Search

Background Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite. Objectives We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated. Method We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias. Results In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sen, BACKGROUND: Prenatal exposures to xenobiotics during the masculinization programming window are suggested to impact male fecundity later in life. Frequently used nitrosatable drugs, such as penicillins and beta2-agonists, contain amines or amides that may form teratogenic compounds in reaction with nitrite.OBJECTIVES: We explored whether maternal nitrosatable drug use during gestation was associated with biomarkers of male fecundity in adulthood; moreover, the potential modifiable effect of nitrate and vitamin intake was investigated.METHOD: We performed a cohort study in the Fetal Programming of Semen Quality cohort that includes semen characteristics, reproductive hormone concentrations, and measures of testis size on 1058 young adult sons in the Danish National Birth Cohort. Information on maternal use of nitrosatable drugs was obtained from questionnaires and interviews around gestational weeks 11 and 16. A multivariable negative binomial regression model was used to obtain relative differences in biomarkers of male fecundity for those whose mothers used nitrosatable drugs compared to those without such maternal use. In sub-analyses, the exposure was categorized according to nitrosatable drug type: secondary amine, tertiary amine, or amide. We investigated dose dependency by examining the number of weeks with intake and explored potential effect modification by low versus high maternal nitrate and vitamin intake from diet and nitrate concentration in drinking water. We added selection weights and imputed values of missing covariates to limit the risk of selection bias.RESULTS: In total, 19.6% of the study population were born of mothers with an intake of nitrosatable drugs at least once during early pregnancy. Relative differences in biomarkers related to male fecundity between exposed and unexposed participants were negligible. Imputation of missing covariates did not fundamentally alter the results. Furthermore, no sensitive subpopulati

Importance Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone. Objective To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers. Design, Setting, and Participants This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023. Exposure Duration of exclusive breastfeeding in infancy. Main Outcomes and Measures Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models. Results A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to, IMPORTANCE: Breastfeeding has been suggested to protect against childhood cancers, particularly acute lymphoblastic leukemia (ALL). However, the evidence stems from case-control studies alone.OBJECTIVE: To investigate whether longer duration of exclusive breastfeeding is associated with decreased risk of childhood ALL and other childhood cancers.DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used administrative data on exclusive breastfeeding duration from the Danish National Child Health Register. All children born in Denmark between January 2005 and December 2018 with available information on duration of exclusive breastfeeding were included. Children were followed up from age 1 year until childhood cancer diagnosis, loss to follow-up or emigration, death, age 15 years, or December 31, 2020. Data were analyzed from March to October 2023.EXPOSURE: Duration of exclusive breastfeeding in infancy.MAIN OUTCOMES AND MEASURES: Associations between duration of exclusive breastfeeding and risk of childhood cancer overall and by subtypes were estimated as adjusted hazard ratios (AHRs) with 95% CIs using stratified Cox proportional hazards regression models.RESULTS: A total of 309 473 children were included (51.3% boys). During 1 679 635 person-years of follow-up, 332 children (0.1%) were diagnosed with cancer at ages 1 to 14 years (mean [SD] age at diagnosis, 4.24 [2.67] years; 194 boys [58.4%]). Of these, 124 (37.3%) were diagnosed with hematologic cancers (81 [65.3%] were ALL, 74 [91.4%] of which were B-cell precursor [BCP] ALL), 44 (13.3%) with central nervous system tumors, 80 (24.1%) with solid tumors, and 84 (25.3%) with other and unspecified malignant neoplasms. Compared with exclusive breastfeeding duration of less than 3 months, exclusive breastfeeding for 3 months or longer was associated with a decreased risk of hematologic cancers (AHR, 0.66; 95% CI, 0.46-0.95), which was largely attributable to decrea

