Maternal SSRI use during pregnancy risks speech/language disorders in offspring

Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring

Key Points

Question
Is exposure to selective serotonin reuptake inhibitors during pregnancy associated with an increased risk of adverse speech, scholastic, or motor outcomes in offspring?

Findings
In this cohort study, offspring of mothers who purchased at least 2 selective serotonin reuptake inhibitors prescriptions during pregnancy had a significantly increased risk of speech/language disorders compared with offspring of mothers diagnosed as having psychiatric disorders who did not take medication during pregnancy.

Meaning
The findings suggest that use of selective serotonin reuptake inhibitors during pregnancy increases the risk of speech/language disorders in offspring.

Abstract

Maternal SSRI use during pregnancy risks speech/language disorders in offspring, JAMA Psychiatry, October 12, 2016.

Image @JAMAPsych.

Importance
Speech/language, scholastic, and motor disorders are common in children. It is unknown whether exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy influences susceptibility to these disorders.

Objective
To examine whether SSRI exposure during pregnancy is associated with speech/language, scholastic, and motor disorders in offspring up to early adolescence.

Design, Setting, and Participants
This prospective birth cohort study examined national population-based register data in Finland from 1996 to 2010. The sampling frame includes 845 345 pregnant women and their singleton offspring with data on maternal use of antidepressants and depression-related psychiatric disorders during pregnancy.

Exposures
There were 3 groups of offspring: 15 596 were in the SSRI-exposed group, ie, had mothers diagnosed as having depression-related psychiatric disorders with a history of purchasing SSRIs during pregnancy; 9537 were in the unmedicated group, ie, had mothers diagnosed as having depression-related psychiatric disorders without a history of purchasing SSRIs during pregnancy; and 31 207 were in the unexposed group, ie, had mothers without a psychiatric diagnosis or a history of purchasing SSRIs.

Main Outcomes and Measures
Cumulative incidence of speech/language, scholastic, or motor disorders (829, 187, and 285 instances, respectively) from birth to 14 years. All hypotheses tested were formulated before data collection.

Results
Of the 56 340 infants included in the final cohort, 28 684 (50.9%) were male and 48 782 (86.6%) were 9 years or younger. The mean (SD) ages of children at diagnosis were 4.43 (1.67), 3.55 (2.67), and 7.73 (2.38) for speech/language, scholastic, and motor disorders, respectively. Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group vs 0.0061 in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004). There was a significantly increased risk of these disorders in offspring in the SSRI-exposed and unmedicated groups compared with offspring in the unexposed group. For scholastic and motor disorders, there were no differences between offspring in the SSRI-exposed group and in the unmedicated group.

Conclusions and Relevance
Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.

Cosmetics use and age at menopause: is there a connection?

Endocrine disrupting chemicals and reproductive disorders

Abstract

Cosmetics contain a vast number of chemicals, most of which are not under the regulatory purview of the Food and Drug Administration.

Only a few of these chemicals have been evaluated for potential deleterious health impact: parabens, phthalates, polycyclic aromatic hydrocarbons, and siloxanes.

A review of the ingredients in the best-selling and top-rated products of the top beauty brands in the world, as well as a review of highlighted chemicals by nonprofit environmental organizations, reveals 11 chemicals and chemical families of concern: butylated hydroxyanisole/butylated hydroxytoluene, coal tar dyes, diethanolamine, formaldehyde-releasing preservatives, parabens, phthalates, 1,4-dioxane, polycyclic aromatic hydrocarbons, siloxanes, talc/asbestos, and triclosan.

Cosmetics use and age at menopause: is there a connection?, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 978–990, September 15, 2016.

“Cosmetics” image akiraohgaki.

Age at menopause can be affected by a variety of mechanisms, including endocrine disruption, failure of DNA repair, oxidative stress, shortened telomere length, and ovarian toxicity.

There is a lack of available studies to make a conclusion regarding cosmetics use and age at menopause. What little data there are suggest that future studies are warranted. Women with chronic and consistent use of cosmetics across their lifespan may be a population of concern.

