Through a critical analysis of the international scientific literature, this most recent publication takes stock of what we know about the links between exposure to pesticides and human health. © Adobe Stock

Pesticides are all products that are used to control undesirable plant species and organisms considered harmful, raising many concerns about their potential effects on human health and the environment. In 2013, at the request of the French Directorate General for Health (DGS), Inserm had published a Collective Expert Review called “Pesticides: Effects on Health”. In 2018, five ministerial directorate generals1 had tasked the Institute with updating its publication and including new topics.

The group of experts gathered by Inserm analyzed the recent scientific literature in order to examine the link between pesticides and some twenty diseases. It also analyzed the health effects of two active substances and one family of pesticides: chlordecone, glyphosate, and succinate dehydrogenase inhibitor (SDHI) fungicides.

Through a critical analysis of the international scientific literature, the 2021 Collective Expert Review takes stock of what we know about the links between exposure to pesticides and human health. It looks at neuropsychological and motor development disorders in children, cognitive disorders, anxiety and depression in adults, as well as neurodegenerative diseases and cancers in people of any age. Respiratory health, thyroid diseases, and endometriosis are also discussed. All in all, the multidisciplinary group of researchers analyzed over 5,300 documents.

For each topic, the experts studied the new epidemiological data available in order to evaluate whether there was a presumed link between the exposure of different populations to the pesticides and the onset of a disease. As in 2013, this presumed link was then graded as being strong (++), moderate (+), or weak (±). These results were then examined in relation to those of the toxicological studies, in order to evaluate the biological plausibility of the links observed.

Links established between exposure to pesticides and certain diseases

The first epidemiological studies on the subject tended to characterize exposure to pesticides without precisely distinguishing the family of pesticides or the active substance. They often concerned people who in principle were most exposed due to having regularly handled such products as part of their work. More recent studies have sought to specify the disease subtypes (for example, the different types of leukemia), identify the active substances involved or investigate the link with populations supposedly less exposed than those who work with pesticides, such as those living near agricultural areas, the general population, or more sensitive populations such as children.

• In adults

The expert review confirms a strong presumed link between occupational exposure to pesticides and four diseases: non-Hodgkin lymphomas (NHLs), multiple myeloma, prostate cancer, and Parkinson’s disease. It also highlights the strong presumed link between occupational exposure to pesticides and two other diseases: cognitive disorders and chronic obstructive pulmonary disease (COPD)/chronic bronchitis (see boxed text).

A moderate presumed link has also been revealed between exposure to pesticides, mainly in an occupational context, and Alzheimer’s disease, anxiety, depression, certain cancers (central nervous system, bladder, kidney, leukemia, soft tissue sarcomas), asthma and thyroid diseases.

• In children

Certain periods of life such as pregnancy and early childhood are more vulnerable in the face of a toxic event or agent.

The recent results have made it possible to specify the type of pediatric leukemia concerned during exposure of the mother during pregnancy: acute leukemia and domestic uses (strong presumed link) and acute myeloid leukemia and occupational exposure. A new link has been found between the risk of acute lymphoblastic leukemia in case of paternal occupational exposure in the preconception period (moderate presumption).

Concerning central nervous system tumors, the expert review confirms the strong presumed link between the occupational exposure of the parents to pesticides (without distinction) during the prenatal period. In addition, the recent results lead to a strong presumed link between central nervous system tumors and domestic exposure to pesticides (without distinction) during pregnancy or childhood.

Other research focuses on the links between occupational or environmental exposure of mothers during pregnancy and neuropsychological and motor developmental disorders in children. They confirm the existence of a strong presumed link, especially for certain families of pesticides, such as the organophosphates. Regarding the pyrethroids, whose use has increased as a replacement for organophosphate insecticides, the results of new studies are consistent and show a link between pyrethroid exposure during pregnancy and an increase in internalized behavioral problems such as anxiety (strong presumed link). Toxicological data support the biological plausibility of an effect based on the modes of action of these pesticides.

Consider the most recent scientific data to better protect populations

The confirmation and highlighting of strong presumed links between certain diseases and exposure to pesticides should encourage the authorities to take better account of these issues. In addition, the scientific literature on the subject is raising new concerns, particularly regarding the indirect effects of certain pesticides on human health through their effects on ecosystems, which should be taken into account more by researchers and decision-makers.

