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UNLABELLED: Childhood leanness is associated with an increased risk of schizophrenia, but the effects of gender, age at anthropometric measurements and age at first diagnosis on this relationship are unclear. The present study aimed at elucidating these associations.METHODS: Population-based cohort study with childhood anthropometric measures obtained annually from the age of 7 to 13 years in 253,353 Danes born 1930-1976 and followed to 31 December 2010. During this period, 4936 were registered with schizophrenia. The associations of childhood BMI with risk of schizophrenia were estimated with Cox regression models.RESULTS: Childhood BMI was significantly inversely associated with risk of schizophrenia, however with different patterns among boys and girls. In boys, childhood BMI had an inverse non-linear association with schizophrenia risk dependent on age at diagnosis; in particular, a surprisingly strong association was found between leanness and later onset of schizophrenia. In girls, the risk of schizophrenia decreased linearly with increasing BMI z-score (HR: 0.93; 95% CI: 0.88-0.98). In both boys and girls, birth weight was inversely associated with later risk. In girls, but not in boys, birth weight appeared to significantly modify the associations; there was a somewhat stronger inverse association in the lowest birth weight category.CONCLUSION: Birth weight as well as childhood BMI at ages 7 through 13 years is associated with risk of schizophrenia in both genders, but with a particular high risk of late-onset in lean boys irrespective of birth weight, and in lean girls with low birth weight. If replicated, these observations may inform preventive efforts build on schizophrenia trajectories rooted in early life.

BACKGROUND: Increased consumption of sweetened beverages has previously been linked to the degree of childhood obesity.OBJECTIVE: The aim of the present study was to assess whether the intake of sweetened beverages, candy, snacks or fast food at baseline in a multidisciplinary childhood obesity treatment program was associated with the baseline degree of obesity or the treatment effect.METHODS: This prospective study included 1349 overweight and obese children (body mass index standard deviation scores (BMI SDS) ≥ 1.64) enrolled in treatment at The Children's Obesity Clinic, Copenhagen University Hospital Holbaek. The children were evaluated at baseline and after up to 5.9 years of treatment (median 1.3 years).RESULTS: Both boys and girls decreased their BMI SDS during treatment with a mean decrease in boys of 0.35 (p < 0.0001) and in girls of 0.22 (p < 0.0001) after 1 year of treatment. There were no associations between the baseline intake of sweetened beverages, candy, snacks, and/or fast food and BMI SDS at baseline or the change in BMI SDS during treatment.CONCLUSIONS: The intake of sweetened beverages, candy, snacks or fast food when entering a childhood obesity treatment program was not associated with the degree of obesity at baseline or the degree of weight loss during treatment.

BACKGROUND: Endometrial cancer risk factors include adult obesity and taller stature, but the influence of size earlier in life is incompletely understood. We examined whether childhood body mass index (BMI; kg m(-2)) and height were associated with histologic subtypes of endometrial cancer.METHODS: From the Copenhagen School Health Records Register, 155 505 girls born 1930-1989 with measured weights and heights from 7 to 13 years were linked to health registers. BMI and height were transformed to age-specific z-scores. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox regressions.RESULTS: A total of 1020 endometrial cancers were recorded. BMI was non-linearly associated with all endometrial cancers, oestrogen-dependent cancers and the subtype of endometrioid adenocarcinomas; associations were statistically significant and positive above a z-score=0 and non-significant below zero. Compared with a 7-year-old girl with a BMI z-score=0, an equally tall girl who was 3.6 kg heavier (BMI z-score=1.5) had a hazard ratio=1.53 (95% confidence interval: 1.29-1.82) for endometrioid adenocarcinoma. BMI was not associated with non-oestrogen-dependent cancers, except at the oldest childhood ages. Height at all ages was statistically significant and positively associated with all endometrial cancers, except non-oestrogen-dependent cancers. At 7 years, per ~5.2 cm (1 z-score), the risk of endometrioid adenocarcinoma was 1.18 (95% confidence interval: 1.09-1.28). Among non-users of unopposed oestrogens, associations between BMI and endometrioid adenocarcinoma strengthened, but no effects on height associations were observed.CONCLUSIONS: Endometrial carcinogenesis is linked to early-life body size, suggesting that childhood BMI and height may be useful indicators for the risk of later development of endometrial cancer and might aid in the early prevention of obesity-related endometrial cancers.

BACKGROUND: Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life.METHODS: We assessed associations between childhood body mass index (BMI) and height-measured annually between ages 7 and 13-with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255 053 children born during 1930-1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression.RESULTS: During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages.CONCLUSION: Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.

