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Background The obligation to pay for asthma medication in a country with universal healthcare might lead to increased asthma exacerbations and inequitable healthcare access for children from low-income households. Thus, the aim of this study was to examine the association between household income and childhood/preschool asthma regarding hospitalization and medication receipt. Methods In this nationwide register-based cohort study, we encompassed all 3-year-old children residing in Denmark, born between 2000 and 2014, along with their linked parents and followed them until their sixth birthday. Household income was divided into quartiles. Asthma was categorized in two mutually exclusive groups as either the redemption of two prescriptions for asthma medication or receiving a hospital diagnosis. We utilized Poisson regression to estimate the risk ratio (RR). Results The analysis included 834 422 preschool children. The prevalence of asthma dependent on medication alone was 7.3%, while 1.8% of children necessitated asthma-related hospitalization. Income inequality was evident across all income quartiles. Notably, children from the lowest income quartile had a RR of 0.95 (95% CI: 0.92–0.98) of redeeming asthma medication and conversely a RR of 1.18 (95% CI: 1.14–1.23) of asthma-related hospitalization. Conclusions Despite universal healthcare, income inequality has a dual impact on children from low-income households. They face a diminished risk of redeeming asthma medication and a higher susceptibility to asthma-related hospitalizations indicating an unequal access to healthcare. Prioritizing efforts to reduce childhood health inequalities is crucial. However, further research, particularly qualitative studies, is needed to better comprehend the underlying mechanisms to address the complexities of income inequality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0–19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5) and PM with aerodynamic diameter ≤10 μm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m³ in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m³ increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. [ABSTRACT FROM AUTHOR]

PURPOSE: The Wii Balance Board (WBB) can be used for assessment of steady state balance (SSB), but its reliability has not been studied in children aged 6–9 years. This study aimed to determine the test-retest reliability of the WBB for measuring SSB in this population. A secondary aim was to determine the minimum detectable change (MDC) and standard error of measurement (SEM) of the WBB in children aged 6–9 years. METHODS: 52 children between 6–9 years of age participated. "One leg stand balance" was used to assess center of pressure velocity (COPV) and center of pressure area (COPA) on three occasions by the same tester. Two tests were conducted on the same day (Day 1) and the third test was performed on another day (Day 2), with a period of 5–13 days between the two test days. Intraclass correlation coefficient (ICC 3,1), SEMs, and MDC were calculated. RESULTS: Intra-day test-retest reliability of COPA was found to be good (ICC3,1 =0.86; 95% confidence interval [CI]: 0.75, 0.92) and that of COPV was also found to be good (ICC3,1 =0.87; 95% CI: 0.77, 0.92). Inter-day test-retest reliability was found to be good for COPA (ICC3,1 = 0.87; 95% CI: 0.75, 0.93) and COPV (ICC3,1 = 0.89; 95% CI: 0.81, 0.94). SEM for COPA in intra-day testing was 18.90 mm2 (15.78%), and in inter-day testing it was 16.44 mm2 (13.61%). SEM for COPV in intra-day testing was 1.12 mm/s (7.6%), and in inter-day testing it was 1.01 mm/s (6.9%). MDC for COPA in intra-day testing was 52.41mm2 (42.75%), and in inter-day testing was 45.58 mm2 (35.75%). MDC for COPV in intra-day testing was 3.11 mm/s (21.2%), and in inter-day testing it was 2.80 mm/s (18.9%). CONCLUSION: The WBB has good test-retest reliability for assessing SSB of children between 6-9 years. COPA measurements appear to be less sensitive to clinical changes in SSB when compared to COPV. Assessment of validity of the WBB in this age group is recommended before it can be considered as a potential balance assessment tool in children. [ABSTRACT FROM AUTHOR]

Introduction: In the Kell blood group system, the K and k antigens are the clinically most important ones. Maternal anti-K IgG antibodies can lead to the demise of a K-positive fetus in early pregnancy. Intervention can save the fetus. Prenatal K status prediction of the fetus in early pregnancy is desirable and gives a good basis for pregnancy risk management. We present the results from 7 years of clinical experience in predicting fetal K status as well as some theoretical considerations relevant for design of the assay and evaluation of results. Methods: Blood was collected from 43 women, all immunized against K, at a mean gestational age of 18 weeks (range 10–38). A total of 56 consecutive samples were tested. The KEL*01.01/KEL*02 single nucleotide variant that determines K status was amplified from maternal plasma DNA by PCR without allele specificity. The PCR product was sequenced by NGS technology, and the number of sequenced KEL*01.01 and KEL*02 reads were counted. Prediction of the fetal K status was based on this count and was compared with the serologically determined K status of the newborns. Results: All fetal K predictions were in accordance with postnatal serology where available (n = 34), using our current data analysis. Conclusion: We have developed an NGS-based method for the non-invasive prediction of fetal K status. This approach requires special considerations in terms of primer design, stringent preanalytical sample handling, and careful analytical procedures. We analyzed samples starting at GA 10 weeks and demonstrated the correct prediction of fetal K status. This assay enables timely clinical intervention in pregnancies at risk of hemolytic disease of the fetus and newborn caused by maternal anti-K IgG antibodies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widespread persistent pollutants. Evidence regarding neurodevelopmental effects of PFAS have been mixed. The relation between PFAS exposure and anatomical markers that have been suggested to correlate with fetal brain development have not been studied. OBJECTIVES: We investigated the association between prenatal PFAS exposures and three craniofacial features in children measured at 5 years of age. METHODS: Measures of palpebral fissure length (PFL), philtrum groove, and upper-lip thickness were generated from standardized digital facial photographs from 656 children in the Danish National Birth Cohort. PFL was classified into two groups (shorter; normal), and the philtrum (grooved; smooth; normal) and upper-lip (thick; thin; normal) measures into three groups each. Six PFAS were measured in maternal plasma (median = 8 gestational wk). Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for each facial feature using the normal group as the reference according to log2-PFAS concentration (in nanograms per milliliter) or PFAS tertiles, adjusting for potential confounders, including maternal alcohol intake and smoking. Stratified analyses by maternal alcohol intake or child’s sex were performed. RESULTS: Prenatal exposure to each PFAS was associated with elevated odds for a shorter PFL, with the strongest association observed for perfluorodecanoic acid (PFDA; per doubling OR = 2.02; 95% CI: 1.11, 3.70). Some nonlinear associations were found for philtrum measures: the second tertile of PFDA and perfluorononanoic acid were associated with grooved philtrum, whereas the second tertile of perfluoroheptane sulfonate with smooth philtrum. The associations between PFAS exposure and a shorter PFL were stronger among mothers who consumed alcohol in the first trimester, some sex-specific associations were noted for philtrum and upper-lip measures. DISCUSSION: Prenatal PFAS exposures might influence fetal craniofacial development. A larger study is needed to replicate the potential modifying effects observed for alcohol exposure and to clarify whether associations of craniofacial markers observed reflect specific neurologic deficits. [ABSTRACT FROM AUTHOR]

Current research shows that children with sensory processing (SP) difficulties have limited participation and enjoyment in their daily activities at school. The aim of this study was to explore the prevalence of SP difficulties among Danish children and to explore possible associated factors. Since SP difficulties can affect children's prerequisites for participation in school activities and learning possibilities, this study focused on primary school children. Method. The study was designed as a cross-sectional survey. The sample consisted of 1723 children age 5 to 11 years, who were attending Danish public school (45.5% girls, 53.2% boys). The parents or caregivers of the child completed a Short Sensory Profile (SSP) questionnaire and a demographic questionnaire. One-way ANOVA was used to examine differences between girls and boys regarding sports, geographic area, and parental level of education. Chi-square analysis was used to explore the relationship between sex and SPP scores in the different behavioral sections. Logistic regression analysis was used to investigate possible associations between SP difficulties and sex and the included demographics. Results. A total of 21.3% of the children had SSP scores suggesting SP difficulties. Boys had a higher probability of having SP difficulties than girls (odds ratio OR = 1.55 , confidence level (Cl): 1.22, 1.97). An association was found between participating in sports outside of school and SP difficulties (OR = 0.55 , Cl: 0.47, 0.65 (p ≤ 0.001)). Additionally, a slight association between SP difficulties and parental education level (OR = 0.80) was found. No association was found regarding geographic area, i.e., where in Denmark the children attended school (OR = 1.00). Conclusion. The study results suggest that approximately 20% of the children in Danish public schools might have SP difficulties and over 20% might be at risk of having SP difficulties. The results suggest that Danish schools should focus on both identifying children with SP difficulties and implement interventions such as sensory integration through occupational therapy to help children with SP difficulties, in order to improve their ability to participate and learn from school activities. [ABSTRACT FROM AUTHOR]

