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Ann-Dorthe Zwisler,1 Henriette Knold Rossau,1 Anne Nakano,2,3 Sussie Foghmar,4 Regina Eichhorst,5 Eva Prescott,6 Charlotte Cerqueira,7 Anne Merete Boas Soja,4 Gunnar H Gislason,8–10 Mogens Lytken Larsen,5 Ulla Overgaard Andersen,11 Ida Gustafsson,4 Kristian K Thomsen,12 Lene Boye Hansen,13 Signe Hammer,14 Lone Viggers,15 Bo Christensen,16 Birgitte Kvist,17 Cecilie Lindström Egholm,18 Ole May19 On behalf of the Working Group of Preventive Cardiology and Rehabilitation, Danish Society of Cardiology, and the Working Group of Cardiac Clinical Registries, Danish Society of Cardiology 1Danish Centre for Rehabilitation and Palliative Care, Odense University Hospital and University of Southern Denmark, Odense, 2Department of Clinical Epidemiology, Aarhus University Hospital, 3Registry Support Centre (West) – Clinical Quality Improvement & Health Informatics, Aarhus, 4Department of Cardiology, Copenhagen University Hospital, Hvidovre, 5Department of Cardiology, Aalborg University Hospital, Aalborg, 6Department of Cardiology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, 7Registry Support Centre (East) – Epidemiology and Biostatistics, Research Centre for Prevention and Health, the Capital Region of Denmark, Glostrup, 8Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, 9The Danish Heart Foundation, Copenhagen, 10The National Institute of Public Health, University of Southern Denmark, 11Department of Cardiology, Holbaek Hospital, University of Copenhagen, Copenhagen, 12Department of Cardiology, Hospital of Southwest Jutland, Esbjerg, 13Department of Cardiology, Gentofte Hospital, Gentofte, 14Department of Occupational Therapy and Physiotherapy, Herlev Hospital, Herlev, 15Department of Nutrition, Regional Hospital West Jutland, Holstebro, 16Department of General Medicine, School of Public Health, Aarhus University, Aarhus, 17Department of Health Care and Prevention, Municipality of Frederikshavn, Frederikshavn, 18The Regional Research Unit, Region Zealand, Roskilde, 19Department of Medicine, Cardiovascular Research Unit, Regional Hospital Herning, Herning, Denmark Aim of database: The Danish Cardiac Rehabilitation Database (DHRD) aims to improve the quality of cardiac rehabilitation (CR) to the benefit of patients with coronary heart disease (CHD).Study population: Hospitalized patients with CHD with stenosis on coronary angiography treated with percutaneous coronary intervention, coronary artery bypass grafting, or medication alone. Reporting is mandatory for all hospitals in Denmark delivering CR. The database was initially implemented in 2013 and was fully running from August 14, 2015, thus comprising data at a patient level from the latter date onward.Main variables: Patient-level data are registered by clinicians at the time of entry to CR directly into an online system with simultaneous linkage to other central patient registers. Follow-up data are entered after 6 months. The main variables collected are related to key outcome and performance indicators of CR: referral and adherence, lifestyle, patient-related outcome measures, risk factor control, and medication. Program-level online data are collected every third year.Descriptive data: Based on administrative data, approximately 14,000 patients with CHD are hospitalized at 35 hospitals annually, with 75% receiving one or more outpatient rehabilitation services by 2015. The database has not yet been running for a full year, which explains the use of approximations.Conclusion: The DHRD is an online, national quality improvement database on CR, aimed at patients with CHD. Mandatory registration of data at both patient level as well as program level is done on the database. DHRD aims to systematically monitor the quality of CR over time, in order to improve the quality of CR throughout Denmark to benefit patients. Keywords: secondary prevention, coronary heart disease, cardiovascular prevention, clinical quality registry, clinical database, quality improvement

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with reduced antibody response to childhood vaccinations. Previous studies have mostly focused on antibodies against diphtheria or tetanus, while fewer studies have assessed antibodies toward attenuated viruses, such as measles, mumps or rubella (MMR). Therefore, we set out to determine associations between prenatal and early postnatal PFAS exposure and vaccine-specific Immunoglobulin G (IgG) in the background-exposed Odense Child Cohort. Blood samples were drawn in pregnancy at gestation weeks 8-16 and from the offspring at age 18 months. In the maternal serum samples we quantified perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). In the offspring serum samples we quantified the same five PFAS compounds and IgG towards diphtheria, tetanus and MMR. A total of 880 and 841 children were included in the analyses of diphtheria and tetanus or MMR, respectively. Multiple linear regression models were used for estimation of difference in virus-specific IgG per doubling of PFAS concentrations. Maternal PFAS concentrations were non-significantly inversely associated with most vaccine-specific antibody concentrations. Likewise, child PFAS concentrations were associated with non-significant reductions of antibodies towards tetanus and MMR. A significant reduction in the percent difference in mumps antibody concentration per doubling of child PFNA (-9.2% (95% confidence interval: -17.4;-0.2)), PFHxS (-8.3% (-15.0;-1.0) and PFOS (-7.9% (-14.8;-0.4) was found. These findings are of public health concern, as inadequate response towards childhood vaccines may represent a more general immune dysfunction., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest. Philippe Grandjean has provided paid expert assistance in legal cases involving PFAS-exposed populations., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union's Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising 'real-life' chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children's development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.