BACKGROUND/OBJECTIVES: Prenatal vitamin-D deficiency may be associated with increased risk of obesity later in life. Using two national vitamin-D fortification programs as the setting for a societal experiment, we investigated whether exposure to vitamin-D from fortified margarine and low-fat milk during foetal life was associated with body size at 7 years of age.SUBJECTS/METHODS: Vitamin-D fortification of margarine was mandatory in Denmark from 1961 to 1985, and voluntary fortification of low-fat milk was permitted from 1972 to 1976. Using information on body mass index (BMI) Z-score at the age of 7 years of 54 270 children, who were measured during the mandatory Copenhagen School Health examination, we compared children according to whether the mothers were pregnant during the fortification programs or not. The comparisons were performed for children born just before and after initiation or termination of margarine and milk fortification periods, respectively. In total four sets of analyses were performed.RESULTS: We observed no difference in mean BMI Z-score between children exposed to vitamin-D fortification in utero and non-exposed children. Similar results were observed for overweight and obesity.CONCLUSIONS: Prenatal exposure to vitamin-D from fortification of margarine and low-fat milk showed no association with body size at 7 years.

BACKGROUND: Adult body size is positively associated with aggressive and fatal prostate cancers. It is unknown whether these associations originate in early life. Therefore, we investigated if childhood height, body mass index (BMI; kg/m(2)) and growth are associated with prostate cancer-specific mortality and survival.METHODS: Subjects were 125,208 men from the Copenhagen School Health Records Register, born 1930-1969 with height and weight measurements at ages 7-13years. Linkage to the Danish Cancer Registry and the Register of Causes of Death enabled identification of incident and fatal prostate cancers. Cox proportional hazards regressions were performed.RESULTS: 630 men had prostate cancer recorded as the underlying cause of death. Childhood height at age 13years was positively associated with prostate cancer-specific mortality (hazard ratio [HR]per z-score=1.2, 95% confidence interval [CI]: 1.1-1.3). Associations were significant at all other childhood ages. Growth analyses showed that height at age 13years had a stronger association with prostate cancer-specific mortality than height at age 7, suggesting the association at age 7 is largely mediated through later childhood height. The tallest boys at age 13years had a significantly worse survival, but only when restricted to a diagnosis at <60years of age (HRz-score of 1=1.7, 95% CI: 1.3-2.4). These associations were significant at all other childhood ages. Childhood BMI was not associated with prostate cancer mortality or survival.CONCLUSION: Childhood height was positively associated with the hard end-point of prostate cancer-specific mortality, which strengthens prior epidemiologic observations of a positive association with prostate cancer incidence.

BACKGROUND: Prostate cancer aetiology is poorly understood. It may have origins early in life; previously we found a positive association with childhood height. The effects of early life body mass index (BMI; kg m(-2)) on prostate cancer remain equivocal. We investigated if childhood BMI, independently and adjusted for height, is positively associated with adult prostate cancer.METHODS: Subjects were a cohort of 125208 boys formed from the Copenhagen School Health Records Register, born 1930-1969 with height and weight measurements at 7-13 years. Cases were identified through linkage to the Danish Cancer Registry. Cox proportional hazards regressions were performed.RESULTS: Overall, 3355 men were diagnosed with prostate cancer. Body mass index during childhood was positively associated with adult prostate cancer. The hazard ratio of prostate cancer was 1.06 (95% confidence interval (CI): 1.01-1.10) per BMI z-score at age 7, and 1.05 (95% CI: 1.01-1.10) per BMI z-score at age 13. Estimates were similar and significant at all other ages. However, adjustment for childhood height attenuated the associations at all but the youngest ages as most estimates became nonsignificant.CONCLUSIONS: These results suggest that at most childhood ages, BMI does not confer an additional risk for prostate cancer beyond that of height.

Fetal exposure to the perfluoroalkyl acids, perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA), has been associated with lower birth weight and lower weight and body mass index (weight (kg)/height (m)(2)) in early infancy. It is, however, unclear if exposure to prenatal PFOS and PFOA has a lasting influence on growth. We estimated the associations between the maternal plasma level of PFOS or PFOA and the children's body mass index, waist circumference, and risk of overweight at 7 years of age. A total of 1,400 women were randomly selected from the Danish National Birth Cohort among those who provided blood samples early in pregnancy and gave birth to liveborn singletons in 1996-2002. Weight and height information at 7 years was available for 811 children. Multiple linear and logistic regression models were used for analyses. Maternal PFOS and PFOA concentrations were overall inversely but nonsignificantly associated with the children's body mass index, waist circumference, and risk of overweight at 7 years of age. In conclusion, plasma levels of PFOS and PFOA in pregnant women did not seem to have any appreciable influence on their children's anthropometry at this point in childhood.

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.

Objective: To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (<6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. Design: Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. Methods: A total of 28¿354 mother–child dyads from the Danish National Birth Cohort, with information on maternal pre-pregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. Results: Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95–1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09–2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30–0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41–1.76). Conclusion: The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.

Background: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. Methods/Principal Findings: We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. Conclusions/Significance: The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk. © 2009 Andersen et al.

BACKGROUND: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. METHODS/PRINCIPAL FINDINGS: We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. CONCLUSIONS/SIGNIFICANCE: The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk