identified using practical, achievable scientific standards in detailed comments on a draft guidance document for implementing criteria for the identification of EDCs.

An EDC is a chemical or mixture of chemicals that can cause adverse health effects by interfering with hormones in the body. There are more than 85,000 manufactured chemicals, of which thousands may be EDCs. Endocrine-disrupting chemicals are found in everyday products and throughout the environment.

The European Commission requested that the European Food Safety Agency (EFSA) and European Chemicals Agency (ECHA) develop the guidance for implementing new criteria for regulating EDCs. While the two agencies offered a thoughtful and practical approach to regulation of EDCs, the Society’s experts noted several concerns in the draft guidance that need to be addressed to ensure EDCs posing a risk to public health can be identified.

The Endocrine Society encourages the authors of the guidance to ensure that regulatory agencies can identify chemicals that interfere with hormone action and define them as EDCs based on a realistic standard of scientific information, minimizing the potential for mischaracterization of harmful chemicals. The Society also asked for more clarify on situations where agencies may not have sufficient information to evaluate a chemical.

The Society called for broadening the scope of the guidance to incorporate all potential toxicity effects that are relevant to endocrine disruption. The current draft focuses on tests and endpoints for EDCs that mimic, block, or interfere with estrogen, androgen, and thyroid hormones and the body’s production of steroids. However, chemicals can disrupt other endocrine pathways that depend on proper hormone function, such as metabolism. Disrupting these pathways can lead to adverse consequences such as weight gain and insulin resistance.

The Society encouraged regulatory agencies to review and update the guidance in the future as necessary to incorporate the latest scientific evidence on EDCs. The Society also highlighted problems in the thyroid section of the guidance recommending that regulators strengthen this section to ensure that this important and complex pathway is properly assessed.

Society experts will continue to provide input to the European Commission, EFSA and ECHA as they revise the guidance and European Union regulations. Science based regulations on EDCs are crucial to ensure a high level of health and environmental protection and protect the public from the harms due to EDC exposure.

It’s My Ovaries, Stupid !

Dr. Vliet offers a different perspective on hormones

This landmark work in women’s health identifies and offers solutions to the hormonal dysfunctions afflicting millions of young women, teens, and even children, that rob women of future fertility and contribute to devastating problems — from early onset puberty and obesity to depression and increased cancer risk. Women’s health is more than breast cancer, pregnancy, and menopause. In this groundbreaking new work, Dr. Elizabeth Lee Vliet identifies and explains rarely acknowledged, pervasive threats to young women’s health and fertility — PCOS (Polycystic Ovary Syndrome), POD (Premature Ovarian Decline), and Premature Ovarian Failure (menopause in the young) — and the overlooked causes of endometriosis, cystitis, early puberty, allergies, heart disease, mood disorders, depression, chronic fatigue, fibromyalgia, bone loss, anxiety, obesity, and diabetes.

A kind of “Silent Spring” of women’s health, “It’s My Ovaries, Stupid!” presents compelling evidence from worldwide research that common environmental toxins and endocrine disruptors in pesticides, plastic food wrappers, food additives, preservatives, soy supplements, aspartame in diet sodas and junk food, and more — as well as lifestyle factors such as stress — can all profoundly disrupt hormone function, even in childhood.Insidious robbers of quality of life, fertility, and health, hormone dysfunctions are on the rise today, afflicting younger and younger women.Why? What can you do about it? How can you get tested? What treatments are available? Dr. Vliet interprets the latest scientific research and draws on more than twenty years of clinical experience to answer these and many other crucial questions about commonhealth problems in young women.Whose job is it to take care of the ovaries…beyond their function in reproduction? Why do you have trouble getting help for “hormone problems” that are clearly linked to your monthly cycle?

It’s My Ovaries, Stupid!” bridges this gap in women’s health care and shows you how to understand your symptoms and get reliable tests, how to receive treatment and improve your health, how to wade through the controversies surrounding hormone replacement therapy, and how to explore cutting-edge options for thyroid problems.You can’t afford “not” to read this book. Your life, your fertility, and your long-term health may depend on it. It’s not all in your head, and it’s not just stress. It’s your ovaries!

