Prenatal and early postnatal exposure to perfluoroalkyl substances and bone mineral content and density in the Odense child cohort.

INTRODUCTION: Exposure to perfluoroalkyl substances (PFAS) has been associated with lower bone mineral density (BMD) in animal and human studies, but prospective data from children are limited. OBJECTIVES: To determine associations between prenatal and early postnatal PFAS exposure and BMD at age 7 years. METHODS: In the Odense Child Cohort, Denmark, pregnant women were recruited in 2010-2012, and their children were invited for subsequent health examinations. At 12 weeks of gestation the pregnant women delivered a serum sample, and at age 18 months serum was obtained from the child to measure perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) by LC-MS/MS. At age 7 years DXA scans were performed to measure bone mineral content (BMC) and BMD Z-score. PFAS in pregnancy (n = 924) and/or at age 18 months (n = 511) were regressed against DXA measurements, adjusted for maternal education, child height Z-score, sex (for BMC) and for postnatal exposure, additionally duration of total breastfeeding. We additionally performed structural equation models determining combined effects of pre-and postnatal PFAS exposures. RESULTS: Higher prenatal and early postnatal serum concentrations of all measured PFAS were associated with lower BMC and BMD Z-scores at age 7 years, all estimates were negative although not all significant. For each doubling of prenatal or 18-month exposure to PFDA, BMD Z-scores were lowered by -0.07 (95 % CI -0.10; -0.03) and -0.14 (-0.25; -0.03), respectively after adjustment. Pre- and postnatal PFAS were correlated, but structural equation models suggested that associations with BMD were stronger for 18-month than prenatal PFAS exposure. DISCUSSION: Bone density is established in childhood, and a reduction in BMD during early childhood may have long-term implication for peak bone mass and lifelong bone health. Future studies of the impact of PFAS exposure on fracture incidence will help elucidate the clinical relevance.

Effects of two physical education programmes on health- and skill-related physical fitness of Albanian children.

This study aims to evaluate the effectiveness of two school-based physical education (PE) programmes (exercise-based and games-based) compared with traditional PE, on health- and skill-related physical fitness components in children in Tirana, Albania. Participants were 378 first-grade (6.8 years) and 389 fourth-grade (9.8 years) children attending four randomly selected schools in Tirana. Twenty-four school classes within these schools were randomly selected (stratified by school and school grade) to participate as exercise group (EG), games group (GG) and control group (CG). Both EG and GG intervention programmes were taught by professional PE teachers using station/circuit teaching framework while CG referred to traditional PE school lessons by a general teacher. All programmes ran in parallel and lasted 5 months, having the same frequency (twice weekly) and duration (45 min). Heart rate (HR) monitoring showed that intensity during PE lessons was significantly higher in the intervention groups compared with control (P < 0.001). Both PE exercise- and games programmes significantly improved several health- and skill-related fitness indicators compared with traditional PE lessons (e.g. gross motor skill summary score: 9.4 (95% CI 7.9; 10.9) for exercise vs. control and 6.5 (95% CI 5.1; 8.1) for games vs. control, cardiorespiratory fitness: 2.0 ml O2 · min(-1) · kg(-1) (95% CI 1.5; 2.4) for exercise vs. control and 1.4 ml O2 · min(-1) · kg(-1) (95% CI 1.0; 1.8) for games vs. control). Furthermore, compared to games-based PE, exercise-based PE showed more positive changes in some gross motor coordination skills outcomes, coordination skills outcomes and cardiorespiratory fitness. The results from this study show that exercise- and games-based PE represents a useful strategy for improving health- and skill-related physical fitness in Albanian elementary school children. In addition, the study shows that exercise-based PE was more effective than games-based PE in improving gross motor function and cardiorespiratory fitness.

Examining the causal association of fasting glucose with blood pressure in healthy children and adolescents: a Mendelian randomization study employing common genetic variants of fasting glucose.