More research is required to better elucidate the relationship and time windows of vulnerability and the effects of mixtures and combinations of products on ovarian health.

Concerns about the implications from the presence of harmful flame retardants chemicals in furniture products

Flame retardant free furniture is necessary to ensure protection of human health and the environment

Photo: HEAL’s Lisette van Vliet with Jamie Page, The Cancer Prevention and Education Society (CPES).

Policy Paper PDF.

The Case for Flame Retardant Free Furniture, env-health.org, Brussels, Belgium, 8 September 2016.

HEAL joins a coalition of NGOs to stress concerns about the implications from the presence of harmful flame retardants chemicals in furniture products.

A variety of flammability standards for furniture exist in Europe. Some standards lead to the use of hazardous flame retardants chemicals without providing a demonstrated fire safety benefit. Flame retardants may cause serious harm to human health and the environment, they prevent the EU’s goal of a circular economy and impose a costly burden to furniture producers.

The signatories of this paper share and stress the same concerns about the implications from the presence of harmful flame retardants chemicals (FRs) in furniture products. More effective and less harmful ways to achieve fire safety exist and need to be evaluated.

Increasing evidence shows that an EU-action in favour of flame retardant free furniture is necessary to ensure protection of human health and the environment, and promote competition and fire safety.

If screening had been a drug, it would have been withdrawn from the market

Which country will be first to stop mammography screening?

Key points

  • Screening with mammography does not reduce the occurrence of advanced cancers.
  • Rigorous observational studies in Europe have failed to find an effect of mammography screening.
  • Mammography screening produces patients with breast cancer from among healthy women and increases the number of mastectomies performed.
  • The most effective method we have to reduce the occurrence of breast cancer is to stop screening.

Time to stop mammography screening?

The Canadian Task Force on Preventive Health Care should be congratulated for its new recommendations on screening for breast cancer in women at average risk aged 40–74 years. These guidelines are more balanced and more in accordance with the evidence than any previous recommendations.

The recommendations against routine clinical breast examinations, breast self-examinations and magnetic resonance imaging to screen for breast cancer in this age and risk group are all straightforward.

The recommendations on mammography screening are even more conservative than the change in policy suggested by the US Preventive Services Task Force in 2009, which created an uproar in the United States from people interested in maintaining the status quo. The new Canadian guidelines are appropriately cautious, advising against routinely screening women aged 40–49 years. The task force recommends screening women aged 50–69 years every two to three years, although it admits that this is a weak recommendation based on moderate-quality evidence, and screening women aged 70–74 years on the same schedule based on low-quality evidence. The task force also suggests that women who do not place a high value on a small reduction in breast cancer mortality, and who are concerned with false-positive results on mammography and overdiagnosis, may decline screening.

These guidelines are an important step in the right direction, away from the prevailing attitude that a woman who does not undergo screening is irresponsible. Recent research even suggests that it may be most wise to avoid screening altogether, at any age, as outlined below.

The Canadian Task Force on Preventive Health Care decided not to include observational studies in its systematic review unless they were needed to elucidate the harms of screening or the values and preferences of patients. However, important observational studies have been published in recent years, without which a systematic review would be incomplete. These observational studies have been discussed elsewhere and have also been included in an update (currently submitted for publication) of our 2009 Cochrane review of mammography screening.

Doubtful effect of screening

Time to stop mammography screening?; National Institutes of Health PMC3225414 183(17): 1957–1958, Nov 22 2011.

Programming a latest-gen mammography station, nicoyogui.

If screening does not reduce the occurrence of advanced cancers, it does not work. A systematic review of studies from seven countries showed that, on average, the rate of malignant tumours larger than 20 millimetres was not affected by screening. Because the size of a tumour is linearly correlated to the risk of metastasis, this result is evidence against an effect of screening.

Denmark has a unique control group within its population — only 20% of its population was screened during a 17-year period. The annual decrease in breast cancer mortality in the relevant age group (55–74 years) and period was 1% in the areas with screening and 2% in the non-screened areas.Among women who were too young to benefit from screening, the decreases were larger (5% for screened areas, 6% for unscreened areas). Similar results have been reported from the United Kingdom, Sweden and Norway.