More Information
Endocrine Disruptors

Perinatal BPA exposure induces chronic inflammation in offspring by modulating gut bacteria

Exposure to Bisphenol A During Pregnancy Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

A chemical called bisphenol A (BPA) used in plastic packaging and in the linings of food and beverage cans, may be passed from a mother to her offspring during pregnancy and cause changes in the gut bacteria of the offspring.

Emerging evidence from a research study in rabbits suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA exposure just before or after birth leads to reduced gut bacterial diversity, bacterial metabolites such as short-chain fatty acids (SCFA) and elevated gut permeability – three common early markers of inflammation-promoted chronic diseases.

The researchers observed that exposure to BPA during pregnancy caused chronic inflammation in the offspring’s intestines and liver. The researchers also noted signs of increased gut permeability – or leaky gut – and a decrease in the diversity of gut bacteria and anti-inflammatory bacterial metabolites, such as short-chain fatty acids.

2017 Study Abstract

Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation.

IMPORTANCE
Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability-three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life.

Sources

  • Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolite, msystems asm, DOI: 10.1128/mSystems.00093-17, 2017 Oct.
  • Exposure to chemical during pregnancy may cause health problems for offspring, The Pennsylvania State University, story/491849, November 8, 2017.
  • Microbial responses to the perinatal bisphenol A (BPA) exposure in rabbit offspring featured image credit PMC5634791/figure/fig2, 2017 Oct 10.

Serious health hazards for infants and children living near fracking sites

Neurodevelopmental and neurological effects of chemicals associated with unconventional oil and natural gas operations and their potential effects on infants and children

Multiple pollutants found in the air and water near fracked oil and gas sites are linked to brain problems in children.

2017 Study Abstract

Heavy metals (arsenic and manganese), particulate matter (PM), benzene, toluene, ethylbenzene, xylenes (BTEX), polycyclic aromatic hydrocarbons (PAHs) and endocrine disrupting chemicals (EDCs) have been linked to significant neurodevelopmental health problems in infants, children and young adults.

These substances are widely used in, or become byproducts of unconventional oil and natural gas (UOG) development and operations. Every stage of the UOG lifecycle, from well construction to extraction, operations, transportation and distribution can lead to air and water contamination. Residents near UOG operations can suffer from increased exposure to elevated concentrations of air and water pollutants.

Here we focus on five air and water pollutants that have been associated with potentially permanent learning and neuropsychological deficits, neurodevelopmental disorders and neurological birth defects. Given the profound sensitivity of the developing brain and central nervous system, it is reasonable to conclude that young children who experience frequent exposure to these pollutants are at particularly high risk for chronic neurological diseases.

More research is needed to understand the extent of these concerns in the context of UOG, but since UOG development has expanded rapidly in recent years, the need for public health prevention techniques, well-designed studies and stronger state and national regulatory standards is becoming increasingly apparent.

More Information

  • Full study (free access) Neurodevelopmental and neurological effects of chemicals associated with unconventional oil and natural gas operations and their potential effects on infants and children, Reviews on Environmental Health, doi.org/10.1515/reveh-2017-0008, 2017-10-25.
  • Fracking chemicals and kids’ brains don’t mix: Study, Environmental Health News, 2017-10-25.
  • Featured image credit WildEarth Guardians and @EnvirHealthNews.

EU Parliament MEPs reject endocrine disrupters proposal

Identifying endocrine disruptors : Parliament blocks plans exempting some pesticides,
European Commission will have to come up with a new proposal without delay

Strasbourg : on 4th October, the European Parliament MEPs took a plenary vote – Objection pursuant to Rule 106: draft Commission regulation amending Annex II to Regulation (EC)1107/2009 by setting out scientific criteria for the determination of endocrine disrupting properties – and rejected the criteria to identify endocrine disruptors by 389 votes against and 235 for (majority at 376).

Substances having endocrine disrupting properties are substances that alter functions of the body’s endocrine (hormone) system and hence may have harmful effects on humans and wildlife.

