DES and Psychiatric Disorders, Prescrire international, 2011
2011 Study Abstract
Between the 1950s and the late 1970s, millions of women worldwide took diethylstilbestrol (DES) during pregnancy. It was claimed that DES prevented miscarriage, even though a clinical trial was interrupted in 1953 when an interim analysis showed no beneficial effect in the prevention of miscarriage. In 1971, it emerged that DES exposure in utero was associated with somatic effects in adulthood, including female genital abnormalities with obstetric consequences, vaginal cancer, and male urogenital disorders.
This article examines the psychological effects of exposure to DES in utero, based on a review of the literature using the standard Prescrire methodology.
In two experimental studies, mice exposed to DES during gestation were found to be more aggressive than unexposed mice.
A randomised clinical trial and epidemiological studies have pointed to a risk of psychological disorders during adolescence and adulthood after DES exposure in utero.
A placebo-controlled randomised trial of DES was conducted in London in the 1950s but was never published.
In the 1980s, a research team recovered some of the original data and obtained information on the adult health status of the persons exposed in utero. Compared to the placebo group, psychological disorders were twice as frequent in the adults who were likely to have been exposed to DES in utero.
Three large epidemiological studies were also conducted.
One study showed that major depressive episodes were about 1.5 times more frequent in women exposed to DES in utero than in unexposed women;
the second showed that exposed women had an episode of major weight loss more often than unexposed women;
while the third showed no significant difference between the groups in terms of depressive episodes.
Smaller studies also suggest that depressive episodes tend to be more frequent after DES exposure in utero.
In practice, these data suggest that persons exposed to DES in utero have an increased risk of experiencing psychological disorders and should be monitored accordingly.
Sources and more information
Psychological consequences of DES exposure in utero, Prescrire international, NCBI PMID: 22066313, 2011 Nov.
Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years
2015 Study Abstract
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate).
In this report, we examine fetal AED exposure effects on adaptive and emotional/behavioral functioning at 6 years of age in 195 children (including three sets of twins) whose parent (in most cases, the mother) completed at least one of the rating scales.
Adjusted mean scores for the four AED groups were in the low average to average range for parent ratings of adaptive functioning on the Adaptive Behavior Assessment System-Second Edition (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning on the Behavior Assessment System for Children (BASC). However, children whose mothers took valproate during pregnancy had significantly lower General Adaptive Composite scores than the lamotrigine and phenytoin groups. Further, a significant dose-related performance decline in parental ratings of adaptive functioning was seen for both valproate and phenytoin. Children whose mothers took valproate were also rated by their parents as exhibiting significantly more atypical behaviors and inattention than those in the lamotrigine and phenytoin groups. Based upon BASC parent and teacher ratings of attention span and hyperactivity, children of mothers who took valproate during their pregnancy were at a significantly greater risk for a diagnosis of ADHD.
The increased likelihood of difficulty with adaptive functioning and ADHD with fetal valproate exposure should be communicated to women with epilepsy who require antiepileptic medication. Finally, additional research is needed to confirm these findings in larger prospective study samples, examine potential risks associated with other AEDs, better define the risks to the neonate that are associated with AEDs for treatment of seizures, and understand the underlying mechanisms of adverse AED effects on the immature brain.
Sources and more information
Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning at age 6 years, Epilepsy Behav. NIHMSID: NIHMS 539674, PMCID: PMC3902100, 2014 Nov 1.
Tumor patients exhibit an increased peripheral demand of fatty acids and protein. Contrarily, tumors utilize glucose as their main source of energy supply. Thus, a diet supplying the cancer patient with sufficient fat and protein for his demands while restricting the carbohydrates (CHO) tumors thrive on, could be a helpful strategy in improving the patients’ situation. A ketogenic diet (KD) fulfills these requirements. Therefore, we performed a pilot study to investigate the feasibility of a KD and its influence on the quality of life of patients with advanced metastatic tumors.
