Pubertal development in Norwegian girls

Background: Evidence suggests that girls worldwide are experiencing a decrease in age at pubertal onset, but data from Norwegian girls have not been available. Early pubertal timing is associated with adverse health outcomes. Pubertal breast development is currently categorized using the Tanner B scale and relies on visual inspection and/or palpation. Breast ultrasound appears to be a good alternative to this Tanner B assessment because it can separate adipose tissue from breast tissue and facilitates both staging and volumetric measurements. Objectives: The objectives were to explore ultrasound as an alternative method to assess breast development throughout puberty, to investigate the timing of puberty in Norwegian girls and construct pubertal references, and to shed light on the relationship between anthropometric indicators of body composition and the timing of puberty. Methods: This thesis is based on data from the Bergen Growth Study 1 (BGS1; 2003–2006, n = 1485, aged 8–15.5 years) and the Bergen Growth Study 2 (BGS2; 2016 and 2017, n = 703, aged 6–16 years). Data on menarche were recorded in both studies, while breast development was assessed only in the BGS2. Six distinct ultrasound-based breast stages were described, and the performance of these were evaluated in terms of observer agreement and in relation to the standardized Tanner B scale. Descriptive pubertal references were estimated from the BGS2. The associations between indirect (body mass index, BMI) and direct (skinfolds and waist circumference (WC)) measurements of fat with the timing of menarche were explored based on data from the BGS1. The ages at menarche between the studies were compared. Results: The ultrasound staging system performed well in terms of the agreement between one and two observers; however, direct measurements of size and volume lacked the necessary precision. When comparing ultrasound staging and Tanner B staging, an overall good agreement was found. A modest decline in the age at menarche was observed during the last decade, although pubertal references suggest that pubertal timing in Norway is similar to that of neighbouring countries. After adjustment for age and sex, both high and low levels of BMI, WC, subscapular skinfold (SSF) and triceps skinfold were all associated with an earlier and later menarche. In a fully adjusted analysis of all the measurements together, only a high BMI was related to earlier menarche, while a low BMI and a low SSF were associated with later menarche. Conclusions: Ultrasound is a feasible method to determine the breast developmental stage. This research has clinical implications for the evaluation of puberty in paediatric and adolescent female patients in Norway by providing descriptive references based on a healthy sample of girls. The decline in age at menarche was not explained by BMI and therefore warrants further investigations in population-based studies. BMI was the strongest anthropometric predictor of early and late menarche

References for ultrasound staging of breast maturation, tanner breast staging, pubic hair, and menarche in Norwegian girls

Context - Discriminating adipose and glandular tissue is challenging when clinically assessing breast development. Ultrasound facilitates staging of pubertal breast maturation (US B), but has not been systematically compared to Tanner breast (Tanner B) staging, and no normative data have been reported. Objective - To present normative references for US B along with references for Tanner B, pubic hair (PH), and menarche. Design, Setting, and Participants - A cross-sectional sample of 703 healthy girls aged 6 to 16 years were examined. Main Outcome Measures - Breast development was determined with US B and Tanner B staging. Tanner PH and menarcheal status were recorded. The age distributions of entry in US B, Tanner B, and PH stages and menarche were estimated with generalized linear and generalized additive models with a probit link. Method agreement was tested with weighted Cohen’s kappa. Results - The median (±2SD) ages for thelarche, US B2 and Tanner B2, were 10.2 (7.7, 12.8) and 10.4 (8.0, 12.7) years. The median (±2SD) ages at Tanner PH2 and menarche were 10.9 (8.5, 13.3) and 12.7 (11.0, 16.2) years. Cohen’s kappa of agreement (95% confidence interval) between US B and Tanner B was 0.87 (0.85–0.88). When the methods disagreed, US B was usually more advanced. Conclusion - Thelarche occurred at a slightly younger age when assessed with ultrasound compared to clinical Tanner staging, although the 2 methods had a very good agreement when determining pubertal breast maturation. A significant decrease of 2.8 months in age at menarche was observed during the past decade in Norwegian girls

Perceived barriers in family-based behavioural treatment of paediatric obesity – Results from the FABO study

