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New research finding health benefits to humans from a four day low calorie diet - the Fasting Mimic Diet (FMD). Cutting calories to 34 to 54% of normal for a few days is obviously much easier to do than actual fastiing, so these results look very promising. In summary: the researchers found that in a small human trial, three cycles of this diet given to 19 subjects once a month for five days decreased risk factors and biomarkers for aging, diabetes, cardiovascular disease and cancer (and with no major adverse side effects). Three earlier posts on various types of minifasting health benefits: Minifasting May Benefit Health, Health Benefits of Feast and Famine Diet, Fasting and the Immune System. From Science Daily:

Diet that mimics fasting appears to slow aging

Want to lose abdominal fat, get smarter and live longer? New research led by USC's Valter Longo shows that periodically adopting a diet that mimics the effects of fasting may yield a wide range of health benefits. In a new study, Longo and his colleagues show that cycles of a four-day low-calorie diet that mimics fasting (FMD cut visceral belly fat and elevated the number of progenitor and stem cells in several organs of old mice -- including the brain, where it boosted neural regeneration and improved learning and memory.

The mouse tests were part of a three-tiered study on periodic fasting's effects -- testing yeast, mice and humans...Mice, which have relatively short life spans, provided details about fasting's lifelong effects. Yeast, which are simpler organisms, allowed Longo to uncover the biological mechanisms that fasting triggers at a cellular level. And a pilot study in humans found evidence that the mouse and yeast studies were applicable to humans.

In a pilot human trial, three cycles of a similar diet given to 19 subjects once a month for five days decreased risk factors and biomarkers for aging, diabetes, cardiovascular disease and cancer with no major adverse side effects, according to Longo.

The diet slashed the individual's caloric intake down to 34 to 54 percent of normal, with a specific composition of proteins, carbohydrates, fats and micronutrients. It decreased amounts of the hormone IGF-I, which is required during development to grow, but it is a promoter of aging and has been linked to cancer susceptibility. It also increased the amount of the hormone IGFBP-, and reduced biomarkers/risk factors linked to diabetes and cardiovascular disease, including glucose, trunk fat and C-reactive protein without negatively affecting muscle and bone mass.

Longo has previously shown how fasting can help starve out cancer cells while protecting immune and other cells from chemotherapy toxicity. 'It's about reprogramming the body so it enters a slower aging mode, but also rejuvenating it through stem cell-based regeneration,' Longo said. 'It's not a typical diet because it isn't something you need to stay on.'

For 25 days a month, study participants went back to their regular eating habits -- good or bad -- once they finished the treatment. They were not asked to change their diet and still saw positive changes. Longo believes that for most normal people, the FMD can be done every three to six months, depending on the abdominal circumference and health status. For obese subjects or those with elevated disease risk factors, the FMD could be recommended by the physician as often as once every two weeks. His group is testing its effect in a randomized clinical trial, which will be completed soon, with more than 70 subjects.

Despite its positive effects, Longo cautioned against water-only fasting and warned even about attempting the fasting mimicking diet without first consulting a doctor and seeking their supervision throughout the process....Longo also cautioned that diabetic subjects should not undergo either fasting or fasting mimicking diets while receiving insulin, metformin or similar drugs. He also said that subjects with body mass index less than 18 should not undergo the FMD diet.

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Elderly people (average age was 77 years) who have been married a long time (average length of marriage was 44 years, but one couple was married 76 years!) give advice on marriage and love. The gerontologist  Karl Pillemer details the finding of the Cornell Marriage Advice Project in his book, "30 Lessons for Loving: Advice from the Wisest Americans on Love, Relationships, and Marriage."  From Science Daily:

Love, factually: Gerontologist finds the formula to a happy marriage

A gerontologist has uncovered common advice for couples walking down the aisle or decades into marriage. To capture the voice of lived experience, the study included a random national survey of nearly 400 Americans age 65 and older, asking how to find a compatible partner and other advice on love and relationships. In subsequent in-person interviews with more than 300 long-wedded individuals -- those in unions of 30, 40, 50, or more years -- the study captured more insights for overcoming common marriage troubles. The team of researchers interviewed divorced individuals, too, asking how others might avoid marital breakups.

