Telephone follow-up as a substitute for standard out-clinic follow-up in CPAP therapy for obstructive sleep apnea patients: a randomized controlled trial.

PURPOSE: This study assessed the feasibility of telephone follow-up consultations (TC) using an online data sharing and editing function (Airview™), as alternative to standard out-clinic follow-up consultations (SC) on adherence to continuous positive airway pressure (CPAP) in obstructive sleep apnea (OSA) patients. Furthermore, we investigated compliance to follow-up consultations and examined potential influencing factors, including baseline AHI (apnea-hypopnea-index), age, and distance from home to the hospital on consultation compliance. METHODS: Two hundred OSA patients, with AHI ≥ 5 were randomly assigned (1:1) to receive TC or SC with follow-up after one month and 12 month of CPAP initiation. Adherence goal was defined as achieving ≥ 4 h of CPAP use daily in 70% of the days in a 365-days period. RESULTS: The proportion of participants achieving CPAP adherence was non-significantly lower in the TC group compared to the SC group (TC: 30% versus SC: 36%, adjusted OR 0.84, p = 0.59). Of participants who completed the study, the TC group had a significant average of 107 min less use of CPAP compared to the SC group (p = 0.048). However, a higher proportion of participants was compliant to consultations in the TC group. The only influencing factor found was increasing baseline AHI, which might be a predictor for compliance to consultations and adherence to CPAP therapy. CONCLUSION: TC might serve as substitute for SC in some part of the OSA population. If TC becomes a part of CPAP therapy management, it is important to consider patient characteristics and treatment-related issues to prevent decline in adherence.

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.

BACKGROUND: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression. METHODS: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites. FINDINGS: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2). INTERPRETATION: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications. FUNDING: Funding acknowledgements for each cohort can be found in the Supplementary Note.

Ocular and systemic associations and heritability of retinal arterial wall-to-lumen ratios in a twin cohort.

PURPOSE: To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and environmental variation to WLR in healthy adults. METHODS: This cross-sectional twin study included 78 monozygotic and 67 dizygotic same-sex twin pairs aged 58.4 ± 9.8 (mean ± SD) years. Lumen diameter (LD) and outer diameter (OD) of a superotemporal retinal artery were measured using adaptive optics fundus photography, and the WLR was calculated. Linear mixed model regression analysis of associations with WLR comprised the descriptive variables ocular axial length (AL), intraocular pressure (IOP), height, weight, body mass index (BMI), smoking, blood pressure, high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins, total cholesterol and triglycerides. The relative influence of genes and environment on WLR was calculated through polygenetic modelling. RESULTS: Increasing age and arterial blood pressure were associated with a higher WLR, while increasing retinal artery OD and ocular AL were associated with a lower WLR. Sex, smoking status, BMI, IOP, cholesterol levels or triglycerides had no detectable impact on the WLR. Broad-sense heritability of WLR was 21% (95% CI: 1-41%), while environmental factors accounted for the remaining 79% of the interindividual variance (95% CI: 59-99%). CONCLUSION: Retinal artery wall thickness was closely linked to increasing age and higher arterial blood pressure, the latter being mediated by the environment over genes.

Predictors of serum- per- and polyfluoroalkyl substance (PFAS) concentrations among infants in Guinea-Bissau, West Africa.

BACKGROUND: Knowledge about PFAS exposure in Africa is limited. We have previously detected six types of PFAS in the serum of infants from Guinea-Bissau, West Africa. The aim of this study was to identify predictors of the infant serum-PFAS concentrations. METHODS: This cross-sectional study was based on a subset of data from a randomized controlled trial of early measles vaccination performed in 2012-2015 in three rural regions of Guinea-Bissau. Blood samples were obtained from 237 children aged 4-to-7 months, and six types of PFAS were quantified in serum. Location of residence was recorded, and information about predictors related to socioeconomic status as well as maternal and child characteristics were obtained through structured interviews with the mothers through routine surveillance. Associations between potential predictors and infant serum-PFAS concentrations were examined in linear regression models while adjusting for potential confounding and mediating factors as identified in a directed acyclic graph. RESULTS: Infants from the Cacheu region had the lowest concentrations of perfluorooctanoic acid (PFOA), while infants from the Oio region had the lowest concentrations of all other PFAS. Compared to infants from Oio, infant serum-perfluorooctane sulfonic acid (PFOS) concentrations were 94.1% (95% CI: 52.4, 147.1%) and 81.9% (95% CI: 45.7, 127.1%) higher in Cacheu and Biombo, respectively. Higher maternal age and lower parity were associated with slightly higher child-serum perfluorohexane sulfonic acid (PFHxS) concentrations, while infants with higher socioeconomic status and infants breastfed without supplementary solid foods at inclusion had higher average concentrations of most PFAS, although the confidence intervals were wide and overlapped zero. DISCUSSION: Location of residence was the most important determinant of serum-PFAS concentrations among Guinea-Bissau infants, indicating a potential role of diet as affected by the global spread of PFAS, but future studies should explore reasons for the regional differences in PFAS exposure.