1 The Directorates General for Risk Prevention, Health, Labor, Research and Innovation, and the Secretary General of the Ministry of Agriculture and Food

Fruit and vegetables, some of which contain carotenoids © Engin Akyurt/Unsplash photos

A Mediterranean diet – high in fruit, vegetables, legumes, whole grains, olive oil and oily fish – may prevent the development of age-related macular degeneration (AMD), which is the leading cause of visual impairment in people over the age of 50. A new study published by researchers from Inserm and University of Bordeaux at the Bordeaux Population Health Research Center reveals in an unprecedented way a link between circulating carotenoids – plant pigments that protect the retina – and the reduced risk of developing advanced AMD. Based on the follow-up of 609 people over an eight-year period, this research constitutes the first longitudinal study to identify this link and has been published in the journal Nutrients.

Age-related macular degeneration (AMD) is the leading cause of vision loss in industrialized countries. This degenerative disease affects the central part of the retina, which is crucial for daily living tasks (reading, driving, recognition of faces, etc.). At an advanced stage, it takes two forms: the neovascular “wet” form which is treated with anti-VEGF[1] injected directly into the eye, and the atrophic “dry” form for which there is no treatment at present.

Although there is no cure, it is possible to prevent or slow the progression of the disease. We are already familiar with the risk factors for AMD, which are linked to age and genetic background – factors which we cannot do anything about.

For the past twenty years, researchers have studied the link between nutrition and AMD. We now know that many foods make it possible to slow the degeneration: fatty acid (omega 3), antioxidants (vitamin C, zinc, etc.). These protect the macula, the area of the eye affected by the disease and which is located in the center of the retina.

Through a prospective study based on the eight-year follow-up period of the ALIENOR cohort, the researchers’ objective was to study the link between the presence of lutein and zeaxanthin in plasma and the development of AMD.

Unlike previous studies, based only on information given by participants about their diet, the team of Inserm researcher and study author Bénédicte Merle analyzed blood samples and demonstrated an objective link between circulating levels of lutein and zeaxanthin and a reduction in the risk of AMD.

This research reveals that higher plasma levels of carotenoids, particularly lutein and zeaxanthin, reduce the risk of developing advanced AMD by 37%.

This result remains similar, whether the form is atrophic or neovascular. However, apart from lutein and zeaxanthin, no other carotenoids have been associated with such a reduction in risk.

Lutein and zeaxanthin provide real protection to the retina. They absorb blue light, which is known to damage it over the long term, and act as antioxidants to protect it from oxidative stress[2] – which is a factor of AMD.

What to eat to prevent or slow the progression of AMD

For sufficient plasma levels of lutein and zeaxanthin, yellowy-orange fruits and vegetables should be preferred (tomatoes, carrots, citrus fruits), and leafy green vegetables (cabbage, spinach). “In addition to this, the most beneficial diet for preventing AMD is a Mediterranean diet high in fruit and vegetables and enough omega 3 from oily fish,” emphasizes Merle.

Beyond the nutritional recommendations, the discovery of the role of these carotenoids opens up avenues for identifying the population groups most at risk of developing AMD based on their diet. This study therefore offers strategies for prevention but also for the identification of risk factors that will be useful for the future of research.

[1] Anti-VEGFs are novel therapies that act on the cell membrane and are often used to prevent tumor survival.

[2] Oxidative stress refers to the various aggressions of our body’s cells caused by molecules derived from oxygen. The most well-known of these harmful substances are free radicals.

With the number of vulnerable students increasing under the effects of the health crisis, detecting those in severe distress and at risk of suicide is essential to enable the earliest possible intervention. © Ben Blennerhassett – Unsplash

How do we predict suicide risk in students? This is a pertinent issue at a time when the harmful effects of the health crisis on student mental health are becoming increasingly apparent and the importance of early detection and management of this risk is well-known. A team of researchers from Inserm and Université de Bordeaux, in collaboration with the Universities of Montreal and McGill in Quebec, have used artificial intelligence to identify a small set of mental health indicators that accurately predict suicidal behavior in students. Their findings have been published in Scientific Reports.

