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Background: Being breastfed has established benefits for infant health, but its long-term effects on adult diseases, including cancer, remain underexplored. We examined associations between being breastfed in infancy and the risks of common cancers., Methods: Data from 339,115 participants (191,117 women) enrolled in the UK Biobank with self-reported breastfeeding data were linked to national cancer registries. Cox models estimated sex-specific hazard ratios (HR) and 95% confidence intervals (CI) for the associations between being breastfed (ever/never) and risks of overall cancer as well as common cancer sites., Results: In total, 34,392 incident cancers (17,895 in women) were registered. The HR of overall cancer associated with being breastfed was 1.05 (95% CI 1.01-1.09) in women and 1.00 (95% CI 0.96-1-04) in men. In site-specific analysis being breastfed was associated with an increased risk of breast and ovarian cancer in women and a reduced risk of oesophageal cancer in men., Discussion: We found that having been breastfed was associated with a marginally increased risk of adult cancer in women, but we found no evidence of an association in men. These findings should be viewed within the study limitations, and do not outweigh the many benefits that breastfeeding provides., (© 2024. The Author(s).)

Background: The early life factors of birthweight, child weight, height, body mass index (BMI) and pubertal timing are associated with risks of breast cancer. However, the predictive value of these factors in relation to breast cancer is largely unknown. Therefore, using a machine learning approach, we examined whether birthweight, childhood weights, heights, BMIs, and pubertal timing individually and in combination were predictive of breast cancer., Methods: We used information on birthweight, childhood height and weight, and pubertal timing assessed by the onset of the growth spurt (OGS) from 164,216 girls born 1930-1996 from the Copenhagen School Health Records Register. Of these, 10,002 women were diagnosed with breast cancer during 1977-2019 according to a nationwide breast cancer database. We developed a feed-forward neural network, which was trained and tested on early life body size measures individually and in various combinations. Evaluation metrics were examined to identify the best performing model., Results: The highest area under the receiver operating curve (AUC) was achieved in a model that included birthweight, childhood heights, weights and age at OGS (AUC = 0.600). A model based on childhood heights and weights had a comparable AUC value (AUC = 0.598), whereas a model including only childhood heights had the lowest AUC value (AUC = 0.572). The sensitivity of the models ranged from 0.698 to 0.760 while the precision ranged from 0.071 to 0.076., Conclusion: We found that the best performing network was based on birthweight, childhood weights, heights and age at OGS as the input features. Nonetheless, this performance was only slightly better than the model including childhood heights and weights. Further, although the performance of our networks was relatively low, it was similar to those from previous studies including well-established risk factors. As such, our results suggest that childhood body size may add additional value to breast cancer prediction models., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Svendsen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Associations of birthweight, childhood body size and pubertal timing with breast cancer risks by menopausal status and tumor receptor subtypes are inconclusive. Thus, we investigated these associations in a population-based cohort of Danish women., Methods: We studied 162,419 women born between 1930 and 1996 from the Copenhagen School Health Records Register. The register includes information on birthweight, measured childhood weights and heights at the age of 7-13 years, and computed ages at the onset of the growth spurt (OGS) and at peak height velocity (PHV). The Danish Breast Cancer Cooperative Group database provided information on breast cancer (n = 7510), including estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and menopausal status. Hormone replacement therapy use came from the Danish National Prescription Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression., Results: We found that birthweight was not associated with any breast cancer subtypes. While childhood BMI was not statistically significantly associated with ER+ tumors nor consistently with ER- tumors among pre-menopausal women, consistent inverse associations were found among postmenopausal women. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 0.90 (95% CI 0.87-0.93) and 0.84 (95% CI 0.79-0.91) per BMI z-score, respectively. Similarly, childhood BMI was inversely associated with pre- and postmenopausal HER2- tumors, but not with HER2+ tumors. Childhood height was positively associated with both pre- and postmenopausal ER+ tumors, but not with ER- tumors. At the age of 7 years, the HRs for postmenopausal ER+ and ER- tumors were 1.09 (95% CI 1.06-1.12) and 1.02 (95% CI 0.96-1.09) per height z-score, respectively. In general, childhood height was positively associated with HER2+ and HER2- tumors among pre- and postmenopausal women. Ages at OGS and PHV were not associated with any breast cancer subtypes., Conclusions: We showed that a high BMI and short stature in childhood are associated with reduced risks of certain breast cancer subtypes. Thus, childhood body composition may play a role in the development of breast cancer., (© 2022. The Author(s).)