Small hard drusen and associated factors in early seniority.

PURPOSE: The purpose of this study was to examine the ocular and systemic risk profile of the fundus phenotype ≥ 20 small hard (macular) drusen (< 63 µm in diameter). METHODS: This single-center, cross-sectional study of 176 same-sex twin pairs aged 30 to 80 (median 60) years was a component of a framework study of the transition from not having age-related macular degeneration to having early AMD. Drusen categories assessed using fundus photography and optical coherence tomography included small hard drusen (diameter < 63 µm), intermediate soft drusen (63-125 µm), and large soft drusen (> 125 µm), of which the soft drusen are compatible with a diagnosis of AMD. RESULTS: Having ≥ 20 small hard drusen within or outside the macula was associated with increasing age, lower body mass index, shorter axial length, hyperopia, female sex, increasing high-density lipoprotein (HDL), high alcohol consumption, and with the presence of soft drusen. CONCLUSIONS: Having ≥ 20 small hard drusen was associated with some AMD-related risk factors, but not with smoking, increasing body mass index, and higher blood pressure. Having ≥ 20 small hard drusen was also associated with soft drusen, in agreement with previous studies. These findings suggest that small hard drusen are not an early manifestation of AMD but the product of a distinct process of tissue alteration that promotes the development of AMD or some subtype thereof.

Heritability and Risk Factors of Incident Small and Large Drusen in the Copenhagen Twin Cohort Eye Study: A 20-Year Follow-Up.

INTRODUCTION: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 µm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. METHODS: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 µm, or (4) ≥20 small hard drusen combined with drusen ≥63 µm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects. RESULTS: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 µm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 µm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 µm at follow-up (p = 0.02). Development of drusen ≥63 µm was attributable to 49% genetic effects and 51% environmental effects. CONCLUSION: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 µm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 µm at baseline was associated with incident drusen ≥63 µm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.

Dietary patterns and survival to 100 + years: an empty systematic review of cohort and case-control studies.

BACKGROUND: Centenarians are used as a model of healthy ageing and longevity. Diet is a factor known to affect mortality in middle aged adults and elderly. However, it is unknown whether diet has an impact on survival to 100 + years. The aims of this systematic review were to summarize the evidence on (i) the association between dietary patterns in late adult life and survival to 100 + years and (ii) the common characteristics across dietary patterns that are shown to be positively associated with survival to 100 + years. METHODS: We performed a systematic literature search in MEDLINE and EMBASE, and a hand search at four longevity projects homepages up to 4 June 2021. We searched for cohort and case-control studies investigating the association between dietary patterns and all-cause mortality among individuals aged ≥ 65 years at enrolment regardless of their health status and residence. Studies were excluded if follow-up was performed too soon to allow the population or a subgroup of it to have become 100 + years of age. RESULTS: Of 3,685 identified records 108 reports were retrieved and full text screened. No studies met our inclusion criteria, thus the review process resulted in no eligible studies found. Hence, no risk of bias assessment and no synthesis of data was performed. CONCLUSIONS: No studies have investigated dietary patterns in late adult life in relation to survival to 100 + years of age. We have observed that as of June 2021 published cohort studies exist investigating all-cause mortality risk from different dietary patterns among the oldest old, but follow-up has been performed before the cohort could have reached 100 years of age. However, cohorts do exist where data on dietary habits in adult life has been collected decades ago and where follow-up in 2022 will allow the participants to have become 100 + years old. REGISTRATION: The review protocol is published at University of Southern Denmark's Research Portal (Poulsen et al. Dietary Patterns and Survival to 100 + Years: Protocol for a Systematic Review of cohort and case-control studies University of Southern Denmark's Research Portal: University of Southern Denmark, 2021) available at  https://portal.findresearcher.sdu.dk/en/publications/kostm%C3%B8nstre-og-overlevelse-til-100-%C3%A5r-protokol-for-en-systematisk . We have specified aim (i) of our research question in this report compared to the protocol, by adding "late" to "adult life".