Pillemer uncovered common advice for couples walking down the aisle or decades into marriage. The top five lessons from the elders..:

Learn to communicate: "For a good marriage, the elders overwhelmingly tell us to 'talk, talk, talk.' They believe most marital problems can be solved through open communication, and conversely many whose marriages dissolved blamed lack of communication."

Get to know your partner very well before marrying: "Many of the elders I surveyed married very young; despite that fact, they recommend the opposite.

Treat marriage as an unbreakable, lifelong commitment

Learn to work as a team: ...Concretely, this viewpoint involves seeing problems as collective to the couple, rather than the domain of one partner. Any difficulty, illness, or setback experienced by one member of the couple is the other partner's responsibility."

Chose a partner who is very similar to you: "Marriage is difficult at times for everyone, the elders assert, but it's much easier with someone who shares your interests, background and orientation. The most critical need for similarity is in core values regarding potentially contentious issues like child-rearing, how money should be spent and religion."

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This latest study finding health benefits of eating nuts was a review of 36 observational studies, involving a total of 30,000 people. Nut consumption was associated with a lower risk of cancer in general, and a decreased risk of some types of cancer (colorectal, endometrial, pancreatic), but not with type 2 diabetes. So go ahead - eat a small handful of nuts for your health at least several times a week.From Medpage Today:

A Nutty Way to Prevent Cancer?

Nut consumption was associated with a decreased risk of some types of cancer but not with type 2 diabetes in a large review.When patients eating the most nuts were compared with those eating the least, those in the first group had a lower risk of colorectal cancer in three studies (RR 0.76, 95% CI 0.61-0.96; I2=51.3%), of endometrial cancer in two studies (RR 0.58, 95% CI 0.43-0.79; I2=0%), and pancreatic cancer in one study (RR 0.68, 95% CI 0.48-0.96; I2 not available). Those results were reported in the meta-analysis of 36 observational studies, with a total population of more than 30,000 patients.

Nut consumption was also associated with a lower risk of cancer in general (RR 0.85, 95% CI 0.76-0.95;I2=66.5%), according to the authors. But it was not associated with other types of cancer or with type 2 diabetes (RR 0.98, 95% CI 0.84-1.14; I2=74.2%), found the researchers, who were led by Lang Wu, a PhD candidate at the Mayo Clinic. They published their results on June 16 in Nutrition Reviews.

"Overall, nut intake was associated with a decreased risk of cancer," wrote Wu and colleagues. "Given the scarcity of currently available data, however, evidence from additional studies is required to more precisely determine the relationship between nut consumption and risk of individual cancer types." Evidence for the association between nuts and cancer has been mixed, according to the authors. Follow-up time in the studies ranged from 4.6 years to 30 years, found the review.

The amount of nuts eaten ranged from none for some of the patients to eating nuts more than seven times a week....No associations were found between nut consumption and acute myeloid leukemia, breast cancer, gastric cancer, glioma, hepatocellular carcinoma, leukemia, lymphoma, ovarian cancer, prostate cancer, or stomach cancer.

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Drawing of colon seen from front (the appendix is colored red). Credit: Wikipedia.

For more than 100 years, the standard treatment for appendicitis has been surgery. Now a large Finnish study provides the best evidence to date that most patients can be treated with antibiotics alone.

How did the usual treatment of doing an appendectomy (appendix removal) arise? In 1886 Dr. Reginald Fitz, while investigating pelvic infections (which resulted in many deaths in those days), decided that an inflamed appendix progresses from a mild inflammation, to gangrene, then perforation, which would result in pelvic abscess.

This reason for an appendectomy (that it would prevent serious infection) became established in medical thought and still guides appendicitis management today. But nowadays we have antibiotics! And the researchers noted that some cases resolved on their own without any treatment.

And instead of the prevailing view for many years that the appendix is a "vestigial organ with no purpose",  it turns out that the appendix has a great reason for existence. It seems to provide a safe haven for good bacteria when gastrointestinal illness flushes those bacteria from the rest of the intestines. This reservoir of gut microbes then repopulates the digestive system following the illness.

It makes me wonder why some people get appendicitis and others don't - do they have inflammation for some reason so that their bacterial communities are out of whack (dysbiosis)? Would dietary changes help prevent recurrences?

