Studies have suggested that number of siblings and birth order is associated with obesity. However, studies combining these exposures are needed. This study aimed at investigating obesity in children and young adults in regard to different combinations of family size and birth order.
Two cohorts selected from the general population were investigated: The Copenhagen School Health Records Register (CSHRR) and a Draft Board (DB) sample with measured heights and weights in childhood (age 13 years) and young adulthood (age 19 years), respectively. Information on birth order, number of siblings, and relevant covariates were available on 29 327 children, as well as on 323 obese young men and 575 randomly selected controls of young men representing approximately 58 000. The relation between number of siblings and birth order, respectively, and having a Body Mass Index (BMI) z-score above or equal to the 95th percentile in childhood or having a BMI of at least 31.00 kg/m2 in young adulthood was analysed using logistic regression analyses adjusted for relevant confounders.
Only children had significantly higher odds of obesity both in childhood and in young adulthood compared with children with siblings, odds ratio (OR) = 1.44 (95% Confidence Interval (CI): 1.26–1.66) and OR = 1.76 (95% CI: 1.18–2.61), respectively. No association between first-born status and obesity was found. The OR of last-born children being obese was also significantly increased in childhood, e.g. OR = 1.93 (95% CI: 1.09−3.43) of obesity if last-born in a family of four children. This was not found in young adulthood. Additionally, higher spacing to previous sibling (average 1872 vs. 1303 days; p = 0.026 in four children families) was observed in obese last-born compared to non-obese last-born children.
Being an only or last-born child is associated with obesity. These associations may provide leads to targeted prevention of obesity in children.
Prevalence of obesity is the result of preceding incidence of newly developed obesity and persistence of obesity. We investigated whether increasing incidence and/or persistence during childhood drove the prevalence of childhood obesity during the emerging epidemic.
Height and weight were measured at ages 7 and 13 years in 192,992 Danish school children born 1930–1969. Trends in the incidence (proportion obese at 13 years among those not obese at 7 years) and persistence (proportion obese at 13 years among those obese at 7 years) across birth cohort periods (1930–41 with low stable prevalence of obesity, 1942–51 with increasing prevalence, 1952–69 with the higher, but stable prevalence) were investigated. Logistic regression was used to examine the associations between BMI at 7 years as a continuous trait, allowing interactions with the birth cohorts, and occurrence of obesity at 13 years.
The prevalence of obesity was similar at 7 and 13 years and increased across birth cohorts in boys from around 0.1% to 0.5% and in girls from around 0.3% to 0.7%. The incidence of obesity between ages 7 and 13 years increased from 0.15% to 0.35% in boys and from 0.20% to 0.44% in girls. The persistence increased from 28.6% to 41.4% in boys and from 16.4% to 31.0% in girls. Despite a decrease over time, the remission of obesity occurred in >60% of obese children in the last birth cohort. However, the odds ratios of obesity at age 13 years in relation to the full range of BMI at 7 years remained unchanged across the birth cohort periods.
The development of the obesity epidemic in children was due to an increase in both incidence and persistence of obesity. Contrary to prevailing expectations, a large, although declining, proportion of children obese at an early age underwent remission during childhood.
Background: The genetic predisposition to obesity may have contributed to the obesity epidemic through assortative mating. We investigated whether spouses were positively assorted by body mass index (BMI; = kg/m2) in late childhood, and whether changes in assorted marriage by upper BMI-percentiles occurred during the obesity epidemic. Methods: In the Copenhagen School Health Records Register (CSHRR) boys and girls with measures of BMI at age 13 years later became 37,792 spousal-pairs who married between 1945 and 2010. Trends in the spousal BMI correlations using sex-, age-, and birth cohort-specific BMI z-scores across time were investigated. Odds ratios (ORs) of marriage among spouses both with BMI z-scores >90th or >95th percentile compared with marriage among spouses ≤90th percentile were analyzed for marriages entered during the years prior to (1945–1970), and during the obesity epidemic (1971–2010). Findings: Spousal BMI correlations were around 0.05 and stayed similar across time. ORs of marriage among spouses with BMIs >90th percentile at age 13 were 1.21, 1.05–1.39, in 1945–1970, and increased to 1.63, 1.40–1.91, in 1971–2010 (p = 0.006). ORs of marriage among spouses both >95th BMI percentile were higher and increased more; from 1.39, 1.10–1.81, to 2.39, 1.85–3.09 (p = 0.004). Interpretation: Spousal correlations by pre-marital BMIs were small and stable during the past 65 years. Yet, there were assorted marriages between spouses with high BMI at age 13 years and the tendency increased alongside with the obesity epidemic which may increase the offsprings' predisposition to obesity.
assortative mating; body mass index; childhood; obesity; overweight; phenotype; human genetics
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 (OR 0.98 (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.