Sixteen patients with advanced metastatic tumors and no conventional therapeutic options participated in the study. The patients were instructed to follow a KD (less than 70 g CHO per day) with normal groceries and were provided with a supply of food additives to mix a protein/fat shake to simplify the 3-month intervention period. Quality of life [assessed by EORTC QLQ-C30 (version 2)], serum and general health parameters were determined at baseline, after every two weeks of follow-up, or after drop out. The effect of dietary change on metabolism was monitored daily by measuring urinary ketone bodies.
One patient did not tolerate the diet and dropped out within 3 days. Among those who tolerated the diet, two patients died early, one stopped after 2 weeks due to personal reasons, one felt unable to stick to the diet after 4 weeks, one stopped after 6 and two stopped after 7 and 8 weeks due to progress of the disease, one had to discontinue after 6 weeks to resume chemotherapy and five completed the 3 month intervention period. These five and the one who resumed chemotherapy after 6 weeks report an improved emotional functioning and less insomnia, while several other parameters of quality of life remained stable or worsened, reflecting their very advanced disease. Except for temporary constipation and fatigue, we found no severe adverse side effects, especially no changes in cholesterol or blood lipids.
These pilot data suggest that a KD is suitable for even advanced cancer patients. It has no severe side effects and might improve aspects of quality of life and blood parameters in some patients with advanced metastatic tumors.
Sources and more information
Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial, NCBI PMCID: PMC3157418, 2011 Jul 27.
PRENATAL EXPOSURE TO DIETHYLSTILBESTROL IN MALES AND GENDER-RELATED DISORDERS: RESULTS FROM A 5-YEAR STUDY
For many years, researchers and public health specialists have been assessing the human health impact of prenatal exposure to the estrogenic anti-miscarriage drug, diethylstilbestrol (commonly known as DES or “stilbestrol”). The scope of adverse effects in females exposed to DES (often called “DES daughters“) has been more substantially documented than the effects in males (“DES sons“).
This paper contributes three areas of important research on DES exposure in males:
an overview of published literature discussing the confirmed and suspected adverse effects of prenatal exposure in DES sons;
preliminary results from a 5-year online study of DES sons involving 500 individuals with confirmed (60% of sample) and suspected prenatal DES exposure;
documentation of the presence of gender identity disorders and male-to-female transsexualism reported by more than 100 participants in the study.
Sources and related posts
PRENATAL EXPOSURE TO DIETHYLSTILBESTROL (DES) IN MALES AND GENDER-RELATED DISORDERS: RESULTS FROM A 5-YEAR STUDY, shb-info, 8/09/2009.
Cancer drugs prices survey in high-income countries
2015 Study abstract
Cancer drugs challenge health-care systems because of their high prices. No cross-country price comparison of cancer drugs for a large number of countries has been published. We aimed to survey the prices of cancer drugs in high-income countries (Europe, Australia, and New Zealand).
Based on comparability in terms of the economic situation and of the pharmaceutical system, we surveyed official list prices per unit at ex-factory price level of 31 originator cancer drugs in 16 European countries, Australia, and New Zealand as of June, 2013. Drug price data for the European countries were provided by the Pharma Price Information (PPI) service; Australian and New Zealand drug price data were retrieved from the respective pharmaceutical schedules.
In Austria, Denmark, Finland, Germany, Italy, Norway, Sweden, and the UK, price information was available for all or all but one drug surveyed whereas the availability of price data was restricted for some drugs in other countries, especially in New Zealand and Portugal. The difference of a drug price between the highest priced country and the lowest priced country varied between 28% and 388%. A few drugs had lower outliers, especially Greek and UK prices, and upper outliers (particularly prices in Switzerland, Germany, and Sweden). Overall, Greek prices ranked at a low level, whereas Sweden, Switzerland, and Germany showed price data in similarly high ranges.
Our results showed variations in ex-factory prices of originator cancer drugs in the 18 surveyed countries. However, the surveyed prices do not include discounts negotiated by funding organisations because these discounts are confidential. Because pricing authorities can also only use these official undiscounted prices when they set prices through the common policy of external price referencing, they risk overpaying. Our findings provide an evidence base for policy makers to decide whether further policy measures related to drug prices are needed.