From the NY Times: Antibiotics Are Effective in Appendicitis, Study Says

For more than 100 years, the standard treatment for appendicitis has been surgery. Now a large Finnish study provides the best evidence to date that most patients can be treated with antibiotics alone. The study, published Tuesday in JAMA, involved 530 patients aged 18 to 60 who agreed to have their treatment — antibiotics or surgery — decided at random. Three out of four who took antibiotics recovered easily, the researchers found. And none who had surgery after taking antibiotics were worse off for having waited.

The new study comes amid growing questions about the routine use of surgery to treat appendicitis, which strikes about 300,000 Americans a year, afflicting one out of 10 adults at some point in their lives.

The results only apply to uncomplicated appendicitis, stressed Dr. Paulina Salminen, a surgeon at Turku University Hospital in Finland and lead author of the new study. She and her colleagues excluded from their trial the 20 percent of patients with complicated cases — people with perforated appendices or abdominal abscesses, and those with a little, rock like blockage of the appendix called an appendicolith.

In the 1950s, soon after antibiotics were discovered, some doctors reported success using them to treat patients with appendicitis. But, Dr. Livingston wrote in his editorial, “So powerful is the perceived benefit of appendectomy for appendicitis that surgical treatment for appendicitis remains unquestioned, with seemingly little interest in studying the problem.”

Dr. Livingston also found that most appendices that perforate have already done so by the time the patient shows up at an emergency room. Those that have not perforated when the patient seeks medical help almost never do so. People with so-called uncomplicated appendicitis, he concluded, seem to have a different disease — one that can be treated with antibiotics.

“The reason we take the appendix out and do it as an emergency is the belief, dating back to 1886, that the appendix will eventually become gangrenous and cause a pelvic abscess,” Dr. Livingston said.

Even with the results of the Finnish study, many questions remain. A person who has had one episode of appendicitis is at higher than usual risk for another....Accumulating data has led other experts to raise an even more controversial idea: Perhaps antibiotics aren’t always necessary, either. It is possible, some researchers say, that most people with appendicitis would get better on their own if doctors did nothing. The Finnish team is now planning a clinical trial to test that theory.

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There is growing evidence that women around a lot of endocrine disrupting chemicals at home or in jobs such as cleaners, hairdressers and laboratory workers during pregnancy are more likely to have baby boys with a genital defect called hypospadias (a condition where the opening of the urethra is on the underside of the penis rather than at the tip). From Environmental Health News:

Genital defect in baby boys linked to moms’ chemical exposure

Mothers around a lot of endocrine disrupting chemicals at home or in jobs such as cleaners, hairdressers and laboratory workers during pregnancy are more likely to have baby boys with a genital defect, according to a new study in the south of France.The study adds to mounting evidence that fetal exposure to chemicals that mimic people’s natural hormones may cause hypospadias, a condition where the opening of the urethra is on the underside of the penis rather than at the tip.

French researchers examined more than 600 children in the south of France and found that babies exposed to endocrine disrupting chemicals while their genitals were developing were more likely to suffer from hypospadias. Half the boys had hypospadias and half did not. The risk for those exposed was 68 percent higher than the unexposed boys. The researchers ruled out baby boys with known genetic risks for such defects.

The defect, which can be minor or quite severe depending on how far the opening is from the tip, can lead to problems with urination and, later in life, sexual difficulty....It is one of the most common genital defects in baby boys, and most cases require surgery, often done before they reach two years old. In the United States, an estimated five out of 1,000 boys are born annually with hypospadias, while Europe’s rate is slightly less than two out of 1,000.

The researchers estimated the unborn babies’ exposure by looking at their parents’ jobs and where they lived. Working with hormone disrupting chemicals and living in homes near heavy polluters were both linked to more baby boys having the defect. However, the researchers did say a limit of the study was attempting to estimate fetal exposure to such chemicals.Mothers were most likely to have boys with hypospadias if they worked as a cleaner, hairdresser or beautician.  

Some of the endocrine disrupting chemicals linked to the professions involved in the study were bisphenol-A (BPA), phthalates, polychlorinated compounds, alkylphenolic compounds and organic solvents. Most exposures—78 percent—occurred in the window of development when babies’ genitals are forming.... but detergents, pesticides, and cosmetics accounted for 75 percent of the cases,” the authors wrote in the study published in the European Urology journal this month.