Exposures during fetal life may have long-term health consequences including risk of childhood overweight. We investigated the associations between maternal recreational exercise during early and late pregnancy and the children's body mass index (BMI) and risk of overweight at 7 years. Data on 40,280 mother-child pairs from the Danish National Birth Cohort was used. Self-reported information about exercise was obtained from telephone interviews around gestational weeks 16 and 30. Children's weight and height were reported in a 7-year follow-up and used to calculate BMI and overweight status. Data was analyzed using multiple linear and logistic regression models. Recreational exercise across pregnancy was inversely related to children's BMI and risk of overweight, but all associations were mainly explained by smoking habits, socioeconomic status, and maternal pre-pregnancy BMI. Additionally, we did not find exercise intensity or changes in exercise habits in pregnancy related to the children's BMI or risk of overweight.
Adult height is inversely associated with the risk of coronary heart disease (CHD), but it is still unknown which phase of the human growth period is critical for the formation of this association. We investigated the association between growth in height from 7 to 13 years of age and the risk of CHD in adulthood.
Methods and Findings
The heights of almost all children born 1930 through 1976 who attended school in the Copenhagen municipality (232,063 children) were measured annually from 7 to 13 years of age. Birth weight data were available since 1936. Fatal and non-fatal CHD events were ascertained by register linkage until 2008 (25,214 cases). Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards regression for height z-scores (standard deviation units) and change in height z-scores. Height z-scores were inversely related to the risk of CHD. The association was strongest at 7 years of age (HR = 0.91, CI 0.90–0.92 in boys and 0.88, CI 0.86–0.90 in girls) and steadily weakened thereafter, yet it still remained at 13 years of age (HR = 0.95, CI 0.94–0.97 and 0.91, CI 0.89–0.93, boys and girls respectively). The associations were not modified by birth weight. Independent of the age-specific risk, rapid growth was associated with an increased CHD risk, most pronounced between 9 and 11 years in girls (HR = 1.22, CI 1.14–1.31) and between 11 and 13 years in boys (HR = 1.28, CI 1.22–1.33) per unit increase in z-score. Adjustment for body mass index somewhat strengthened the associations of CHD risk with height and weakened the association with growth.
Risk of CHD in adulthood is inversely related to height at ages 7 through 13 years, but strongest in the youngest, and, independently hereof, the risk increased by growth velocity.
We attempt to elucidate whether there might be a causal connection between the socioeconomic status (SES) of the rearing environment and obesity in the offspring using data from two large-scale adoption studies: (1) The Copenhagen Adoption Study of Obesity (CASO), and (2) The Survey of Holt Adoptees and Their Families (HOLT). In CASO, the SES of both biological and adoptive parents was known, but all children were adopted. In HOLT, only the SES of the rearing parents was known, but the children could be either biological or adopted. After controlling for relevant covariates (e.g., adoptee age at measurement, adoptee age at transfer, adoptee sex) the raw (unstandardized) regression coefficients for adoptive and biological paternal SES on adoptee body mass index (BMI: kg/m2) in CASO were -.22 and -.23, respectively, both statistically significant (p = 0.01). Controlling for parental BMI (both adoptive and biological) reduced the coefficient for biological paternal SES by 44% (p = .034) and the coefficient for adoptive paternal SES by 1%. For HOLT, the regression coefficients for rearing parent SES were -.42 and -.25 for biological and adoptive children, respectively. Controlling for the average BMI of the rearing father and mother (i.e., mid-parental BMI) reduced the SES coefficient by 47% in their biological offspring (p≤.0001), and by 12% in their adoptive offspring (p = .09). Thus, despite the differing structures of the two adoption studies, both suggest that shared genetic diathesis and direct environmental transmission contribute about equally to the association between rearing SES and offspring BMI.
