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Objective: To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs., Methods: A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs., Results: Of the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m 2 , adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m 2 , aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m 2 , aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m 2 , aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m 2 was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m 2 : aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m 2 : aOR 1.36, 95% CI 1.08-1.68)., Conclusion: The risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs., (© 2024. The Author(s).)

Background: Childhood adversity has previously been associated with overweight and obesity in adult life, but there is a need for larger population-based studies using prospectively obtained adversity trajectories across childhood to confirm these associations. Moreover, childhood adversity may also be associated with underweight, which is less often studied. The aim of the current study is to investigate the association between childhood adversity trajectories from 0-15 years with weight categories in young adult men., Methods: The Danish Life Course Cohort (DANLIFE) was linked with the Danish Conscription Registry resulting in a study sample of 359,783 men, who have been assigned to one of five previously identified adversity trajectories from 0-15 years: "low adversity", "early material deprivation", "persistent material deprivation", "loss or threat of loss", and "high adversity". Height and weight in young adulthood was assessed at a draft board examination at age 18-26 years. Associations of adversity trajectories and weight categories were investigated in multinomial regression models., Results: Compared with the "low adversity" group, the four other adversity groups had higher risks of underweight, overweight, and obesity. The "high adversity" group showed the strongest associations with both underweight (1.44 (1.32, 1.58)) and obesity (1.50 (1.39, 1.61)) when adjusted for parental origin, birth year, age at draft board examination, and maternal age., Conclusion: Childhood adversity, experienced between 0 and 15 years of life, was associated with a higher risk of underweight, overweight, and obesity in young adulthood among men., (© 2024. The Author(s).)

Background: Obesity is now the most common health problem in the younger population in Western societies and obesity rates are higher in lower socioeconomic status (SES) groups. We investigated whether overweight in childhood, independently of overweight in adulthood, influenced adult employment status and later risk of having disabilities. Using data from the Danish Female Nurse Cohort study, we examined associations between overweight in childhood/adolescence, and young adulthood and disabilities and early retirement in later adulthood (>44 years) and whether it was influenced by menopausal age (

Background: Excess abdominal visceral adipose tissue (VAT) is associated with metabolic diseases and poor survival in colon cancer (CC). We assessed the impact of different types of CC surgery on changes in abdominal fat depots., Material and Methods: Computed tomography (CT)-scans performed preoperative and 3 years after CC surgery were analyzed at L3-level for VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) areas. We assessed changes in VAT, SAT, TAT and VAT/SAT ratio after 3 years and compared the changes between patients who had undergone left-sided and right-sided colonic resection in the total population and in men and women separately., Results: A total of 134 patients with stage I-III CC undergoing cancer surgery were included. Patients who had undergone left-sided colonic resection had after 3 years follow-up a 5% (95% CI: 2-9%, p < 0.01) increase in abdominal VAT, a 4% (95% CI: 2-6%, p < 0.001) increase in SAT and a 5% increase (95% CI: 2-7%, p < 0.01) in TAT. Patients who had undergone right-sided colonic resection had no change in VAT, but a 6% (95% CI: 4-9%, p < 0.001) increase in SAT and a 4% (95% CI: 1-7%, p < 0.01) increase in TAT after 3 years. Stratified by sex, only males undergoing left-sided colonic resection had a significant VAT increase of 6% (95% CI: 2-10%, p < 0.01) after 3 years., Conclusion: After 3 years follow-up survivors of CC accumulated abdominal adipose tissue. Notably, those who underwent left-sided colonic resection had increased VAT and SAT, whereas those who underwent right-sided colonic resection demonstrated solely increased SAT., (© 2023. The Author(s).)