A study involving women from 30 European countries showed that the mean decrease in breast cancer mortality between 1989 and 2005 among women less than 50 years of age was 37%; the corresponding decrease was 21% among women aged 50–69 years. The declines began before the start of organized screening programs in many countries and are more likely explained by the introduction of tamoxifen. The introduction of tamoxifen could explain the larger decline seen among young women who often have estrogen-sensitive tumours.

Another study compared three pairs of similar neighbouring countries that had introduced screening 10–15 years apart. The pairs were Northern Ireland and the Republic of Ireland, the Netherlands and Belgium, and Sweden and Norway. There was no relation between start of screening and the reduction in breast cancer mortality.The fall in breast cancer mortality was about the same in all countries. Furthermore, the decline was also about the same as that seen in the United States, where screening started as early as in Sweden.

Screening seems to be ineffective in today’s world for two reasons. First, adjuvant therapy, such as tamoxifen and chemotherapy, is highly effective (even when the cancer has metastasized) but was not often used at the time of the old trials. Second, public awareness of breast cancer has increased, and women tend to see a doctor much earlier today when they have noticed something unusual in their breast. In Denmark, the average size of a tumour decreased by nine millimetres from 1979 to 1989, a reduction that occurred before screening started. In addition, this decrease was larger than the average difference in tumour size seen between screened and control groups in trials (5 mm), despite the tendency for small, overdiagnosed tumours to spuriously exaggerate the difference.

It has often been claimed that mammography screening reduces breast cancer mortality by 30%. However, thorough systematic reviews have estimated only a 15% reduction, and data on tumour size from the trials are compatible with only a 12% effect.This effect is similar to the results seen in the most reliable studies, which showed a 10% effect after 13 years.

Overdiagnosis

Any possible effect of screening on breast cancer mortality must be marginal and could be counteracted by the life-shortening effect that radio-therapy and chemotherapy have when used in healthy women in whom breast cancer has been overdiagnosed (i.e., a diagnosis of breast cancer that would not have been made in the woman’s remaining life had she not undergone screening). The main effect of screening is to produce patients with breast cancer from among healthy women who would have remained free of breast disease for the rest of their lives had they not undergone screening. Compelling data from the US, Norway and Sweden show that most overdiagnosed tumours would have regressed spontaneously without treatment.  In addition, screening substantially increases the number of mastectomies performed, despite routine claims to the contrary by advocates of screening.

The best method we have to reduce the risk of breast cancer is to stop the screening program. This could reduce the risk by one-third in the screened age group, as the level of overdiagnosis in countries with organized screening programs is about 50%.

If screening had been a drug, it would have been withdrawn from the market. Thus, which country will be first to stop mammography screening?

Peter Gøtzsche, MD, 2011.

Autism outcomes in DES grandchildren : support the first study !

Help Fund Research into Neurodevelopment and Behavioral Impacts of DES

” My name is Jill Escher. I’m a science philanthropist who kickstarts pioneering research projects investigating the generational toxicity of certain potent exposures, including DES, tobacco and other drugs. While I’m not a DES daughter, I was exposed to a multitude of other synthetic steroid hormones in utero as part of a then-popular, if ineffective, “anti-miscarriage” practice. You can read my story here. You can see my science website at GermlineExposures.org.

Based on human, animal, and in vitro studies, as well as family interviews, I hypothesize that diethylstilbestrol DES, along with several other toxic substances, can damage the genomic information in early fetal-stage gametes. For a variety of reasons, the early gamete is probably the single most vulnerable stage of the human lifecycle. Damage during that phase, which could be genetic or epigenetic in nature, can manifest as abnormal development in the subsequent offspring.

For example, I hypothesize that the intensive synthetic steroid hormone drug regimen to which I was subjected as a fetus subtly deranged the molecular programming of my early eggs. This derangement I believe resulted in the starkly abnormal neurodevelopment — autism — of my children. I have met many other families with the same story.