Background and Objectives
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic.
The data comprised height and weight measurements of 1,474,065 Swedish conscripts at age 18–19 y born between 1951 and 1983. The data were linked to the Swedish Multi-Generation Register and the Swedish Twin Register from which 264,796 full-brother pairs, 1,736 monozygotic (MZ) and 1,961 dizygotic (DZ) twin pairs were identified. The twin pairs were analysed to identify the most parsimonious model for the genetic and environmental contribution to BMI variance. The full-brother pairs were subsequently divided into subgroups by year of birth to investigate trends in the genetic variance of BMI.
The twin analysis showed that BMI variation could be explained by additive genetic and environmental factors not shared by co-twins. On the basis of the analyses of the full-siblings, the additive genetic variance of BMI increased from 4.3 [95% CI 4.04–4.53] to 7.9 [95% CI 7.28–8.54] within the study period, as did the unique environmental variance, which increased from 1.4 [95% CI 1.32–1.48] to 2.0 [95% CI 1.89–2.22]. The BMI heritability increased from 75% to 78.8%.
The results confirm the hypothesis that the additive genetic variance of BMI has increased strongly during the obesity epidemic. This suggests that the obesogenic environment has enhanced the influence of adiposity related genes.
Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in three independent, prospective studies.
The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses’ Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively.
S447X-carriers tended to have lower TG and higher HDL-C concentrations than non-carriers. The S447X variant was associated with a lower risk of CHD in the NHS, the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56–1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD-risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies.
The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all three cohorts. LPL is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.
Genetic epidemiology; CHD; prospective study; lipoprotein lipase; plasma lipids
Waist circumference (WC) measured at one point in time is positively associated with the risk of acute myocardial infarction (MI), but the association with changes in WC (DWC) is not clear. We investigated the association between DWC and the risk of MI in middle-aged men and women, and evaluated the influence from concurrent changes in BMI (DBMI).
Data on 38,593 participants from the Danish Diet, Cancer and Health study was analysed. Anthropometry was assessed in 1993–97 and 1999–02. Information on fatal and non-fatal MI was obtained from National Registers. Cases were validated by review of the medical records. Hazard ratios (HR) were calculated from Cox proportional hazard models with individuals considered at risk from 1999–02 until December 30 2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was positively associated with the risk of MI, but weakly after adjustment for BMI. DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95, 1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with MI occurring within the first years of follow-up were excluded.
WC was positively associated with the risk of MI in middle-aged men and women, but changes in WC were not. These findings suggest that a reduction in WC may be an insufficient target for prevention of MI in middle-aged men and women.
Waist circumference (WC) is positively associated with diabetes, but the association with changes in WC (DWC) is less clear. We investigated the association between DWC and the subsequent risk of diabetes in middle-aged men and women, and evaluated the influence from concurrent changes in body mass index (DBMI).
Data on 15,577 men and 20,066 women from the Danish Diet, Cancer and Health study were analyzed. Anthropometry was assessed in 1993–97 and 1999–02. Information on diabetes was obtained from The Danish National Diabetes Register. Hazard ratios (HR) were calculated from Cox' proportional hazard models with individuals considered at risk from 1999–02 until December 31 2006. During 5.4 years of follow-up, 1,027 and 876 new cases of diabetes occurred among men and women, respectively. WC was positively associated with diabetes in both sexes also with adjustment for covariates and BMI. DWC was positively associated with diabetes in women, but not in men (HR per 5 cm change = 1.09 (1.04∶1.15) in women, and 1.00 (0.94, 1.07) in men with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with diseases or diabetes occurring within the first years of follow-up were excluded.
While this study confirmed that WC is positively associated with the risk of diabetes in middle-aged men and women, it surprisingly showed that changes in WC were not associated with the subsequent risk of diabetes in men, and only weakly positively associated with the risk of diabetes in women. Accordingly, these findings suggest that a reduction in WC may be a weak or insufficient or target for prevention of diabetes in middle-aged men and women.
Background and objectives
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin studies suggest that genetic differences are responsible for the major part of the variation in body mass index (BMI) and other measures of body fatness within populations. Several recent studies suggest that the genetic effects on adiposity may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that a higher prevalence of obesity and overweight and a higher BMI mean is associated with a larger genetic variation in BMI.