Objective: We examined whether childhood adversity experienced in early childhood (0-5 years) is related to body mass index (BMI) in childhood (6-7 years) and adolescence (12-15 years)., Methods: This study combined data from the nationwide register-based DANLIFE study on childhood adversities with data on height and weight of school children in Copenhagen. Data were available for 53,401 children born in Denmark between 1980 and 1996. Children were divided into groups of early childhood adversity by applying group-based multi-trajectory modelling using their yearly count of childhood adversity in three dimensions (i.e., material deprivation, loss or threat of loss, and family dynamics) from 0-5 years. Direct and total associations between the early childhood adversity groups and BMI z-scores in childhood and adolescence were estimated using sex-stratified structural equation models., Results: Five exclusive and exhaustive groups of early childhood adversity were identified, which were characterized by low adversity (51%), moderate material deprivation (30%), high material deprivation (14%), loss or threat of loss (3%) and high adversity (2%). Boys and girls exposed to moderate or high material deprivation and loss or threat of loss had a slightly higher BMI z-score, especially in adolescence, compared with those in the low adversity group, with the strongest association found for girls in the loss or threat of loss group (b (95% CI) = 0.18 (0.10, 0.26)). Additionally, boys in the high adversity group had a slightly lower BMI z-score in childhood than boys in the low adversity group (b (95% CI) = -0.12 (-0.22, -0.02))., Conclusions: Whereas associations with BMI were found for children and adolescents exposed to material deprivation, loss or threat of loss, and high adversity, the effect sizes were generally small. Contrary to prevailing hypotheses, weight changes in childhood is probably not a major explanatory mechanism linking early childhood adversity with later-life morbidity., (© 2023. The Author(s).)

Objective: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD., Methods: Cohort study of 346,586 persons born during 1930-1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18-49 and from age 50., Results: During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98-1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11-1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85-1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34-1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83-0.99) per 500 g higher birthweight]., Conclusion: BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height., Methods: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age., Results: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood., Conclusions: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity., (© 2022. The Author(s).)

Background/objectives: Many personality traits correlate with BMI, but the existence and direction of causal links between them are unclear. If personality influences BMI, knowing this causal direction could inform weight management strategies. Knowing that BMI instead influences personality would contribute to a better understanding of the mechanisms of personality development and the possible psychological effects of weight change. We tested the existence and direction of causal links between BMI and personality., Subjects/methods: We employed two genetically informed methods. In Mendelian randomization, allele scores were calculated to summarize genetic propensity for the personality traits neuroticism, worry, and depressive affect and used to predict BMI in an independent sample (N = 3 541). Similarly, an allele score for BMI was used to predict eating-specific and domain-general phenotypic personality scores (PPSs; aggregate scores of personality traits weighted by BMI). In a direction of causation (DoC) analysis, twin data from five countries (N = 5424) were used to assess the fit of four alternative models: PPSs influencing BMI, BMI influencing PPSs, reciprocal causation, and no causation., Results: In Mendelian randomization, the allele score for BMI predicted domain-general (β = 0.05; 95% CI: 0.02, 0.08; P = 0.003) and eating-specific PPS (β = 0.06; 95% CI: 0.03, 0.09; P < 0.001). The allele score for worry also predicted BMI (β = -0.05; 95% CI: -0.08, -0.02; P < 0.001), while those for neuroticism and depressive affect did not (P ≥ 0.459). In DoC, BMI similarly predicted domain-general (β = 0.21; 95% CI:, 0.18, 0.24; P < 0.001) and eating-specific personality traits (β = 0.19; 95% CI:, 0.16, 0.22; P < 0.001), suggesting causality from BMI to personality traits. In exploratory analyses, links between BMI and domain-general personality traits appeared reciprocal for higher-weight individuals (BMI > ~25)., Conclusions: Although both genetic analyses suggested an influence of BMI on personality traits, it is not yet known if weight management interventions could influence personality. Personality traits may influence BMI in turn, but effects in this direction appeared weaker., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: Genetic predisposition and maternal body mass index (BMI) are risk factors for childhood adiposity, defined by either BMI or overweight. We aimed to investigate whether childhood-specific genetic risk scores (GRSs) for adiposity-related traits are associated with childhood adiposity independent of maternal BMI, or whether the associations are modified by maternal BMI., Methods: We constructed a weighted 26-SNP child BMI-GRS and a weighted 17-SNP child obesity-GRS in overall 1674 genotyped children within the Danish National Birth Cohort. We applied a case-cohort (N = 1261) and exposure-based cohort (N = 912) sampling design. Using logistic regression models we estimated associations of the GRSs and child overweight at age 7 years and examined if the GRSs influence child adiposity independent of maternal BMI (per standard deviation units)., Results: In the case-cohort design analysis, maternal BMI and the child GRSs were associated with increased odds for childhood overweight [OR for maternal BMI: 2.01 (95% CI: 1.86; 2.17), OR for child BMI-GRS: 1.56 (95% CI: 1.47; 1.66), and OR for child obesity-GRS 1.46 (95% CI: 1.37; 1.54)]. Adjustment for maternal BMI did not change the results, and there were no significant interactions between the GRSs and maternal BMI. However, in the exposure-based cohort design analysis, significant interactions between the child GRSs and maternal BMI on child overweight were observed, suggesting 0.85-0.87-fold attenuation on ORs of child overweight at higher values of maternal BMI and child GRS., Conclusion: GRSs for childhood adiposity are strongly associated with childhood adiposity even when adjusted for maternal BMI, suggesting that the child-specific GRSs and maternal BMI contribute to childhood overweight independent of each other. However, high maternal BMI may attenuate the effects of child GRSs in children., (© 2021. The Author(s).)