Vinding, Stokholm, Chaves, Bønnelykke and others, in the present issue of the American Journal of Clinical Nutrition, report potentially harmful offspring effects of taking supplements with long chain n-3 fatty acids, also known as n-3 polyunsaturated fatty acids (LCPUFAs) in pregnancy [1]. They examined the impact of maternal supplementation with fish oil during gestation, starting in week 24, on offspring growth and metabolic health assessed when the children were 10 y old. The study was based on follow-up from an influential trial in the field, the COPSAC2010 Study, which in 2016 provided evidence that fish oil could reduce offspring risk of persistent wheeze or asthma and infections of the lower respiratory tract, assessed up to age 5 y [2]. A number of additional studies focusing on a range of different outcomes in children have since been published based on this very same trial population. In the present work, the authors undertook physical examinations of the children at 10 y of age [1]. This publication succeeds 2 earlier publications from the trial cohort, where related outcomes were studied, one reporting increased birth weight for gestational age after maternal supplementation with n-3 LCPUFA, and the other reporting increased BMI during ages 1 to 6 y (several assessments were undertaken of BMI during this age span), as well as increased lean mass, bone mass, and fat mass (assessed by dual x-ray absorptiometry scan) at 6 y. Based on this new analysis, the authors infer that children of mothers receiving long chain n-3 fatty acids in pregnancy seem to have increased BMI, increased risk of being overweight, a tendency of increased fat percentage, and higher metabolic syndrome score at the age of 10

Introduction The number of people adhering to plant-based diets has been increasing dramatically in recent years, fueled by both environmental and animal welfare concerns. Beneficial or possible adverse consequences of such diets, particularly the most restrictive forms during pregnancy, have been minimally explored. The aim of this prospective observational study was to examine associations between different forms of plant-based diets during pregnancy with birth outcomes and pregnancy complications. Material and methods The Danish National Birth Cohort included 100 413 pregnancies to 91 381 women in 1996–2002. The population consisted of 66 738 pregnancies, about which sufficient dietary data were available and included in the study. Dietary and supplemental intake was assessed by Food Frequency Questionnaire in gestational week 25 and women were characterized as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans or omnivorous, based on their self-report in gestational week 30. Main outcome measures were pregnancy and birth complications, birth weight and small for gestational age. Results A total of 98.7% (n = 65 872) of participants were defined as omnivorous, whereas 1.0% (n = 666), 0.3% (n = 183) and 0.03% (n = 18) identified themselves as fish/poultry vegetarians, lacto/ovo-vegetarians or vegans, respectively. Protein intake was lower among lacto/ovo-vegetarians (13.3%) and vegans (10.4%) than among omnivorous participants (15.4%). Intake of micronutrients was also considerably lower among vegans, but when dietary supplements were taken into consideration, no major differences were observed. Compared with omnivorous mothers, vegans had a higher prevalence of preeclampsia and their offspring had on average −240 g (95% confidence interval −450 to −30) lower birth weight. Conclusions The women reporting that they adhered to vegan diets during pregnancy had offspring with lower mean birth weight and higher risk of pr, Introduction: The number of people adhering to plant-based diets has been increasing dramatically in recent years, fueled by both environmental and animal welfare concerns. Beneficial or possible adverse consequences of such diets, particularly the most restrictive forms during pregnancy, have been minimally explored. The aim of this prospective observational study was to examine associations between different forms of plant-based diets during pregnancy with birth outcomes and pregnancy complications. Material and methods: The Danish National Birth Cohort included 100 413 pregnancies to 91 381 women in 1996–2002. The population consisted of 66 738 pregnancies, about which sufficient dietary data were available and included in the study. Dietary and supplemental intake was assessed by Food Frequency Questionnaire in gestational week 25 and women were characterized as fish/poultry-vegetarians, lacto/ovo-vegetarians, vegans or omnivorous, based on their self-report in gestational week 30. Main outcome measures were pregnancy and birth complications, birth weight and small for gestational age. Results: A total of 98.7% (n = 65 872) of participants were defined as omnivorous, whereas 1.0% (n = 666), 0.3% (n = 183) and 0.03% (n = 18) identified themselves as fish/poultry vegetarians, lacto/ovo-vegetarians or vegans, respectively. Protein intake was lower among lacto/ovo-vegetarians (13.3%) and vegans (10.4%) than among omnivorous participants (15.4%). Intake of micronutrients was also considerably lower among vegans, but when dietary supplements were taken into consideration, no major differences were observed. Compared with omnivorous mothers, vegans had a higher prevalence of preeclampsia and their offspring had on average −240 g (95% confidence interval −450 to −30) lower birth weight. Conclusions: The women reporting that they adhered to vegan diets during pregnancy had offspring with lower mean birth weight and higher risk of preeclampsia compared with omnivorous