The aim of the study was to determine whether genetically raised fasting glucose (FG) levels are associated with blood pressure (BP) in healthy children and adolescents. We used 11 common genetic variants of FG discovered in genome-wide association studies (GWAS), including the rs560887 single-nucleotide polymorphism (SNP) located in the G6PC2 locus found to be robustly associated with FG in children and adolescents, as an instrument to associate FG with resting BP in 1506 children and adolescents from the European Youth Heart Study (EYHS). Rs560887 was associated with increased FG levels corresponding to an increase of 0.08 mmol l(-1) (P=2.4 × 10(-8)). FG was associated with BP, independent of other important determinants of BP in conventional multivariable analysis (systolic BP z-score: 0.32 s.d. per increase in mmol l(-1) (95% confidence interval (CI) 0.20-0.44, P=1.9 × 10(-7)), diastolic BP z-score: 0.13 s.d. per increase in mmol l(-1) (95% CI 0.04-0.21, P=3.2 × 10(-3)). This association was not supported by the Mendelian randomization approach, neither from instrumenting FG from all 11 variants nor from the rs560887, where non-significant associations of glucose with BP were observed. The results of this study could not support a causal association between FG and BP in healthy children and adolescents; however, it is possible that rs560887 has pleiotropic effects on unknown factors with a BP lowering effect or that these results were due to a lack of statistical power.

Associations between bicycling and carotid arterial stiffness in adolescents: The European Youth Hearts Study.

The aim of the study was to investigate the associations between bicycling and carotid arterial stiffness, independent of objectively measured moderate-and-vigorous physical activity. This cross-sectional study included 375 adolescents (age 15.7 ± 0.4 years) from the Danish site of the European Youth Heart Study. Total frequency of bicycle usage was assessed by self-report, and carotid arterial stiffness was assessed using B-mode ultrasound. After adjusting for pubertal status, body height, and objectively measured physical activity and other personal lifestyle and demographic factors, boys using their bicycle every day of the week displayed a higher carotid arterial compliance {standard beta 0.47 [95% confidence interval (CI) 0.07-0.87]} and distension [standard beta 0.38 (95% CI -0.04 to 0.81)]. Boys using their bicycle every day of the week furthermore displayed a lower Young's elastic modulus [standard beta -0.48 (95% CI -0.91 to -0.06)]. Similar trends were observed when investigating the association between commuter bicycling and carotid arterial stiffness. These associations were not observed in girls. Our observations suggest that increasing bicycling in adolescence may be beneficial to carotid arterial health among boys.

Prospective association of adiposity and cardiorespiratory fitness with cardiovascular risk factors in healthy children.

This study aimed to examine the prospective association of three different measures of adiposity and cardiorespiratory fitness (CRF) with 2-year change in cardiovascular disease (CVD) risk factors in children. Two-year longitudinal data in schoolchildren aged 7-11 years (n = 365-729) was used. Total body fat (TBF) from dual-energy x-ray absorptiometry, body mass index (BMI), waist circumference (WC), CRF, blood samples, and blood pressure were obtained in 2008 and 2010 in the Childhood Health, Activity, and Motor Performance School Study in Denmark (CHAMPS study-DK). Greater adiposity at baseline was associated with increased CVD risk factor levels at follow-up. The magnitudes of associations were similar regardless of adiposity measure [TBF%: ß 0.30, 95% confidence interval (CI): 0.21-0.39; BMI: ß 0.24, 95% CI: 0.14-0.33; WC: ß 0.20, 95% CI: 0.10-0.31], and no evidence of nonlinear relationships was observed. We found less strong associations of CRF with increase in CVD risk factor levels after adjusting for adiposity; however, increasing CRF was still favorably associated with decrease in CVD risk factor levels among boys. Results suggest that any effort to shift the population distribution of adiposity downward would be valuable for early CVD prevention. The association of CRF with CVD risk factors was largely explained by adiposity, particularly among girls.

Sugar-sweetened beverages consumption in relation to changes in body fatness over 6 and 12 years among 9-year-old children: the European Youth Heart Study.