Background: In the general population, body mass index (BMI = weight (kg)/(height (m)) 2 ) shows a U-shaped relation to mortality, which is attributable to a combination of an inverse association with fat-free mass index (FFMI) and a direct association with fat mass index (FMI). However, preceding changes in body composition related to diseases, health behaviors, or social conditions that are also influencing later mortality may confound these associations., Objective: To examine associations of FFMI and FMI, adjusted for preceding changes in FFMI and FMI over a 6 years period, with all-cause mortality in a healthy general population., Methods: The study population was a random subset of adult Danes, participating in the Danish MONICA project; 989 men and 962 women, born 1922, 1932, 1942, and 1952, and examined in 1987-88 and 1993-94. They had no known major co-morbidities until start of follow-up in 1993-94, and were followed up for 18 years. Measures included height, weight, and bio-impedance, from which BMI, FFMI, and FMI were calculated, and information on educational level, smoking, alcohol drinking, leisure-time physical activity, which were obtained by questionnaires. We analyzed the relation between body composition and all-cause mortality by Cox proportional hazards model with splines, stratified by birth cohorts, and with adjustment for preceding changes in body composition and for the covariates including gender. We estimated hazard ratios (HR) with 95% confidence intervals (CI) relative to HR = 1.00 at the median values of BMI, FMI, and FFMI., Results: During 18 years of follow-up, 286 men and 200 women died. BMI showed the well-known U-shaped association with mortality, and FMI was directly and FFMI inversely associated with mortality. Associations were not significantly modified by gender. Preceding changes in BMI, FMI, and FFMI were only weakly and not significantly associated with mortality. Associations for FMI and FFMI were monotonic, but curve-linear with a higher mortality above and below the respective median values of FMI and FFMI: at the 5th percentiles of FMI and FFMI, HRs were 0.80 (CI 0.57-1.13) and 2.01 (1.24-3.27), and at the 95th percentiles, HRs were 2.16 (1.38-3.38) and 0.81 (0.52-1.27), respectively., Conclusions: In an apparently healthy general population, a large fat mass and a small fat-free mass are associated with greater risk of early mortality, also after adjusting for preceding changes in body composition, health behaviors, and educational level.

Background: Although weight gain in mid- to late adult life is associated with an increased risk of colon cancer, it is unclear if increases or losses in weight from childhood to early adulthood are differentially associated with risks of adult colon cancer., Methods: Weight and height were measured at 7 or 13 years and in early adulthood (17-26 years) in 64,675 boys in the Copenhagen School Health Records Register and the Danish Conscription Database. Cases of colon cancer (n = 751) were identified in the Danish Cancer Registry. Boys and young men were categorized as normal weight or overweight. Associations between changes in weight and colon cancer were examined using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Compared with men with a normal weight at 7 years and in early adulthood, men with overweight at both ages had an increased risk of adult colon cancer (HR: 2.73, 95% CI 1.80-4.15). In contrast, men with overweight at 7 years, but not in early adulthood did not have an increased risk of colon cancer (HR: 0.73, 95% CI 0.35-1.54), nor did men with a normal weight at 7 years and overweight in early adulthood (HR: 1.28, 95% CI 0.96-1.70). Similar results were observed for weight status at age 13 years combined with early adulthood., Conclusions: Childhood overweight that persists into early adulthood is associated with an increased risk of colon cancer, whereas overweight that disappears before early adulthood or developed after childhood is not.