The data consisted of self-reported height and weight from two Danish twin surveys in 1994 and 2002. A total of 15,017 monozygotic and dizygotic twin pairs were divided into subgroups by year of birth (from 1931 through 1982) and sex. The genetic and environmental variance components of BMI were calculated for each subgroup using the classical twin design. Likewise, the prevalence of obesity, prevalence of overweight and the mean of the BMI distribution was calculated for each subgroup and tested as explanatory variables in a random effects meta-regression model with the square root of the additive genetic variance (equal to the standard deviation) as the dependent variable.
The size of additive genetic variation was positively and significantly associated with obesity prevalence (p = 0.001) and the mean of the BMI distribution (p = 0.015). The association with prevalence of overweight was positive but not statistically significant (p = 0.177).
The results suggest that the genetic variation in BMI increases as the prevalence of obesity, prevalence of overweight and the BMI mean increases. The findings suggest that the genes related to body fatness are expressed more aggressively under the influence of an obesity-promoting environment.
Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits.
RESEARCH DESIGN AND METHODS
MTNR1B was sequenced in 47 probands with clinical maturity-onset diabetes of the young (MODY), in 51 probands with early-onset familial type 2 diabetes, and in 94 control individuals. Six nonsynonymous variants (G24E, L60R, V124I, R138C, R231H, and K243R) were genotyped in up to 22,142 Europeans. Constitutive and melatonin-induced signaling was characterized for the wild-type melatonin receptor type 1B (MT2) and the 24E, 60R, and 124I MT2 mutants in transfected COS-7 cells.
No mutations in MTNR1B were MODY specific, and none of the investigated MTNR1B variants associated with type 2 diabetes. The common 24E variant associated with increased prevalence of obesity (odds ratio 1.20 [1.08–1.34]; P = 8.3 × 10−4) and increased BMI (β = 0.5 kg/m2; P = 1.2 × 10−5) and waist circumference (β = 1.2 cm; P = 9 × 10−6) in combined Danish and French study samples. 24E also associated with decreased FPG (β = −0.08 mmol/l; P = 9.2 × 10−4) in the Danish Inter99 population. Slightly decreased constitutive activity was observed for the MT2 24E mutant, while the 124I and 60R mutants displayed considerably decreased or completely disrupted signaling, respectively.
Nonsynonymous mutations in MTNR1B are not a common cause of MODY or type 2 diabetes among Danes. MTNR1B 24E associates with increased body mass and decreased FPG. Decreased MT2 signaling does apparently not directly associate with FPG or type 2 diabetes.
Genetic differences have been proposed to play a strong role in risk of death from infectious diseases. The study base of 44,005 included all same-sex twin pairs born in 1870–2001, with both twins alive on January 1, 1943, or those born thereafter. Cause of death was obtained from the Danish Cause of Death Register and was available for 18,359 deaths. The authors classified death due to infections by 3 definitions (narrow, broader, and broadest) and calculated concordance rates for same-sex monozygotic and dizygotic twin pairs. Heritability was estimated by using structural equation models. When the 3 definitions were applied, 211 (1.1%), 1,089 (5.9%), and 2,907 (15.8%) deaths, respectively, were due to infections. The probandwise concordance rates for monozygotic twin pairs were consistently higher than for dizygotic twin pairs regardless of the definition (9% vs. 0% (P = 0.04), 10% vs. 3% (P < 0.01), and 19% vs. 15% (P = 0.07), respectively). For the broader and broadest definitions, heritability was 40% (95% confidence interval: 12, 50) and 19% (95% confidence interval: 3, 35), respectively. The concordance rates were generally low, and, although a genetic influence on the risk of death from infectious diseases could be demonstrated, the absolute effect of the genetic component on mortality was small.
cause of death; genetics; infection; twins
The worldwide epidemic of childhood obesity is progressing at an alarming rate. Risk factors for coronary heart disease (CHD) are already identifiable in overweight children. The severity of the long-term effects of excess childhood weight on CHD, however, remains unknown.
We investigated the association between body-mass index (BMI) in childhood (7 through 13 years of age) and CHD in adulthood (25 years of age or older), with and without adjustment for birth weight. The subjects were a cohort of 276,835 Danish schoolchildren for whom measurements of height and weight were available. CHD events were ascertained by linkage to national registers. Cox regression analyses were performed.