BACKGROUND/OBJECTIVES: In parallel with the obesity epidemic, consumption of sugar-sweetened beverages (SSB) has risen over the same period. Our aim was to investigate associations between the consumption of SSB in childhood and adolescence with subsequent changes in body fatness in early adulthood. SUBJECTS/METHODS: A longitudinal study of 9-year-old children (n=283) enrolled in the Danish part of the European Youth Heart Study with a 6-year and 12-year follow-up. Data were collected at ages 9, 15 and 21 years. Multivariate regression analyses with adjustment for potential confounders were used to evaluate the effect of SSB consumption at 9 and 15 years and change in SSB consumption from 9-15 years on subsequent change in body fatness until 21 years. RESULTS: Subjects who consumed more than one serve of SSB daily at age 15 years had larger increases in body mass index (BMI) (ß=0.92, P=0.046) and waist circumference (WC) (ß=2.69, P=0.04) compared to non-consumers over the subsequent 6 years. In addition, subjects who increased their SSB consumption from age 9-15 years also had larger increases in BMI (ß=0.91, P=0.09) and WC (ß=2.72, P=0.04) from 15-21 years, compared to those who reported no change in consumption. No significant association was observed from 9-21 years. CONCLUSION: This study provides new evidence that SSB consumption in adolescence and changes in SSB consumption from childhood to adolescence are both significant predictors of change in body fatness later in early adulthood.

Physical activity intensity and subclinical atherosclerosis in Danish adolescents: the European Youth Heart Study.

The aim was to investigate the associations between physical activity (PA), cardiorespiratory fitness (CRF) and intima media thickness (IMT) or stiffness. This was a population-based cross-sectional study (n = 336) of Danish adolescents [mean age (standard deviation, SD): 15.6 (0.4) years]. PA intensity was assessed objectively (ActiGraph model GT3X) and CRF using a progressive maximal bicycle test. Carotid IMT and arterial stiffness were assessed using B-mode ultrasound. In a multivariate analysis (adjusted for pubertal development and smoking status), CRF was inversely associated with measures of carotid stiffness (standard beta: -0.20 to -0.15, P < 0.05) in boys, but not in girls. No associations were observed between any of PA and IMT. Boys in the least fit quartile had significantly stiffer carotid arteries compared to the most fit quartile (difference between lowest and highest quartile ranging between 0.4 and 0.5 SD, P < 0.05). This difference in arterial stiffness between low and high quartiles was similar for moderate-to-vigorous PA (MVPA). Further adjustment for sedentary time attenuated the difference observed between quartiles MVPA slightly. Adiposity did not attenuate these differences. Our observations suggest that increasing CRF or MVPA in the least active group of the population may be beneficial for vascular health.

Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.

BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based samples. DESIGN: Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods. RESULTS: We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (ß=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3). CONCLUSION: Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

Hemodynamic variables during exercise in childhood and resting systolic blood pressure levels 6 years later in adolescence: the European Youth Heart Study.

The aim of this study was to analyze whether systolic blood pressure (SBP), heart rate (HR) and rate pressure product (RPP) during exercise in childhood can predict resting SBP levels in adolescence independent of resting SBP and conventional cardiovascular risk factors. We studied this in a sample of Danish children followed longitudinally for 6 years. The study comprised 226 children randomly sampled at age 9, who had their blood pressure and HR measured during ergometer exercise to exhaustion and was reassessed in adolescence. SBP and RPP during exercise in stage two of the test were positively associated with future resting SBP, independent of resting SBP in childhood (P=0.045 and P=0.013, respectively). After additional adjustment for conventional cardiovascular risk factors the associations with SBP and RPP during stage two on future resting SBP only slightly materially change, although only RPP remained significant (P=0.059 and P=0.012, respectively). No significant independent associations were observed for HR during exercise, but associations were in the same direction. Our results supports that measuring SBP and RPP, during a standard acute ergometer exercise test in children, improves the prediction of future SBP levels during rest in adolescence independent of resting SBP and conventional cardiovascular risk factors.

Chronic otitis media sequelae in skeletal material from medieval Denmark.

OBJECTIVES: Chronic otitis media sequelae (COMS) have been identified in archaeological skeletal materials from various ages. COMS reflecting episodes of upper respiratory tract infection may be used as a paleopathological indicator of general health. Estimation of the frequency of COMS may be useful in the gross evaluation of general standard of living. MATERIALS AND METHODS: Temporal bones and auditory ossicles from 659 individuals from two Danish medieval rural parish cemeteries, dated to 1050-1200 and 1150-1350, respectively, were examined otomicroscopically. RESULTS: Osseous fistulae from mastoid abscesses, remodelling of the hypotympanon, and erosion of the incus were among the convincing indications of COMS. A minimum frequency of COMS of 1% to 7% was found. The youngest material displayed the highest frequency of pathological changes. CONCLUSION: Indications of a rising incidence of infectious middle ear disease in early medieval Denmark were found. This may reflect a deterioration of living conditions from the 11th through the 14th centuries.

