Body mass index trajectories from 2 to 18 years - exploring differences between European cohorts.

BACKGROUND: In recent decades, there has been an increase in the prevalence of childhood overweight in most high-income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations. METHODS: We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991-1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990-1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution. RESULTS: Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2-3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age. CONCLUSION: Population-level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right-hand tail of the BMI distribution

Association of Childhood Fat Mass and Weight With Adult-Onset Type 2 Diabetes in Denmark

Importance Childhood obesity, defined by cutoffs based on the weight-based marker of body mass index, is associated with adult type 2 diabetes (T2D) risk. Whether childhood fat mass (FM) is the driver of these associations is currently unknown. Objective To quantify and compare height-independent associations between childhood FM and weight with adult T2D risk in a historic Danish cohort. Design, Setting, and Participants This population-based retrospective cohort study included schoolchildren from The Copenhagen School Health Records Register born between January 1930 and December 1985 with follow-up to adulthood through December 31, 2015. Analyses were based on 269 913 schoolchildren aged 10 years with 21 896 established adult T2D cases and 261 192 children aged 13 years with 21 530 established adult T2D cases for whom childhood height and weight measurements, as well as predicted FM, were available. Statistical analyses were performed between April 2019 to August 2020. Exposures Childhood FM and weight at ages 10 and 13 years. Main Outcomes and Measures Diagnoses of T2D were established by linkage to national disease registers for adults aged at least 30 years. Sex-specific Cox regression quantified associations, adjusted for childhood height, which were evaluated within 5 birth-cohort groups. Group-specific results were pooled using random-effects meta-analyses accounting for heterogeneity across group-specific associations. Results This cohort study analyzed data from 269 913 children aged 10 years (135 940 boys [50.4%]) with 21 896 established adult T2D cases and 261 192 children aged 13 years (131 025 boys [50.2%]) with 21 530 established adult T2D cases. After adjusting for childhood height, increases in FM and weight (per kilogram) among boys aged 10 years were associated with elevated T2D risks at age 50 years of 12% (hazard ratio [HR], 1.12; 95% CI, 1.10-1.14) and 7% (HR, 1.07; 95% CI, 1.05-1.09), respectively, and among girls aged 10 years of 15% (HR, 1.15; 95% CI, 1.13-1.17) and 10% (HR, 1.10; 95% CI, 1.08-1.11), respectively. Among children aged 13 years, increases in FM and weight (per kilogram) were associated with increased T2D risks at age 50 years of 10% (HR, 1.10; 95% CI, 1.09-1.10) and 6% (HR, 1.06; 95% CI, 1.05-1.07) for boys, respectively, and of 10% (HR, 1.10; 95% CI, 1.10-1.11) and 7% (HR, 1.07; 95% CI, 1.06-1.08), respectively, for girls. Conclusions and Relevance This cohort study found that a 1-kg increase in childhood FM was more strongly associated with increased adult T2D risk than a 1-kg increase in weight, independent of childhood height. Information on FM, rather than weight-based measures, focuses on a modifiable component of weight that may be associated with adult T2D risk. These findings support the assessment of childhood FM in adiposity surveillance initiatives in an effort to reduce long-term T2D risk

Excess Mortality Rate During Adulthood Among Danish Adoptees

BACKGROUND AND OBJECTIVE: Adoption studies have been used to disentangle the influence of genes from shared familial environment on various traits and disease risks. However, both the factors leading to adoption and living as an adoptee may bias the studies with regard to the relative influence of genes and environment compared to the general population. The aim was to investigate whether the cohort of domestic adoptees used for these studies in Denmark is similar to the general population with respect to all-cause mortality and cause-specific mortality rates. METHODS: 13,111 adoptees born in Denmark in 1917, or later, and adopted in 1924 to 1947 were compared to all Danes from the same birth cohorts using standardized mortality ratios (SMR). The 12,729 adoptees alive in 1970 were similarly compared to all Danes using SMR as well as cause-specific SMR. RESULTS: The excess in all-cause mortality before age 65 years in adoptees was estimated to be 1.30 (95% CI 1.26-1.35). Significant excess mortality before age 65 years was also observed for infections, vascular deaths, cancer, alcohol-related deaths and suicide. Analyses including deaths after age 65 generally showed slightly less excess in mortality, but the excess was significant for all-cause mortality, cancer, alcohol-related deaths and suicides. CONCLUSION: Adoptees have an increased all-cause mortality compared to the general population. All major specific causes of death contributed, and the highest excess is seen for alcohol-related deaths

Morbidity, Including Fatal Morbidity, throughout Life in Men Entering Adult Life as Obese