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: To date, few studies have investigated perceived barriers among those who participate in and drop out of family-based behavioural treatment (FBT) for paediatric obesity. Examining experienced barriers during treatment, and their role in participation and completion of treatment has important implications for clinical practice. Objectives: To compare perceived barriers to participating in a family-based behavioural social facilitation treatment (FBSFT) for obesity among families who completed and did not complete treatment. Methods: Data were analysed from 90 families of children and adolescents (mean (M) age = 12.8 years, standard deviation (SD) = 3.05) with severe obesity enrolled in a 17-session FBSFT program. After completing 12 sessions or at the time of dropout, parents and therapists completed the Barriers to Treatment Participation Scale (BTPS), a 5-point Likert scale (1 = never a problem, 5 = very often a problem) which includes four subscales: 1. Stressors and obstacles that compete with treatment, 2. Treatment demands and issues, 3. Perceived relevance of treatment, 4. Relationship with the therapist. Results: Families who did not complete treatment scored significantly higher on the BTPS subscales stressors and obstacles that compete with treatment (M = 2.03, SD = 0.53 vs. M = 1.70, SD = 0.42), p = 0.010 and perceived relevance of treatment (M = 2.27, SD = 0.48 vs. M = 1.80, SD = 0.50), p < 0.001 than families who completed treatment. No other significant differences between groups were observed. Conclusion: Families are more likely to drop out of FBSFT when experiencing a high burden from life stressors or when treatment is not meeting the expectations and perceived needs of the family.publishedVersio

Testicular ultrasound to stratify hormone references in a cross-sectional Norwegian study of male puberty

Context: Testicular growth represents the best clinical variable to evaluate male puberty, but current pediatric hormone references are based on chronological age and subjective assessments of discrete puberty development stages. Determination of testicular volume (TV) by ultrasound provides a novel approach to assess puberty progression and stratify hormone reference intervals. Objective: The objective of this article is to establish references for serum testosterone and key hormones of the male pituitary-gonadal signaling pathway in relation to TV determined by ultrasound. Design, Setting, and Participants: Blood samples from 414 healthy Norwegian boys between ages 6 and 16 years were included from the cross-sectional “Bergen Growth Study 2.” Participants underwent testicular ultrasound and clinical assessments, and serum samples were analyzed by liquid chromatography tandem–mass spectrometry and immunoassays. Main Outcome Measures: We present references for circulating levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin in relation to TV, chronological age, and Tanner pubic hair stages. Results: In pubertal boys, TV accounted for more variance in serum testosterone levels than chronological age (Spearman r = 0.753, P < .001 vs r = 0.692, P < .001, respectively). Continuous centile references demonstrate the association between TV and hormone levels during puberty. Hormone reference intervals were stratified by TV during the pubertal transition. Conclusions: Objective ultrasound assessments of TV and stratification of hormone references increase the diagnostic value of traditional references based on chronological age or subjective staging of male puberty.acceptedVersio

Hormone references for ultrasound breast staging and endocrine profiling to detect female onset of puberty

Context - Application of ultrasound (US) to evaluate attainment and morphology of glandular tissue provides a new rationale for evaluating onset and progression of female puberty, but currently no hormone references complement this method. Furthermore, previous studies have not explored the predictive value of endocrine profiling to determine female puberty onset. Objective - To integrate US breast staging with hypothalamic-pituitary-gonadal hormone references and test the predictive value of an endocrine profile to determine thelarche. Design Setting and Participants - Cross-sectional sample of 601 healthy Norwegian girls, ages 6 to 16 years. Main Outcome Measures - Clinical and ultrasound breast evaluations were performed for all included girls. Blood samples were analyzed by immunoassay and ultrasensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) to quantify estradiol (E2) and estrone (E1) from the subpicomolar range. Results - References for E2, E1, luteinizing hormone, follicle-stimulating hormone, and sex hormone–binding globulin were constructed in relation to chronological age, Tanner stages, and US breast stages. An endocrine profile index score derived from principal component analysis of these analytes was a better marker of puberty onset than age or any individual hormone, with receiver-operating characteristic area under the curve 0.91 (P < 0.001). Ultrasound detection of nonpalpable glandular tissue in 14 out of 264 (5.3%) girls with clinically prepubertal presentation was associated with significantly higher median serum levels of E2 (12.5 vs 4.9 pmol/L; P < 0.05) and a distinct endocrine profile (arbitrary units; P < 0.001). Conclusions - We provide the first hormone references for use with US breast staging and demonstrate the application of endocrine profiling to improve detection of female puberty onset

Reference curves for pediatric endocrinology: leveraging biomarker z-scores for clinical classifications

Context: Hormone reference intervals in pediatric endocrinology are traditionally partitioned by age and lack the framework for benchmarking individual blood test results as normalized z-scores and plotting sequential measurements onto a chart. Reference curve modeling is applicable to endocrine variables and represents a standardized method to account for variation with gender and age. Objective: We aimed to establish gender-specifc biomarker reference curves for clinical use and benchmark associations between hormones, pubertal phenotype, and body mass index (BMI). Methods: Using cross-sectional population sample data from 2139 healthy Norwegian children and adolescents, we analyzed the pubertal status, ultrasound measures of glandular breast tissue (girls) and testicular volume (boys), BMI, and laboratory measurements of 17 clinical biomarkers modeled using the established “LMS” growth chart algorithm in R. Results: Reference curves for puberty hormones and pertinent biomarkers were modeled to adjust for age and gender. Z-score equivalents of biomarker levels and anthropometric measurements were compiled in a comprehensive beta coeffcient matrix for each gender. Excerpted from this analysis and independently of age, BMI was positively associated with female glandular breast volume (β = 0.5, P < 0.001) and leptin (β = 0.6, P < 0.001), and inversely correlated with serum levels of sex hormone-binding globulin (SHBG) (β = −0.4, P < 0.001). Biomarker z-score profles differed signifcantly between cohort subgroups stratifed by puberty phenotype and BMI weight class. <p<Conclusion: Biomarker reference curves and corresponding z-scores provide an intuitive framework for clinical implementation in pediatric endocrinology and facilitate the application of machine learning classifcation and covariate precision medicine for pediatric patients