Effects of human exposure to hormone-disrupting chemicals examined in landmark UN report
An assessment of the state of the science of endocrine disruptors prepared by a group of experts for the United Nations Environment Programme (UNEP) and WHO
This document provides the global status of scientific knowledge on exposure to and effects of endocrine disrupting chemicals (EDCs).
The work is based on the fact that endocrine systems are very similar across vertebrate species and that endocrine effects manifest themselves independently of species. The effects are endocrine system related and not necessarily species dependent. Effects shown in wildlife or experimental animals may also occur in humans if they are exposed to EDCs at a vulnerable time and at concentrations leading to alterations of endocrine regulation. Of special concern are effects on early development of both humans and wildlife, as these effects are often irreversible and may not become evident until later in life. The third and final chapter of this document discusses exposure of humans and wildlife to EDCs and potential EDCs.
Pesticides as bad for kids’ lungs as cigarette smoke
2015 Study Abstract
Organophosphate pesticides are heavily used in agriculture, and adverse associations with respiratory health in occupational settings have been reported. However, most of the evidence comes from studies where there were no biomarkers of exposure and no objective outcome measurement. Non-occupational chronic effects among residents living in agricultural communities are less well described.
To evaluate associations between early-life organophosphate exposure and lung function of children living in an agricultural community.
Participants were 279 children from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal birth cohort. The area under the curve for organophosphate exposure was determined by urinary diethyl and dimethyl dialkylphosphate metabolites of organophosphate pesticides, which were measured five times during childhood (6–60 months). Spirometry was performed at age 7 years. Regression models controlled for maternal smoking during pregnancy, season of birth, particulate matter concentrations with aerodynamic diameter ≤2.5 μm (PM2.5), breast feeding duration, mould and pets at home, distance of home from a highway, food insecurity, maternal education, season of spirometry, sex, height and technician.
Childhood diethyl, dimethyl and total dialkylphosphate concentrations were associated with significant decreases in lung function at age 7. Specifically, we found lower FEV1, (L/s) (ß=−0.16, 95% CI −0.30 to −0.02, p=0.03) and FVC (L) (ß=−0.17, 95% CI −0.34 to 0.01, p=0.06) per 10-fold increase of total dialkylphosphate levels.
Early-life organophosphate exposure as assessed by dialkylphosphate concentrations was adversely associated with 7-year-old children’s lung function.
Weight gain between pregnancies linked to stillbirths and infant deaths
2015 Study Abstract
Maternal overweight and obesity are risk factors for stillbirth and infant mortality. Whether temporal changes in maternal weight affect these risks is not clear. We aimed to assess whether change of BMI between first and second pregnancies affects risks of stillbirth and infant mortality in the second-born offspring.
In a Swedish population-based cohort of women who gave birth to their first and second child between Jan 1, 1992, and Dec 31, 2012, we investigated associations between change in maternal body-mass index (BMI) during early pregnancy from first to second pregnancies and risks of stillbirth and neonatal, postneonatal, and infant mortality after the second pregnancy. Relative risks (RRs) for each outcome according to BMI change categories were calculated with binomial regression.
Complete information was available for 456 711 (77·7%) of 587 710 women who had their first and second single births in the study period. Compared with women with a stable BMI (change between −1 kg/m2 and
Our findings emphasise the need to prevent weight gain before pregnancy in healthy and overweight women and that weight loss should be promoted in overweight women.
Sources and more information
Weight change between successive pregnancies and risks of stillbirth and infant mortality: a nationwide cohort study,
theLancet, PIIS0140-6736(15)00990-3, 02 December 2015.
Weight gain between pregnancies linked to stillbirths and infant deaths, theGuardian, 2 December 2015.
Weight gain between pregnancies ‘linked to stillbirth’, NHS Choices, December 3 2015.