Vitamin D status and tooth enamel hypomineralization are not associated in 4-y-old children: An Odense Child Cohort study.

Early fetal stages of tooth development are vitamin D-dependent, suggesting an impact of vitamin D status in pregnancy on tooth mineralization in human populations. We examined the association between pregnancy and cord serum 25-hydroxyvitamin D (s-25(OH)D) and hypomineralization of the second primary molars (HSPM) in the 4-year-old children in the prospective, population-based Odense Child Cohort, Denmark. S-25(OH)D was measured in early pregnancy (<20 weeks, n = 753); late pregnancy (≥20 weeks, n = 841); and in umbilical cord blood (n = 1,241) using liquid chromatography-tandem mass spectrometry. HSPM was scored using modified European Academy of Paediatric Dentistry judgment criteria. The median [Q1;Q3] s-25(OH)D was 65.0 [49.4;78.0], 79.2 [60.4;95.8], and 45.1 [31.2;60.5] nmol/L in early pregnancy, late pregnancy, and cord blood, respectively. The prevalence of HSPM was 54.7%; creamy/white demarcated opacities 79.5%; yellowish/brownish demarcated opacities 14.9%; post-eruptive breakdown 5.2%; atypical restoration 0.4%. No univariate or adjusted associations with HSPM were detected for pregnancy or cord s-25(OH)D as a continuous variable or categorized into quartiles or routine clinical cut-offs, or when classifying HSPM by severity. In exploratory multiple regression analysis, HSPM was inversely associated with the length of gestation, adjusted odds ratio (aOR) 0.82 (95% C.I 0.74-0.92, p < 0.001), and directly associated with maternal education, aOR 1.57 (95% C.I 1.18-2.08, p = 0.002). In a population with relatively high s-25(OH)D concentrations and generally healthy mothers and children, pregnancy and cord blood vitamin D status was not associated with HSPM. The associations between HSPM and shorter gestational length and higher maternal education warrant further study.

Early pregnancy vitamin D status is associated with blood pressure in children: an Odense Child Cohort study.

BACKGROUND: Blood pressure in childhood tracks into later life. Vitamin D status in adults is associated with blood pressure, but the impact of vitamin D status in pregnancy and childhood on blood pressure still needs investigation. OBJECTIVE: We investigated whether fetal rather than current vitamin D status is associated with blood pressure in children. METHODS: In a prospective observational study within the population-based Odense Child Cohort (OCC), we examined serum 25-hydroxyvitamin D2+3 [s-25(OH)D] in early and late pregnancy, cord blood, and at 5 y age, and the associations with systolic and diastolic blood pressure (SBP/DBP) in the 5-y-old children (n = 1,677). Multiple regression models were adjusted for maternal country of origin, parity, smoking during pregnancy, 5-y height, and weight. Two-stage mixed effect modeling was performed, integrating all s-25(OH)D data from pregnancy and cord blood. RESULTS: The median (IQR) s-25(OH)D in early pregnancy, late pregnancy, the umbilical cord, and at 5 y was 65.5 (50.7-78.5), 78.5 (60.3- 95.8), 45.4 (31.1- 60.7), and 71.9 (54.6- 86.5) nmol/L, respectively. The mean ±SD 5-y SBP/DBP was 101.0/63.8 (7.1/5.9) mmHg. In adjusted analyses, a 10 nmol/L increase of s-25(OH)D in early pregnancy associated with a 0.3/0.2 mmHg lower SBP/DBP at 5 y (P < 0.05). Optimal s-25(OH)D (>75 nmol/L) in early pregnancy was associated with lower 5-y SBP and DBP, ß (95% CI) -1.45 (-2.6, -0.3), and -0.97 (-1.9, -0.1), compared with reference s-25(OH)D (50-74.9 nmol/L). Two-stage analysis combining early pregnancy, late pregnancy, and cord s-25(OH)D data showed an inverse association with 5-y SBP and DBP for boys (P < 0.025) with significant sex-difference for DBP (Pinteraction = 0.004). No associations were found between s-25(OH)D and 5-y BP above the 90th percentile. CONCLUSION: Early pregnancy s-25(OH)D concentrations, especially >75 nmol/L, were inversely associated with 5-y blood pressure in the offspring. A novel identified protective effect of optimal vitamin D levels in early pregnancy on offspring BP is suggested.