Pubertal development in Norwegian girls

Background: Evidence suggests that girls worldwide are experiencing a decrease in age at pubertal onset, but data from Norwegian girls have not been available. Early pubertal timing is associated with adverse health outcomes. Pubertal breast development is currently categorized using the Tanner B scale and relies on visual inspection and/or palpation. Breast ultrasound appears to be a good alternative to this Tanner B assessment because it can separate adipose tissue from breast tissue and facilitates both staging and volumetric measurements. Objectives: The objectives were to explore ultrasound as an alternative method to assess breast development throughout puberty, to investigate the timing of puberty in Norwegian girls and construct pubertal references, and to shed light on the relationship between anthropometric indicators of body composition and the timing of puberty. Methods: This thesis is based on data from the Bergen Growth Study 1 (BGS1; 2003–2006, n = 1485, aged 8–15.5 years) and the Bergen Growth Study 2 (BGS2; 2016 and 2017, n = 703, aged 6–16 years). Data on menarche were recorded in both studies, while breast development was assessed only in the BGS2. Six distinct ultrasound-based breast stages were described, and the performance of these were evaluated in terms of observer agreement and in relation to the standardized Tanner B scale. Descriptive pubertal references were estimated from the BGS2. The associations between indirect (body mass index, BMI) and direct (skinfolds and waist circumference (WC)) measurements of fat with the timing of menarche were explored based on data from the BGS1. The ages at menarche between the studies were compared. Results: The ultrasound staging system performed well in terms of the agreement between one and two observers; however, direct measurements of size and volume lacked the necessary precision. When comparing ultrasound staging and Tanner B staging, an overall good agreement was found. A modest decline in the age at menarche was observed during the last decade, although pubertal references suggest that pubertal timing in Norway is similar to that of neighbouring countries. After adjustment for age and sex, both high and low levels of BMI, WC, subscapular skinfold (SSF) and triceps skinfold were all associated with an earlier and later menarche. In a fully adjusted analysis of all the measurements together, only a high BMI was related to earlier menarche, while a low BMI and a low SSF were associated with later menarche. Conclusions: Ultrasound is a feasible method to determine the breast developmental stage. This research has clinical implications for the evaluation of puberty in paediatric and adolescent female patients in Norway by providing descriptive references based on a healthy sample of girls. The decline in age at menarche was not explained by BMI and therefore warrants further investigations in population-based studies. BMI was the strongest anthropometric predictor of early and late menarche

Timing of menarche in Norwegian girls: associations with body mass index, waist circumference and skinfold thickness

Abstract Background Research studies show conflicting results regarding the association between menarche and body weight. The purpose of the present study was to investigate if anthropometric indicators of body composition, body mass index (BMI), waist circumference (WC), triceps (TSF) and subscapular skinfold (SSF) thicknesses, were differentially associated with age at menarche in Norwegian girls. Methods The association between menarche and BMI, WC, TSF and SSF was investigated in 1481 girls aged 8–15.5 years, and in a subgroup of 181 girls with menarche during the 12 months prior to examination. Anthropometric measures were categorized as low ( 1SDS), and menarche according to this classification was analysed with Kaplan-Meier curves and unadjusted and adjusted Cox regression. Results The median age at menarche in the total sample was 13.1 years. In the unadjusted models, low categories of all traits were associated with later menarche, and high categories with earlier menarche. When adjusted for other covariates, earlier menarche was only related with a high BMI (Hazard Ratio 1.41, 95% confidence interval (CI) 1.07, 1.85), and later menarche with a low BMI (HR 0.53, 95%CI 0.38, 0.75) and low SSF (HR 0.54, 95%CI 0.39, 0.75). In girls with recent menarche, early menarche was significantly associated with a high BMI in the final model (HR 1.79, 95%CI 1.23, 2.62). Conclusions The timing of menarche was associated with the BMI, WC, TSF and SSF, but more strongly so with the BMI. These associations may be related to a common tempo of growth, as the mean age at menarche has remained stable during the last decades during a time period while the prevalence of overweight and obesity has increased significantly