Background: Perfluoroalkyl substances (PFAS) are endocrine disrupting chemicals with elimination half-lives ranging from four to eight years. Experimental studies found PFAS able to interfere with thyroid hormone-binding proteins. During the first 20 weeks of gestation (GW), the fetus is reliant on placental transfer of maternal thyroid hormones, mainly free thyroxine (FT4). However, previous studies investigating associations between exposure to PFAS and thyroid hormone status mainly focused on blood samples from late pregnancy or umbilical cord with mixed findings., Objectives: To investigate associations between serum-PFAS concentrations and thyroid hormone status in early pregnancy as reflected by FT4 and thyroid-stimulating hormone (TSH)., Methods: In the Odense Child Cohort, a single-center study, we measured maternal pregnancy serum concentrations of five PFAS: perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA); and FT4 and TSH in 1048 pregnant women at median GW 12 (25th, 75th percentile: 10, 15). Multivariate linear regression models were performed to estimate associations between PFAS exposure and thyroid hormone status., Results: A doubling in PFOS, PFOA, and PFNA concentrations was associated with an increment in FT4 concentration by 1.85% (95% CI: 0.66%, 3.05%), 1.29% (95% CI: 0.21%, 2.39%), and 1.70% (95% CI: 0.48%, 2.94%), respectively, in adjusted analyses. A statistically significant dose-response relationship was observed across exposure quartiles for PFOS, PFOA, and PFNA in the association with FT4. No association was found between concentrations of PFAS and TSH in adjusted analyses., Conclusion: Exposure to PFOS, PFOA, and PFNA was associated with higher FT4 concentrations in women during early pregnancy. The potential clinical implications of these findings remain to be clarified., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Bisphenol A (BPA) is frequently used in the production of plastics. It is an endocrine disruptor, and BPA exposure in mice has been associated with reduced offspring growth due to insufficient milk production. However, human studies of associations between BPA exposure and duration of breastfeeding are sparse., Methods: Pregnant women from the Odense Child Cohort (n = 725) donated a third trimester morning urine sample, which was analyzed for BPA by LC-MS/MS. Information about duration of exclusive and any breastfeeding was obtained through questionnaires three and 18 months postpartum, and a subgroup of women responded to weekly text messages about breastfeeding. Associations between pregnancy BPA exposure and duration of breastfeeding were analyzed using Cox regression adjusting for potential confounders., Results: The median urine BPA concentration was 1.29 ng/mL. Compared to women within the lowest tertile of BPA exposure, women in the second and third tertile were slightly more likely to terminate breastfeeding at any given time; HRs (95% CI) were 1.05 (0.87; 1.26) and 1.06 (0.89; 1.27), respectively, and to terminate exclusive breastfeeding at any time up to 20 weeks after birth, HRs (95% CI) were 1.07 (0.88; 1.28) and 1.06 (0.88; 1.27), respectively. However, confidence intervals were also compatible with no effect or even a protective effect., Discussion: This study indicated that high BPA exposure in pregnancy was associated with shorter duration of breastfeeding. Although our findings were not statistically significant, all estimates were above one suggesting increased risk of early breastfeeding termination with high exposure. Using a single spot morning urine sample to measure BPA has likely caused imprecision as it might not adequately reflect long term exposure. Future studies should consider measuring BPA more than once, including other timepoints during pregnancy and after birth., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neonatal jaundice (NNJ) is a major cause of preventable childhood mortality and long-term impairment especially in countries with significant prevalence of the inherited condition, glucose-6-phosphate dehydrogenase (G6PD) defect. In Ghana, routine screening of pregnant women for G6PD defect is standard care. Prevention of poor health outcomes from NNJ is contingent on population health literacy and early diagnosis. As part of a project to evaluate a screening tool for NNJ, we assessed the knowledge, attitude, and perceptions of Ghanaian mothers on NNJ at baseline., Methods: Using a cross-sectional design, mothers attending antenatal and postnatal