In 5,063,622 person-years of follow-up, 10,235 men and 4318 women for whom childhood BMI data were available received a diagnosis of CHD or died of CHD as adults. The risk of any CHD event, a nonfatal event, and a fatal event among adults was positively associated with BMI at 7 to 13 years of age for boys and 10 to 13 years of age for girls. The associations were linear for each age, and the risk increased across the entire BMI distribution. Furthermore, the risk increased as the age of the child increased. Adjustment for birth weight strengthened the results.
Higher BMI during childhood is associated with an increased risk of CHD in adulthood. The associations are stronger in boys than in girls and increase with the age of the child in both sexes. Our findings suggest that as children are becoming heavier worldwide, greater numbers of them are at risk of having CHD in adulthood.
Obesity is more common among the less educated, suggesting education-related environmental triggers. Such triggers may act differently dependent on genetic and environmental predisposition to obesity. In a Danish Twin Registry survey, 21,522 twins of same-sex pairs provided zygosity, height, weight, and education data. Body mass index (BMI = kg weight/ m height2) was used to measure degree of obesity. We used quantitative genetic modeling to examine how genetic and shared and nonshared environmental variance in BMI differed by level of education and to estimate how genetic and shared and nonshared environmental correlations between education and BMI differed by level of education, analyzing women and men separately. Correlations between education and BMI were −.13 in women, −.15 in men. High BMI's were less frequent among well-educated participants, generating less variance. In women, this was due to restriction of all forms of variance, overall by a factor of about 2. In men, genetic variance did not vary with education, but results for shared and nonshared environmental variance were similar to those for women. The contributions of the shared environment to the correlations between education and BMI were substantial among the well-educated, suggesting importance of familial environmental influences common to high education and lower BMI. Family influence was particularly important in linking high education and lower levels of obesity.
A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men.
In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m2, all of whom were above the 99th percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1β, IL-6, IL-10, IL-18, mip1α, mip1β, sTNFα-R1, TGF-β, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively.
No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.
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.
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.
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.
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.
Low birth weight and high childhood body mass index (BMI) is each associated with an increased risk of coronary heart disease (CHD) in adult life. We studied individual and combined associations of birth weight and childhood BMI with the risk of CHD in adulthood.
Birth weight and BMI at age seven years were available in 216,771 Danish and Finnish individuals born 1924–1976. Linkage to national registers for hospitalization and causes of death identified 8,805 CHD events during up to 33 years of follow-up (median = 24 years) after age 25 years. Analyses were conducted with Cox regression based on restricted cubic splines. Using median birth weight of 3.4 kg as reference, a non-linear relation between birth weight and CHD was found. It was not significantly different between cohorts, or between men and women, nor was the association altered by childhood BMI. For birth weights below 3.4 kg, the risk of CHD increased linearly and reached 1.28 (95% confidence limits: 1.13 to 1.44) at 2 kg. Above 3.4 kg the association weakened, and from about 4 kg there was virtually no association. BMI at age seven years was strongly positively associated with the risk of CHD and the relation was not altered by birth weight. The excess risk in individuals with a birth weight of 2.5 kg and a BMI of 17.7 kg/m2 at age seven years was 44% (95% CI: 30% to 59%) compared with individuals with median values of birth weight (3.4 kg) and BMI (15.3 kg/m2).
Birth weight and BMI at age seven years appeared independently associated with the risk of CHD in adulthood. From a public health perspective we suggest that particular attention should be paid to children with a birth weight below the average in combination with excess relative weight in childhood.
Waist circumference (WC) adjusted for body mass index (BMI) is positively associated with mortality, but the association with changes in WC is less clear. We investigated the association between changes in WC and mortality in middle-aged men and women, and evaluated the influence from concurrent changes in BMI.