Suicide is the second leading cause of death among 15-24-year-olds, and students are at particular risk of suicidal behaviors. Several known factors may contribute to the increased risk in this population: the transition from high school to college, the added workload, psychosocial stress and academic pressures, and the adaptation to a new environment. Risks that have also been exacerbated by the health crisis related to the COVID-19 pandemic.

The early detection of suicidal behaviors (suicidal thoughts and attempts) is essential to enable access to appropriate treatment. Using a machine learning method[1], researchers at Inserm and Université de Bordeaux have developed an algorithm that accurately identifies the main predictive factors of suicidal behaviors in a student population.

Over 5,000 French students followed for one year

The findings of this study are based on the analysis of data collected from 5,066 students who were followed for at least one year between 2013 and 2019. They all belong to the i-Share cohort on student health led by Christophe Tzourio, professor of epidemiology at Université de Bordeaux, practitioner at Bordeaux University Hospital and director of the Bordeaux Population Health research center.  

The participants are over 18 years old, French-speaking and enrolled in a French university. They completed two detailed online questionnaires: one at the time of enrollment, the other a year later. The information gathered through this process provides researchers with information about their health, their drug and alcohol use, their medical and psychiatric history, and their psychological state.

This follow-up revealed that approximately 17% of the participating students, both girls (17.4%) and boys (16.8%), exhibited suicidal behaviors in the year elapsing between the two questionnaires.

Before initiating the modeling work based on artificial intelligence, the researchers identified 70 potential predictive factors, collected in the inclusion questionnaire, having an influence on suicidal behaviors according to the scientific literature. These include sociodemographic data, certain physical and mental health parameters, personal and family history of suicidal behaviors, living conditions and lifestyle, substance use, and childhood trauma.

The machine learning method, which simultaneously analyses many factors associated with suicidal risk, then ranked these 70 potential predictors according to their importance in predicting student suicidal behaviors.

The results of the study show that out of these 70 potential predictors measured at inclusion, four detect around 80% of suicidal behaviors at follow-up. These are suicidal thoughts, anxiety, depressive symptoms and self-esteem.

To the researchers, these findings suggest that validated and commonly used psychological scales, such as the Rosenberg Self-Esteem Scale, Spielberger’s STAI-YB scale for anxiety, and the PHQ-9 for depression, would be sufficiently informative to identify students at risk for suicidal behavior.

“This research needs to be confirmed, but it opens up the possibility of large-scale screening by identifying students at risk of suicide using short, simple questionnaires, in order to refer them to appropriate care,” explains Tzourio, coordinator of the study.

Self-esteem: an important and previously unrecognized marker

In secondary analyses conducted on a subsample of 3,946 students who did not exhibit suicidal behaviors at cohort entry, the primary predictors that stood out in the statistical analysis were depressive symptoms, self-esteem, and academic stress in girls and predominantly self-esteem in boys. Self-esteem would therefore represent an independent and important predictive marker of suicidal risk.

“The mental health specialists on our teams did not expect self-esteem to be one of the four major predictors of suicidal behaviors,” says Melissa Macalli, a doctoral student in epidemiology and author of the study. “This finding, which would not have been obtained without the use of artificial intelligence techniques making it possible to cross-tabulate a large number of data simultaneously, opens up new avenues for both research and prevention,” she concludes.

[1]Machine learning is a form of artificial intelligence (AI) that allows a system to learn from data rather than through explicit programming.

Between 3 and 6 years of age, children spend an average of around 2 hours a day in front of screens. © iStock – skynesher

Between 3 and 6 years of age, children spend an average of around 2 hours a day in front of screens[1]. While many researchers have identified links between screen time and cognitive development in children, few have looked at the context in which screens are used. Inserm researchers at the Center of Research in Epidemiology and Statistics – Université de Paris (CRESS) have identified a link between the television being on all the time during family meals and poorer language development. Their findings have been published in Scientific Reports.

Language is a social practice and human interaction plays an important role in its acquisition. Language development in children is therefore greatly influenced by their immediate environment, namely the interactions they have with their parents, siblings, and other children. Over the last few decades, screens have become an essential part of this environment. Even preschoolers spend a considerable amount of time in front of them.