Background N-nitroso compounds (NOCs) can be formed by endogenous reactions between nitrosatable drugs and nitrite. Animal studies have found that several NOCs are teratogenic, and epidemiological studies report associations between prenatal exposure to nitrosatable drugs and adverse birth outcomes. It is unknown whether prenatal exposure to nitrosatable drugs is harmful to the child's reproductive health, including pubertal development. Objectives We investigated whether prenatal exposure to nitrosatable drugs was associated with timing of puberty and whether nitrate, nitrite and antioxidant intake modified any association. Methods The population-based Danish National Birth Cohort (DNBC) Puberty Cohort, which includes 15,819 children, was used to investigate the association between prenatal exposure to nitrosatable drugs and timing of puberty. Around gestational week 11 and gestational week 18, mothers provided information about drug use during pregnancy. The children's self-reported information on onset of pubertal milestones was collected every six months from 11 years of age and throughout puberty. To investigate potential effect modification by nitrite, nitrate and antioxidant intake, information on these factors was obtained from a food frequency questionnaire completed by the mothers in gestational week 25, and information on nitrate concentration in maternal drinking water at her residential address was obtained from monitoring data from public waterworks. Data were analysed using a multivariable regression model for interval-censored data estimating difference in months in timing of puberty between exposure groups. Results A total of 2,715 children were prenatally exposed to nitrosatable drugs. We did not find an association between prenatal exposure to nitrosatable drugs and timing of puberty. This finding was supported by null-findings in the following sub-analyses investigating: 1. subtypes of nitrosatable drugs, Background: N-nitroso compounds (NOCs) can be formed by endogenous reactions between nitrosatable drugs and nitrite. Animal studies have found that several NOCs are teratogenic, and epidemiological studies report associations between prenatal exposure to nitrosatable drugs and adverse birth outcomes. It is unknown whether prenatal exposure to nitrosatable drugs is harmful to the child's reproductive health, including pubertal development. Objectives: We investigated whether prenatal exposure to nitrosatable drugs was associated with timing of puberty and whether nitrate, nitrite and antioxidant intake modified any association. Methods: The population-based Danish National Birth Cohort (DNBC) Puberty Cohort, which includes 15,819 children, was used to investigate the association between prenatal exposure to nitrosatable drugs and timing of puberty. Around gestational week 11 and gestational week 18, mothers provided information about drug use during pregnancy. The children's self-reported information on onset of pubertal milestones was collected every six months from 11 years of age and throughout puberty. To investigate potential effect modification by nitrite, nitrate and antioxidant intake, information on these factors was obtained from a food frequency questionnaire completed by the mothers in gestational week 25, and information on nitrate concentration in maternal drinking water at her residential address was obtained from monitoring data from public waterworks. Data were analysed using a multivariable regression model for interval-censored data estimating difference in months in timing of puberty between exposure groups. Results: A total of 2,715 children were prenatally exposed to nitrosatable drugs. We did not find an association between prenatal exposure to nitrosatable drugs and timing of puberty. This finding was supported by null-findings in the following sub-analyses investigating: 1. subtypes of nitrosatable drugs (secondary and tertiary amines and

OBJECTIVE It has been hypothesized that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children can increase risk of developing type 1 diabetes. RESEARCH DESIGN AND METHODS We undertook a prospective, register-based analysis of children in Denmark by investigating the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes. During the pandemic, Denmark had one of the highest test rates per capita in the world, and 90% of all Danish children were tested. RESULTS Compared with children with a history of only negative SARS-CoV-2 tests, we did not observe a higher risk of first-time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test (hazard ratio 0.85; 95% CI 0.70–1.04). CONCLUSIONS Our data do not support that SARS-CoV-2 infection is associated with type 1 diabetes or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children., OBJECTIVE: It has been hypothesized that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children can increase risk of developing type 1 diabetes. RESEARCH DESIGN AND METHODS: We undertook a prospective, register-based analysis of children in Denmark by investigating the association between SARS-CoV-2 infection and subsequent risk of type 1 diabetes. During the pandemic, Denmark had one of the highest test rates per capita in the world, and 90% of all Danish children were tested. RESULTS: Compared with children with a history of only negative SARS-CoV-2 tests, we did not observe a higher risk of first-time diagnosis of type 1 diabetes in children 30 days or more after a positive SARS-CoV-2 test (hazard ratio 0.85; 95% CI 0.70-1.04). CONCLUSIONS: Our data do not support that SARS-CoV-2 infection is associated with type 1 diabetes or that type 1 diabetes should be a special focus after a SARS-CoV-2 infection in children.