Auditory ossicles in archaeological skeletal material from medieval Denmark.

Auditory ossicles were collected from two skeletal materials from early medieval Denmark. A total of 147 and 1,162 ossicles were obtained from the 2 materials, constituting 23% and 55% of the possible in vivo ossicles. The numbers and percentages found are among the highest reported from studies of archaeological skeletal material. Archaeological ossicles may be used in palaeopathological evaluation of chronic otitis media and otosclerosis, and morphometric studies of the ossicles might be valuable in analysis of population genetics and taxonomy.

Tympanoplasty with ionomeric cement.

Patients with isolated erosion of the long incus process suffer from severe hearing loss caused by lack of continuity of the ossicular chain. This study is a retrospective evaluation of the hearing results using two different surgical procedures. Since January 1993, 12 consecutive patients with isolated erosion of the long incus process have been treated with a new surgical technique in which the ossicular chain was rebuilt with ionomeric cement. The results in hearing performance (mean pure-tone average (PTA) 0.5, 1 and 2 kHz) were evaluated pre- and post-surgery, and compared to those in a group of 20 historical controls who underwent surgery in 1991 and 1992 using incus autograft interposition. Among the 12 index patients, 7 (58%) achieved improvement in PTA of > 10 dB, in 3 there was no difference and in 2 a slight decline. Among the 20 controls, 14 (70%) achieved improvement in PTA of > 10 dB, in 4 there was a slight improvement and in 2 a decline. The difference was not statistically significant. Hearing improvement using ionomeric cement in type II tympanoplasty was satisfactory. Reconstruction of the ossicular chain with ionomeric cement is recommended, as the procedure is easy to perform, presents less risk of damage to the stapes and cochlea, requires less extensive surgery and does not exclude other surgical methods in cases of reoperation.

Cochlear implantation and change in quality of life.

The aim of this study was to assess the benefits of cochlear implantation (CI) in adults and to evaluate the average implant usage per day. Ten profoundly deaf adults were implanted during the period April 1994 to September 1997. The patients answered questionnaires 1 year or more after receiving their cochlear implants. All of the patients used their implant daily. The average implant usage per day was 16 h. The patients stated that, given the choice, they would again opt for a cochlear implant and would recommend a cochlear implant for a deaf friend. A paired comparison showed that the implants led to significant improvements in a number of factors: self-perceived communication skills, frequency of conversation with others, telephone usage, self-confidence and the impact of hearing impairments on family life. CI dramatically changed the quality of life for all patients. No surgical complications were observed.

Complaints and satisfaction after uvulopalatopharyngoplasty.

A questionnaire administered 2 years after classical laser uvulopalatopharyngoplasty (UPPP) showed that 42% of 69 patients had complaints. Most of the complaints, however, were comparatively minor. The most frequent complaint was a tendency to nasal regurgitation (13%), although only two patients needed treatment. Other complaints were pharyngeal hypersecretion (10%), swallowing problems (9%) and speech disturbances (7%). Fourteen per cent of the 69 patients were not satisfied with the effect of the operation. In the group with complaints, 25% were dissatisfied with the result of the operation, whereas only 8% of those with no complaints were dissatisfied (p < 0.05). Continued snoring after UPPP was closely correlated to dissatisfaction with the general result (p < 0.01). It is very important to carry out follow-up after UPPP because complaints and dissatisfaction are common. Every effort should be made to reduce the tendency to nasal regurgitation. The results are relatively good and the procedure justified in cases of severe snoring and continuous positive airway pressure (CPAP)-resistant obstructive sleep apnoea (OSA). The severity and number of complaints were found to be acceptable in this difficult treatable entity.

pH monitoring in patients with benign voice disorders.