Background: It remains unknown whether maternal early life body size and changes in height and BMI from childhood to pregnancy are associated with risks of having a preterm delivery., Objectives: We investigated whether a woman's birth weight, childhood height, BMI, and changes in height and BMI from childhood to pregnancy were associated with preterm delivery., Methods: We studied 47,947 nulliparous women born from 1940 to 1996 who were included in the Copenhagen School Health Records Register with information on birth weight and childhood heights and weights at ages 7 and/or 13 years. Gestational age was obtained from the Danish Birth Register, as was prepregnancy BMI, for 13,114 women. Deliveries were classified as very (22 to <32 weeks) or moderately (32 to <37 weeks) preterm. Risk ratios (RRs) and 95% CIs were estimated using binomial regression., Results: A woman's birth weight and childhood height were inversely associated with having very and moderately preterm delivery. Childhood BMI had a U-shaped association with having a very preterm delivery; at age 7 years, compared to a BMI z score of 0, the RRs were 1.31 (95% CI, 1.11-1.54) for a z score of -1 and 1.18 (95% CI, 1.01-1.38) for a z score of +1. Short stature in childhood and adulthood was associated with higher risks of very and moderately preterm delivery. Changing from a BMI at the 85th percentile at 7 years (US CDC reference) to a prepregnancy BMI of 22.5 kg/m2 was associated with RRs of 1.12 (95% CI, 0.91-1.37) and 0.88 (95% CI, 0.78-0.99) for very and moderately preterm delivery, respectively, compared to a reference woman at the 50th percentile at 7 years (22.5 kg/m2 prepregnancy BMI)., Conclusions: Maternal birth weight, childhood height, and BMI are associated with very and moderately preterm delivery, although in different patterns. Consistent short stature is associated with very and moderately preterm delivery, whereas normalizing BMI from childhood to pregnancy may reduce risks of having a very preterm delivery., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Introduction: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown., Objective: To investigate associations between a woman's own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS., Methods: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960-1996, with information on birthweight and measured weight and height at the ages of 7-13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15-50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis., Results: Birthweight was not associated with PCOS. At the age of 7-13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34-3.42) at age 7 years and 2.99 (95% CI 2.38-3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth., Conclusion: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Maternal overweight (including obesity) is an established risk factor for gestational hypertension and pre-eclampsia. However, it is largely unknown whether body size before adulthood relates to these diseases., Objectives: We examined whether childhood BMI (in kg/m2) and changes in BMI from childhood to adulthood were associated with gestational hypertension and pre-eclampsia., Methods: Using the Copenhagen School Health Records Register, we studied 49,600 women born between 1940 and 1996 with height and weight measurements at 7 y and/or 13 y who had their first singleton birth between ages 18 and 45 y. Women with gestational hypertension (n = 496) and pre-eclampsia (n = 1804) were identified from the International Classification of Disease codes in the Danish National Patient Register. Adult overweight (including obesity) was defined as a BMI ≥25. We used log-linear binomial regression to estimate risk ratios (RRs) and 95% CIs., Results: At 13 y, as BMI increased above average (z score >0, or the 42nd percentile of the CDC BMI reference), RR for gestational hypertension was 1.66 (95% CI: 1.42, 1.94) and that for pre-eclampsia was 1.57 (95% CI: 1.46, 1.70) per BMI z score. In a subset of 13,160 women, development of overweight from childhood to adulthood