Changes in life expectancy and disease burden in Norway, 1990-2019: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties. METHODS: Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient. FINDINGS: Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71·9 years (95% uncertainty interval 71·4-72·4) and 63·0 years (60·5-65·4) in 1990 to 81·3 years (80·0-82·7) and 70·6 years (67·4-73·6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71·9 years (71·5-72·4) and 63·5 years (60·9-65·6) in 1990 to 80·3 years (79·4-81·2) and 70·0 years (66·8-72·2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100 000 [95% UI 7801-8944] vs 7536 per 100 000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors. INTERPRETATION: Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors. FUNDING: Bill & Melinda Gates Foundation, Research Council of Norway, and Norwegian Institute of Public Health.

Low BMI, but not high BMI, influences the timing of puberty in boys.

BACKGROUND: Previous studies investigating the association between weight status and onset of puberty in boys have been equivocal. It is currently unclear to what extent weight class influences puberty onset and progression. OBJECTIVES: To explore the relationship between degree of sexual maturation and anthropometric measures in Norwegian boys. METHODS: The following endpoints were collected in a Norwegian cross-sectional study of 324 healthy boys aged 9-16: ultrasound-determined testicular volume (USTV), total serum testosterone, Tanner pubic hair stage, height, weight, waist circumference (WC), subscapular skinfolds (SSF), and body fat percentage (%BF). Testicular volume-for-age z-scores were used to classify "early," "average," or "late" maturing boys. Ordinal logistic regression analyses with a proportional odds model were applied to analyze the association between anthropometric variables and age-adjusted degree of pubertal development, with results expressed as age-adjusted odds ratios (AOR). Cumulative incidence curves for reaching pubertal milestones were stratified by BMI. RESULTS: Boys with a low BMI for age (BMIz  < -1) were less likely to have reached a pubertal testicular volume (USTV ≥ 2.7 mL) or a pubertal serum level of testosterone (≥0.5 nmol/L) compared to normal weight boys (AOR 0.3, p = 0.038, AOR 0.3, p = 0.026, respectively), and entered puberty on average with a delay of approximately eight months. Boys with high BMI for age (BMIz  > 1) exhibited a comparable timing as normal weight boys. The same was found for WC. Pubertal markers were not associated with SSF or %BF. CONCLUSION: By examining the association between puberty and weight status classified as low, average, or high, we found that a low BMI or WC for age were associated with a less advanced pubertal development and delayed timing of puberty in boys. No significant association was observed for a high BMI or WC. Moreover, no significant effects of SSF or %BF were observed. A low weight status should also be considered when assessing pubertal development in boys.

Health-Related Behaviors in Adolescents Mediate the Association between Subjective Social Status and Body Mass Index.

The aim of this study was to explore the association between adolescent subjective social status (SSS) and body mass index (BMI) at two different time points and to determine whether this association was mediated by health-related behaviors. In 2002 (n = 1596) and 2017 (n = 1534), tenth-grade students (15-16 years old) in schools in the District of Oppland, Norway, completed a survey. Four categories of perceived family economy were measured as SSS, and structural equation modeling was performed, including a latent variable for unhealthy behavior derived from cigarette smoking, snuff-use, and alcohol-drinking as well as dietary and exercise as mediators. No linear association was found between SSS and BMI in 2002 (standardized ß -0.02, (95% confidence interval (CI) -0.07, 0.03)). However, an association was present in 2017 (standardized ß -0.05 (95% CI -0.10, -0.001)), indicating that BMI decreased by 0.05 standard deviations (0.05 × 3.1 = 0.16 BMI unit) for every one-category increase in SSS. This association was mediated by exercise (standardized ß -0.013 (95% CI -0.02, -0.004) and unhealthy behavior (standardized ß -0.009 (95% CI -0.002, -0.04)). In conclusion, a direct association between SSS and BMI was found in 2017 in this repeated cross-sectional survey of 15-16-year-old Norwegian adolescents. This association was mediated through health-related behavior.

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 data for testicular volume measured with ultrasound and pubic hair in Norwegian boys are comparable with Northern European populations.

AIM: To estimate references for testicular volume measured with ultrasound and Tanner stages of pubic hair in Norwegian boys, and to compare the timing of puberty with data from similar populations. METHODS: Testicular volume was derived from ultrasound measurements of testicular volume in a cross-sectional study of 514 healthy boys. A continuous testicular volume for age reference curve was estimated with the LMS method. Tanner stages for pubic hair were clinically assessed in 452 boys. Age references for pubertal milestones were estimated with probit regression. RESULTS: Puberty onset, defined by an ultrasound testicular volume of 2.7 mL, equivalent to an orchidometer volume of 4 mL, occurred at a mean (SD) age of 11.7 (1.1) years. The reference range was 9.7 (3rd) to 13.7 years (97th percentile). Pubic hair (Tanner stage 2) appeared on average at 11.8 (1.2) years with a corresponding reference range of 9.5-14.1 years. CONCLUSION: The references for testicular volume measured with ultrasound are continuous in age and allow for the quantification of pubertal development. The age distribution of reaching pubertal milestones was comparable with data from other Northern European countries.

PAPSS2-related brachyolmia: Clinical and radiological phenotype in 18 new cases.

Brachyolmia is a skeletal dysplasia characterized by short spine-short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short-spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over-faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi-parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under-recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester.

Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial.