Other possible causes of the birth defect include older, obese mothers, and fertility or hormone treatments during pregnancy, according to the U.S. Centers for Disease Control and Prevention.

This wasn’t the first time scientists have found a link between certain chemicals and hypospadias. Mothers in southeast England who were heavily exposed to endocrine disrupting phthalates on the job were about three times as likely to have a baby boy with hypospadias. Phthalates are used in some cosmetics, fragrances, food packaging and PVC plastics.

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Looks like another procedure is found not to be beneficial and possibly harmful - this time arthroscopic surgery as a treatment for the middle aged or older person with a painful arthritic knee or torn meniscus (the shock absorbing cartilage between the knee bones). The researchers also found that "exercise therapy" had more benefits. From Medical Xpress:

Benefit of knee surgery for middle aged or older patients 'inconsequential', say experts

The benefit of surgery for middle aged or older patients with persistent knee pain is inconsequential and such surgery is potentially harmful, say researchers in a study published in The BMJ this week.Their findings do not support arthroscopic surgery as a treatment for the middle aged or older person with a painful arthritic knee or torn meniscus (the shock absorbing cartilage between the knee bones).

The article is part of The BMJ's Too Much Medicine campaign - to highlight the threat to human health and the waste of resources caused by unnecessary care. Over 700,000 knee arthroscopies (a type of keyhole surgery) are carried out in the USA and 150,000 in the UK each year on middle aged and older adults with persistent knee pain. Yet the evidence for arthroscopic surgery is known to be weak, with all but one published trials showing no added benefit for surgery over control treatment.Despite this, many specialists are convinced of the benefits of surgery.

So researchers based in Denmark and Sweden reviewed the results of 18 studies on the benefits and harms of arthroscopic surgery compared with a variety of control treatments (ranging from placebo surgery to exercise) for middle aged and older people with persistent knee pain.s.

Overall, surgery was associated with a small but significant effect on pain at three and six months (but no longer) compared with control treatments. No significant benefit on physical function was found. A further nine studies reporting on harms found that, although rare, deep vein thrombosis (DVT) was the most frequently reported adverse event, followed by infection, pulmonary embolism (a blockage of the main artery of the lung), and death.

"Interventions that include arthroscopy are associated with a small benefit and with harms," say the authors, and the benefit is "markedly smaller than that seen from exercise therapy." These findings "do not support the practice of arthroscopic surgery as treatment for middle aged or older patients with knee pain with or without signs of osteoarthritis," they conclude.

"It is difficult to support or justify a procedure with the potential for serious harm, even if it is rare, when that procedure offers patients no more benefit than placebo," argues Professor Andy Carr from Oxford University in an accompanying editorial.

 

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Image result for dark chocolate My kind of study! Eating up to 100 grams of chocolate every day is linked to lowered heart disease and stroke risk. Not just dark chocolate, but milk chocolate also. Note that 100 grams of chocolate is equal to about 3.5 ounces chocolate.From Science Daily:

Chocolate for your heart

Eating up to 100 g of chocolate every day is linked to lowered heart disease and stroke risk. The calculations showed that compared with those who ate no chocolate higher intake was linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated death.

They base their findings on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of diet on the long term health of 25,000 men and women in Norfolk, England, using food frequency and lifestyle questionnaires.... were monitored for an average of almost 12 years, during which time 3013 (14%) people experienced either an episode of fatal or non-fatal coronary heart disease or stroke. Around one in five (20%) participants said they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with some eating up to 100 g.

Higher levels of consumption were associated with younger age and lower weight (BMI), waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular physical activity --all of which add up to a favourable cardiovascular disease risk profile.Eating more chocolate was also associated with higher energy intake and a diet containing more fat and carbs and less protein and alcohol.

And among the 16,000 people whose inflammatory protein (CRP) level had been measured, those eating the most chocolate seemed to have an 18% lower risk than those who ate the least.The highest chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking account of other potential risk factors.

Of nine relevant studies included in the systematic review, five studies each assessed coronary heart disease and stroke outcome, and they found a significantly lower risk of both conditions associated with regular chocolate consumption. And it was linked to a 25% lower risk of any episode of cardiovascular disease and a 45% lower risk of associated death.