Background: The association between obesity in adults and excess morbidity and mortality is well established, but the health impact throughout adult life of being obese in early adulthood needs elucidation. We investigated somatic morbidity, including fatal morbidity, throughout adulthood in men starting adult life as obese. Methods: Among 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (defined as BMI$31.0 kg/m 2), and, as controls, a random 1 % sample of the others was identified. In the age range of 18–25 years, there were 1,862 obese, which encompass the men above the 99.5 percentile, and 3,476 controls. Information on morbidity was obtained via national registers. Cox regression models were used to estimate the relative morbidity assessed as first incidence of disease, occurrence of disease in the year preceding death and prevalent disease at time of death. Results: From age 18 through 80 years the obese had an increased risk of becoming diseased by or die from a broad range of diseases. Generally, the incidence of first event, occurrence in the year prior to death, and prevalence at time of death showed the same pattern. As an example, the relative hazard of type 2 diabetes was constant throughout life at 4.9 (95% confidence intervals [CI]: 4.1–5.9), 5.2 (95 % CI: 3.6–7.5), and 6.8 (95 % CI: 4.6–10.1), respectively. Conclusions: Our findings strongly support the continued need to avoid beginning adult life as obese, as obese young me

Genetic Influences on Incidence and Case-Fatality of Infectious Disease

BACKGROUND: Family, twin and adoption studies suggest that genetic susceptibility contributes to familial aggregation of infectious diseases or to death from infections. We estimated genetic and shared environmental influences separately on the risk of acquiring an infection (incidence) and on dying from it (case fatality). METHODS: Genetic influences were estimated by the association between rates of hospitalization for infections and between case-fatality rates of adoptees and their biological full- and half- siblings. Familial environmental influences were investigated in adoptees and their adoptive siblings. Among 14,425 non-familial adoptions, granted in Denmark during the period 1924-47, we selected 1,603 adoptees, who had been hospitalized for infections and/or died with infection between 1977 and 1993. Their siblings were considered predisposed to infection, and compared with non-predisposed siblings of randomly selected 1,348 adoptees alive in 1993 and not hospitalized for infections in the observation period. The risk ratios presented were based on a Cox regression model. RESULTS: Among 9971 identified siblings, 2829 had been hospitalised for infections. The risk of infectious disease was increased among predisposed compared with non-predisposed in both biological (1.18; 95% confidence limits 1.03-1.36) and adoptive siblings (1.23; 0.98-1.53). The risk of a fatal outcome of the infections was strongly increased (9.36; 2.94-29.8) in biological full siblings, but such associations were not observed for the biological half siblings or for the adoptive siblings. CONCLUSION: Risk of getting infections appears to be weakly influenced by both genetically determined susceptibility to infection and by family environment, whereas there appears to be a strong non-additive genetic influence on risk of fatal outcome

Predisposition to Obesity: Should We Target Those Most Susceptible?

Obesity prevention should remain a priority, even if there is some suggestion that the epidemic may presently have reached a stable level. However, previous interventions have not been effective in preventing overweight and obesity, and at the same time studies suggest that some subgroups are more predisposed to future obesity. The purpose of this paper is to review interventions on obesity prevention published during the past year, and to examine if interventions targeting predisposed groups or individuals seem more efficient in preventing obesity than studies targeting general populations. Among 15 identified studies, 7 targeted predisposed children or adolescents. More of the studies targeting predisposed individuals were able to show significant effects than the studies targeting general populations. Most studies targeting predisposed defined the predisposition based on ethnicity or socioeconomic status. Thus, we may be more successful in preventing obesity when targeting predisposed individuals, but more studies are needed before a firm conclusion can be drawn

Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness – in Cohorts of Danish Men

The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system.Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system

Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight

BACKGROUND: It has been suggested that prenatal stress contributes to the risk of obesity later in life. In a population-based cohort study, we examined whether prenatal stress related to maternal bereavement during pregnancy was associated with the risk of overweight in offspring during school age. METHODOLOGY/PRINCIPAL FINDINGS: We followed 65,212 children born in Denmark from 1970-1989 who underwent health examinations from 7 to 13 years of age in public or private schools in Copenhagen. We identified 459 children as exposed to prenatal stress, defined by being born to mothers who were bereaved by death of a close family member from one year before pregnancy until birth of the child. We compared the prevalence of overweight between the exposed and the unexposed. Body mass index (BMI) values and prevalence of overweight were higher in the exposed children, but not significantly so until from 10 years of age and onwards, as compared with the unexposed children. For example, the adjusted odds ratio (OR) for overweight was 1.68 (95% confidence interval [CI] 1.08-2.61) at 12 years of age and 1.63 (95% CI 1.00-2.61) at 13 years of age. The highest ORs were observed when the death occurred in the period from 6 to 0 month before pregnancy (OR 3.31, 95% CI 1.71-6.42 at age 12, and OR 2.31, 95% CI 1.08-4.97 at age 13). CONCLUSIONS/SIGNIFICANCE: Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood

Birth size and gestational age in opposite-sex twins as compared to same-sex twins: An individual-based pooled analysis of 21 cohorts

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), including 67,850 dizygotic twin individuals. Linear regression analyses showed that boys having a co-twin sister were, on average, 31 g (95% CI 18 to 45) heavier and 0.16 cm (95% CI 0.045 to 0.274) longer than those with a co-twin brother. In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co-twin sister