Background: To investigate the effectiveness of chiropractic spinal manipulation versus sham manipulation in children aged 7–14 with recurrent headaches. Methods: Design: A two-arm, single-blind, superiority randomised controlled trial. Setting: One chiropractic clinic and one paediatric specialty practice in Denmark, November 2015 to August 2020. Participants: 199 children aged 7 to 14 years, with at least one episode of headache per week for the previous 6 months and at least one musculoskeletal dysfunction identified. Interventions: All participants received standard oral and written advice to reduce headaches. In addition, children in the active treatment group received chiropractic spinal manipulation and children in the control group received sham manipulation for a period of 4 months. Number and frequency of treatments were based on the chiropractor's individual evaluation in the active treatment group; the children in the control group received approximately eight visits during the treatment period. Primary outcome measures: 'Number of days with headache', 'pain intensity' and 'medication' were reported weekly by text messages, and global perceived effect by text message after 4 months. A planned fixed sequence strategy based on an initial outcome data analysis was used to prioritize outcomes. 'Number of days with headache' and 'pain intensity' were chosen as equally important outcomes of highest priority, followed by global perceived effect and medication. The significance level for the first two outcomes was fixed to 0.025 to take multiplicity into account. Results: Chiropractic spinal manipulation resulted in significantly fewer days with headaches (reduction of 0.81 vs. 0.41, p = 0.019, NNT = 7 for 20% improvement) and better global perceived effect (dichotomized into improved/not improved, OR = 2.8 (95% CI: 1.5–5.3), NNT = 5) compared with a sham manipulation procedure. There was no difference between groups for pain intensity during headache episodes. Due to methodological shortcomings, no conclusions could be drawn about medication use. Conclusions: Chiropractic spinal manipulation resulted in fewer headaches and higher global perceived effect, with only minor side effects. It did not lower the intensity of the headaches. Since the treatment is easily applicable, of low cost and minor side effects, chiropractic spinal manipulation might be considered as a valuable treatment option for children with recurrent headaches. Trial registration: ClinicalTrials.gov, identifier NCT02684916, registered 02/18/2016 – retrospectively registered. [ABSTRACT FROM AUTHOR]

High infant weight increases the risk of childhood overweight, while breastfeeding may reduce the risk. However, some infants have a very high weight gain even though they are exclusively breastfed. We examined the risk of a high body mass index (BMI) and overweight in childhood for infants ≥2.5 SD above the median weight‐for‐age (WAZ) at age 5 months according to duration of exclusive breastfeeding (≤2, >2 to <4 or ≥4 months). The study is based on 13,401 7‐year‐old and 9,819 11‐year‐old children enrolled into the Danish National Birth Cohort (born 1997–2003). Linear and logistic regression analyses were used to examine the associations while adjusting for presumed confounders including birth weight. The results showed that infants ≥2.5 SD at 5 months, breastfed exclusively ≤2, >2 to <4 or ≥4 months had adjusted odds ratios (ORs) for overweight at age 7 at 3.67 (95% confidence interval [CI] [2.10, 6.43]), 3.42 (95% CI [2.32, 5.04]) and 3.19 (95% CI [1.90, 5.36]) respectively, when compared with infants <2.5 SD WAZ exclusively breastfed ≥4 months. The corresponding results for BMI z‐scores were 0.82 (95% CI [0.60, 1.04]), 0.63 (95% CI [0.48, 0.78]) and 0.57 (95% CI [0.38, 0.77]). For the ≥2.5 SD infants, the differences in risk of overweight and BMI according to duration of exclusive breastfeeding were neither significantly different among the 7‐year nor among the 11‐year‐old children. A high infant weight increases the odds of overweight and is associated with a higher BMI in childhood. Whereas the odds and BMI z‐scores tended to be lower for those exclusively breastfed longer, the differences were not statistically significant. [ABSTRACT FROM AUTHOR]

BACKGROUND: Manganese (Mn) in drinking water may increase the risk of several neurodevelopmental outcomes, including attention-deficit hyperactivity disorder (ADHD). Earlier epidemiological studies on associations between Mn exposure and ADHD-related outcomes had small sample sizes, lacked spatiotemporal exposure assessment, and relied on questionnaire data (not diagnoses)—shortcomings that we address here. OBJECTIVE: Our objective was to assess the association between exposure to Mn in drinking water during childhood and later development of ADHD. METHODS: In a nationwide population-based registry study in Denmark, we followed a cohort of 643,401 children born 1992–2007 for clinical diagnoses of ADHD. In subanalyses, we classified cases into ADHD-Inattentive and ADHD-Combined subtypes based on hierarchical categorization of International Classification of Diseases (ICD)-10 codes. We obtained Mn measurements from 82,574 drinking water samples to estimate longitudinal exposure during the first 5 y of life with high spatiotemporal resolution. We modeled exposure as both peak concentration and time-weighted average. We estimated sex-specific hazard ratios (HRs) in Cox proportional hazards models adjusted for age, birth year, socioeconomic status (SES), and urbanicity. RESULTS: We found that exposure to increasing levels of Mn in drinking water was associated with an increased risk of ADHD-Inattentive subtype, but not ADHD-Combined subtype. After adjusting for age, birth year, and SES, females exposed to high levels of Mn (i.e., >100µg/L) at least once during their first 5 y of life had an HR for ADHD-Inattentive subtype of 1.51 [95% confidence interval (CI): 1.18, 1.93] and males of 1.20 (95% CI: 1.01, 1.42) when compared with same-sex individuals exposed to <5µg/L. When modeling exposure as a time-weighted average, sex differences were no longer present. DISCUSSION: Mn in drinking water was associated with ADHD, specifically the ADHD-Inattentive subtype. Our results support earlier studies suggesting a need for a formal health-based drinking water guideline value for Mn. Future Mn-studies should examine ADHD subtype-specific associations and utilize direct subtype measurements rather than relying on ICD-10 codes alone. [ABSTRACT FROM AUTHOR]

Background: Knowledge about the occurrence and distribution of musculoskeletal problems in early life is needed. The objectives were to group children aged 8 to 16 according to their distribution of pain in the spine, lower- and upper extremity, determine the proportion of children in each subgroup, and describe these in relation to sex, age, number- and length of episodes with pain. Method: Data on musculoskeletal pain from about 1,000 Danish schoolchildren was collected over 3 school years (2011 to 2014) using weekly mobile phone text message responses from parents, indicating whether their child had pain in the spine, lower extremity and/or upper extremity. Result are presented for each school year individually. Results: When pain was defined as at least 1 week with pain during a school year, Danish schoolchildren could be divided into three almost equally large groups for all three school years: Around 30% reporting no pain, around 40% reporting pain in one region, and around 30% reporting pain in two or three regions. Most commonly children experienced pain from the lower extremities (~ 60%), followed by the spine (~ 30%) and the upper extremities (~ 23%). Twice as many girls reported pain in all three sites compared to boys (10% vs. 5%) with no other statistically significant sex or age differences observed. When pain was defined as at least 3 weeks with pain during a schoolyear, 40% reported pain with similar patterns to those for the more lenient pain definition of 1 week. Conclusion: Danish schoolchildren often experienced pain at more than one pain site during a schoolyear, and a significantly larger proportion of girls than boys reported pain in all three regions. This could indicate that, at least in some instances, the musculoskeletal system should be regarded as one entity, both for clinical and research purposes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Perfluoroalkyl substances (PFAS) are a group of widely used persistent chemicals with suspected immunotoxic effects. OBJECTIVES: The present study aimed to examine the association between infant PFAS exposure and antibody responses to measles vaccination as well as morbidity in a low-income country. METHODS: In a randomized controlled trial, children from Guinea-Bissau, West Africa, were followed from inclusion (4–7 months of age) through 2 years of age. Half the children received two measles vaccinations (at inclusion and at 9 months of age), and the other half received only one (at 9 months of age). In a subset of 237 children, six PFAS were quantified in serum at inclusion, and measles antibody concentrations were assessed at inclusion and at approximately 9 months and 2 years of age. At inclusion and at the 9-month visit, mothers were interviewed about infant morbidity. RESULTS: All but one child had detectable serum concentrations of all six PFAS, although levels were lower than seen elsewhere. A doubling in perfluorooctane sulfonic acid (PFOS) and perfluorodecanoic acid (PFDA) were associated with 21% (95% CI: 2, 37%) and 25% (95% CI: 1, 43%), respectively, lower measles antibody concentrations at the 9-month visit among the children who had received a measles vaccine at inclusion. Elevated serum PFAS concentrations were also associated with reduced prevaccination measles antibody concentrations and increased morbidity. DISCUSSION: The present study documents that PFAS exposure has reached West Africa and that infants show PFAS-associated increases in morbidity and decreases in measles-specific antibody concentrations before and after vaccination. These findings support the evidence on PFAS immunotoxicity at comparatively low serum concentrations. [ABSTRACT FROM AUTHOR]

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 β=0.26; 95% confidence interval (CI): 0.03, 0.49 and β=0.58; 95% CI: -0.03, 1.19, respectively, for 1-ng/mL increases] and ponderal index SDS (β=0.36; 95% CI: 0.13, 0.59 and β=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, β=0.40; 95% CI: 0.04, 0.75), and PFDA was associated with total cholesterol SDS at 18 months (β=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. [ABSTRACT FROM AUTHOR]