This is an observational study so no definitive conclusions about cause and effect can be drawn. ...Nevertheless, they add: "Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events."And they point out that as milk chocolate, which is considered to be less 'healthy' than dark chocolate, was more frequently eaten by the EPIC-Norfolk participants, the beneficial health effects may extend to this type of chocolate too. 

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Could this be true? Eating fermented foods linked to fewer social anxiety symptoms? Fifteen years ago before the world of bacteria could be explored with state of the art genetic tests, this would have sounded too woo-woo. And now we say - could be. Next the researchers will test an experimental version of this study to see if they find causation. Right now all we can say they are linked or that we see an association.

But note that exercise also reduced social anxiety (this was also a finding in other studies). From Science Daily:

Decreased social anxiety among young adults who eat fermented foods

A possible connection between fermented foods, which contain probiotics, and social anxiety symptoms, is the focus of recent study...The researchers found that young adults who eat more fermented foods have fewer social anxiety symptoms, with the effect being greatest among those at genetic risk for social anxiety disorder as measured by neuroticism. "It is likely that the probiotics in the fermented foods are favorably changing the environment in the gut, and changes in the gut in turn influence social anxiety," said Hilimire. "I think that it is absolutely fascinating that the microorganisms in your gut can influence your mind."

The researchers designed a questionnaire that was included in a mass testing tool administered in the university's Introduction to Psychology courses during the fall 2014 semester; about 700 students participated. The questionnaire asked students about the fermented foods over the previous 30 days; it also asked about exercise frequency and the average consumption of fruits and vegetables so that the researchers could control for healthy habits outside of fermented food intake, said Hilimire.

"The main finding was that individuals who had consumed more fermented foods had reduced social anxiety but that was qualified by an interaction by neuroticism. What that means is that that relationship was strongest amongst people that were high in neuroticism," Hilimire said.The secondary finding was that more exercise was related to reduced social anxiety. 

"However, if we rely on the animal models that have come before us and the human experimental work that has come before us in other anxiety and depression studies, it does seem that there is a causative mechanism," said Hilimire. "Assuming similar findings in the experimental follow-up, what it would suggest is that you could augment more traditional therapies (like medications, psychotherapy or a combination of the two) with fermented foods -- dietary changes -- and exercise, as well."

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This latest study confirms the benefits of eating peanuts and nuts. The Netherlands Cohort Study has studied 120, 000 Dutch men and women since 1986, and they found that eating approximately 1/2 handful of peanut or nuts per day is linked to a lower risk of mortality. However, this beneficial effect did not apply to peanut butter, and they theorize that it may be due to the added ingredients in it (salt and vegetable oils that are trans fats) that negate the beneficial effects of nuts. And perhaps eating an all natural peanut butter would have the same beneficial effects as plain nuts.

Note: Since 2013 even the United States FDA has said that partially hydrogenated oils (they are artificially made through an industrial process and contain trans fats) are no longer "generally recognized as safe" because they are linked to heart disease. So in general avoid all products with "partially hydrogenated" in the ingredients. From Science Daily:

Nuts and peanuts -- but not peanut butter -- linked to lower mortality rates, study finds

A paper published in the International Journal of Epidemiology confirms a link between peanut and nut intake and lower mortality rates, but finds no protective effect for peanut butter. Men and women who eat at least 10 grams of nuts or peanuts per day have a lower risk of dying from several major causes of death than people who don't consume nuts or peanuts.

The reduction in mortality was strongest for respiratory disease, neurodegenerative disease, and diabetes, followed by cancer and cardiovascular diseases. The effects are equal in men and women. Peanuts show at least as strong reductions in mortality as tree nuts, but peanut butter is not associated with lower mortality, researchers from Maastricht University found. This study was carried out within the Netherlands Cohort Study, which has been running since 1986 among over 120,000 Dutch 55-69 year old men and women. 

The associations between nuts and peanut intake and cardiovascular death confirm earlier results from American and Asian studies that were often focused on cardiovascular diseases. However, in this new study, it was found that mortality due to cancer, diabetes, respiratory, and neurodegenerative diseases was also lowered among users of peanuts and nuts. Project leader and epidemiologist Professor Piet van den Brandt commented: "It was remarkable that substantially lower mortality was already observed at consumption levels of 15 grams of nuts or peanuts on average per day (half a handful). A higher intake was not associated with further reduction in mortality risk. This was also supported by a meta-analysis of previously published studies together with the Netherlands Cohort Study, in which cancer and respiratory mortality showed this same dose-response pattern."