Heritability of retinal drusen in the Copenhagen Twin Cohort Eye Study.

PURPOSE: To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort. METHODS: This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location. RESULTS: The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 µm), ≥20 small hard extramacular drusen, intermediate drusen (63-125 µm) anywhere, and large drusen (>125 µm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier. CONCLUSION: Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.

Maternal Testosterone Concentrations in Third Trimester and Offspring Handgrip Strength at 5 Years: Odense Child Cohort.

BACKGROUND: Maternal testosterone in pregnancy may have conditioning effects on offspring muscle strength. PURPOSE: To investigate possible associations between maternal testosterone concentrations in third trimester and offspring handgrip strength (HGS) at 5 years. METHODS: In the prospective, population-based Odense Child Cohort, total testosterone (TT) at gestational week 27-28 and 5-year HGS were measured in 1017 mother-child pairs. TT was measured by liquid chromatography-tandem mass spectrometry and free testosterone (FT) was calculated from TT and sex hormone-binding globulin (SHBG). Multivariable regression analyses were performed with HGS < 10th percentile as cutoff for low HGS. RESULTS: Third-trimester FT concentration was 0.004 (0.002-0.007) nmol/L, geometric mean (mean - SD; mean + SD). The mean (SD) 5-year HGS was 8.7 (1.8) kg in boys and 8.1 (1.7) kg in girls (P < 0.001). Higher FT concentrations were associated with lower HGS (ß = -0.186, P = 0.048), after adjustment for maternal age, parity, offspring sex, and 5-year height and weight. FT > 0.004 nmol/L was associated with higher risk of 5-year HGS < 10th percentile with odds ratios (95% CI) of 1.58 (1.01, 2.47; P = 0.047; n = 1,017) and 1.69 (1.05, 2.74; P = 0.032) after further adjustment for children's organized sports in subgroup analysis (n = 848). Lower HGS in relation to higher FT concentrations was found in all linear models but was not always statistically significant. HGS was not associated with maternal TT and SHBG levels. CONCLUSION: Third trimester FT was inversely associated with offspring muscle strength assessed by HGS at 5 years of age, which may suggest a negative effect of maternal FT on offspring muscle strength.

Disentangling the relationship between bone turnover and glucose homeostasis: A prospective, population-based twin study.

BACKGROUND: Biochemical markers of bone turnover are lower in patients with type 2 diabetes, which may be explained by genetic variants being associated with type 2 diabetes and bone turnover as well as environmental factors. We hypothesized that bone turnover markers associate with and predict changes in glucose homeostasis after control for genetics and shared environment. METHODS: 1071 healthy, non-diabetic (at baseline, 1997-2000) adult mono- and dizygotic twins participating in the prospective study GEMINAKAR were reassessed between 2010 and 2012 with clinical evaluation, biochemical tests and oral glucose tolerance test. Fasting bone turnover markers (CTX, P1NP and osteocalcin) were measured. The association between bone turnover, glucose homeostasis and the ability of bone turnover markers to predict changes in glucose homeostasis were assessed in cross-sectional and longitudinal analyses. Analyses were performed both at an individual level and adjusted for shared environmental and genetic factors. RESULTS: Glucose levels increased with age, and 33 (3%) participants had developed type 2 diabetes at follow-up. In women, bone turnover markers increased with age, whereas for men only osteocalcin increased with age. Bone turnover markers were not associated with fasting glucose, insulin, or HOMA-IR at baseline or follow-up before or after adjustment for age, sex, BMI, smoking, and use of medication at baseline. Variation in bone turnover markers was mainly explained by unique environmental factors, 70%, 70% and 55% for CTX, P1NP and osteocalcin, respectively, whereas additive genetic factors explained 7%, 13% and 45% of the variation in CTX, P1NP and osteocalcin. CONCLUSIONS: Bone turnover markers were not associated with baseline plasma glucose levels and did not predict changes in glucose homeostasis. Variation in bone turnover markers is mainly explained by environmental factors, however, compared to CTX and P1NP, genetic factors have a larger impact on osteocalcin levels.