EU Parliament Press Release

MEPs say that the Commission exceeded its mandate by proposing to exempt substances which are actually designed to attack an organism’s endocrine system, e.g. in pests, from the identification criteria.

Next steps

The objection, proposed by MEPs Jytte Guteland and Bas Eickhout, was approved by  389 votes to 235, with 70 abstentions, producing the absolute majority needed to block the proposal. The European Commission will therefore have to draft a new version of the text, taking into account Parliament’s input.

Quick Facts

EU legislation requires that pesticides or biocide substances have no endocrine-disrupting effects on other species than the ones targeted. To apply  this legislation, the EU needs a list of scientific criteria for identifying endocrine disruptors.

The Commission proposal related to the scientific criteria for identifying endocrine-disrupting properties of chemical substances. The identification of these scientific criteria is a first step towards measures reducing their presence and protecting citizens’ health.

The European Court of Justice ruled in December 2015 that the EU Commission had breached EU law by failing to publish criteria for determining endocrine disrupters due at the end of 2013. MEPs have repeatedly urged the EU to clamp down on the substances.

A UNEP/WHO report called endocrine disruptors a “global threat”, referring inter alia to the upward trends in many endocrine-related disorders in humans and wildlife populations. There is evidence of adverse reproductive effects (infertility, cancers, malformations) which could also affect thyroid function, brain function, obesity, metabolism, insulin and glucose homeostasis, it says.

  • Identifying endocrine disruptors: Parliament blocks plans exempting some pesticides, EU Press Room Ref.: 20171002IPR85122 Created: 04-10-2017 – 13:45
  • EU Report on the proposal for a regulation of the European Parliament and of the Council laying down rules on the making available on the market of CE marked fertilising products and amending Regulations (EC) No 1069/2009 and (EC) No 1107/2009 (COM(2016)0157 – C8-0123/2016 – 2016/0084(COD)), PE 599.728v02-00 A8-0270/2017.
  • EU MOTION FOR A RESOLUTION pursuant to Rule 106(2), (3) and (4)(c) of the Rules of Procedure, on the draft Commission regulation amending Annex II to Regulation (EC) 1107/2009 by setting out scientific criteria for the determination of endocrine disrupting properties (D048947/06 – 2017/2872(RSP)), PE611.468v01-00 B8-0542/2017.

Endocrine Society eager to collaborate with EU lawmakers on science-based regulations

Washington, DC – The Endocrine Society, the world’s largest organization of endocrinologists, welcomed the European Parliament vote Wednesday objecting to proposed criteria that would have failed to identify endocrine-disrupting chemicals (EDCs) currently causing harm to public health.

In the months leading up to the vote, the Society, whose members are scientists and physicians who specialize in researching and treating hormone health conditions, repeatedly expressed concerns the rejected criteria would not ensure a high level of health and environmental protection.

An EDC is a chemical or mixture of chemicals that can cause adverse health effects by interfering with hormones in the body. EDCs contribute to serious health problems such as diabetes, obesity, and neurodevelopmental and reproductive disorders. Scientific criteria to effectively and regulate EDCs are critical to ensure the health and wellbeing of the public for this and future generations.

There are more than 85,000 manufactured chemicals, of which thousands may be EDCs. EDCs are found in everyday products and throughout the environment.

The rejected criteria failed to support the latest scientific evidence. The proposal contained arbitrary exemptions for chemicals specifically designed to disrupt target insect endocrine systems that have similarities in humans and wildlife. The Endocrine Society, the European Society for Endocrinology, and the European Society for Paediatric Endocrinology previously released a statement strongly objecting to the addition of loopholes in the criteria as they create frameworks where potentially dangerous chemicals cannot be defined as EDCs by law.

New, science-based criteria need to be developed to maximize the ability to identify chemicals that pose a threat to human health. It will be critical for scientists with expertise in hormone biology and endocrine systems to be deeply involved in the processes to identify EDCs. The Endocrine Society’s experts are prepared to play a role providing scientific guidance on the development of effective criteria for identifying EDCs.