he food frequency questionnaire (FFQ) is designed to capture an individual’s habitual dietary intake and is the most applied method in nutritional epidemiology. Our aim was to assess the relative validity and reproducibility of the FFQ used in the Diet, Cancer, and Health—Next Generations cohort (DCH-NG). We included 415 Danish women and men aged 18–67 years. Spearman’s correlations coefficients, Bland–Altman limits of agreement and cross-classification between dietary intakes estimated from the FFQ administered at baseline (FFQbaseline), and the mean of three 24-h dietary recalls (24-HDRs) and the FFQ administered after 12 months (FFQ12 months) were determined. Nutrient intakes were energy-adjusted by Nutrient Density and Residual methods. Correlation coefficients ranged from 0.18–0.58 for energy and energy-adjusted nutrient intakes, and the percentage of participants classified into the same quartile ranged from 28–47% between the FFQbaseline and the 24-HDRs. For the FFQ12 months compared with FFQbaseline, correlation coefficients ranged from 0.52–0.88 for intakes of energy, energy-adjusted nutrients, and food groups, and the proportion of participants classified into the same quartiles ranged from 43–69%. Overall, the FFQ provided a satisfactory ranking of individuals according to energy, nutrient, and food group intakes, making the FFQ suitable for use in epidemiological studies investigating diet in relation to disease outcomes. Keywords: food frequency questionnaire; 24-h dietary recall; web-based; relative validity; reproducibility; epidemiology; nutrition; diet; cancer, The food frequency questionnaire (FFQ) is designed to capture an individual’s habitual dietary intake and is the most applied method in nutritional epidemiology. Our aim was to assess the relative validity and reproducibility of the FFQ used in the Diet, Cancer, and Health—Next Generations cohort (DCH-NG). We included 415 Danish women and men aged 18–67 years. Spearman’s correlations coefficients, Bland–Altman limits of agreement and cross-classification between dietary intakes estimated from the FFQ administered at baseline (FFQbaseline), and the mean of three 24-h dietary recalls (24-HDRs) and the FFQ administered after 12 months (FFQ12 months) were determined. Nutrient intakes were energy-adjusted by Nutrient Density and Residual methods. Correlation coefficients ranged from 0.18–0.58 for energy and energy-adjusted nutrient intakes, and the percentage of participants classified into the same quartile ranged from 28–47% between the FFQbaseline and the 24-HDRs. For the FFQ12 months compared with FFQbaseline, correlation coefficients ranged from 0.52–0.88 for intakes of energy, energy-adjusted nutrients, and food groups, and the proportion of participants classified into the same quartiles ranged from 43–69%. Overall, the FFQ provided a satisfactory ranking of individuals according to energy, nutrient, and food group intakes, making the FFQ suitable for use in epidemiological studies investigating diet in relation to disease outcomes.

Importance: Preterm birth, particularly extremely preterm birth, has been associated with substantial morbidity and mortality. Research during SARS-CoV-2-related lockdowns revealed reductions in the more severe subtypes of preterm birth in some countries, suggesting the presence of preventable risk factors, such as infectious diseases or social behavior. Seasonality may provide a similar means of assessing natural changes in the daily life of pregnant individuals that were similar to those experienced during the COVID-19 lockdown period. Objective: To evaluate the association between seasonality and extremely preterm birth. Design, Setting, and Participants: This nationwide cohort study included 1 136 143 pregnancies in Denmark with onset between January 1, 1997, and December 31, 2016, in which the fetuses survived 21 completed weeks of gestation. Pregnancies were followed up until preterm birth, fetal death, or 37 completed weeks of gestation. Data were analyzed from September 2020 to September 2021. Exposures: Season during gestation (primary exposure) and season of pregnancy onset. Main Outcomes and Measures: The main outcome of extremely preterm birth was defined as a live birth occurring between 22 weeks, 0 days' gestation and 27 weeks, 6 days' gestation. Cox regression analyses were used to estimate hazard ratios (HRs) for season during gestation and season of pregnancy onset, with adjustment for socioeconomic and demographic factors. Results: Among 662 338 pregnant individuals, the median age at pregnancy onset was 30.0 years (IQR, 6.0 years). Of 1 136 143 pregnancies, 2009 extremely preterm births (cumulative incidence, 0.18%) were identified during follow-up. Season during gestation was associated with extremely preterm birth, with cumulative incidences of 0.17% (95% CI, 0.16%-0.19%) in spring, 0.18% (95% CI, 0.17%-0.20%) in summer, 0.20% (95% CI, 0.18%-0.21%) in autumn, and 0.16% (95% CI, 0.14%-0.17%) in winter. Compared with winter, the adjusted HRs (A