Increased serum SP-D in identification of high-risk smokers at high risk of COPD.

Pulmonary surfactant protein D (SP-D) is an important component of the pulmonary innate immune system with the ability to dampen cigarette smoke-induced lung inflammation. However, cigarette smoking mediates translocation of SP-D from the lung to the blood, and serum SP-D (sSP-D) has therefore previously been suggested as marker for smoke-induced lung injury. In support of this notion, associations between high sSP-D and low lung function measurements have previously been demonstrated in smokers and in chronic obstructive lung disease (COPD). The present investigations employ a 12-yr longitudinal Danish twin study to test the hypothesis that baseline sSP-D variation has the capacity to identify smokers with normal baseline lung function who are at high risk of significant future smoke-induced lung function decline. We find that sSP-D is significantly increased in those with normal lung function at baseline who develop lung function decline during follow-up compared with those who stay lung healthy. Moreover, we demonstrate that it is the smoke-induced baseline sSP-D level, and not the constitutional level, which has capacity as biomarker, and which is linearly increased with the decline in lung function during follow-up. In conclusion, we here present first observation of increased sSP-D for identification of high-risk smokers.

Bone mineral density at age 7 years does not associate with adherence to vitamin D supplementation guidelines in infancy or vitamin D status in pregnancy and childhood: an Odense Child Cohort study.

Vitamin D supplementation in infancy is recommended to prevent rickets. At the population level, its effects on bone mineralisation are largely unknown. We aimed to explore whether adherence to national vitamin D supplementation guidelines (10 µg/d up to the age of 2 years), supplementation at the ages of 5 and 7 years, and serum 25-hydroxyvitamin D (s-25(OH)D) at various time points associated with bone mineral density (BMD) at the age of 7 years in the Odense Child Cohort, Denmark (n 1194). High adherence was defined as supplementation with 10 µg of vitamin D 6-7 times per week during ≥80 % of the observation time. s-25(OH)D was analysed using LC-MS/MS. Total-body-less-head (TBLH) BMD was measured by dual-energy X-ray absorptiometry. At the median age of 18·1 months, 53·9 % (n 475/881) reported high adherence. The median s-25(OH)D was 64·7, 78·8, 46·0 and 71·8 nmol/l in early pregnancy, late pregnancy, cord blood and at 5 years, respectively. The mean TBLH BMD at the median age of 7·1 years was 0·613 (SD 0·049) g/cm2 (z-score +0·363 (SD 0·824)). In adjusted analyses, vitamin D supplementation up to 18 months, and at 5 and 7 years, was not associated with TBLH BMD. Similarly, no robust associations were found between TBLH BMD and s-25(OH)D at any time point. No associations were found for TBLH bone mineral concentration or bone area. In this population with relatively high s-25(OH)D concentrations, no consistent associations were found between adherence to vitamin D supplementation recommendations or vitamin D status in pregnancy or childhood, and bone mineralisation at the age of 7 years.

Prenatal Exposures to Perfluoroalkyl Acids and Associations with Markers of Adiposity and Plasma Lipids in Infancy: An Odense Child Cohort Study.