Vote to reject flawed EDC criteria creates opportunity to protect public health, endocrine news-room, October 04, 2017.

Endocrine Disruptors
An Investigation
  1. The Manufacture of a Lie.
  2. A Denial of the State of the Science.
  3. The Interference of the United States.
  4. The Discreet but Major Gift to the Pesticides Lobby.

EU ENVI Committee opposes endocrine disrupters proposal with 36 votes to 26

MEPs in European Parliament Committee on Environment, Public Health and Food Safety adopted an objection to the EU Commission proposal for endocrine disruptors criteria

On 28 September, the ENVI Committee considered and voted Objection pursuant to Rule 106: endocrine disrupting properties – adopts rejection of endocrine disrupters criteria from EU Commission with 36 votes to 26.

Substances having endocrine disrupting properties are substances that alter functions of the body’s endocrine (hormone) system and hence may have harmful effects on humans and wildlife.

Plenary vote to take place next week

Endocrine Disruptors
An Investigation
  1. The Manufacture of a Lie.
  2. A Denial of the State of the Science.
  3. The Interference of the United States.
  4. The Discreet but Major Gift to the Pesticides Lobby.

Toxic Time Bombs

Decades of evidence point to the untoward health effects of endocrine disruptor exposures, yet little is being done to regulate the chemicals

Abstract

… “Although the U.S. has been slow to control endocrine disruptors, pressure is mounting for legislators to make significant regulatory changes in Europe, although the European Commission has also dragged its feet. In December 2015, the European Union’s Court of Justice decreed that the Commission had breached EU law by failing to adopt scientific criteria for identifying and regulating endocrine disruptors. The European Parliament met in February 2017 to consider a proposal defining those criteria, but member states decided to postpone a decision. France did not wait for the E.U. to take effective action. As of January 2015, new French legislation outlawed any contact between the known endocrine disruptor bisphenol A (BPA) and beverages or food.

The challenge to developing appropriate regulations for endocrine disruptors is that evidence from epidemiology for health effects is indirect and difficult to collect. Cancers abound in modern industrialized societies. Environmental factors are surely involved, yet hard to pinpoint. It took three decades to establish that DDT (dichloro-diphenyl-trichloroethane) and DES (diethylstilbestrol) impair health. Both are now strictly controlled, but their effects persist across generations.” …

  • Read Opinion: Toxic Time Bombs, by Robert Martin for The Scientist, September 25, 2017.
  • Featured image Portrait of Sir Edward Charles Dodds credit wikimedia.
More DES DiEthylStilbestrol Resources

Call on MEPs to protect us all from the real dangers of endocrine disruptors

Tell the Members of the European Parliament to put public health before corporate profits and ban harmful EDCs

Monsanto, Bayer, and BASF are about to score a major win by keeping toxic endocrine disrupting chemicals (EDCs) that poison our health off the radar.

Recently, a majority of EU member countries accepted a European Commission legislative proposal on EDCs that would leave us vulnerable to these toxic substances — especially children and pregnant women most susceptible to EDCs.

Experts are slamming the proposal, which sets criteria for which chemicals get classified as EDCs. They say it sets the burden of proof of harm so high that most of these harmful chemicals will go unregulated.

Even more, this dangerous text is now in danger of becoming law throughout the EU.

But it’s not over yet. The Commission’s proposal must now be approved by the European Parliament on 3 October, which means there’s still time for our voices to be heard.

Call on MEPs to block the European Commission’s proposal to identify EDCs that leaves us vulnerable to unregulated chemicals.

EDC’s are linked to hormone-related cancers, birth defects, and other serious developmental disorders.

Besides requiring a level of proof to identify a chemical as an EDC that is way too high, the text proposed by the European Commission also foresees unacceptable exemptions. Moreover, it is limited to endocrine disruptors in pesticides and biocides, while these toxic substances hide everywhere –- from our cosmetics and food packaging, to medical devices used in hospitals.

Nearly half a million SumOfUs members and supporters of the EDC-Free Europe coalition have been standing up to the dangerous EU commission proposal on regulating these chemicals already.