clinics at 3 selected health facilities in 2 geographical regions of Ghana were interviewed. Data on mothers' understanding, perceptions, beliefs, and actions towards NNJ were evaluated. Chi-square test was used to determine the association between selected maternal characteristics and knowledge, attitude, and perception to NNJ., Results: Of the 504 mothers interviewed, 428(85.4%) had heard about NNJ, 346 (68.7%) said the earliest signs are seen in the eyes, 384(76.2%) knew NNJ may be harmful and 467(92.7%) recommended seeking healthcare for the jaundiced newborn. None of the women knew about G6PD or their G6PD status following antenatal screening. Most did not know the signs/symptoms of severe NNJ. Of the 15 mothers who had had a jaundiced neonate, cost was the most perceived (8 out of 15) barrier to accessing health care. There were significant associations (p-value ≤ 0.05) between maternal age, educational level, and knowledge of NNJ., Conclusion: Despite the high level of awareness of NNJ, gaps still exit in the knowledge, attitudes and perceptions of mothers concerning NNJ. Improving education of women about the causes, symptoms/signs, and the role of G6PD in severe NNJ is recommended. Addressing barriers to accessing healthcare for the jaundiced infant may enhance timely management of NNJ and reduce the associated complications and mortality., Competing Interests: The authors have declared that no competing interests exist.

Context: Human exposure to perfluoroalkyl substances (PFAS) has been associated with reduced duration of breastfeeding, although not consistently so, and mechanisms by which PFAS might affect breastfeeding are unknown., Objective: To examine the association between early pregnancy serum-PFAS concentrations and breastfeeding termination and to elucidate the potential role of serum-prolactin concentrations in pregnancy., Materials and Methods: Pregnant women from the Odense Child Cohort provided blood samples for analysis of 5 major PFAS (n = 1300) and prolactin concentrations (n = 924). They subsequently provided information about the duration of breastfeeding in questionnaires at 3 and 18 months postpartum, and a subgroup also provided breastfeeding information via weekly cell phone text messages. Associations between serum-PFAS concentrations and breastfeeding termination were analyzed using Cox regressions, while linear regression was used to assess associations between serum-PFAS and prolactin concentrations., Results: Increased serum concentrations of perfluorooctane sulfonic acid, perfluorooctanoic acid, perfluorononanoic acid, and ∑PFAS were associated with a 16% (95% CI: 4%-30%), 14% (95% CI: 2%-26%), 14% (95% CI: 3%-27%), and 20% (95% CI: 6%-36%), respectively, increased risk of terminating breastfeeding at any given time after childbirth. Serum-PFAS concentrations were not associated with serum-prolactin concentrations., Conclusions: These findings are of public health importance due to the global exposures to PFAS. Because breastfeeding is crucial to promote both child health and maternal health, adverse PFAS effects on the ability to breastfeed may have long-term health consequences., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: Parvovirus B19 has a marked tropism for erythroid progenitor cells and this may lead to chronic anemia in predisposed individuals. It was the purpose of the present study to investigate prospectively the frequency of parvovirus B19 infections in patients with a diagnosis of chronic anemia., Methods and Results: Evidence of parvovirus B19 infection was found in 13/43 (30%) patients by demonstrating viral DNA and/or specific IgM antibodies through the use of PCR and ELISA techniques. Parvovirus B19 infection was established in 4 of 7 patients with hemolytic anemia, in 2 of 3 patients with pure red cell aplasia, in 2 of 9 patients with myelodysplastic syndrome, and in 2 of 10 patients with aplastic anemia. In 8 of the 13 positive patients only parvovirus B19 DNA could be detected, while 4 patients tested positive for both parvovirus B19 DNA and specific IgM. In the remaining positive patient only specific IgM could be detected., Conclusions: Since no predictive paraclinical or clinical features were observed we recommend that all cases of chronic anemia be tested for the presence of parvovirus B19 infection. Due to the discrepancies between DNA and IgM results, the diagnostic procedures should include a search for specific DNA by PCR methods if specific IgM has been found to be negative.