BACKGROUND: Perfluoroalkyl acids (PFAA) are repellants that cross the placental barrier, enabling interference with fetal programming. Maternal PFAA concentrations have been associated with offspring obesity and dyslipidemia in childhood and adulthood, but this association has not been studied in infancy. OBJECTIVES: We investigated associations between maternal PFAA concentrations and repeated markers of adiposity and lipid metabolism in infancy. METHODS: In the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAA: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured in 649 women. Offspring were examined at birth (n=613) and at 3 months (n=602) and 18 months (n=503) of age. Total cholesterol, LDL, HDL, and triglyceride were evaluated at 3 months (n=262) and 18 months (n=198) of age. Mixed effects linear regression models estimated associations between PFAA and standardized (SDS) body mass index (BMI), ponderal index, and waist circumference. Associations between PFAA and body fat% (BF%) and plasma lipids SDS at 3 months and 18 months of age were investigated with linear regression models. RESULTS: PFNA and PFDA were associated with higher BMI SDS [adjusted ß=0.26; 95% confidence interval (CI): 0.03, 0.49 and ß=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (ß=0.36; 95% CI: 0.13, 0.59 and ß=1.02; 95% CI: 0.40, 1.64, respectively) at 3 and 18 months of age (pooled) in girls. Corresponding estimates for boys were closer to the null but not significantly different from estimates for girls. In boys and girls (combined), PFNA and PFDA were associated with BF% at age 3 months (for 1-ng/mL PFDA, ß=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (ß=1.06; 95% CI: 0.08, 2.03) (n=83). DISCUSSION: Prenatal PFAA were positively associated with longitudinal markers of adiposity and higher total cholesterol in infancy. These findings deserve attention in light of rising rates of childhood overweight conditions and dyslipidemia. https://doi.org/10.1289/EHP5184.

Heritability of Curve Patterns in Oral Glucose Tolerance Test.

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.

Associations of Fish Oil Supplement Use With Testicular Function in Young Men.

Importance: Many young men have poor semen quality, and the causes are often unknown. Supplement intake of ω-3 polyunsaturated fatty acid has been found to improve semen quality among men with infertility, but the association with semen quality among healthy men is unknown. Objective: To determine if intake of ω-3 fatty acid supplements is associated with testicular function as measured by semen quality and reproductive hormone levels among healthy men. Design, Setting, and Participants: This cross-sectional study included young Danish men from the general population recruited between January 1, 2012, and December 31, 2017, at compulsory examinations to determine their fitness for military service. Young unselected men were approached after the examination and invited to participate in a study of reproductive function, regardless of their fitness for military service. Data analysis was conducted from September 1, 2018, to June 30, 2019. Exposures: Intake of supplements, including fish oil, during the past 3 months. Main Outcomes and Measures: Semen quality, measured as volume, concentration, total sperm count, percentage of morphologically normal spermatozoa, and motility, and serum reproductive hormone levels, measured as follicle-stimulating hormone, luteinizing hormone, testosterone, free testosterone, and inhibin B levels. Results: Among 1679 young Danish men (median [interquartile range] age, 18.9 [18.7-19.4] years) recruited to participate, 98 men (5.8%) reported use of fish oil supplements during the past 3 months, of whom 53 (54.1%) reported intake on 60 or more days. After adjustment and compared with men with no supplement intake, men with fish oil supplement intake on fewer than 60 days had semen volume that was 0.38 (95% CI, -0.03 to 0.80) mL higher, and men with fish oil supplement intake on 60 or more days had semen volume that was 0.64 (95% CI, 0.15 to 1.12) mL higher (P for trend < .001). Similarly, testicular size in men with supplement intake on fewer than 60 days was 0.8 (95% CI, -0.2 to 1.9) mL larger and in men with fish oil supplement intake on 60 or more days was 1.5 (95% CI, 0.2 to 2.8) mL larger compared with men with no supplement intake (P for trend = .007). After adjustment, men with fish oil supplement intake had a 20% (95% CI, 9%-31%) lower follicle-stimulating hormone level and 16% (95% CI, 8%-24%) lower luteinizing hormone level compared with men with no supplement intake. There were no associations of intake of other supplements with measures of testicular function. Conclusions and Relevance: These findings suggest that intake of fish oil supplements was associated with better testicular function, which is less likely to be due to confounding by indication, as no associations of intake of other supplements with testicular function were found. This cross-sectional study did not examine the actual content of ω-3 fatty acids in the supplements; therefore, these findings need confirmation in well-designed randomized clinical trials among unselected men.

Pregnancy or cord 25-hydroxyvitamin D is not associated with measures of body fat or adiposity in children from three months to three years of age. An Odense Child Cohort study.