and having overweight at both ages were associated with higher risks of the outcomes than in those with a normal BMI at both ages. No increased risks were observed in women whose BMI normalized from childhood to adulthood: RR was 2.04 (95% CI: 0.93, 4.47) for gestational hypertension and 1.11 (95% CI: 0.63, 1.93) for pre-eclampsia., Conclusions: Above-average childhood BMI values and development of overweight from childhood to adulthood were associated with increased risks of gestational hypertension and pre-eclampsia, whereas normalizing BMI from childhood to conception attenuated the risks. Thus, interventions aiming at normalizing BMI in girls with high values may be warranted to help prevent these obstetric diseases., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Objective: We investigated the association between changes in weight status from childhood through adulthood and subsequent type 2 diabetes risks and whether educational attainment, smoking, and leisure time physical activity (LTPA) modify this association., Research Design and Methods: Using data from 10 Danish and Finnish cohorts including 25,283 individuals, childhood BMI at 7 and 12 years was categorized as normal or high using age- and sex-specific cutoffs (<85th or ≥85th percentile). Adult BMI (20-71 years) was categorized as nonobese or obese (<30.0 or ≥30.0 kg/m 2 , respectively). Associations between BMI patterns and type 2 diabetes (989 women and 1,370 men) were analyzed using Cox proportional hazards regressions and meta-analysis techniques., Results: Compared with individuals with a normal BMI at 7 years and without adult obesity, those with a high BMI at 7 years and adult obesity had higher type 2 diabetes risks (hazard ratio [HR] girls 5.04 [95% CI 3.92-6.48]; HR boys 3.78 [95% CI 2.68-5.33]). Individuals with a high BMI at 7 years but without adult obesity did not have a higher risk (HR girls 0.74 [95% CI 0.52-1.06]; HR boys 0.93 [95% CI 0.65-1.33]). Education, smoking, and LTPA were associated with diabetes risks but did not modify or confound the associations with BMI changes. Results for 12 years of age were similar., Conclusions: A high BMI in childhood was associated with higher type 2 diabetes risks only if individuals also had obesity in adulthood. These associations were not influenced by educational and lifestyle factors, indicating that BMI is similarly related to the risk across all levels of these factors., (© 2020 by the American Diabetes Association.)

Observed associations between breastfeeding and reduced risk of type 2 diabetes in adulthood may be confounded. We examined if the duration of breastfeeding in infancy was associated with the risk of type 2 diabetes in adulthood after adjustment for a range of prenatal and postnatal risk factors. We prospectively followed 6,044 individuals from the Copenhagen Perinatal Cohort born 1959-1961. Duration of any breastfeeding (≤0.5, >0.5-1, >1-2, >2-4, >4 months) was assessed at the infant's 1-year health examination. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for type 2 diabetes (at age ≥30 years, 237 persons) by breastfeeding duration without and with adjustment for parental social status and education, maternal pre-pregnancy body mass index (BMI), maternal diabetes and smoking during pregnancy, gestational weight gain, parity, preterm birth, birth weight, sex, and BMI at ages 7 and 41-43 years. In the unadjusted analysis, compared with infants breastfed for ≤0.5 month, those breastfed for >4 months had a 51% reduced risk of type 2 diabetes (HR = 0.49; 95% CI [0.32, 0.75]). After the stepwise adjustment for putative early life confounders, this was attenuated to a nonsignificant 31% reduced risk (HR = 0.69; 95% CI [0.44, 1.07]). Adjustment for childhood and adulthood BMI minimally changed the results. We found that the inverse association between the duration of breastfeeding and risk of type 2 diabetes in adulthood is considerably weakened and no longer significant after adjustment for prenatal and postnatal factors in the infant and mother., (© 2019 John Wiley & Sons Ltd.)