Background The offspring of parents with severe mental illness (SMI) are at higher risk of mortality and of developing certain somatic diseases. However, across the full spectrum of somatic illness, there remains a gap in knowledge regarding morbidity. Methods We conducted a register-based nationwide cohort study of all 2 000 694 individuals born in Denmark between 1982 and 2012. Maximum age of offspring at follow-up was 30 years. Information on parents' psychiatric diagnoses of schizophrenia, bipolar disorder, and unipolar depression was retrieved from the Psychiatric Central Register. We estimated incidence rate ratio (IRR), cumulative incidence percentage and mortality rate ratio of first hospital contact for a broad spectrum of somatic illnesses according to the International Statistical Classification of Diseases and Related Health Problems. Analyses were adjusted for important confounders. Results Offspring of individuals with SMI had higher risk of somatic hospital contacts IRR: 1.17 (95% CI: 1.16–1.18) with maternal depression being associated with the highest IRR (1.22, 95% CI: 1.20–1.24). Offspring of parents with SMI had higher risk within most broad diagnostic categories with highest IRRs for unclassified somatic diagnoses, infections and endocrine diseases ranging from 1.27 (95% CI: 1.25–1.28) to 1.26 (95% CI: 1.23–1.29) (all P <.0001). Morbidity was particularly increased in children aged 0–7 years. The mortality rate ratio associated with parental SMI was 1.31 (95% CI: 1.21–1.41) with excess mortality mainly due to unnatural causes. Conclusion Our findings indicate that offspring of parents with SMI experienced increased mortality and somatic morbidity warranting heightened vigilance and support for this population. [ABSTRACT FROM AUTHOR]

Fe deficiency (ID) defined as plasma ferritin <12 µg/l is associated with delayed cognitive development in early childhood and increased incidence of infections; however, the longitudinal association between early-life factors and ID in 18-month-old children in Denmark is unknown. The present study aimed to determine the prevalence of ID and to describe risk factors associated with ID in healthy 18-month-old Danish children. Blood samples, anthropometric measurements and self-reported questionnaire data had been obtained in the birth cohort, Odense Child Cohort. The questionnaires were modified from those used in the Danish National Birth Cohort. Plasma ferritin and C-reactive protein in venous, non-fasting samples were analysed in the final sample size of 370 children after exclusion of seventy-nine children due to chronic disease, acute infection, C-reactive protein >10 mg/l, twin birth or prematurity. Associations with ID were analysed by logistic regression, adjusting for sex, maternal education, duration of partial breast-feeding and current intake of milk, fish and meat. Overall, fifty-six children had ID (15·1 %). Factors associated with increased risk were exclusive breast-feeding beyond 4 months (OR 5·97; 95 % CI 1·63, 21·86) and no intake of oral Fe supplements from 6 to 12 months (OR 3·99, 95 % CI 1·33, 11·97. Duration of partial breast-feeding and current diet was not associated with ID. In conclusion, the ID prevalence was 15·1 %, and both exclusive breast-feeding beyond 4 months and no intake of oral Fe supplements from 6 to 12 months were associated with increased risk of ID in 18-month-old children. [ABSTRACT FROM AUTHOR]

Background Fish oil improves cardiometabolic markers in adults, but results in children are inconsistent. Few children meet the recommended fish intake and no randomized trials have investigated how fish intake per se affects children's cardiometabolic profile. Objective We investigated whether oily fish consumption modulated serum triacylglycerol and diastolic blood pressure (coprimary outcomes) and other cardiometabolic markers in healthy Danish children and whether effects were sex-specific. Methods In a randomized controlled 12-wk trial, 199 children (aged 8–9 y) received ∼300 g/wk of oily fish or poultry (control). We measured blood pressure, heart rate, and heart rate variability (HRV) via 3-h continuous electrocardiograms and collected fasting blood samples for analysis of erythrocyte EPA [20:5n–3 (ω-3)] + DHA (22:6n–3) and serum triacylglycerol, LDL and HDL cholesterol, glucose, and insulin. Results One hundred and ninety-seven children (99%) completed the trial. The fish group consumed a median (IQR) of 375 (325–426) g oily fish/wk and the poultry group consumed 400 (359–452) g poultry/wk, which resulted in 2.25 (95% CI: 1.88, 2.62) fatty acid percentage-point higher erythrocyte EPA + DHA in the fish group (P  < 0.001). In the fish group, serum triacylglycerol decreased by 0.05 mmol/L (95% CI: 0.00, 0.11 mmol/L) (P  = 0.04) and HDL cholesterol increased by 0.07 mmol/L (95% CI: 0.01, 0.13 mmol/L) (P  = 0.02); the triacylglycerol effect showed dose-dependency with erythrocyte EPA + DHA (r  = −0.15, P  = 0.04), whereas HDL showed a tendency for such an association(r  = 0.13, P  = 0.08). Additional analyses indicated sex-specificity (P diet*sex < 0.10), because triacylglycerol was reduced by 0.09 mmol/L (95% CI: 0.02, 0.16 mmol/L) in boys only (girls: −0.00; 95% CI: −0.07, 0.07 mmol/L) and heart rate was reduced by 3.4 bpm (95% CI: 0.2, 6.6 bpm) in girls only (boys: 0.6; 95% CI: −2.6, 3.8 bpm). Blood pressure, HRV, and glucose homeostasis were unaffected. Conclusions Oily fish intake improved serum triacylglycerol and HDL cholesterol in a dose-dependent manner in 8- to 9-y-old children, but had no effect on blood pressure, HRV, or glucose homeostasis. This supports recommendations for fish intake in children and underlines the importance of initiatives to increase children's intake of oily fish. This trial was registered at clinicaltrials.gov as NCT02809508. [ABSTRACT FROM AUTHOR]

Background The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non–tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high-income setting. Hospitalization for infection was a secondary outcome in a randomized trial with the primary aim to estimate the potential non-specific effects of BCG vaccination at birth on all-cause hospitalization. Methods A total of 4262 children included in the Danish Calmette Study were assigned randomly to either receive the BCG vaccine or not and were followed through the Danish National Patient Register. The outcome was number of hospitalizations for infection until the age of 15 months. Data were analyzed by Cox regression in intention-to-treat (ITT) and per-protocol (PP) analyses. Results In the ITT analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.85–1.15]). The PP analysis yielded an HR of 1.00 (95% CI, 0.86–1.16). Predefined interaction ITT analyses showed that among 740 children with a BCG-vaccinated mother, the HR for BCG-vaccinated children was 0.65 (95% CI, 0.45–0.94); the HR for children who had a non–BCG-vaccinated mother was 1.10 (95% CI, 0.93–1.29) (P =.01, test of no interaction). Cesarean delivery modified the effect of BCG vaccination (HRs, 0.73 [95% CI, 0.54–0.99] in children born by cesarean section vs 1.10 [95% CI, 0.92–1.30] in other children; P =.02). When the outcome was defined as time to first hospitalization, the HR for premature children after BCG vaccination was 1.81 (95% CI, 0.95–3.43), whereas the HR was 0.94 (95% CI, 0.82–1.08) for children born at term (P =.05). Conclusion BCG vaccination did not affect the rate of hospitalization for infection up to the age of 15 months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration. [ABSTRACT FROM AUTHOR]

Background Health inequalities are rooted in education and we investigate the association between early parental death and attainment across the educational spectrum. Methods Using total population data on Danes born between 1982 and 2000 (n = 1 043 813), we assess incidence rate ratios (RRs) by gender for attainment of each educational level (basic school, high school or vocational training, bachelor degree or professional programme, and university graduate degree) according to loss of a parent before the age of 18 years. We adjust for family income, education and psychiatric illness and examine parent's gender, cause of death and child's age at time of death as potential moderators. Results Bereaved people had significantly lower attainment rates than non-bereaved people: basic school (RR = 0.95; 95% CI: 0.93–0.97 for men and 0.96; 0.94–0.98 for women), high school or vocational training (0.78; 0.76–0.80 for men and 0.82; 0.80–0.84 for women), bachelor degree or professional programme (0.74; 0.70–0.79 for men and 0.83; 0.79–0.86 for women) and university graduate degree (0.77; 0.68–0.86 for men and 0.77; 0.69–0.86 for women). Parent's gender, cause of death and child's age at the death did not modify the associations. Conclusions As education impacts population health, support for bereaved school children may be more important than realized. [ABSTRACT FROM AUTHOR]

Studies have suggested that vitamin D status at birth may be associated with a range of neonatal outcomes. The aim of this study was to assess the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration and gestational age, birth weight, Ponderal Index and size for gestational age. Neonatal capillary blood stored as dried blood spots was used to assess 25(OH)D3 concentrations among 2686 subjects selected from a random population sub-sample of individuals, born in Denmark from 1 May 1981 to 31 December 2002. There was an inverse association between 25(OH)D3 concentration and gestational age at birth of −0·006 (95 % CI −0·009, −0·003, P<0·001) weeks of gestation per 1 nmol/l increase in 25(OH)D3 concentration. An inverted U-shaped association between 25(OH)D3 and birth weight and Ponderal Index (P=0·04) was found, but no association with size for gestational age was shown. This study suggests that neonatal 25(OH)D3 concentration is associated with anthropometric measures at birth known to be correlated with many subsequent health outcomes such as obesity and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To examine the trend in social inequality in low intake of vegetables among adolescents in Denmark from 2002 to 2014 using occupational social class (OSC) as socio-economic indicator.Design: Repeated cross-sectional school surveys including four waves of data collection in 2002-2014. The analyses focused on absolute social inequality (difference between high and low OSC in low vegetable intake) as well as relative social inequality (OR for low vegetable intake by OSC).Setting: The nationally representative Health Behaviour in School-aged Children (HBSC) study in Denmark.Subjects: The study population was 11-15-year olds (n 17 243).Results: Low intake of vegetables was defined as less than weekly intake measured by food frequency items. OSC was measured by student reports of parents' occupation. The proportion of participants who reported eating vegetables less than once weekly was 8·9 %, with a notable decrease from 11·9 % in 2002 to 5·9 % in 2014. The OR (95 % CI) for less than weekly vegetable intake was 2·28 (1·98, 2·63) in the middle compared with high OSC and 3·12 (2·67, 3·66) in the low compared with high OSC. The absolute social inequality in low vegetable intake decreased from 2002 to 2014 but the relative social inequality remained unchanged.Conclusions: The study underscores that it is important to address socio-economic factors in future efforts to promote vegetable intake among adolescents. The statistical analyses of social inequality in vegetable intake demonstrate that it is important to address both absolute and relative social inequality as these two phenomena may develop differently. [ABSTRACT FROM AUTHOR]

