Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years--a prospective study

Background: In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5-9 years of age. Methods: Maternal sera from the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010-2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses. Results: In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (beta (95% CI) = 1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (beta (95% CI) = 0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties. Conclusions: Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children's neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest

Fetal programming of semen quality (Fepos) cohort – a dnbc male-offspring cohort

Background: Prenatal exposures may contribute to male infertility in adult life, but large-scale epidemiological evidence is still lacking. The Fetal Programming of Semen quality (FEPOS) cohort was founded to provide means to examine if fetal exposures can interfere with fetal reproductive development and ultimately lead to reduced semen quality and reproductive hormone imbalances in young adult men. Methods: Young adult men at least 18 years and 9 months of age born to women in the Danish National Birth Cohort living in relative proximity to Copenhagen or Aarhus and for whom a maternal blood sample and two maternal interviews during pregnancy were available were invited to FEPOS. Recruitment began in March 2017 and ended in December 2019. The participants answered a comprehensive questionnaire and underwent a physical examination where they delivered a semen, urine, and hair sample, measured their own testicular volume, and had blood drawn. Results: In total 21,623 sons fulfilled eligibility criteria of whom 5697 were invited and 1058 participated making the response rate 19%. Semen characteristics did not differ between sons from the Copenhagen and Aarhus clinics. When comparing the FEPOS semen parameters to similar cohorts, the median across all semen characteristics was slightly lower for FEPOS participants, although with smaller variation. Conclusion: With its 1058 young adult men, the FEPOS cohort is the largest population-based male-offspring cohort worldwide specifically designed to investigate prenatal determinants of semen quality. Wide-ranging information on maternal health, lifestyle, socioeconomic status, occupation, and serum concentrations of potential reproductive toxicants during pregnancy combined with biological markers of fertility in their sons collected after puberty allow for in-depth investigations of the ‘fetal origins of adult disease hypothesis’

The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders:a systematic review and meta-analysis

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders. OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism. SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data. OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91–1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure to one of the four compounds, p,p′-DDE, was related to an elevated risk: OR 1.35 (95% CI 1.04–1.74). The data did not indicate that this increased risk was driven by any specific disorder. WIDER IMPLICATIONS: The current epidemiological evidence is compatible with a small increased risk of male reproductive disorders following prenatal and postnatal exposure to some persistent environmental chemicals classified as endocrine disruptors but the evidence is limited. Future epidemiological studies may change the weight of the evidence in either direction. No evidence of distortion due to publication bias was found, but exposure–response relationships are not evident. There are insufficient data on rapidly metabolized endocrine disruptors and on specific exposure–outcome relations. A particular data gap is evident with respect to delayed effects on semen quality and testicular cancer. Although high quality epidemiological studies are still sparse, future systematic and transparent reviews may provide pieces of evidence contributing to the narrative and weight of the evidence assessments in the field

Reduction in the use of benzodiazepines and cyclopyrrolones in general practice

In 2003, the Danish Minister for the Interior and Health instructed general practitioners to reduce prescriptions of benzodiazepines (BZD) and cyclopyrrolones (CP) by 50%. However, no effective methods were specified. In Denmark, it is estimated that there are approximately 100,000 BZD-dependent patients, constituting approximately 2% of the population. OBJECTIVE: This article describes the implementation of a successful, simple and voluntary intervention to reduce the use of dependence-inducing drugs, while at the same time challenging practitioners’ ingrained habits and prejudices in this field. METHODS: The rules implemented were essentially in accordance with the official Danish rules, such that a prescription for BZD and CP could only be issued for one month at a time, and only following consultation. Use was monitored using the Danish registration system, Ordiprax, which monitors sales of prescription medicine. Two Danish general practices, comprising a patient base of approximately 2300 were studied. With the exception of the severely physically or mentally ill, all users of BZD and CP were included. RESULTS: After 2½ years, the use of BZD and CP was reduced by 75% and 90%, respectively. The reorganization of prescription patterns was seen to be significantly easier than physicians had expected. During the first three months, only four to five additional visits per week per 1000 patients were required. Subsequently, this number was stabilized at one to two additional visits. The usual collaborative partners, such as psychiatrists, homecare services, hospitals and substance abuse units were essentially not deployed. No serious withdrawal effects arose. CONCLUSION: The implementation of the aforementioned simple procedures is to be recommended for the prescription of BZD and CP drugs, as the effect is immediate and easily attainable, with a reasonable work input required on the part of general practitioners

The ups and downs of lifestyle modification : An existential journey among persons with severe obesity

Background: Maintaining a healthy living after the end of a lifestyle intervention is a challenge for persons with severe obesity. Measurable outcomes are often emphasised, but there is a need for understanding the process of lifestyle change and the long-term perspectives among persons with severe obesity. Aim and objective: To describe and deepen the understanding of how persons with severe obesity experience making and maintaining lifestyle changes in everyday life three years after lifestyle intervention. Methodology and methods: The study used a hermeneutic phenomenological approach. A purposive sample of seven adults with BMI ≥ 40 was recruited from a lifestyle intervention programme. Data were generated through individual follow-up interviews. The analysis was based on theoretical framework on dwelling and mobility. Ethical approvals were received from the Danish Data Protection Agency and the ethical principles of the Declaration of Helsinki were followed. Results: One overarching theme emerged: ‘The journey of ups and downs’. Three sub-themes were: ‘Living with and tackling the demands of life's hassles’, ‘Deliberating the fight for weight loss’ and ‘Needing a trusted person to feel met as a human being’. Conclusions: Everyday life among persons with severe obesity is experienced as a dynamic process of shifting experiences of dwelling and mobility. Sustained lifestyle changes require ongoing adjustments of action, which healthcare providers can influence in ways that either support or obstruct. Collaboration and a humanised approach across disciplines and sectors are suggested to promote sustained healthy living

Reducing the use of benzodiazepines and cyclopyrrolones in clinical practice

Objective: Recently, the use of benzodiazepines (BZD) and cyclopyrrolones (CP) has drawn a great deal of attention. About 100,000 patients - approximately 2% of the Danish population - are believed to be addicted to BZD. This article describes a simple and effective method of reducing the use of dependency-producing drugs in clinical practice.Methods: Design: Local rules were implemented according to Danish directive CIR nr 12 13/01/2003 regarding addictive drugs. Prescriptions for BZD and CP were only issued on a monthly basis, and only following personal consultation. This monthly requirement forced the physician as well as the patient to evaluate whether the existing prescription pattern was indicated, or whether a drug-reducing regime should be introduced. The prescription pattern was monitored using the Ordiprax System (Institute for Rational Pharmacotherapy, IRF), which records pharmacy's sales of prescription drugs as prescribed by clinical practices. Two individual clinics in Thyborøn - Harboøre Community, covering some 2300 patients, were surveyed. All patients using BZD or CP were included in this study, with the exception of patients suffering from serious psychiatric or physical disorders.Results:  After 15 months, the use of BZD and CP was reduced by 50% and 75%, respectively. The process of changing prescription habits was far easier than expected. A whole group of patients, initially invisible to the physician, was exposed. During the first three months, as few as 4-5 additional consultations for every 1000 patients was required. There was essentially no need for assistance from our usual partners, including psychiatrists, hospitals, specialist units for addictive treatment.Conclusion: We strongly recommend that these simple procedures be incorporated into daily routine when prescribing either a BD or a CP