Support Research into the Far-Reaching Generational Toxicity of DES, germline exposures, 10/10/2016.

Autism by pycik.

I am pleased to announce that I am funding the world’s first research study into the grandchild effects of DES (3d gen), looking specifically at neurodevelopment and behavioral impacts. This work will be done in collaboration with Harvard University, based on the Nurses’ Health Study II.

Thank you for your support! If you have any questions, please do not hesitate to email me. “

Jill Escher, President of Autism Society San Francisco Bay Area, 10/10/2016.

More DES DiEthylStilbestrol Resources

Endocrine disrupting chemicals and uterine fibroids

Endocrine disruptors and reproductive disorders

Abstract

Uterine fibroids are the most frequent gynecologic tumor, affecting 70% to 80% of women over their lifetime.

Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy.

Many risk factors for these tumors have been identified, including environmental exposures to endocrine-disrupting chemicals (EDCs) such as genistein and diethylstilbestrol.

Endocrine disrupting chemicals and uterine fibroids, Fertility and Sterility, Volume 106, Issue 4, Pages Pages 967–977, September 15, 2016.

“Feeling ill” image Maria Morri.

Uterine development may be a particularly sensitive window to environmental exposures, as some perinatal EDC exposures have been shown to increase tumorigenesis in both rodent models and human epidemiologic studies.

The mechanisms by which EDC exposures may increase tumorigenesis are still being elucidated, but epigenetic reprogramming of the developing uterus is an emerging hypothesis.

Given the remarkably high incidence of uterine fibroids and their significant impact on women’s health, understanding more about how prenatal exposures to EDCs (and other environmental agents) may increase fibroid risk could be key to developing prevention and treatment strategies in the future.

DES DiEthylStilbestrol Resources

Le dépistage organisé, systématique, des cancers du sein

Réflexions d’une radiologue sur la mammographie et le dépistage actuel

Vidéo publiée le 5 février 2016 par Surmédicalisation.

Raisons et circonstances qui ont amené le Dr Cécile Bour, Médecin Radiologue, à participer au dépistage organisé des cancers du sein, puis à cesser après des années de pratique.

En savoir plus

Medical Science Editors, Publishers, Impact Factors, and Reprint Income

Is much of the clinical research that is published still believable?

Editors under Pressure—Avoiding Conflicts

Editors would like to imagine they are simply gatekeepers who facilitate the interaction between authors who wish to impart information and people who want to read it. In fact, they are subject to a raft of external pressures that interfere with this core task. Coauthors are prone to disputes with each other and with reviewers; rejected authors may protest; readers may be dissatisfied; institutions may react inadequately to editors’ concerns about probity; editorial freedom may be compromised by the demands of the learned society that owns the journal; and a commercial publisher might exert subtle—or unsubtle—pressure to increase profitability. All of these distractions increase the possibility of competing interests corrupting the editorial process.

Influence of the Impact Factor

Editors, Publishers, Impact Factors, and Reprint Income, PLoS Medicine, PMC2964337, Oct 26 2010.

Added to this toxic mixture is the impact factor (IF). Just as many clinicians claim that contacts by pharmaceutical company representatives do not affect their prescribing behaviour, so editors are likely to deny that thoughts of a rising IF might influence their acceptance rates. In their paper published this week in PLoS Medicine, Andreas Lundh and colleagues analysed randomised controlled trials published in six high-impact general medical journals during two time periods a decade apart; they calculated the putative fall in IF that would have occurred had publication been denied to papers that were commercially sponsored.