Thanks to the follow-up over several years of children from the French cohort EDEN[2], researchers from Inserm and Université de Paris have been able to measure the amount of screen time and more specifically the frequency of exposure during family meals, which are key moments of verbal interaction between adults and children. Language assessments were conducted alongside this to identify how the context of screen exposure may influence language development in children.

1,562 children followed up at 2, 3 and 5.5 years of age

In order to measure the times and contexts of screen use, questionnaires were completed by the parents of the 1,562 children in the cohort followed up at 2, 3, and 5.5 years of age. In the study, the parents noted how often the television was on during meals. For the children’s screen time, only the time spent in front of the television, computer, and playing video games was taken into consideration.

The children’s language development was assessed by questionnaires completed by the parents when the children were 2 years old[3], and then by psychologists when they reached 3 and 5.5 years of age. In order to consider the potential role played by other factors, several other variables were included in the statistical analysis, such as family socioeconomic characteristics (income, parental level of education, etc.) and child-related characteristics (sex, childcare arrangements, activities with parents, etc.).

Cross-tabulation of these data revealed that the more the television was on (whether watched or simply used as a sound or image backdrop) during family meals, the poorer the language outcomes. In contrast, the children’s language did not appear to be directly related to the amount of time spent in front of screens.

In an approach that analyzed these relationships at each age, the language level at age 2 was lower among children who were “always” exposed to television during family meals compared to children who were “never” exposed[4]. At ages 3 and 5.5, the language assessment and verbal IQ results were higher for children who were “never” exposed to television during family meals, compared to those who were “sometimes” or more frequently exposed.

In an approach looking at the temporality between screen exposure and language development, the verbal IQ tested at 5.5 years of age was found to be lower in children who were always exposed to television during family meals at 2 years of age compared to those who were never exposed (mean difference of 3 IQ points). These results therefore encourage us to take better account of the context of screen exposure, and not just the duration.

“Although children are exposed to language through cartoons and other programs viewed on screens, verbal interaction between adult and child is strongly associated with better child language development. Having the television on during meals can therefore act as a brake on children’s verbal interactions, reducing both the quality and quantity of exchanges between children and adults,” explains Jonathan Bernard, Inserm researcher and co-author of the study.

Having the television on during family meals can affect both the child, by distracting him or her, and the parents, by diverting the conversations with their children.

[1] Figures from the INCA 3 survey (Anses), 2014-2015

[2] The Eden cohort was created from the recruitment of 2,002 pregnant women between 2003 and 2006 in the public maternity hospitals of Poitiers and Nancy. EDEN is the first generalist cohort study conducted in France on early pre- and post-natal determinants of child health and psychomotor development.

[3] At 2 years of age, the children’s language skills were assessed using the French Communicative Development Inventories (IFDC). At 3 years of age, the NEPSY and ELOLA verbal language assessment batteries were used. And at 5-6 years of age, an IQ test was used.

[4] Exposure to television during family meals was assessed repeatedly at all three ages with the following question: “How often is the television on in the dining room when the child is eating at home?” with four response items: never, sometimes, often, or always.

Alcohol was the world’s 7th leading cause of healthy life years lost in 2016 and is the leading cause of hospitalization in France. © adobe stock

Alcohol consumption is both directly and indirectly implicated in the onset of some 60 diseases, making it a major health risk factor. In France, around 43 million people consume alcohol. Faced with its inherent health, social and financial impacts, the country’s Health Directorate and Interdepartmental Mission to Combat Drugs and Addictive Behavior asked Inserm to take stock of the harm related to alcohol and formulate research avenues and measures to tackle it. The group of experts gathered by Inserm for the collective expert review procedure has published a report concerning the reduction of alcohol-related harm. It discusses social prevention strategies and uses data taken from the scientific literature available in the first half of the year 2020.

The collective expert review coordinated by Inserm began by making a critical analysis of the latest scientific knowledge in the field and establishing findings. The expert group then made recommendations aimed at reducing the risks and harm to health associated with alcohol consumption. Around 3,600 documents were collected from a variety of disciplines, such as clinical research, social marketing and sociology.