It’s time to channel that same energy and remind MEPs from all over Europe that they should put the health and voices of citizens like you before the interests of Bayer and Monsanto lobbyists.

Call on the Members of the European Parliament (MEPs) to listen to the facts and reject the Commission’s dangerous proposal for endocrine disrupters.

While companies like Monsanto make money off of them, EDCs cost society an estimated 163 billion euros per year in Europe.

But the agrochemical industry is trying to drown out the voices of concerned scientists, public health experts and citizens, with an army of lobbyists in Brussels.

SumOfUs and EDC-Free Europe coalition members have already achieved major victories in the fight against toxic products in Europe. Because we keep coming together to take action, the renewal of toxic pesticides like glyphosate keeps being postponed.

Now, it’s time to pool our efforts once again to remind MEPs to put public health before the profits of Monsanto and Bayer.

We don’t have a moment to lose — the decisive vote will be held in Parliament in just a couple of weeks!

Tell our MEPs to prioritise citizens’ voices over corporate interests and to protect us all from the real dangers of endocrine disruptors.

Endocrine Disruptors
An Investigation
  1. The Manufacture of a Lie.
  2. A Denial of the State of the Science.
  3. The Interference of the United States.
  4. The Discreet but Major Gift to the Pesticides Lobby.

EDCs : evidence that co-exposures should be considered when evaluating the risk of a single chemical

Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants

2017 Study Abstract

BACKGROUND
Numerous chemicals are capable of disrupting androgen production, but the possibility that they might act together to produce effects greater than those of the most effective component in the mixture has not been studied directly in human tissues. Suppression of androgen synthesis in fetal life has been associated with testis maldescent, malformations of the genitalia at birth, and poor semen quality later in life.

OBJECTIVES
Our aim was to investigate whether chemicals can act together to disrupt androgen production in human fetal testis explants and to evaluate the importance of mixture effects when characterizing the hazard of individual chemicals.

METHODS
We used an organotypic culture system of human fetal testes explants called FEtal Gonad Assay (FEGA) with tissue obtained at 10 and 12 gestational wk (GW 10–12), to screen 27 chemicals individually for their possible anti-androgenic effect. Based on the results of the screen, we selected 11 compounds and tested them as mixtures.

RESULTS
We evaluated mixtures composed of four and eight antiandrogens that contained the pharmaceuticals ketoconazole and theophylline and several previously untested chemicals, such as the pesticides imazalil and propiconazole. Mixtures of antiandrogens can suppress testosterone synthesis in human fetal testicular explants to an extent greater than that seen with individual chemicals. This revealed itself as a shift towards lower doses in the dose–response curves of individual antiandrogens that became more pronounced as the number of components increased from four to eight.

CONCLUSIONS
Our results with the FEGA provide the foundations of a predictive human mixture risk assessment approach for anti-androgenic exposures in fetal life.

Discussion

Concerns that the traditional focus of chemical risk assessment on single chemical exposures might underestimate the risks associated with adverse effects of multiple chemicals have been expressed earlier (Kortenkamp 2014), but the impact on risk estimates has been proven difficult to define. This is partly due to incomplete information about the complexity of combined human exposures and to a lack of clarity about the approaches and methods that should be used for mixture risk assessment. Our study provides important advances in improving the scientific basis for human mixture risk assessment. To our knowledge, we demonstrate for the first time that the mixture assessment concept of dose addition is applicable to human tissues. This not only enabled us to avoid certain uncertainties associated with animal-to-human extrapolations, but also enabled us to use a predictive approach. Rather than studying every conceivable combination of chemicals within a mixture, the joint effects of anti-androgenic chemicals in the FEGA can now be approximated on the basis of the effects of each single component by using dose addition as the default assumption.

To utilize the FEGA in multi-component mixture studies required making a leap from qualitative studies to quantitative dose–response analyses. Due to the inhomogeneity of the material and the variations inevitably introduced through the age differences of the fetal testes, the assay outcome (fetal testosterone production) shows high variability, which we had to deal with by rigorously controlling experimental conditions. We achieved good reproducibility, which was essential for realizing our goal of analyzing whether the combined effects of multiple chemicals can be predicted accurately on the basis of the effects of individual mixture components and of assessing the impact of co-exposures on the dose–response curves of single chemicals.