Children with obesity have a cardiometabolic risk profile that may predispose them to cardiovascular diseases. We examined the associations of childhood body mass index (BMI) and changes in BMI with the risk of atrial fibrillation and flutter (AFF) in adulthood. We conducted a population-based cohort study of Danish schoolchildren aged 7-13 years born from 1930 to 1989. Among 314,140 children, 17,594 were diagnosed with AFF as adults (1977-2014). In both men and women, above-average BMIs in childhood were associated with increased risks of AFF. Children who were persistently heavy at ages 7 and 13 years and children whose BMIs increased from the internal 25.0th-75.0th percentiles or from the internal 75.1th-90.0th percentiles between ages 7 and 13 years had higher risks of AFF in adulthood than children whose BMIs remained in the internal 25.0th-75.0th percentiles at both ages. A decrease in BMI percentile categories between 7 and 13 years of age reduced risks of AFF in adulthood, with risks of AFF reverting to levels similar to those in the reference group for women but not for men. In conclusion, risks of AFF in adulthood increased with higher childhood BMIs. Remission from overweight by age 13 years reduced AFF risks, especially in women., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Objective: This study investigated how a wide spectrum of body mass index (BMI) values at ages 7 to 13 years are associated with type 2 diabetes throughout adulthood, including potential modifying effects of sex and birth weight., Methods: From the Copenhagen School Health Records Register, 292,827 individuals, born between 1930 and 1989, were followed in national registers for type 2 diabetes (women, n = 7,472; men, n = 11,548). Heights and weights were measured at ages 7 to 13 years., Results: Below-average BMIs, with few exceptions, were not associated with type 2 diabetes. Above-average BMIs had positive associations that were stronger in women than men, stronger in younger birth cohorts, and weaker with older age at diagnosis. Women born 1930-1947, 1948-1965, and 1966-1983 with above-average BMIs at 13 years (≥18.2 kg/m 2 ) had hazard ratios (95% confidence intervals) ranging from 2.12 (1.91-2.36) to 2.84 (2.31-3.49) per z score when diagnosed at 30 to 47 years. Birth weight did not modify these associations., Conclusions: Childhood BMIs below average are not associated with type 2 diabetes, whereas childhood BMIs above average are strongly associated with type 2 diabetes in adulthood, corresponding to excess risks even at levels below international definitions of overweight. The associations are stronger in women than men but are not affected by birth weight., (© 2017 The Obesity Society.)

Background: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg m(-2)) tracking from childhood to late adulthood., Methods: From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed., Results: Correlations between BMI at 7 years and young adult ages (18-19 years) were r=0.55 for men and r=0.55 for women. At late ages (60-69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18-19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14-16.19) for men and 10.46 (95% CI: 4.82-22.70) for women. At ages 60-69 years ORs were 5.46 (95% CI: 0.95-31.36) for men and 1.61 (95% CI: 0.83-3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar., Conclusions: BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.

Background: Weight and weight gain throughout infancy are related to later obesity, but whether the strength of the associations varies during the infancy period is uncertain., Aims: Our aims were to identify the period of infancy when change in body weight has the strongest association with adult body mass index (BMI) and also the extent to which these associations during infancy are mediated through childhood BMI., Methods: The Copenhagen Perinatal Cohort, in which participants were followed from birth through 42 years of age, provided information on weight at 12 months and BMI at 42 years for 1633 individuals. Information on weight at birth, 2 weeks, 1, 2, 3, 4 and 6 months was retrieved from health visitors' records and information on BMI at ages 7 and 13 years from school health records. The associations of infant weight and weight gain standard deviation scores (SDS) with adult BMI-SDS were analyzed using multiple linear regression and path analysis., Results: Higher-weight-SDS at all ages from birth to an age 12 months were associated with higher-BMI-SDS at 42 years (regression coefficients 0.08-0.12). Infant weight gain-SDS was associated with greater BMI-SDS at 42 years only between birth and 3 months (0.09, 95% confidence intervals (CI) 0.04, 0.15) driven by an association between 2 and 3 months (0.12, 95% CI: 0.04, 0.20). The latter was partly mediated through later BMI in the path analysis. Infant weight gain-SDS between 3 and 12 months was not associated with greater BMI-SDS at 42 years., Conclusions: Faster weight gain during only the first 3 months of infancy was associated with increased adult BMI, although not in a consistent monthly pattern. Adult BMI is more sensitive to high weight gain during early infancy than late infancy, but not specifically to the first month of life.