Background: The correlates of prenatal and postnatal growth on Intelligence Quotient (IQ) in childhood in term-born children living in high-income countries are not well known. Objectives: We examined how birth size and growth in infancy and childhood were associated with IQ at age 5 y in term-born children using path analysis. Methods: The study sample comprised 1719 children from the Danish National Birth Cohort who participated in a substudy in which psychologists assessed IQ using the Wechsler Primary and Preschool Scales of Intelligence-Revised. Measured weight, length/height, and head circumference at birth, 5 mo, 12 mo, and 5 y were included in a path model to estimate their total, indirect, and direct effects on IQ. All growth measures were included in the model as sex- and age-standardized z-scores. Results: After adjusting for potential confounders, a positive association between birth weight and IQ was observed, and 88% of the association was direct. Weight gain in infancy was associated with IQ [per z-score increase from 5 to 12 mo, IQ increased by 1.53 (95% CI: 0.14; 2.92) points] whereas weight gain from 12 mo to 5 y was not associated with IQ. Height and head circumference growth in childhood was associated with IQ [per z-score increase from 12 mo to 5 y, IQ increased by 0.98 (95% CI: 0.17; 1.79) and 2.09 (95% CI: 0.78; 3.41) points, respectively]. Conclusions: In children born at term in an affluent country with free access to health care, higher IQ was seen with greater size at birth and greater weight gain in infancy. Also, greater growth in height and head circumference throughout the first 5 y of life was associated with higher childhood IQ whereas greater weight gain after the first year of life was not.

Context and Objective: Being born small or large for gestational age and intrauterine exposure to gestational diabetes (GDM) increase the risk of type 2 diabetes (T2D) in the offspring, however, the potential combined deleterious effects of size at birth and GDM exposure remains unknown. We aimed to examine the independent effect of size at birth as well as the influence of GDM exposure in utero on cardio-metabolic traits, body composition, and puberty status in children.Design, Participants and Methods: This study is a longitudinal birth cohort study. We used clinical data from 490 offspring of mothers with GDM and 527 control offspring aged 9-16 years, born singleton at term from the Danish National Birth Cohort with available birth weight data.Results: We found no evidence of a U-shaped association between size at birth (expressed as birth weight, sex and gestational age adjusted z-score) and cardio-metabolic traits. Body size in childhood and adolescence reflected size at birth, but was not reflected in any metabolic outcome. No synergistic adverse effect of being born small or large for gestational age and being exposed to GDM was shown. However, GDM was associated with an adverse metabolic profile and earlier onset of female puberty in childhood and adolescence independently of size at birth.Conclusion: In childhood and adolescence, GDM is a stronger predictor of dysmetabolic traits than size at birth. The combination of being born small or large and being exposed to GDM does not exacerbate the metabolic profile in the offspring.

Background: The Developmental Origins of Health and Disease (DOHaD) hypothesis postulates that exposures during early life, such as maternal dietary intake during pregnancy, may have a lifelong impact on the individual's susceptibility to diseases. The individual's own lifestyle habits are obviously an additional factor, but we have only limited knowledge regarding how it may interact with prenatal exposures in determining later disease. To gain further insight into these potentially complex relationships, we examined the longitudinal association between maternal diet quality during pregnancy and diet quality in early adolescence in a contemporary cohort.Methods and findings: From 1996 to 2003, the Danish National Birth Cohort (DNBC) was established. Women from across the country were enrolled, and dietary intake in midpregnancy was assessed concurrently with a 360-item food frequency questionnaire (FFQ) (https://www.dnbc.dk/-/media/arkiv/projekt-sites/dnbc/kodeboeger/dnbc-food-frequency-questionnaire/dnbc-food-frequency-questionnaire-pdf.pdf?la=en). During 2013-2018, dietary intake was assessed at age 14 years with a 150-item FFQ (https://www.dnbc.dk/-/media/arkiv/projekt-sites/dnbc/kodeboeger/ffq-14/dnbc-ffq-14-english-translation.pdf?la=en) in the DNBC children. Among the 19,582 mother-offspring pairs included in the analyses, the mean age (±standard deviation [SD]) was 30.7 (±4.1) years and 14.0 (±0.0) years for mothers and offspring, respectively. The majority of both mothers (67%) and offspring (76%) were classified as normal weight. For both questionnaires, a Healthy Eating Index (HEI) was developed as an indicator for diet quality based on current Danish Food-Based Dietary Guidelines (FBDG) including eight components: fruits and vegetables, fish, dietary fibres, red meat, saturated fatty acids (SFAs), sodium, sugar-sweetened beverages (SSBs), and added sugar. The HEI score was divided into quartiles; individuals in