Background: Infant feeding may play an important role in the development of childhood overweight and obesity. Objective: The objective of this study was to examine whether duration of breastfeeding (BF), timing of introduction of complementary food, and protein intake at age 18 mo are associated with body mass index [BMI (measured in kg/m2)] and overweight at ages 7 and 11 y, independent of BMI during infancy. Design: Children participating in the Danish National Birth Cohort were followed up at ages 7 and 11 y. Information on infant feeding, protein intake at age 18 mo, Ponderal Index at birth, child BMI (at ages 5 mo, 12 mo, 7 y, and 11 y), and several parental factors was available. Path analysis was used to assess the direct and indirect effects of infant feeding on BMI z scores (BMIz) at ages 7 (n = 36,481) and 11 y (n = 22,047). Logistic regression analyses were used to examine associations with overweight. Results: Duration of BF was not associated with childhood BMIz at ages 7 and 11 y. Earlier introduction of complementary food (<4 mo old) was not associated with BMIz at age 7 y, but with a 0.069 (95% CI: 0.021, 0.117, P = 0.005) higher BMIz at age 11 y and increased risk of overweight at age 11 y (OR 1.44; 95% CI: 1.04, 2.00; P = 0.03). Protein intake from dairy products (per 5 g/d) was associated with higher BMIz only at age 7 y (OR: 0.012; 95% CI: 0.003, 0.021; P = 0.007). Protein intake from meat and fish (per 2 g/d) was associated with a 0.010 (95% CI: 0.004, 0.017; P = 0.003) higher BMIz at age 7 y, a 0.013 (95% CI: 0.005, 0.020; P = 0.002) higher BMIz at age 11 y and increased odds of overweight at age 7 y (OR: 1.07; 95% CI: 1.03, 1.10; P < 0.001), but not at age 11 y. Conclusions: Intake of protein from meat and fish at age 18 mo was associated with higher BMIz and risk of overweight in childhood. However, the effect sizes were small. Early introduction of complementary food may be associated with child BMIz and child overweight. This study was registered at www.clinicaltrials.gov as NCT03334760. [ABSTRACT FROM AUTHOR]

Background: Whether antenatal and neonatal vitamin D status have clinical relevance in fracture prevention has not been examined extensively, although observational studies indicate that fetal life may be a sensitive period in relation to bone growth and mineralization during childhood. Objective: We examined whether 25-hydroxyvitamin D3 [25(OH)D3] concentrations in stored neonatal dried blood spot (DBS) samples are associated with pediatric fracture risk. We hypothesized that in particular, low neonatal vitamin D status may be a risk factor for fracture incidence among children. Design: In a register-based case-cohort study design, the case group was composed of 1039 individuals who were randomly selected from a total of 82,154 individuals who were born during 1989-1999 and admitted to a Danish hospital with a fracture of the forearm, wrist, scaphoid bone, clavicle, or ankle at age 6-13 y. The subcohort was composed of 1600 individuals randomly selected from all Danish children born during 1989-1999. The neonatal 25(OH)D3 concentrations in DBS samples were assessed by using highly sensitive chromatography-tandem mass spectrometry. Results: The mean ± SD 25(OH)D3 concentration for all subjects was 27.7 ± 18.9 nmol/L [median (IQR): 23.5 nmol/L (13.3, 37.3 nmol/L)] and showed significant monthly variation (P < 0.0001) with the highest values in July and August. Individuals in the middle quintile of neonatal 25(OH)D3 had lower odds of sustaining a fracture than did those in the lowest quintile (adjusted OR: 0.75; 95%CI: 0.58, 0.96), but a global test did not show any significant overall association (adjusted P = 0.13). Conclusions: This study suggested that neonatal vitamin D status does not influence subsequent fracture risk in childhood. This is in accordance with studies that report no association between antenatal maternal vitamin D status and childhood fractures. Further studies are needed to examine fracture risk in relation to prenatal vitamin D status in a randomized controlled setting. [ABSTRACT FROM AUTHOR]

Prenatal low vitamin D may have consequences for bone health. By means of a nationwide mandatory vitamin D fortification programme, we examined the risk of fractures among 10–18-year-old children from proximate birth cohorts born around the date of the termination of the programme. For all subjects born in Denmark during 1983–1988, civil registration numbers were linked to the Danish National Patient Registry for incident and recurrent fractures occurring at ages 10–18 years. Multiplicative Poisson models were used to examine the association between birth cohort and fracture rates. The variation in fracture rates across birth cohorts was analysed by fitting an age-cohort model to the data. We addressed the potential modification of the effect of vitamin D availability by season of birth. The risk of fractures was increased among both girls and boys who were born before the vitamin D fortification terminated in 1985 (rate ratio (RR) exposed v. non-exposed girls: 1·15 (95 % CI 1·11, 1·20); RR exposed v. non-exposed boys: 1·11 (95 % CI 1·07, 1·14). However, these associations no longer persisted after including the period effects. There was no interaction between season of birth and vitamin D availability in relation to fracture risk. The study did not provide evidence that prenatal exposure to extra vitamin D from a mandatory fortification programme of 1·25 µg vitamin D/100 g margarine was sufficient to influence the risk of fractures in late childhood, regardless of season of birth. Replication studies are needed. [ABSTRACT FROM AUTHOR]

We investigated the exercise intensity and fitness effects of frequent school-based low-volume high-intensity training for 10 months in 8–10-year-old children. 239 Danish 3rd-grade school children from four schools were cluster-randomised into a control group (CON, n=116) or two training groups performing either 5×12 min/wk small-sided football plus other ball games (SSG, n=62) or interval running (IR, n=61). Whole-body DXA scans, flamingo balance, standing long-jump, 20 m sprint, and Yo-Yo IR1 children’s tests (YYIR1C) were performed before and after the intervention. Mean running velocity was higher (p<0.05) in SSG than in IR (0.88±0.14 versus 0.63±0.20 m/s), while more time (p<0.05) was spent in the highest player load zone (>2; 5.6±3.4 versus 3.7±3.4%) and highest HR zone (>90% HRmax; 12.4±8.9 versus 8.4±8.0%) in IR compared to SSG. After 10 months, no significant between-group differences were observed for YYIR1C performance and HR after 2 min of YYIR1C (HRsubmax), but median-split analyses showed that HRsubmax was reduced (p<0.05) in both training groups compared to CON for those with the lowest aerobic fitness (SSG versus CON: 3.2%  HRmax [95% CI: 0.8–5.5]; IR versus CON: 2.6%  HRmax [95% CI: 1.1–5.2]). After 10 months, IR had improved (p<0.05) 20 m sprint performance (IR versus CON: 154 ms [95% CI: 61–241]). No between-group differences (p>0.05) were observed for whole-body or leg aBMD, lean mass, postural balance, or jump length. In conclusion, frequent low-volume ball games and interval running can be conducted over a full school year with high intensity rate but has limited positive fitness effects in 8–10-year-old children. [ABSTRACT FROM AUTHOR]

Background: Children in northern latitudes are at high risk of vitamin D deficiency during winter because of negligible dermal vitamin D3 production. However, to our knowledge, the dietary requirement for maintaining the nutritional adequacy of vitamin D in young children has not been investigated. Objective: We aimed to establish the distribution of vitamin D intakes required to maintain winter serum 25-hydroxyvitamin D [25(OH)D] concentrations above the proposed cutoffs (25, 30, 40, and 50 nmol/L) in white Danish children aged 4-8 y living at 55°N. Design: In a double-blind, randomized, controlled trial 119 children (mean age: 6.7 y) were assigned to 0 (placebo), 10, or 20 μg vitamin D3/d supplementation for 20 wk. We measured anthropometry, dietary vitamin D, and serum 25(OH)D with liquid chromatography- tandem mass spectrometry at baseline and endpoint. Results: The mean ± SD baseline saum 25(OH)D was 56.7 ± 12.3 nmol/L (range: 28.7-101.4 nmol/L). Serum 25(OH)D increased by a mean ± SE of 4.9 ± 1.3 and 17.7 ± 1.8 nmol/L in the groups receiving 10 and 20 mg vitamin D3/d, respectively, and decreased by 24.1 ± 1.2 nmol/L in the placebo group (P < 0.001). A nonlinear model of serum 25(OH)D as a function of total vitamin D intake (diet and supplements) was fit to the data. The estimated vitamin D intakes required to maintain winter serum 25(OH)D >30 (avoiding deficiency) and >50 nmol/L (ensuring adequacy) in 97.5% of participants were 8.3 and 19.5 μg/d, respectively, and 4.4 μg/d was required to maintain serum 25(OH)D >40 nmol/L in 50% of participants. Conclusions: Vitamin D intakes between 8 and 20 μg/d are required by white 4- to 8-y-olds during winter in northern latitudes to maintain serum 25(OH)D >30-50 nmol/L depending on chosen serum 25(OH)D threshold. This trial was registered at clinicaltrials. gov as NCT02145195. [ABSTRACT FROM AUTHOR]