Peanuts and tree nuts both contain various compounds such as monounsaturated and polyunsaturated fatty acids, various vitamins, fiber, antioxidants, and other bioactive compounds, that possibly contribute to the lower death rates. In contrast to peanuts, no association was found between peanut butter intake and mortality risk. However, besides peanuts, peanut butter contains also added components like salt and vegetable oils. In the past, it has been shown that peanut butter contains trans fatty acids and therefore the composition of peanut butter is different from peanuts. The adverse health effects of salt and trans fatty acids could inhibit the protective effects of peanuts.

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Two studies showing detrimental effects on children from pyrethroids in 2 weeks! The June 3 post was about research linking household pyrethroid exposure to ADHD in children and young teens. The second study found that low level childhood exposures to pyrethroid insecticides was linked to lower scores on an IQ test (Wechsler Intelligence Scale for Children - verbal comprehension and working memory) in 6 year old children. The researchers viewed this as evidence that pyrethroid insecticides may "negatively affect neurocognitive development".

Bottom line: even though pyrethroid pesticides are considered safer than many other pesticides, they still can have undesirable effects on humans, especially developing children. To be safe, use least toxic pest control that uses non-toxic, safe "alternative" or "natural" methods rather than just "spraying a chemical". Another possibility is looking for "organic pest control" or"least-toxic Integrated Pest Management" (IPM) that looks to deal with pest problems with non-toxic methods (which may include sealing holes, heat, caulking, trapping, using sticky traps, and even vacuuming up insects). From Science Daily:

Impact of insecticides on the cognitive development of 6-year-old children

Researchers have provided new evidence of neurotoxicity in humans from pyrethroid insecticides, which are found in a wide variety of products and uses. An increase in the urinary levels of two pyrethroid metabolites (3-PBA and cis-DBCA) in children is associated with a significant decrease in their cognitive performances , particularly verbal comprehension and working memory. This study was carried out on nearly 300 mother and child pairs from the PELAGIE cohort (Brittany).

Pyrethroids constitute a family of insecticides widely used in a variety of sectors: agriculture (various crops), veterinary (antiparasitics) and domestic (lice shampoo, mosquito products). Their mode of action involves blocking neurotransmission in insects, leading to paralysis. Because of their efficacy and relative safety for humans and mammals, they have replaced older compounds (organochlorides, organophosphates, carbamate) considered more toxic.

Exposure of children to pyrethroids is common. It is different to adult exposure, due to the closer proximity of children to ground-level dust (which stores pollutants), more frequent hand-to-mouth contact, lice shampoos, etc. In children, pyrethroids are mainly absorbed via the digestive system, but are also absorbed through the skin. They are rapidly metabolised in the liver, and mainly eliminated in the urine as metabolites within 48 hours.

Pregnancy is also an important period of life for the future health of the child. For this reason, the researchers studied the PELAGIE mother-child cohort established between 2002 and 2006, which monitors 3,500 mother-child pairs. This cohort simultaneously considers exposure to pyrethroid insecticides during fetal life and childhood. A total of 287 women, randomly selected from the PELAGIE cohort and contacted successfully on their child's sixth birthday, agreed to participate in this study.

Two psychologists visited them at home. One assessed the child's neurocognitive performances using the WISC scale (verbal comprehension index, VCI, and working memory index, WMI). The other psychologist characterised the family environment and stimuli that might have had a role on the child's intellectual development, collected a urine sample from the child, and collected dust samples. Exposure to pyrethroid insecticides was estimated by measuring levels of five metabolites (3-PBA, 4-F-3-PBA, cis-DCCA, trans-DCCA and cis-DBCA) in urine from the mother (collected between the 6th and 19th weeks of pregnancy) and from the child (collected on his/her 6th birthday).

Results show that an increase in children's urinary levels of two metabolites (3 PBA and cis-DBCA) was associated with a significant decrease in cognitive performances, whereas no association was observed for the other three metabolites (4-F-3-PBA, cis-DCCA and trans-DCCA). With respect to metabolite concentrations during pregnancy, there was no demonstrable association with neurocognitive scores.