Alcohol consumption, leading cause of hospitalization in France

In France, high levels of consumption affect both teenagers and adults. Alcohol consumption in adolescence becomes regular (10 or more times per month) for 8% of 17-year-olds, while 40-50% report binge-drinking (5 or more drinks on one occasion) at least once a month. Among adults, the average daily intake is 27 g of pure alcohol per person (around 3 glasses).

Alcohol was the 7th leading cause of healthy life years lost worldwide in 2016 and is also the leading cause of hospitalization in France. Alcohol accounts for 11% of deaths of men and 4% of those of women from the age of 15, namely 41,000 deaths (30,000 for men and 11,000 for women according to the latest figures from 2015), making them the highest of any European country.

The expert review emphasizes that the price of alcohol, its availability and the norms relating to its consumption are associated with positive perceptions, encouraging its use. It shows that, in addition to individual factors, the marketing of alcohol (product, price, advertising, access) influences the modes and levels of consumption and plays a key role in young people’s drinking behavior. Alcohol producers are particularly present on the Internet and social media, where there is very little regulation of advertising.

The recommendations made by the experts address the issues of the law governing the sale of alcohol and the regulation of that sale, as well as communication and interventions to be considered.

For the tightening of the Évin law on the regulation of advertising and the control of the sale of alcohol

In France, the 1991 Évin law provides a framework to combat alcohol (and tobacco) related harm, but the experts note that not only is its current version not always respected, it has also been considerably modified and weakened by the lobbying of alcohol producers.

The expert group particularly recommends reducing the attractiveness of alcohol and the positive messages disseminated, and limiting its access, namely by:

• reinforcing the Évin law to prohibit advertising on the Internet, in public spaces, and to counter the effects of marketing by making health warnings more visible.
• increasing prices (taxation according to the number of grams of alcohol along the lines of the soda tax, or minimum price as in Scotland) – wine, for example, is subject to very little tax.
• better and automatic control of its access by minors.
• reducing its availability (times during which it can be sold and number of stores or licenses).

For reinforced communication by the authorities and health education for the general public

The expert group recommends the use of prevention messages aimed at the general population that are clear, specific and easy to implement and that are designed to be disseminated by digital means. These messages must also be adapted when aimed at the most vulnerable groups.

According to the collective expert review, the following must be reiterated:

• the recommended maximum intake for those wishing to drink[2],
• the need for zero alcohol, especially during pregnancy and the period before conception,
• that women are biologically more vulnerable to the damaging effects of alcohol.

The expert review highlights that a priority issue when it comes to prevention is reinforcing:

• protection factors while people are still very young. Interventions to target the prevention of consumption and strengthen users’ knowledge and “competence” should be developed, particularly through the use of digital means.
• generic protection factors such as parenting competence and psychosocial competence: such interventions are effective in schools, with parents or families, and in the workplace.
• health warnings and encouraging campaigns to stop drinking, such as “Dry January”, whose benefits (and low cost) have been proven.

For interventions to improve and adapt diagnosis and care

The experts suggest that these preventive actions should be supplemented by a strategy of systematic screening for high-risk alcohol consumption in order to enable appropriate care. The report suggests that primary care professionals should be better trained in screening strategies and effective intervention methods.

As such, the expert group recommends:

• “short interventions” by trained staff, consisting of minimal personalized counseling, aimed at people whose use puts them at risk or who are experiencing difficulties with their consumption. Such interventions are often beneficially associated with screening and have a clearly established positive cost-effectiveness ratio. They can be used on electronic media adapted for community interventions (schools, armed forces, etc.).
• strengthening the quality of the long-term follow-up of alcohol-dependent patients to avoid relapse, promoting effective therapeutic strategies (psychotherapy, medication, cognitive remediation, social rehabilitation, and the management of comorbidities).

The collective expert review concludes by stating that the major health, social and financial consequences of alcohol consumption, even at low levels, represent a burden for French society without the resources assigned to combat them being equal to the challenge. It should be possible for the measures recommended in this expert review, which are intended for the general public and public authorities, to be integrated at the heart of a policy of risk and harm reduction based on reduced consumption.

[1] By establishing a link between genetic variations associated specifically with a given biological trait and by measuring their effects on the risk of disease, Mendelian randomization makes it possible to establish a causal relationship between biological traits and risk of disease.

[2] Santé Publique France (French Public Health Agency): no more than 2 drinks per day and not every day