Objective:To investigate the distribution of antibiotic prescriptions in primary health care among children aged 0–6 years and its association with socioeconomic factors. Design:A cross-sectional study describing antibiotic prescriptions and socioeconomic factors, using different population-based registers from Statistics Denmark. Setting:Antibiotic prescriptions in 2012 from primary health care in the Capital Region of Denmark. Subjects:The population of children aged 0–6 years (n = 139,398) in the Capital Region of Denmark. Main outcome measures:High use of antibiotics identified by number of antibiotic prescriptions (≥ 3 prescriptions per year) and defined daily doses (DDD). A multinomial logistic regression analysis estimating the association between high antibiotic use and parents’ education, employment status, income, child’s sex, and ethnic background. Results:Ten percent of children accounted for 25% of the total use DDD. There was a clear tendency that the risk for high antibiotic use increased as parental educational level decreased. The risk for high use was the highest among children of mothers and fathers with basic schooling ≤10 years (OR 1.60, 95% CI 1.29–1.98, and OR 1.60, 95% CI 1.34–1.91, respectively). Low income and unemployment were not associated with high antibiotic use. Conclusion:Socioeconomic factors can only partially explain differences in antibiotic use. Further research is needed to clarify the unequal distribution of antibiotic prescribing and the association between high antibiotic use and low educational level. This would provide valuable information in the planning of strategies to promote rational use of antibiotics among children.KEY POINTSThe Capital Region of Denmark has the highest rate of antibiotic prescribing in Denmark.Preschool children are among the age groups with the highest use.Ten percent of the children accounted for 25% of the total antibiotic use.Low parental educational level was associated with increased antibiotic use.Parents’ income or employment status was not found to be associated with high antibiotic use. [ABSTRACT FROM PUBLISHER]

Human parechovirus (HPeV) is a cause of severe morbidity among infants and young children. To evaluate the associations between early environmental risk factors and HPeV infections, we carried out a nationwide cohort study linking registry data on birth and sibship characteristics with a laboratory surveillance database, covering all HPeV infections detected in Denmark during 2009-2012 among children <5 years of age. Incidence rate ratios were calculated in log-linear Poisson regression analyses. Overall, 133 HPeV infections, 85 caused by human parechovirus type 3 (HPeV-3) and 48 by human parechovirus other than type 3 (non-HPeV-3), were detected among 132 children. Neither birth weight, mode of delivery, Apgar score, nor gestational age was associated with the risk of HPeV infections. Compared with firstborn children, secondborn children were at a 9-fold increased risk (incidence rate ratio = 8.68, 95% confidence interval: 3.85,19.53) of contracting HPeV-3 infections, but at no increased risk of contracting non-HPeV-3 infections. However, the shorter the age gap to the nearest older sibling, the higher the risk of HPeV-3 as well as non-HPeV-3 infections, although the trend was strongest for HPeV-3 infections. Our study is the first to suggest that having a slightly older sibling increases the risk for severe neonatal HPeV infections. This new knowledge might lead to new preventive measures. [ABSTRACT FROM AUTHOR]

Several studies have investigated the effects of fish oil (FO) on infant growth, but little is known about the effects of FO and sex on insulin-like growth factor-1 (IGF-1), the main regulator of growth in childhood. We explored whether FO v. sunflower oil (SO) supplementation from 9 to 18 months of age affected IGF-1 and its binding protein-3 (IGFBP-3) and whether the potential effects were sex specific. Danish infants (n 115) were randomly allocated to 5 ml/d FO (1·2 g/d n-3 long-chain PUFA (n-3 LCPUFA)) or SO. We measured growth, IGF-1, IGFBP-3 and erythrocyte EPA, a biomarker of n-3 LCPUFA intake and status, at 9 and 18 months. Erythrocyte EPA increased strongly with FO compared with SO (P< 0·001). There were no effects of FO compared with SO on IGF-1 in the total population, but a sex group interaction (P =0·02). Baseline-adjusted IGF-1 at 18 months was 11·1 μg/l (95% CI 0·4, 21·8; P=0·04) higher after FO compared with SO supplementation among boys only. The sex group interaction was borderline significant in the model of IGFBP-3 (P=0·09), with lower IGFBP-3 with FO compared with SO among girls only (P =0·03). The results were supported by sex-specific dose-response associations between changes in erythrocyte EPA and changes in IGF-1 and IGFBP-3 (both P<0·03). Moreover, IGF-1 was sex specifically associated with BMI and length. In conclusion, FO compared with SO resulted in higher IGF-1 among boys and lower IGFBP-3 among girls. The potential long-term implications for growth and body composition should be investigated further. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure to traffic noise has been associated with adverse effects on neuro-psychological outcomes in children, but findings with regard to behavioral problems are inconsistent. OBJECTIVE: We investigated whether residential road traffic noise exposure is associated with behavioral problems in 7-year-old children. METHODS: We identified 46,940 children from the Danish National Birth Cohort with complete information on behavioral problems at 7 years of age and complete address history from conception to 7 years of age. Road traffic noise (Lden) was modeled at all present and historical addresses. Behavioral problems were assessed by the parent-reported Strengths and Difficulties Questionnaire (SDQ). Associations between pregnancy and childhood exposure to noise and behavioral problems were analyzed by multinomial or logistic regression and adjusted for potential confounders. RESULTS: A 10-dB increase in average time-weighted road traffic noise exposure from birth to 7 years of age was associated with a 7% increase (95% CI: 1.00, 1.14) in abnormal versus normal total difficulties scores; 5% (95% CI: 1.00, 1.10) and 9% (95% CI: 1.03, 1.18) increases in borderline and abnormal hyperactivity/inattention subscale scores, respectively; and 5% (95% CI: 0.98, 1.14) and 6% (95% CI: 0.99, 1.12) increases in abnormal conduct problem and peer relationship problem subscale scores, respectively. Exposure to road traffic noise during pregnancy was not associated with child behavioral problems at 7 years of age. CONCLUSIONS: Residential road traffic noise in early childhood may be associated with behavioral problems, particularly hyperactivity/inattention symptoms. [ABSTRACT FROM AUTHOR]

Sufficient summer/autumn vitamin D status appears important to mitigate winter nadirs at northern latitudes. We conducted a cross-sectional study to evaluate autumn vitamin D status and its determinants in 782 Danish 8–11-year-old children (55°N) using baseline data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study, a large randomised controlled trial. Blood samples and demographic and behavioural data, including 7-d dietary recordings, objectively measured physical activity, and time spent outdoors during school hours, were collected during September–November. Mean serum 25-hydroxyvitamin D (25(OH)D) was 60·8 (SD 18·7) nmol/l. Serum 25(OH)D levels ≤50 nmol/l were found in 28·4% of the children and 2·4% had concentrations <25 nmol/l. Upon multivariate adjustment, increasing age (per year) (β −2·9; 95% CI −5·1, −0·7 nmol/l), female sex (β −3·3; 95% CI −5·9, −0·7 nmol/l), sampling in October (β −5·2; 95% CI −10·1, −0·4 nmol/l) and November (β −13·3; 95% CI −17·7, −9·1), and non-white ethnicity (β −5·7; 95% CI −11·1, −0·3 nmol/l) were negatively associated with 25(OH)D (all P<0·05). Likewise, immigrant/descendant background was negatively associated with 25(OH)D, particularly in females (β −16·3; 95% CI −21·9, −10·7) (P<0·001) (Pinteraction=0·003). Moderate-to-vigorous physical activity (MVPA) (min/d) (β 0·06; 95% CI 0·01, 0·12), outdoor walking during school hours (min/week) (β 0·4; 95% CI 0·1, 0·6) and intake of vitamin D-containing supplements ≥3 d/week (β 8·7; 95% CI 6·4, 11·0) were positively associated with 25(OH)D (all P<0·05). The high proportion of children with vitamin D status below the recommended sufficiency level of 50 nmol/l raises concern as levels expectedly drop further during winter months. Frequent intake of vitamin D supplements was strongly associated with status. MVPA and outdoor activity during school hours should be investigated further in interventions to improve autumn vitamin D status in children at northern latitudes. [ABSTRACT FROM AUTHOR]

