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Background: Perfluoroalkyl adds are persistent compounds used in various industrial applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring. Objective: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans. Methods: A prospective cohort of 665 Danish pregnant women was recruited in 1988-1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and bio-markers of adiposity were quantified in a subset (n = 422) of participants. Results: After adjusting for covariates, including maternal prepregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m²) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m² (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years. Conclusions: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Among 83,389 mother-child pairs enrolled in the Danish National Birth Cohort during 1996-2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child's sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother's PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children.

The objective of the present study was to explore past and future primary health care use in preadolescents reporting frequent non-specific health complaints or a low self-rated health compared to that of preadolescents with no frequent health complaints or with good self-rated health. The study was conducted as a cohort study based within the Danish National Birth Cohort (1996–2002). Information on non-specific health complaints and self-rated health was obtained by an 11-year follow-up questionnaire. Information about number of general practitioner (GP) contacts was obtained from the Health Insurance Service Register. A total of 44,877 pre-adolescents gave complete exposure information. Pre-adolescents who reported frequent non-specific health complaints had a higher use of GP compared to pre-adolescents without complaints across the five years following the index date (somatic complaints: IRR = (1.46 [1.38; 1.55], mental complaints: IRR = 1.16 [1.12; 1.19], both complaints: IRR = 1.58 [1.47; 1.69]). The same pattern was found for the association between low self-rated health and number of GP contacts (IRR = 1.41 (1.36; 1.46)). Non-specific health complaints and a poor self-rated health in pre-adolescents was associated with a higher past and future use of GP, indicating a need for development of early interventions with help for symptom management.

BackgroundOphthalmic quality of life (OQoL) has been investigated in selected parts of general populations and in patients with ocular disease, but OQoL in unselected general populations has not been studied in detail. The present study reports OQoL obtained from a representative sample of the adult Danish population 2020–2022.MethodsThe FORSYN study invited 10 350 citizen representatives for the adult Danish population for a non-mydriatic eye examination and answer the National Eye Institute Visual Function Questionnaire with 39 items in the validated Danish translation. The results from the 3384 (32.7%) persons who participated in the study were weighted on the basis of relevant socio-economic factors, and data were projected to represent the total population. Binocular visual acuity was below 0.1 corresponding to legal blindness in 0.22% of this population.ResultsOQoL was positively correlated with binocular visual acuity up to better than 93 ETDRS letters, negatively correlated with age for persons younger than 60 years of age and again positively correlated with age for persons older than 60 years. OQoL was negatively correlated with increasing ametropia and refractive error above 1 dioptre and encompassed more OQoL parameters for hyperopic than for myopic persons.ConclusionsThe study underlines the benefits of improving visual acuity even within the normal range and of adjusting uncorrected refraction errors in the general population. OQoL is positively correlated with age in older persons independently of visual acuity, sex, refractive power and previous cataract surgery.

Participation in cervical cancer screening varies by socioeconomic status. The aims were to assess if offering human papilloma virus (HPV) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally. The study was based on registry data that were applied to data from a randomized controlled trial (n=9,791) measuring how offering HPV self-sampling affected screening participation. The women received either 1) a self-sampling kit mailed directly to their homes (directly mailed group); 2) an invitation to order the kit (opt-in group); or 3) a standard second reminder to attend regular cytology screening (control group). The participation data were linked to registries containing socioeconomic information. Women in the directly mailed group participated significantly more than women in the control group, regardless of their socioeconomic status, but the largest effects were observed in Western immigrants (participation difference [PD]=18.1%, 95% CI=10.2%-26.0%) and social welfare recipients (PD=15.2%, 95% CI=9.7%-20.6%). Compared with the control group, opt-in self-sampling only had an insignificant effect on participation among women who were immigrants, retired, or less educated. Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95% CI=10.2%-26.2% and PD=5.5%, 95% CI=2.9%-8.1%, respectively, =0.01). All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation, but Western immigrants and lower socioeconomic groups seemed to benefit the most. Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling. The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program. Current Controlled Trials NCT02680262. Registered February 10, 2016.

Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.

Out-of-hours (OOH) health care services are often divided into emergency medical services (EMS) and OOH primary care (OOH-PC). EMS and many OOH-PC use telephone triage, yet the patient still makes the initial choice of contacting a service and which service. Sociodemographic characteristics are associated with help-seeking. Yet, differences in characteristics for EMS and OOH-PC patients have not been investigated in any large-scale cohort studies. Such knowledge may contribute to organizing OOH services to match patient needs. Thus, in this study we aimed to explore which sociodemographic patient characteristics were associated with utilizing OOH health care and to explore which sociodemographic characteristics were associated with EMS or OOH-PC contact. A population-based observational cohort study of inhabitants in two regions (North Denmark Region and Capital Region of Copenhagen) with or without contact to OOH services during 2016 was conducted. Associations between sociodemographic characteristics and OOH contacts (and EMS versus OOH-PC contact) were evaluated by regression analyses. We identified 619,857 patients with OOH contact. Female sex (IRR=1.16 (95% CI: 1.16-1.17)), non-western ethnicity (IRR=1.02 (95% CI: 1.01-1.02)), living alone (IRR=1.08 (95% CI: 1.08-1.09)), age groups ≥81 years (IRR=2.00 (95% CI: 1.98-2.02)) and 0-18 years (IRR=1.66 (95% CI: 1.66-1.67)) and low income (IRR=1.41 (95% CI: 1.40-1.42)) were more likely to contact OOH health care compared to males, Danish ethnicity, citizens cohabitating, age 31-65 years and high income. Disability pensioners more often contacted OOH care (IRR=1.79 (95% CI: 1.77-1.81) compared to employees. Old age (≥81 years) (OR=3.21 (95% CI: 3.13-3.30)), receiving cash benefits (OR=2.45 (95% CI: 2.36-2.54)), low income (OR=1.76 (95% CI: 1.72-1.81)) and living alone (OR=1.40 (95% CI: 1.37-1.42)) were all associated with EMS contacts rather than OOH-PC contacts. Several sociodemographic factors were associated with contacting a health care service outside office hours and with contacting EMS rather than OOH-PC. Old age, low income, low education and low socioeconomic status were of greatest importance.

