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Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes
This study addressed whether remission of overweight before early adulthood reduced the risk of type 2 diabetes in adulthood. Men who had been overweight at 7 years of age had an increased risk of adult type 2 diabetes only if overweight continued until puberty or later.
Journal Article
Human ancestry correlates with language and reveals that race is not an objective genomic classifier
Genetic and archaeological studies have established a sub-Saharan African origin for anatomically modern humans with subsequent migrations out of Africa. Using the largest multi-locus data set known to date, we investigated genetic differentiation of early modern humans, human admixture and migration events, and relationships among ancestries and language groups. We compiled publicly available genome-wide genotype data on 5,966 individuals from 282 global samples, representing 30 primary language families. The best evidence supports 21 ancestries that delineate genetic structure of present-day human populations. Independent of self-identified ethno-linguistic labels, the vast majority (97.3%) of individuals have mixed ancestry, with evidence of multiple ancestries in 96.8% of samples and on all continents. The data indicate that continents, ethno-linguistic groups, races, ethnicities, and individuals all show substantial ancestral heterogeneity. We estimated correlation coefficients ranging from 0.522 to 0.962 between ancestries and language families or branches. Ancestry data support the grouping of Kwadi-Khoe, Kx’a, and Tuu languages, support the exclusion of Omotic languages from the Afroasiatic language family, and do not support the proposed Dené-Yeniseian language family as a genetically valid grouping. Ancestry data yield insight into a deeper past than linguistic data can, while linguistic data provide clarity to ancestry data.
Journal Article
Childhood Body-Mass Index and the Risk of Coronary Heart Disease in Adulthood
In this Danish study, body-mass index in childhood was associated with coronary heart disease (CHD) events in adulthood. The association was stronger in boys than in girls, and the risk of an event in adulthood increased in both sexes as the child's age increased from 7 to 13 years. These important data focus attention on the public health significance of the epidemic of childhood obesity.
In this study, body-mass index in childhood was associated with coronary heart disease events in adulthood. The risk of an event in adulthood increased in both sexes as the child's age increased from 7 to 13 years.
Worldwide, children are becoming overweight at progressively younger ages.
1
In the United States, an estimated 19% of children 6 to 11 years of age are classified as overweight, with a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) greater than the 95th percentile for their age and sex according to the Centers for Disease Control and Prevention (CDC) growth charts.
2
Thus, many children are at risk for weight-related orthopedic problems, social stigmatization, and endocrine abnormalities.
3
The epidemic of childhood obesity is of great concern because, in addition to these concurrent effects of . . .
Journal Article
Childhood body mass index trajectories and associations with adult-onset chronic kidney disease in Denmark: A population-based cohort study
Although excess adult adiposity is a strong risk factor for chronic kidney disease (CKD), evidence for associations with early life body size is limited. We investigated whether childhood body mass index (BMI) trajectories are associated with adult-onset CKD and end-stage kidney disease (ESKD) using a population-based cohort. Further, we examined the role of adult-onset type 2 diabetes (T2D) in these associations.
We included 151,506 boys and 148,590 girls from the Copenhagen School Health Records Register, born 1930 to 1987 with information on measured weights and heights at ages 6 to 15 years. Five sex-specific childhood BMI trajectories were analyzed. Information on the main outcomes CKD and ESKD, as well as T2D, came from national health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using Poisson regression adjusted for year of birth. During a median of 30.8 person-years of follow-up, 5,968 men and 3,903 women developed CKD and 977 men and 543 women developed ESKD. For both sexes, the rates of CKD and ESKD increased significantly with higher child BMI trajectories in comparison with the average BMI trajectory (40% to 43% of individuals) and the below-average BMI trajectory (21% to 23% of individuals) had the lowest rates. When including T2D, most associations were significant and men (IRR = 1.39, 95% CI: 1.13 to 1.72) and women (IRR = 1.54, 95% CI: 1.28 to 1.86) with the obese childhood BMI trajectory (2% of individuals) had significantly higher CKD rates than the average BMI trajectory, whereas for ESKD, the associations were positive, but nonsignificant, for men (IRR = 1.38, 95% CI: 0.83 to 2.31) but significant for women (IRR = 1.97, 95% CI: 1.25 to 3.11) with the obese BMI trajectory. A main study limitation is the use of only hospital-based CKD diagnoses.
Individuals with childhood BMI trajectories above average had higher rates of CKD and ESKD than those with an average childhood BMI trajectory. When including T2D, most associations were significant, particularly with CKD, emphasizing the potential information that the early appearance of above-average BMI growth patterns provide in relation to adult-onset CKD beyond the information provided by T2D development.
Journal Article
Update on the Feasibility and Progress on Robotic Breast Surgery
Background
Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however, data regarding the feasibility and safety of the procedure are limited.
Objective
The aim of this study was to present and discuss perioperative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019.
Methods
Patients underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Perioperative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence-free, disease-free, and overall survival were analyzed.
Results
Overall, 73 women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 h and 32 min. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring reoperation was 4.3%, and the rate of flap or nipple necrosis was 1.1%. Median follow-up was 19 months (range 3.1–44.8). No local recurrences occurred. Overall survival at 12, 24, or 60 months was 98% (95% confidence interval 86–100%).
Conclusion
We observed a low complication rate in 94 consecutive RNSM procedures, demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.
Journal Article
Prenatal Stress Exposure Related to Maternal Bereavement and Risk of Childhood Overweight
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.
Journal Article
Birthweight, childhood overweight, height and growth and adult cancer risks: a review of studies using the Copenhagen School Health Records Register
BackgroundMost identified risk factors for cancer primarily occur in adulthood. As cancers generally have long latency periods, it is possible that risk factors acting earlier in life and accumulation of risks across the life course are important. Thus, focusing only on adult overweight as a modifiable risk factor may overlook childhood as an important aetiologic time window when body size is relevant for future cancer risks. The objective of this study was to review the evidence for associations between birthweight, body mass index (BMI), height and growth from 7–13 years and adult cancer risks based on studies using the Copenhagen School Health Records Register.MethodsThe register contains measured anthropometric information on 372,636 children born in 1930–1989. All studies examining associations between early life body size and risks of adult cancer (until 85 years, diagnosed in 1968–2015) were included, comprising 31 studies on 16 different cancer sites. Cancer diagnoses were retrieved via individual-level linkages to the Danish Cancer Registry.ResultsBirthweight was differentially associated with bladder, breast, colon, glioma, Hodgkin’s disease, liver, kidney (renal cell), melanoma, ovarian, rectal, testicular and thyroid cancer. BMI in childhood was positively associated with risks of bladder (only late childhood), colon, endometrial, kidney, liver, oesophageal (only late childhood), ovarian, pancreatic (<70 years), prostate (only before childhood height adjustment) and thyroid cancer, whereas it was inversely associated with breast cancer. Child height was positively associated with breast, colon, endometrial, glioma, Hodgkin’s disease, kidney, melanoma, oesophageal (only women), ovarian, prostate, testicular and thyroid cancer and inversely associated with bladder cancer. Greater than average increases in childhood BMI or linear growth at ages 7–13 increased risks of several cancers.ConclusionsEarly life body size and growth are associated with many, but not all adult cancers, suggesting that the aetiology of several cancers may lie earlier in life than previously thought.
Journal Article
Early life body size and puberty markers as predictors of breast cancer risk later in life: A neural network analysis
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.
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.
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.
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.
Journal Article
Birthweight, childhood body size, and timing of puberty and risks of breast cancer by menopausal status and tumor receptor subtypes
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.
Journal Article