In a prospective cohort study, the association between maternal vitamin D status during pregnancy and offspring forearm fractures during childhood and adolescence was analysed in 30 132 mother and child pairs recruited to the Danish National Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and lifestyle factors were collected on several occasions during pregnancy. We analysed the association between predicted vitamin D status, based on a subsample with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation week 25, and first-time forearm fractures among offspring between birth and end of follow-up. Diagnoses were extracted from the Danish National Patient Register. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between predicted vitamin D status (based on smoking, season, dietary and supplementary vitamin D intake, tanning bed use and outdoor physical activity) in pregnancy and offspring forearm fractures. Likewise, measured 25(OH)D, tanning bed use and dietary vitamin D intake were not associated with offspring forearm fractures. In mid-pregnancy, 91 % of the women reported intake of vitamin D from dietary supplements. Offspring of women who took >10 µg/d in mid-pregnancy had a significantly increased risk for fractures compared with the reference level of zero intake (hazard ratios (HR) 1·31; 95 % CI 1·06, 1·62), but this was solely among girls (HR 1·48; 95 % CI 1·10, 2·00). Supplement use in the peri-conceptional period exhibited similar pattern, although not statistically significant. In conclusion, our data indicated no protective effect of maternal vitamin D status with respect to offspring forearm fractures. [ABSTRACT FROM PUBLISHER]

Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8–11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August–November. Mean serum 25(OH)D was 60·8 (sd 18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (−0·3 mmHg, 95 % CI −0·6, −0·0) (P=0·02), total cholesterol (−0·07 mmol/l, 95 % CI −0·10, −0·05), LDL-cholesterol (−0·05 mmol/l, 95 % CI −0·08, −0·03), TAG (−0·02 mmol/l, 95 % CI −0·03, −0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause–effect relationship and possible long-term implications should be investigated in randomised controlled trials. [ABSTRACT FROM PUBLISHER]

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: ‘school performance’ and ‘reading comprehension’. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved ‘school performance’ (P=0·015), ‘reading comprehension’ (P=0·043) and EPA+DHA status 0·21 (95 % CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer ‘school performance’ in girls, but with better ‘reading comprehension’ in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with ‘school performance’, suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study. [ABSTRACT FROM PUBLISHER]

A New Nordic Diet (NND) was developed in the context of the Danish OPUS Study (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet). Health, gastronomic potential, sustainability and Nordic identity were crucial principles of the NND. The aim of the present study was to investigate the effects of serving NND school meals compared with the usual packed lunches on the dietary intake of NND signature foods. For two 3-month periods, 834 Danish children aged 8–11 years received NND school meals or their usual packed lunches brought from home (control) in random order. The entire diet was recorded over 7 consecutive days using a validated Web-based Dietary Assessment Software for Children. The NND resulted in higher intakes during the entire week (% increase) of root vegetables (116 (95 % CI 1·93, 2·42)), cabbage (26 (95 % CI 1·08, 1·47)), legumes (22 (95 % CI 1·06, 1·40)), herbs (175 (95 % CI 2·36, 3·20)), fresh berries (48 (95 % CI 1·13, 1·94)), nuts and seeds (18 (95 % CI 1·02, 1·38)), lean fish and fish products (47 (95 % CI 1·31, 1·66)), fat fish and fish products (18 (95 % CI 1·02, 1·37)) and potatoes (129 (95 % CI 2·05, 2·56)). Furthermore, there was a decrease in the number of children with zero intakes when their habitual packed lunches were replaced by NND school meals. In conclusion, this study showed that the children increased their intake of NND signature foods, and, furthermore, there was a decrease in the number of children with zero intakes of NND signature foods when their habitual packed lunches were replaced by school meals following the NND principles. [ABSTRACT FROM PUBLISHER]

Objective. To evaluate the effect of two intervention modalities concerning overweight and obesity among children in general practice. Design. Prospective randomized controlled trial. Setting. A total of 60 general practices in the former County of Funen, Denmark. Subjects. Overweight children, identified by International Obesity Task Force criteria, aged 5–9 years. Intervention. Model 1 with health consultations in general practice during a two-year period or Model 2, an educational programme for the children and their families in addition to the health consultations. Main outcome measures. Change in body mass index (BMI) z-score in order to compare the results, independent of gender- and age-related changes over time. Results. A total of 80 children were recruited with 35 and 45 children allocated to Model 1 and Model 2, respectively. No significant differences were found in the change in BMI z-score (SDS) between the two groups. A decrease in the mean BMI z-score from baseline to study end of −0.20 (95%CI −0.38 to −0.01) in Model 1 and −0.26 (95%CI −0.44 to −0.09) in Model 2, respectively, was detected. The majority of the participants (2/3) continued in the study for more than one year in both models, with a mean of 12 consultations in general practice. Conclusion. In this particular setting the two intervention strategies against overweight and obesity did not differ significantly with regard to change in BMI z-scores. [ABSTRACT FROM AUTHOR]

An increasing number of children are exhibiting features of the metabolic syndrome (MetS) including abdominal fatness, hypertension, adverse lipid profile and insulin resistance. Healthy eating practices during school hours may improve the cardiometabolic profile, but there is a lack of evidence. In the present study, the effect of provision of school meals rich in fish, vegetables and fibre on a MetS score (primary outcome) and on individual cardiometabolic markers and body composition (secondary outcomes) was investigated in 834 Danish school children. The study was carried out as a cluster-randomised, controlled, non-blinded, cross-over trial at nine schools. Children aged 8–11 years received freshly prepared school lunch and snacks or usual packed lunch from home (control) each for 3 months. Dietary intake, physical activity, cardiometabolic markers and body composition were measured at baseline and after each dietary period. The school meals did not affect the MetS score (P= 1·00). However, it was found that mean arterial pressure was reduced by 0·4 (95 % CI 0·0, 0·8) mmHg (P= 0·04), fasting total cholesterol concentrations by 0·05 (95 % CI 0·02, 0·08) mmol/l (P= 0·001), HDL-cholesterol concentrations by 0·02 (95 % CI 0·00, 0·03) mmol/l, TAG concentrations by 0·02 (95 % CI 0·00, 0·04) mmol/l (both P< 0·05), and homeostasis model of assessment-insulin resistance by 0·10 (95 % CI 0·04, 0·16) points (P= 0·001) compared with the control diet in the intention-to-treat analyses. Waist circumference increased 0·5 (95 % CI 0·3, 0·7) cm (P< 0·001), but BMI z-score remained unaffected. Complete-case analyses and analyses adjusted for household educational level, pubertal status and physical activity confirmed the results. In conclusion, the school meals did not affect the MetS score in 8–11-year-olds, as small improvements in blood pressure, TAG concentrations and insulin resistance were counterbalanced by slight undesired effects on waist circumference and HDL-cholesterol concentrations. [ABSTRACT FROM PUBLISHER]

Background. Primarily, this study aims to examine whether children attending sports schools are more active than their counterpart attending normal schools. Secondary, the study aims to examine if physical activity (PA) levels in specific domains differ across school types. Finally, potential modifications by status of overweight/obesity and poor cardio-respiratory fitness are examined. Methods. Participants were from the first part of the CHAMPS-study DK, which included approximately 1200 children attending the 0th – 6th grade. At the sports schools, the mandatory physical education (PE) program was increased from 2 to 6 weekly lessons over a 3-year period. Children attending normal schools were offered the standard 2 PE lessons. PA was assessed at two different occasions with the GT3X ActiGraph accelerometer, once during winter in 2009/10 and once during summer/fall in 2010. Leisure time organized sports participation was quantified by SMS track. Based on baseline values in 2008, we generated a high-BMI and a low-cardio-respiratory fitness for age and sex group variable. Results. There were no significant differences in PA levels during total time, PE, or recess between children attending sports schools and normal schools, respectively. However, children, especially boys, attending sports schools were more active during school time than children attending normal schools (girls: β=51, p=0.065; boys: β=113, p<0.001). However, in the leisure time during weekdays children who attended sports schools were less active (girls: β=-41, p=0.004; boys: β=-72, p<0.001) and less involved in leisure time organized sports participation (girls: β=-0.4, p=0.016; boys: β=-0.2, p=0.236) than children who attended normal schools. Examination of modification by baseline status of overweight/obesity and low cardio-respiratory fitness indicated that during PE low fit girls in particular were more active at sports schools. Conclusion. No differences were revealed in overall PA levels between children attending sports schools and normal schools. Sports schools children were more active than normal schools children during school time, but less active during leisure time. In girls, less organized sports participation at least partly explained the observed differences in PA levels during leisure time across school types. Baseline status of cardio-respiratory fitness modified school type differences in PA levels during PE in girls. [ABSTRACT FROM AUTHOR]