Spectacles and contact lenses are important for conducting a normal life in a large part of the general population. The purpose of this study was to estimate the use of these refractive aids in a normal adult population, and to identify characteristics of persons who should be targeted in order to improve uncorrected refraction. In the FORSYN study, 10,350 citizens representative for the adult Danish population were invited for a non-cycloplegic eye examination. The examination was completed in 3,384 persons, and the data were adjusted to represent the frequencies in the originally invited population on the basis of age, sex and socio-economic factors. The frequencies were projected to estimates of absolute numbers in the total adult Danish population. Refractive aids were used by 72.6%, 95% CI: 71.7-73.5% of the adult population. Distance correction was used by 55.7% (95% CI: 54.8-56.7%), contact lenses alone or alternating with spectacles by 11.2% (95% CI: 10.6-11.8%) and reading glasses by 18.8% (95% CI: 18.0-19.5%). Uncorrected refractive error resulted in a reduction in distance visual acuity of 2.99 ETDRS letters per diopter of hyperopia and of 10.3 ETDRS letters per diopter myopia ( p  < 0.0001 for both regressions). Uncorrected refractive error reduced distance visual acuity significantly in persons using single vision spectacle lenses and progressive addition spectacle lenses that had been prescribed more than 3 years previously. Refractive aids were used in approximately 72% of the population and should be checked when more than 3 years have passed since the last visit with a dispensing optometrist.

Growing evidence indicates that metabolic syndrome is rooted in fetal life with a potential key role of nutrition during pregnancy. The objective of the study was to assess the possible associations between the dietary glycemic index (GI) and glycemic load (GL) during pregnancy and biomarkers of the metabolic syndrome in young adult offspring. Dietary GI and GL were assessed by questionnaires and interviews in gestation week 30 and offspring were clinically examined at the age of 20 years. Analyses based on 428 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, pre-pregnancy body mass index (BMI), education, energy intake, and the offspring's ambient level of physical activity. In addition, possible confounding by gestational diabetes mellitus was taken into account. Waist circumference, blood pressure, HOMA insulin resistance (HOMA-IR) and plasma levels of fasting glucose, triglycerides, HDL cholesterol, LDL cholesterol, total cholesterol, insulin, and leptin were measured in the offspring. Significant associations were found between dietary GI in pregnancy and HOMA-IR (the relative increase in HOMA-IR per 10 units' GI increase was 1.09 [95% CI: 1.01, 1.16], p = 0.02), insulin (1.09 [95% CI: 1.02, 1.16], p = 0.01) and leptin (1.21 [95% CI: 1.06, 1.38], p = 0.01) in the offspring; whereas no associations were detected for GL. Our data suggests that high dietary GI in pregnancy may affect levels of markers for the metabolic syndrome in young adult offspring in a potentially harmful direction.

Background To reach non-participants, reluctant to undergo clinician-based cervical cancer screening and vaginal self-sampling, urine collection for high-risk human papillomavirus detection (hrHPV) may be valuable. Using two hrHPV DNA assays, we evaluated the concordance of hrHPV positivity in urine samples in comparison with vaginal self-samples and cervical cytology samples taken by the general practitioner (GP). We also studied women’s acceptance of urine collection and preferences towards the different sampling procedures. Methods One hundred fifty paired self-collected urine and vaginal samples and GP-collected cervical cytology samples were obtained from 30 to 59-year-old women diagnosed with ASC-US within the Danish cervical cancer screening program. After undergoing cervical cytology at the GP, the women collected first-void urine and vaginal samples at home and completed a questionnaire. Each sample was hrHPV DNA tested by the GENOMICA CLART® and COBAS® 4800 assays. Concordance in hrHPV detection between sample types was determined using Kappa ( k ) statistics. Sensitivity and specificity of hrHPV detection in urine was calculated using cervical sampling as reference. Results With the COBAS assay, urine showed good concordance to the vaginal ( k  = 0.66) self-samples and cervical samples ( k  = 0.66) for hrHPV detection. The corresponding concordance was moderate ( k  = 0.59 and k  = 0.47) using CLART. Compared to cervical sampling, urinary hrHPV detection had a sensitivity of 63.9% and a specificity of 96.5% using COBAS; compared with 51.6 and 92.4% for CLART. Invalid hrHPV test rates were 1.8% for COBAS and 26.9% for CLART. Urine collection was well-accepted and 42.3% of the women ranked it as the most preferred future screening procedure. Conclusions Urine collection provides a well-accepted screening option. With COBAS, higher concordance between urine and vaginal self-sampling and cervical sampling for hrHPV detection was found compared to CLART. Urinary hrHPV detection with COBAS is feasible, but its accuracy may need to be improved before urine collection at home can be offered to non-participants reluctant to both cervical sampling and vaginal self-sampling.