Context and Objective Being born small or large for gestational age and intrauterine exposure to gestational diabetes (GDM) increase the risk of type 2 diabetes (T2D) in the offspring, however, the potential combined deleterious effects of size at birth and GDM exposure remains unknown. We aimed to examine the independent effect of size at birth as well as the influence of GDM exposure in utero on cardio-metabolic traits, body composition, and puberty status in children. Design, Participants and Methods This study is a longitudinal birth cohort study. We used clinical data from 490 offspring of mothers with GDM and 527 control offspring aged 9-16 years, born singleton at term from the Danish National Birth Cohort with available birth weight data. Results We found no evidence of a U-shaped association between size at birth (expressed as birth weight, sex and gestational age adjusted z-score) and cardio-metabolic traits. Body size in childhood and adolescence reflected size at birth, but was not reflected in any metabolic outcome. No synergistic adverse effect of being born small or large for gestational age and being exposed to GDM was shown. However, GDM was associated with an adverse metabolic profile and earlier onset of female puberty in childhood and adolescence independently of size at birth. Conclusion In childhood and adolescence, GDM is a stronger predictor of dysmetabolic traits than size at birth. The combination of being born small or large and being exposed to GDM does not exacerbate the metabolic profile in the offspring.

Offspring of women with gestational diabetes mellitus (GDM) are at increased risk of developing metabolic disease, potentially mediated by epigenetic mechanisms. We recruited 608 GDM and 626 control offspring from the Danish National Birth Cohort, aged between 9 and 16 years. DNA methylation profiles were measured in peripheral blood of 93 GDM offspring and 95 controls using the Illumina HumanMethylation450 BeadChip. Pyrosequencing was performed for validation/replication of putative GDM-associated, differentially methylated CpGs in additional 905 offspring (462 GDM, 444 control offspring). We identified 76 differentially methylated CpGs in GDM offspring compared with controls in the discovery cohort (FDR, P < 0.05). Adjusting for offspring BMI did not affect the association between methylation levels and GDM status for any of the 76 CpGs. Most of these epigenetic changes were due to confounding by maternal prepregnancy BMI; however, 13 methylation changes were independently associated with maternal GDM. Three prepregnancy BMI-associated CpGs (cg00992687 and cg09452568 of ESM1 and cg14328641 of MS4A3) were validated in the replication cohort, while cg09109411 (PDE6A) was found to be associated with GDM status. The identified methylation changes may reflect developmental programming of organ disease mechanisms and/or may serve as disease biomarkers.

Introduction Otitis media is the primary cause of antibiotic prescription in children. Two-thirds of all children experience at least one episode of otitis media before the age of 7 years. The aim of this study was to characterise the attributable effect of several modifiable risk exposures on the risk of >3 episodes of otitis media at age 18 months and 7 years within a large prospective national birth cohort. Methods The study used the Danish National Birth Cohort comprising information about otitis media and risk exposures from more than 50,000 mother-child pairs from the period 1996–2002. Logistic regression models were used to estimate odds ratios for the risk factors and to calculate the population attributable fraction. Results Short time with breastfeeding, early introduction to daycare, cesarean section, and low compliance to the national vaccination program were all associated with an increased risk of >3 episodes of otitis media at 18 months of age and at 7 years of age. The fraction of children with otitis media attributed from breastfeeding lasting for less than 6 months was 10%. Introduction to daycare before the age of 12 months attributed with 20% of the cases of >3 episodes of otitis media. Conclusions Short duration of breastfeeding, early introduction into daycare, cesarean section, and low compliance with the national vaccination program increased the risk of experiencing >3 episodes of otitis media at 18 months, and at 7 years of age. These are factors that all can be modulated.

[This corrects the article DOI: 10.1371/journal.pone.0166465.].