A difficulty in using the FEGA as a screening method for the identification of chemicals with endocrine disruptive properties is the limited availability of human fetal tissue. An additional challenge is in the requirement of collecting tissues of comparable age.

Our study provides direct evidence that co-exposures should be considered when evaluating the risk of a single chemical. We show that effects of a single chemical are underestimated when co-exposure to related chemicals are not considered, and that this underestimation is driven by the number, type, and potency of co-occurring chemicals. In this study, overlooking co-exposures to only seven chemicals led to an underestimation of the potency of BPA by a factor of 10. A corollary of the principles of dose addition is that co-exposure to a larger number of chemicals will drive up the extent of such underestimations if these chemicals are present at levels equipotent with the components we used in our experiments. Alternatively, replacement of some components with larger numbers of other chemicals, but at lower levels, may lead to similar underestimations. More studies using the FEGA are needed to establish these assumptions.

Based on our findings, we suggest that the impact of mixture effects on male sexual differentiation during the first trimester of pregnancy may be considerable. However, although in this study the selection of chemicals was empirically based on the results obtained in our dose–response study, analysis of individual chemicals, assessment of the extent of adverse effects in human fetuses will require more knowledge about the spectrum of chemicals capable of suppressing testosterone synthesis. Future FEGA studies will help close this knowledge gap, especially if based on companion studies that identify all of the exogenous chemicals found in maternal and fetal tissues.

Full Study
  • Featured image : predicted and observed testosterone secretion in human fetal testis by four chemical mixtures. Experimental data are shown as mean ± SEM (blue) of at least four independent experiments. Testosterone production is represented as relative to the first day of culture (D0) production and the control level, see text for more details. The mixture effects were predicted according to dose addition (DA) (thick red curve), with dashed curves the respective 95% confidence intervals (CIs) (dotted orange lines) credit ehp.
  • Endocrine Disruption in Human Fetal Testis Explants by Individual and Combined Exposures to Selected Pharmaceuticals, Pesticides, and Environmental Pollutants, Environmental Health Perspectives, DOI:10.1289/EHP1014, AUGUST 2017 | VOLUME 125 | ISSUE 8. Full PDF.
Endocrine Disruptors

Cumulative effects of prenatal-exposure to exogenous chemicals and psychosocial stress on fetal growth

When the human fetus is exposed to chemicals in the environment, fetal growth can be reduced

2017 Study Abstract

Background
Adverse effects of prenatal stress or environmental chemical exposures on fetal growth are well described, yet their combined effect remains unclear.

Objectives
To conduct a systematic review on the combined impact and interaction of prenatal exposure to stress and chemicals on developmental outcomes.

Methods
We used the first three steps of the Navigation Guide systematic review. We wrote a protocol, performed a robust literature search to identify relevant animal and human studies and extracted data on developmental outcomes. For the most common outcome (fetal growth), we evaluated risk of bias, calculated effect sizes for main effects of individual and combined exposures, and performed a random effects meta-analysis of those studies reporting on odds of low birthweight (LBW) by smoking and socioeconomic status (SES).

Results
We identified 17 human- and 22 animal-studies of combined chemical and stress exposures and fetal growth. Human studies tended to have a lower risk of bias across nine domains. Generally, we found stronger effects for chemicals than stress, and these exposures were associated with reduced fetal growth in the low-stress group and the association was often greater in high stress groups, with limited evidence of effect modification. We found smoking associated with significantly increased odds of LBW, with a greater effect for high stress (low SES; OR 4.75 (2.46–9.16)) compared to low stress (high SES; OR 1.95 (95% CI 1.53–2.48)). Animal studies generally had a high risk of bias with no significant combined effect or effect modification.

Conclusions
We found that despite concern for the combined effects of environmental chemicals and stress, this is still an under-studied topic, though limited available human studies indicate chemical exposures exert stronger effects than stress, and this effect is generally larger in the presence of stress.

Sources