BACKGROUND & AIMS: The susceptibility to overweight in adults born during winter season may suggest foetal programming of prenatal vitamin D levels on adiposity. We investigated whether cord or pregnancy serum 25-hydroxyvitamin D (s-25OHD) was associated with infant and child body fat measures in a Danish population-based prospective cohort. METHODS: In the Odense Child Cohort, 1905 singletons had cord s-25OHD and data on waist circumference (WC), weight, body mass index (BMI), and sum of skin folds (SSF) at median 3.7 months, 18.9 months and three years' age. Early and late pregnancy samples of s-25OHD (mean gestational age 12 and 29 weeks) were chosen as secondary exposures. Multiple linear and logistic regression as well as linear mixed models was applied testing the relation between cord and pregnancy s-25OHD and body fat outcomes and their Z-scores by use of updated national reference populations. Models were adjusted for maternal educational level, maternal ethnicity, pre-gestational BMI and season of birth, a priori stratified by sex. RESULTS: The median [IQR] cord s-25OHD was 45.5 [31.1; 60.9] nmol/L. Cord s-25OHD <50 nmol/L was found in 57.5%; values < 25 nmol/L in 16.3%. The mean Z-scores of body fat measures at all ages were in the range of -0.32 to +0.42. No consistent associations were found between s-25OHD in cord, early pregnancy or late pregnancy and WC, weight, BMI, SSF, or their Z-scores at ages 3.7 months, 18.9 months, or 3 years. Neither did a computed composite outcome (WC, SSF, BMI, or weight >90th vs. ≤90 percentile) associate with cord or pregnancy s-25OHD. CONCLUSION: Cord or pregnancy s-25OHD was not associated with measures of body fat or adiposity in children up to three years of age. Our data suggested no programming effect of maternal s-25OHD on offspring obesity in a relatively lean and healthy population of mothers.

Child behaviour and subsequent changes in body weight, composition and shape.

OBJECTIVE: Studies have found an association between child behavioural problems and overweight, but the existing evidence for this relationship is inconsistent, and results from longitudinal studies are sparse. Thus, we examined the association between behavioural problems and subsequent changes in body mass index (BMI) and anthropometry over a follow-up period of 1.3 years among children aged 2-6 years. DESIGN: The study was based on a total of 345 children from The Healthy Start Study; all children were healthy weight but predisposed to develop overweight. The Danish version of the Strengths and Difficulties Questionnaire (SDQ), classified as SDQ Total Difficulties (SDQ-TD) and SDQ Prosocial Behaviour (SDQ-PSB), was used to assess child behaviour. Linear regression analyses were used to examine associations between SDQ scores and subsequent change in BMI z-score, body fat percentage, waist circumference and waist-hip ratio, while taking possible confounding factors into account. RESULTS: We found an association between SDQ-PSB and subsequent change in BMI z-score (ß: 0.040 [95% CI: 0.010; 0.071, p = 0.009]). However, there was no evidence of an association between SDQ-PSB and measures of body composition or body shape. CONCLUSIONS: Among 2 to 6 years old children predisposed to overweight, the association between SDQ-scores and weight gain is either absent or marginal. The SDQ-PSB score may be associated with subsequent increases in BMI z-score, but this association does not seem driven by an increased relative fat accumulation.

The Danish Twin Registry: An Updated Overview.

The Danish Twin Registry (DTR) was established in the 1950s, when twins born from 1870 to 1910 were ascertained, and has since been extended to include twins from birth cohorts until 2009. The DTR currently comprises of more than 175,000 twins from the 140 birth cohorts. This makes the DTR the oldest nationwide twin register and among the largest in the world. The combination of data from several surveys, including biological samples and repeated measurements on the same individuals, and data from Danish national registers provides a unique resource for a wide range of twin studies. This article provides an updated overview of the data in the DTR: First, we provide a summary of the establishment of the register, the different ascertainment methods and the twins included; then follows an overview of major surveys conducted in the DTR since 1994 and a description of the DTR biobank, including a description of the molecular data created so far; finally, a short description is given of the linkage to Danish national registers at Statistics Denmark and some recent examples of studies using the various data resources in the DTR are highlighted.