Unsurprisingly, they found the expected association, since IF depends in turn on recent citation rates, and a body of literature shows that industry-sponsored trials attract more citations than those funded by a nonprofit source. There are reasons: for example, randomised controlled trials and meta-analyses are cited more frequently than clinical studies with less-rigorous design, regardless of funding, and high-impact journals are likely to attract the former. There is “gamesmanship,” with commercial sponsors and publishing companies skilled at obtaining publicity in the mass media, a known stimulant for citations. Only slightly dubious is the habit of commercial companies disseminating papers favourable to their product to individual clinicians at conferences or through sponsorship of review papers—themselves a potent accelerator of IF. More culpable is the fact that studies showing positive outcomes for a drug or device under consideration are more likely to be published than “negative” studies; editors are partly to blame for this but so are commercial sponsors, whose methodologically well-conducted studies with unfavourable results tended not to see the light of day, at least in the pretrial registration era.

Lundh and colleagues do not claim that their findings demonstrate that editors’ judgment on acceptance or rejection is influenced by the paper’s predicted effect on IF. Nonetheless, I have heard editors support a paper at a selection meeting by stating that it is likely to be well cited.

Publishers’ Profits and Sponsored Studies

More intriguingly, the second aim of their study was to investigate the possible financial benefits to publishers of the journals they investigated. Their attempted method was to seek data on income from advertisements, reprints, and industry-supported supplements as a percentage of total income. The editors of the two UK-based journals,BMJ and The Lancet, provided the data. The editors of JAMA and The New England Journal of Medicine (NEJM)declined, as did the publisher of Annals of Internal Medicine. The owners of the latter confirmed the proxy data obtained from the US Internal Revenue Service but the publishers of the former two journals, the American Medical Association and the Massachusetts Medical Society, did not respond.

Again, the authors cannot infer the intentions of their nonrespondent editors. Editors are proud of their independence but independence goes only as far as an owner permits, as we know from the sorry history of dismissed editors of NEJM and the Canadian Medical Association Journal, amongst others.

Journals as Leaders: A Paradox

In many ways, JAMA has led the way in promoting publishing integrity—including its call for independent statistical analysis of submitted industry-sponsored trials and its publication of best practice recommendations for professional medical associations. The authors of the latter paper, who include the journal’s editor-in-chief, state:

“Professional medical associations have a duty to bring to their members the best scientific evidence on the efficacy and suitability of drugs and devices. These efforts must be separate from and not affected by industry promotions.”

It is a paradox that the professional medical association that owns JAMA was less than open and transparent with Lundh and colleagues about potential financial conflicts (such as their income from industry sources) as they expect their authors to be.

Stronger Guidance Needed

The various bodies that advise editors may need to strengthen their guidance. The Council of Science Editors’ White Paper on Promoting Integrity in Scientific Journal Publication includes as a potential conflict for editors “employment by an organisation that would obtain some advantage from a favourable product-related publication.” The International Committee of Medical Journal Editors (ICMJE) states that editors who make the final decisions about manuscripts must have no “personal, professional or financial involvement in any of the issues they might judge.” The Committee on Publication Ethics (COPE) code of conduct for editors requires them to prevent business needs from compromising important intellectual standards. None of these organisations comment on the potential conflicts that might arise when a journal or publisher receives a substantial proportion of its income from reprints (23%, Massachusetts Medical Society; 41%, The Lancet; 53%, American Medical Association).

Journal editors have expended much time and effort in teasing out how to handle authors’ and reviewers’ competing interests. They need now to concentrate on their own and those of their employers, lest we reach the dismal scenario described by Marcia Angell:

“it is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine

Blind women as experts in the detection of breast cancer

Discovering hands’ vision, SparkNewsTv, June 2013

In the near future, a job field will be available for blind and visually-impaired people which they don’t fill despite their disability but because they take advantage of their advanced skills.

Stilbest Diethylstilbestrol Injection

DES Liquid Injection, Veterinary Products, Livestock Development

image of stillbest
DES is still sold under different names.

DES was sold under many names including Distilbène®, Stilbetin®, Stilboestrol-Borne®, Benzestrol®, Chlorotrianisene®, Estrobene® and Estrosyn® to name just a few.

Many different companies manufactured and marketed this drug under more than 200 different brand names.

This Stilbest 10 ml Diethylstilbestrol Injection B.P (Vet.) is a current veterinary product.

DES Drugs Pictures
More DES DiEthylStilbestrol Resources