The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (NND)) School Meal Study investigated the effects on the intake of foods and nutrients of introducing school meals based on the principles of the NND covering lunch and all snacks during the school day in a cluster-randomised cross-over design. For two 3-month periods, 834 Danish children aged 8–11 years from forty-six school classes at nine schools received NND school meals or their usual packed lunches brought from home (control) in random order. The whole diet of the children was recorded over seven consecutive days using a validated Web-based Dietary Assessment Software for Children. The NND resulted in higher intakes of potatoes (130 %, 95 % CI 2·07, 2·58), fish (48 %, 95 % CI 1·33, 1·65), cheese (25 %, 95 % CI 1·15, 1·36), vegetables (16 %, 95 % CI 1·10, 1·21), eggs (10 %, 95 % CI 1·01, 1·19) and beverages (6 %, 95 % CI 1·02, 1·09), and lower intakes of bread (13 %, 95 % CI 0·84, 0·89) and fats (6 %, 95 % CI 0·90, 0·98) were found among the children during the NND period than in the control period (all, P< 0·05). No difference was found in mean energy intake (P= 0·4), but on average children reported 0·9 % less energy intake from fat and 0·9 % higher energy intake from protein during the NND period than in the control period. For micronutrient intakes, the largest differences were found for vitamin D (42 %, 95 % CI 1·32, 1·53) and iodine (11 %, 95 % CI 1·08, 1·15) due to the higher fish intake. In conclusion, the present study showed that the overall dietary intake at the food and nutrient levels was improved among children aged 8–11 years when their habitual packed lunches were replaced by school meals following the principles of the NND. [ABSTRACT FROM PUBLISHER]

Purpose: (1) Examine the influence of extra physical education (EPE) on the number of musculoskeletal injuries in public schools accounting for organized sports participation (OSP) outside school. (2) Examine the major injury subgroup: growth-related overuse (GRO) through the overuse-related injury group. Methods: A longitudinal controlled school-based study among Danish public schools. At baseline, 1216 children participated age 6.2-12.4 yr. Six schools (701 children) with EPE and four control schools (515 children) were followed up with weekly automated mobile phone text messages for information on musculoskeletal problems and OSP. Health care personnel diagnosed the children according to the World Health Organization's International Classification of Diseases, Tenth Revision. Data were analyzed using a two-part zero-inflated negative binomial (ZINB) regression model. Results: School type had no influence on the odds of sustaining an injury but increased the probability of sustaining a higher injury count for children with injuries, with total injuries by a factor of 1.29 (95% confidence interval [CI] = 1.07-1.56), overuse by a factor of 1.29 (95% CI = 1.06-1.55), and GRO by a factor of 1.38 (95% CI = 1.02-1.80). Weekly mean OSP decreased the odds of belonging to the group of children with no injuries, by a factor of 0.29 (95% CI = 0.14-0.58), 0.26 (95% CI = 0.14-0.48), and 0.17 (95% CI = 0.06-0,52) for total, overuse, and GRO, respectively. OSP also increased the probability of sustaining a higher injury count for children with injuries by a factor of 1.11 (95% CI = 1.02-1.22), 1.10 (95% CI = 1.00-1.22), and 1.14 (95% CI = 1.00-1.30), respectively. Conclusions: Children enrolled in EPE schools with high OSP have the highest odds of injury and a high probability of sustaining a higher injury count compared to their peers at schools with normal PE. Special attention should be assigned to these children during compulsory PE. [ABSTRACT FROM AUTHOR]

Fat-soluble vitamins A, E and K have been shown to play roles in immunity and inflammation, but studies on child allergic disease have been few and inconsistent. The aim of the present study was to examine the relationship between maternal intake of vitamins A, E and K in mid-pregnancy and child asthma and allergic rhinitis. We used data on 44 594 mother–child pairs from the Danish National Birth Cohort. Maternal intake of fat-soluble vitamins was calculated based on the information from a validated FFQ completed in mid-pregnancy. At 18 months, interviews with the mothers were conducted to evaluate doctor-diagnosed child asthma. At age 7 years, we assessed child asthma and allergic rhinitis using questions from the International Study of Asthma and Allergies in Childhood questionnaire and by national registries on hospital contacts and medication use. Current asthma was defined as asthma diagnosis and wheeze in the past 12 months by maternal report. We calculated multivariable risk ratios and 95 % CI by comparing the highest v. lowest quintile (Q) of maternal vitamin A, E and K intake in relation to child allergic disease outcomes. Maternal total vitamin K intake was directly associated with ever admitted asthma (Q5 v. Q1: 1·23, 95 % CI 1·01, 1·50) and current asthma at 7 years (Q5 v. Q1: 1·30, 95 % CI 0·99, 1·70). Weak inverse associations were present for maternal vitamin A and E intake during pregnancy with child allergic rhinitis. Maternal vitamin K intake during pregnancy may increase the risk of child asthma, and should be explored further on a mechanistic level. Conversely, maternal vitamin A and E intake may protect against child allergic rhinitis. [ABSTRACT FROM PUBLISHER]

The aim of the present study was to validate thirty-eight picture series of six pictures each developed within the PANCAKE (Pilot study for the Assessment of Nutrient intake and food Consumption Among Kids in Europe) project for portion size estimation of foods consumed by infants, toddlers and children for future pan-European and national dietary surveys. Identical validation sessions were conducted in three European countries. In each country, forty-five foods were evaluated; thirty-eight foods were the same as the depicted foods, and seven foods were different, but meant to be quantified by the use of one of the thirty-eight picture series. Each single picture within a picture series was evaluated six times by means of predefined portions. Therefore, thirty-six pre-weighed portions of each food were evaluated by convenience samples of parents having children aged from 3 months to 10 years. The percentages of participants choosing the correct picture, the picture adjacent to the correct picture or a distant picture were calculated, and the performance of individual pictures within the series was assessed. For twenty foods, the picture series performed acceptably (mean difference between the estimated portion number and the served portion number less than 0·4 (sd < 1·1)). In addition, twelve foods were rated acceptable after adjustment for density differences. Some other series became acceptable after analyses at the country level. In conclusion, all picture series were acceptable for inclusion in the PANCAKE picture book. However, the picture series of baby food, salads and cakes either can only be used for foods that are very similar to those depicted or need to be substituted by another quantification tool. [ABSTRACT FROM PUBLISHER]

Maternal fish intake during pregnancy may influence the risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with these outcomes. We examined the associations of maternal fish intake during pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (n 28 936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined the associations of fish intake with child wheeze, asthma and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (n approximately 22 000) and 7 years (n approximately 17 000) using self-report and registry data on hospitalisations and prescribed medications. Compared with consistently high fish intake during pregnancy (fish as a sandwich or hot meal ≥ 2–3 times/week), never eating fish was associated with a higher risk of child asthma diagnosis at 18 months (OR 1·30, 95 % CI 1·05, 1·63, P= 0·02), and ever asthma by hospitalisation (OR 1·46, 95 % CI 0·99, 2·13, P= 0·05) and medication prescription (OR 1·37, 95 % CI 1·10, 1·71, P= 0·01). A dose–response was present for asthma at 18 months only (P for trend = 0·001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis. The results suggest that high (v. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7-year-old children. [ABSTRACT FROM PUBLISHER]

Background: Perfluoroalkyl acids 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 biomarkers 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. [ABSTRACT FROM AUTHOR]

Objective: The objective of the present study was to evaluate energy intake (EI) estimated from two nonconsecutive 24-hour recalls (24-HDRs) and a pre-coded seven-day food record (7-dFR) against objective measurements of energy expenditure (EE) in children. Design: A total of 67 7-8 year-olds and 64 12-13 year-olds completed the 2 x 24-HDRs, the 7-dFR, and woreActiReg® (PreMed AS, Oslo, Norway), a combined position and motion recording instrument, during thesame seven days as the 7-dFR was filled in. Results: In the 7-8 year-olds, EI from the 2 x 24-HDRs (EI2 x 24-HDR) was overestimated with 3% compared to EE (not significantly different), while EI from the 7-dFR (EI7-dFR) was underestimated with 7% compared to EE (P=0.001). In the 12-13 year-olds, the corresponding figures was underestimation by 10% with the 2 x 24-HDRs (P<0.001) and by 20% with the 7-dFR (P<0.001). For both age groups combined, the 95% limits of agreement were -4 • 38 and 3.52 MJ/d for the 2 x 24-HDRs, and -5.90 and 2.94 MJ/d forthe 7-dFR. Pearson correlation coefficients between EI and EE were 0.51 for EI2 x 24-HDR and 0.29 forEI7-dFR, respectively. The proportion classified in the same or adjacent quartiles was 76% for EI224-HDRand 73% for EI7-dFR in the 78 year-olds, and 83% for EI2 x 24-HDR and 70% for EI7-dFR in the 12-13 year-olds. Conclusion: Misreporting of EI seemed modest with both the 2 x 24-HDRs and the 7-dFR in the 7-8 year-olds when compared to EE measured with ActiReg®. Under-reporting appeared to be more evident inthe 12-13 year-olds, especially with the 7-dFR. Compared to measurements of EE, the 2 x 24-HDRs seemed to perform slightly better than the 7-dFR in terms of ranking of individuals according to EI. [ABSTRACT FROM AUTHOR]

Background. Maternal distress during pregnancy increases the intrauterine level of glucocorticoids, which may have long-term health consequences for the child. Objective. To examine if distress as a combined measure of anxiety, depression, and stress of the mother during pregnancy was associated with offspring childhood overweight at age 7. Methods. We performed a cohort study using prospective data from 37,764 women and child dyads from the Danish National Birth Cohort (1996-2002). At a telephone interview at approximately 30 weeks gestation, the women reported whether they felt anxious, depressed, or stressed. The 95 percentile for body mass index in an international reference defined childhood overweight at any given age. Logistic regression was used for the analyses. Results. The prevalence of overweight children at 7 years of age was 9.9%. Prenatal exposure to maternal distress during pregnancy was not associated with childhood overweight at 7 years of age (adjusted OR 1.06 (95% CI 0.96; 1.18)). In analyses stratified on sex, a small tendency of overweight was seen in boys (OR 1.15 (0.99; 1.33)), but not in girls (OR0.98 (0.85; 1.13)). Conclusions. Maternal distress during pregnancy appeared to have limited, if any, influence on the risk of overweight in offspring at 7 years of age. [ABSTRACT FROM AUTHOR]