Background: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG., Participants and Methods: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight)., Results: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 -8 ) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG., Conclusions: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Background and Objectives: Prenatal risk factors for childhood overweight may operate indirectly through development in body size in early life and/or directly independent hereof. We quantified the effects of maternal and paternal body mass index (BMI), maternal age, socioeconomic position (SEP), parity, gestational weight gain, maternal smoking during pregnancy, caesarean section, birth weight, and BMI at 5 and 12 months on BMI and overweight at 7 and 11 years., Methods: Family triads with information on maternal, paternal and child BMI at ages 7 (n=29 374) and 11 years (n=18 044) were selected from the Danish National Birth Cohort. Information originated from maternal interviews and medical health examinations. Path analysis was used to estimate the direct and indirect effects of prenatal risk factors on childhood BMI z-scores (BMIz per unit score of the risk factor). Logistic regression was used to examine associations with overweight., Results: The strongest direct effects on BMIz at age 7 were found for maternal and paternal BMI (0.19 BMIz and 0.14 BMIz per parental BMIz), low SEP (0.08 BMIz), maternal smoking (0.12 BMIz) and higher BMIz at 5 and 12 months (up to 0.19 BMIz per infant BMIz). For BMIz at age 11 with BMIz at age 7 included in the model, similar effects were found, but the direct effects of BMIz at age 5 and 12 months were mediated through BMI at age 7 (0.62 BMIz per BMIz). Same results were found for overweight. The sum of the direct effects can be translated to approximate absolute measures: 2.4 kg at 7 years, 5.7 kg at 11 years, in a child with average height and BMI., Conclusions: Parental BMI, low SEP and smoking during pregnancy have persisting, strong and direct effects on child BMI and overweight independent of birth weight and infancy BMI.

Objective: The well-established link between body fat distribution and metabolic health has been suggested to act through an impact on the remodeling capacity of the adipose tissue. Remodeling of the adipose tissue has been shown to affect body fat distribution and might affect the ability to lose weight. We aimed to study the effect of weighted genetic risk scores (GRSs) on weight loss based on single-nucleotide polymorphisms (SNPs) associated with waist-hip-ratio adjusted for body mass index (WHRadjBMI)., Design: We included 707 participants (533 women and 174 men) from the NUGENOB multi-center 10-week diet intervention study with weekly weight measurements. We created 3 GRSs, one including all reported WHRadjBMI SNPs (GRS total ), one including only SNPs with genome-wide significance in women or with significantly greater effect in women (GRS women ), and one excluding SNPs in the GRS women (GRS men ). The data were analyzed in a mixed linear model framework., Results: The GRS total and GRS women attenuated weight loss in women. The effect was strongest for the GRS women with an effect of 2.21 g per risk allele per day (95% confidence intereval (CI) (0.90;3.52), P=0.0009). Adjustment for WHR, basal metabolic rate or diet compliance did not affect the result. The GRSs had no effect on weight loss in men. The VEGFA rs1358980-T strongly attenuated weight loss in both men and women (β=15.95 g per risk allele per day, (3.16;26.74), P=0.013) and (β=15.95 g per risk allele per day, (2.58;13.53), P=0.004), respectively)., Conclusion: Our findings suggest that genetic variants influencing body fat distribution attenuate weight loss in women independently on the effect on WHR. The stronger effect of the GRS women implies heterogenic effects of the WHRadjBMI variants on weight loss. A strong effect of rs1358980-T in the VEGFA locus suggests that angiogenesis plays a role, but this needs confirmation from functional studies.