Data on 26,625 healthy men and women from the Danish Diet, Cancer and Health study was analyzed. WC and BMI were assessed in 1993–97 and in 1999–02. Information on mortality was obtained by linkage to the Danish central Person Register. Hazard ratios (HR) were estimated with Cox regression models. During 6.7 years of follow-up, 568 and 361 deaths occurred among men and women, respectively. Changes in WC were positively associated with mortality (HR per 5 cm for the sexes combined = 1.09 (1.02∶1.16) with adjustment for covariates, baseline WC, BMI and changes in BMI), whereas changes in BMI were inversely associated with mortality (HR per kg/m2 for the sexes combined = 0.91 (0.86, 0.97) with adjustment for covariates, baseline WC, BMI and changes in WC). Associations between changes in WC and mortality were not notably different in sub-groups stratified according to changes in BMI, baseline WC or when smokers or deaths occurring within the first years of follow-up were excluded.
Changes in WC were positively associated with mortality in healthy middle-aged men and women throughout the range of concurrent changes in BMI. These findings suggest a need for development of prevention and treatment strategies targeted against redistribution of fat mass towards the abdominal region.
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.
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).
Our results suggest that severe pre-pregnancy stress is associated with an increased risk of overweight in the offspring in later childhood.
Endothelial lipase (LIPG) is implicated in the metabolism of high-density lipoprotein cholesterol (HDL-C). Small studies in selected populations have reported higher HDL-C levels among carriers of the common T111I variant in LIPG, but whether this variant is associated with plasma lipids and risk of coronary heart disease (CHD) in the general population is unclear. The objective of this study was to address the associations of the T111I variant with plasma lipids and risk of CHD in three independent prospective studies of generally healthy men and women.
Methods and results
The T111I variant was genotyped in case–control studies of CHD nested within the Diet, Cancer, and Health study with 998 cases, Nurses’ Health Study with 241 cases, and Health Professionals Follow-up Study with 262 cases. The minor allele frequency in the combined pool of controls was 0.29. The T111I variant was not associated with HDL-C or any other lipid and lipoprotein measures. Compared with wildtype homozygotes, the pooled estimate for risk of CHD was 0.95 (0.85–1.06) per T111I allele.
Our analysis among healthy Caucasian men and women from three independent studies does not support an association between the T111I variant and HDL-C, other plasma lipids, or risk of CHD.
Genetic epidemiology; Endothelial lipase; HDL-cholesterol; CHD-risk
We investigated associations between maternal postpartum distress covering anxiety, depression and stress and childhood overweight.
We performed a prospective cohort study, including 21 121 mother-child-dyads from the Danish National Birth Cohort (DNBC). Maternal distress was measured 6 months postpartum by 9 items covering anxiety, depression and stress. Outcome was childhood overweight at 7-years-of age. Multiple logistic regression analyses were performed and information on maternal age, socioeconomic status, pre-pregnancy BMI, gestational weight gain, parity, smoking during pregnancy, paternal BMI, birth weight, gestational age at birth, sex, breastfeeding and finally infant weight at 5 and 12 month were included in the analyses.
We found, that postpartum distress was not associated with childhood risk of overweight, OR 1.00, 95%CI [0.98–1.02]. Neither was anxiety, depression, or stress exposure, separately. There were no significant differences between the genders. Adjustment for potential confounders did not alter the results.
Maternal postpartum distress is apparently not an independent risk factor for childhood overweight at 7-years-of-age. However, we can confirm previous findings of perinatal determinants as high maternal pre-pregnancy BMI, and smoking during pregnancy being risk factors for childhood overweight.
The inverse associations between birth weight and later adverse health outcomes and the positive associations between adult body size and poor health imply that increases in relative body size between birth and adulthood may be undesirable. In this paper, the authors describe life course path analysis, a method that can be used to jointly estimate associations between body sizes at different time points and associations of body sizes throughout life with health outcomes. Additionally, this method makes it possible to assess both the direct effect and the indirect effect mediated through later body size, and thereby the total effect, of size and changes in size on later outcomes. Using data on childhood body size and adult systolic blood pressure from a sample of 1,284 Danish men born between 1936 and 1970, the authors compared results from path analysis with results from 3 standard regression methods. Path analysis produced easily interpretable results, and compared with standard regression methods it produced a noteworthy gain in statistical power. The effect of change in relative body size on adult blood pressure was more pronounced after age 11 years than in earlier childhood. These results suggest that increases in body size prior to age 11 years are less harmful to adult blood pressure than increases occurring after this age.
birth weight; blood pressure; body mass index; child; epidemiologic methods; growth