Background: Identifying risk factors for adverse health outcomes in children is important. The intrauterine environment plays a pivotal role for health and disease across life. Objectives: We conducted a comprehensive study to determine whether common psychosocial stress during pregnancy is a risk factor for a wide spectrum of pediatric diseases in the offspring. Methods: The study was conducted using prospective data in a population-based sample of mothers with live singleton births (n = 66,203; 71.4% of those eligible) from the Danish National Birth Cohort. We estimated the association between maternal stress during pregnancy (classified based on two a priori-defined indicators of common stress forms, life stress and emotional stress) and offspring diseases during childhood (grouped into 16 categories of diagnoses from the International Classification of Diseases, 10th Revision, based on data from national registries), controlling for maternal stress after pregnancy. Results: Median age at end of follow-up was 6.2 (range, 3.6-8.9) years. Life stress (highest compared with lowest quartile) was associated with an increased risk of conditions originating in the perinatal period [odds ratio (OR) = 1.13; 95% confidence interval (CI): 1.06, 1.21] and congenital malformations (OR=1.17; CI: 1.06, 1.28) and of the first diagnosis of infection [hazard ratio (HR) = 1.28; CI: 1.17, 1.39], mental disorders (age 0-2.5 years: HR = 2.03; CI: 1.32, 3.14), and eye (age 0-4.5 years: HR = 1.27; CI: 1.06, 1.53), ear (HR = 1.36; CI: 1.23, 1.51), respiratory (HR = 1.27; CI; 1.19, 1.35), digestive (HR = 1.23; CI: 1.11, 1.37), skin (HR = 1.24; CI: 1.09, 1.43), musculoskeletal (HR = 1.15; CI: 1.01-1.30), and genitourinary diseases (HR = 1.25; CI; 1.08, 1.45). Emotional stress was associated with an increased risk for the first diagnosis of infection (HR = 1.09; CI: 1.01, 1.18) and a decreased risk for the first diagnosis of endocrine (HR = 0.81; CI; 0.67, 0.99), eye (HR = 0.84; CI; 0.71, 0.99), and circulatory diseases (age 0-3 years: HR = 0.63; CI: 0.42, 0.95). Conclusions: Maternal life stress during pregnancy may be a common risk factor for impaired child health. The results suggest new approaches to reduce childhood diseases. [ABSTRACT FROM AUTHOR]

Animal studies have suggested that prenatal stress could affect the immune system of the offspring. In a nation-wide cohort of all Danish children born from 1977 to 2004, the authors examined the association between prenatal stress, defined as maternal exposure to a stressful life event during pregnancy or in the 3-year period before conception, and the risk of severe or less severe infectious disease hospitalization in childhood. Log-linear Poisson regression models provided estimates of rate ratios. Compared with nonexposed children, children exposed prenatally to stress had a 25% (rate ratio (RR) = 1.25, 95% confidence interval (CI): 1.06, 1.47) and a 31% (RR = 1.31, 95% CI: 1.27, 1.35) increased risk of being hospitalized with a severe or a less severe infectious disease, respectively. Children born to mothers exposed to a stressful life event during pregnancy, during the 11 months before, or during the 12–35 months before conception were at 71% (RR = 1.71, 95% CI: 1.20, 2.45), 42% (RR = 1.42, 95% CI: 1.13, 1.78), and no increased (RR = 0.86, 95% CI: 0.63, 1.18) risk of severe infectious disease hospitalization. No obvious association between risk of less severe infectious disease hospitalization and timing of maternal exposure was observed. Although the authors could not determine whether this is a biologic effect of prenatal stress or an effect of other factors related indirectly to a stressful life event, their results add new information about the consequences of prenatal stress. [ABSTRACT FROM PUBLISHER]

Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are persistent chemicals that may affect growth early in life. The authors estimated the associations between maternal plasma levels of PFOS and PFOA and infants’ weight, length, and body mass index development during the first year of life. Fourteen hundred women were randomly selected from the Danish National Birth Cohort among those who provided blood samples early in pregnancy and gave birth to liveborn singletons between 1996 and 2002. Weight and length information at 5 and 12 months of age was available for 1,010 children. Multiple linear regression models were used for analyses, and maternal PFOS and PFOA concentrations (ng/mL) were inversely related to children's weight in the first year of life: adjusted regression coefficients: −1.1 g (95% confidence interval (CI): −4.6, 2.3) at 5 months and −5.8 g (95% CI: −10.4, −1.2) at 12 months for PFOS; −10.6 g (95% CI: −30.2, 8.9) at 5 months and −19.7 g (95% CI: −45.9, 6.5) at 12 months for PFOA. A similar pattern was observed for body mass index measurements, and no associations with length were found. After sex stratification, the inverse associations with weight and body mass index were more pronounced in boys, and no clear association was seen for girls. [ABSTRACT FROM PUBLISHER]

Background: Acute otitis media (AOM) is a common and most often self-limiting infection in childhood, usually managed in general practice. Even though antibiotics are only recommended when certain diagnostic and clinical criteria are met a high antibiotic prescription rate is observed. The study's objective was to analyse associations between patient- and general practitioner (GP) characteristics and antibiotic prescribing for children with AOM in an effort to explain the high antibiotic prescribing rates. Methods: All general practices in the Northern, Southern and Central regions of Denmark were invited to record symptoms, examinations, findings and antibiotic treatment for all children ≤7 years of age diagnosed with AOM during a four-week winter period in 2017/2018. Associations were analysed by means of multivariate logistic regressions. The study design was cross-sectional. Results: GPs from 60 general practices diagnosed 278 children with AOM of whom 207 (74%) were prescribed antibiotics, most often penicillin V (60%). About half of the children had tympanometry performed. Antibiotic prescribing rates varied considerably between practices (0–100%). Antibiotic prescribing was associated with fever (odds ratio (OR) 3.69 95% confidence interval (CI) 1.93–7.05), purulent ear secretion (OR 2.35 95% CI 1.01–5.50) and poor general condition (OR 3.12 95% CI 1.31–7.46), and the practice's antibiotic prescribing rate to other patients with symptoms of an acute respiratory tract infection (OR 2.85 CI 95% 1.07–7.60) and specifically to other children with AOM (OR 4.15 CI 95% 1.82–9.47). Conclusion: GPs' antibiotic prescribing rates for children with AOM vary considerably even considering the of signs, symptoms, request for antibiotics, and use of tympanometry. Interventions to reduce overprescribing should be targeted high-prescribing practices. [ABSTRACT FROM AUTHOR]

Background: In children, spinal pain is transitory for most, but up to 20% experience recurrent and bothersome complaints. It is generally acknowledged that interventions may be more effective for subgroups of those affected with low back pain. In this secondary analysis of data from a randomized clinical trial, we tested whether five indicators of a potential increased need for treatment might act as effect modifiers for manipulative therapy in the treatment of spinal pain in children. We hypothesized that the most severely affected children would benefit more from manipulative therapy. Method: This study was a secondary analysis of data from a randomised controlled trial comparing advice, exercises and soft tissue treatment with and without the addition of manipulative therapy in 238 Danish school children aged 9–15 years complaining of spinal pain. A text message system (SMS) and clinical examinations were used for data collection (February 2012 to April 2014). Five pre-specified potential effect modifiers were explored: Number of weeks with spinal pain 6 months prior to inclusion, number of weeks with co-occurring musculoskeletal pain 6 months prior to inclusion, expectations of the clinical course, pain intensity, and quality of life. Outcomes were number of recurrences of spinal pain, number of weeks with pain, length of episodes, global perceived effect, and change in pain intensity. To explore potential effect modification, various types of regression models were used depending on the type of outcome, including interaction tests. Results: We found that children with long duration of spinal pain or co-occurring musculoskeletal pain prior to inclusion as well as low quality of life at baseline tended to benefit from manipulative therapy over non-manipulative therapy, whereas the opposite was seen for children reporting high intensity of pain. However, most results were statistically insignificant. Conclusions: This secondary analysis indicates that children more effected by certain baseline characteristics, but not pain intensity, have a greater chance to benefit from treatment that include manipulative therapy. However, these analyses were both secondary and underpowered, and therefore merely exploratory. The results underline the need for a careful choice of inclusion criteria in future investigations of manipulative therapy in children. Trial registration: NCT01504698; results [ABSTRACT FROM AUTHOR]

The article focuses on a summary of a cohort study conducted on children who were born between 1995 and 2003 in Denmark, regarding the analysis of risk of childhood and adolescent mental disability for being conceived after fertility treatment. It highlights that children develop some perinatal problems that are born after fertility treatment. The study depicted that the risk of mental disorders ameliorated in children born after ovulation induction or intrauterine insemination.