The aim of this study was to compare oesophageal pH-metry with laryngeal signs and symptoms in patients suspected of laryngeal reflux disease. A total of 60 patients with voice disorders, who were suspected of laryngeal reflux, were tested by single probe oesophageal pH monitoring. Thirty-two suffered from reflux laryngitis. A comparison of symptoms in patients with proven reflux to patients with no reflux was made. The symptoms were more frequent in the patients in the reflux group than in the non-reflux group. There was a significant difference between the groups with regard to dysphonia, sore throat, thick mucus and heartburn. Clinical signs appeared more frequently in the reflux group than in the non-reflux group. A significant difference was found between the groups regarding oedema of the vocal cords and hyperaemia and oedema of the posterior commisure, contact granuloma, posterior wall granulation and increased muscle tension. The patients in the reflux group were given medical treatment using omeprazole, and 76% logopedic voice training program. More than 50% of the laryngeal reflux patients were treated for more than 4 months before their voice problems had resolved. It is important to realize that signs of reflux laryngitis are not confined to the posterior commisure.

[Cochlear implantation in adults. Results and significance for communication and quality of life]. / Cochleaimplantationer hos voksne. Resultater og betydning for kommunikation og livskvalitet.

The aim of this study was to assess the benefits and complications from cochlear implantation and to evaluate the average implant usage per day. Ten profoundly deaf adults were implanted during the period April 1994 to September 1997. The patients answered questionnaires one year or more after receiving their cochlear implants. The average implant usage per day was 16 hours. The patients would again opt for a cochlear implant and would recommend a cochlear implant for a deaf friend. A paired comparison showed that the implants led to statistically significant improvement in a number of factors; self perceived communication skills, frequency of conversation with others, telephone usage, self-confidence, and the hearing impairment's impact on family life. No serious surgical complications were found.

[Subjective symptoms and sleep apnea among persons referred to a sleep center. A questionnaire survey]. / Subjektive gener og søvnapnø blandt personer henvist til et søvncenter. En spørgeskemaundersøgelse.

The aim of this study was to evaluate the relation between symptoms and clinical characteristics and the frequency of increased apnoea and hypopnoea activity. The study population consisted of 135 persons referred to a sleep centre. One hundred and fifteen patients (85%) completed a questionnaire and were subsequently monitored during one night's sleep. Fifty-two persons (45%) had an Apnoea Hypopnoea Index (AHI = the mean number of apnoea and hypopnoea episodes per hour of sleep) > or = 10. Forty-one (36%) had an Apnoea Index (AI = the mean number of apnoea per hour of sleep) > or = 10. Symptoms and clinical characteristics had no significant correlation to increased apnoea activity; however, there was a significant relationship between self-reported frequent breathing pauses during sleep and increased AHI and AI. Symptoms and clinical characteristics are not capable of identifying persons with increased apnoea activity.

[Mediastinoscopy in bronchogenic carcinoma]. / Mediastinoskopi ved bronkogent karcinom.

During recent years it has been discussed whether mediastinoscopy could be replaced or supplemented by other diagnostic procedures for detection of mediastinal lymph node metastases in patients with pulmonary cancer. The results of 289 mediastinoscopies were analyzed and correlated to thoracotomy in order to evaluate the procedure. Two hundred and six males and 83 females were included in the study. The mean age was 63 years for men and 58 years for women. Mediastinoscopy was positive (N2 disease) in 113 cases (39%) and negative in 176 cases. The 113 N2 patients were not operated upon. One hundred and seven patients (37%) had thoracotomy performed. 12% of these patients had metastases at the time of thoracotomy. Mediastinoscopy is still the most reliable method in selecting patients with bronchogenic carcinoma for thoracotomy. It is important to make a careful dissection during the mediastinoscopy at both tracheo-bronchial angles as well as at the subcarinal. Eleven percent of the metastatic lymph nodes were found only at the subcarinal or at the contralateral tracheo-bronchial angle. Sixteen (5.5%) of the 289 patients are still alive, with a follow up of more than six years. Only resected patients survived.

[Foreign body in the esophagus]. / Corpus alienum esophagi.

A ten year retrospective survey of 346 cases of oesophageal foreign bodies is reported. Although coins were the most frequent foreign bodies in the pediatry group, meat was the most common offender in the material taken as a whole. Rigid oesophagoscopy in general anaesthesia was performed on 312 patients. A foreign body was removed in 281 cases (90%). Only one case of oesophageal cancer was discovered. The risk of iatrogenic perforation of the oesophagus was greatest in old patients who had a lump of meat stuck in the distal third of the oesophagus.