BACKGROUND: Metformin is increasingly used to treat gestational diabetes and type 2 diabetes in pregnancy, and in attempts to improve pregnancy outcomes in polycystic ovary syndrome and obesity. It passes across the placenta with possible long-term consequences for the offspring. We previously explored the effect of metformin, given to women with polycystic ovary syndrome during pregnancy, on children's growth up to 4 years of age. In this 5-10 year follow-up, we examined the cardiometabolic risk factors in these children. METHODS: This is a follow-up of children from the PregMet study, a double-blind, randomised controlled trial comparing metformin with placebo in polycystic ovary syndrome pregnancies. In the PregMet study, between Feb 4, 2005, and Jan 27, 2009, 257 pregnant women aged 18-45 years with polycystic ovary syndrome according to the Rotterdam criteria were included with 274 singleton pregnancies at 5-12 weeks of gestation at 11 study centres in Norway. 17 women participated twice. Pregnant women were randomised to metformin (2000 mg/day) or placebo from inclusion in the first trimester to birth. Randomisation was stratified according to metformin use at conception. In this follow-up, the primary endpoint was body-mass index (BMI) in the offspring at 5-10 years of age assessed by the standard deviation score (Z score). The primary endpoint was analysed with independent sample t tests. ClinicalTrials.gov number NCT00159536. FINDINGS: Of the 255 invited children from the PregMet study, 141 (55%) consented to participate and were included between April 29, 2014, and July 12, 2016. Maternal baseline characteristics in the first trimester were similar between groups. Children in the metformin group had a higher BMI Z score than those in the placebo group (difference in means=0·41, 95% CI 0·03-0·78, p=0·03). INTERPRETATION: The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded. FUNDING: The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.

Ultrasound assessment of pubertal breast development in girls: intra- and interobserver agreement.

BACKGROUND: Clinical assessment of pubertal breast development using Tanner staging is subjective. This has led to the introduction of ultrasound (US), aiming for a more objective analysis. However, information regarding its reliability is lacking. OBJECTIVE: To examine intra- and interobserver agreement of breast maturity staging using US and to examine the precision of direct measurements of the gland. MATERIALS AND METHODS: Fifty-seven healthy girls (mean age: 10.9 years, range: 6.1 to 15.9 years) were examined independently by two observers using US of the left breast to score the glandular maturity stage on a 0-5 scale, and to measure the depth and diameter. One observer repeated the examination after 20 to 35 min to assess intra-observer agreement. Cohen's kappa with linear weights was used to examine intra- and interobserver agreement of the US staging, while the measurement precision was analyzed using Bland-Altman plots and 95% limits of agreement. RESULTS: The agreement of US staging on a 0-5 scale was very good (kappa 0.84; 95% confidence interval [CI] 0.78-0.91) for intra-observer observation and good (kappa 0.71; 95% CI 0.62-0.80) for interobserver observation. Measurements of glandular depth and diameter were unbiased for a single observer, but the variances were large both within and between observers. CONCLUSION: US using a scale from 0 to 5 is a reliable method to stage the development of glandular breast tissue during puberty in healthy girls. Measurements of glandular depth and diameter were found to be imprecise.

Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs.

Context: Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity. Metformin passes the placenta. Objective: To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age. Design: Follow-up study of two randomized, double-blind, placebo-controlled trials. Setting: Secondary care centers. Eleven public hospitals in Norway. Participants: One hundred eighty-two children of mothers with PCOS who participated in two randomized controlled trials. Intervention: Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies. No intervention in the current study. Main Outcome Measures: Height, weight, body mass index (BMI), and overweight/obesity at 4 years of age and head circumference at 1 year of age, converted to z scores. Results: The difference in height z score means between the groups at 4 years of age was nonsignificant (0.07 [95% confidence interval (CI): -0.22 to 0.36]; P = 0.651). At 4 years of age, the metformin group had higher weight z score than the placebo group [difference in means: 0.38 (0.07 to 0.69); P = 0.017] and higher BMI z score [difference in means: 0.45 (0.11 to 0.78); P = 0.010]. There were more overweight/obese children in the metformin group [26 (32%)] than in the placebo group [14 (18%)] at 4 years of age [odds ratio: 2.17 (1.04 to 4.61); P = 0.038]. The difference in mean head circumference z score at 1 year of age was 0.27 (-0.04 to 0.58; P = 0.093). Conclusion: Metformin-exposed children had higher BMI and increased prevalence of overweight/obesity at 4 years of age.

Gender-related differences in cardiometabolic risk factors and lifestyle behaviors in treatment-seeking adolescents with severe obesity.

BACKGROUND: Obesity during adolescence is associated with cardiovascular mortality in adulthood. The adverse obesity-related cardiometabolic risk profile is already observed in adolescence. We aimed to examine possible gender differences in cardiometabolic risk factors and lifestyle behaviors among adolescents with severe obesity, hypothesizing that boys would have both a higher prevalence of the metabolic syndrome as well as less healthy lifestyle behaviors than girls. METHODS: Cross-sectional study of treatment-seeking adolescents with severe obesity who attended the Morbid Obesity Centre at Vestfold Hospital Trust and who were consecutively enrolled in the Vestfold Register of Obese Children between September 2009 and September 2015. A total of 313 adolescents aged 12 to 18 years were recruited, whereof 268 subjects (49% boys) completed a food and activity frequency questionnaire and were included in the analysis. RESULTS: Mean (SD) age, BMI and BMI SDS were 15 (1.6) years, 38.6 (5.9) kg/m2 and 3.5 (0.6). Levels of LDL cholesterol, fasting insulin and glucose and diastolic blood pressure (DBP) did not differ between genders. Compared to girls, boys had significantly higher triglycerides (p = 0.037) and systolic blood pressure (SBP) (p = 0.003), as well as lower HDL cholesterol (p = 0.002). The metabolic syndrome was present in 27% of the boys and 19% of the girls (p = 0.140), and the prevalence of high DBP, dyslipidemia and dysglycemia also did not differ significantly between genders. The prevalence of high SBP was higher in boys than in girls (19% vs. 9%, p = 0.021). Gender was associated with a number of lifestyle habits, as a larger proportions of boys had higher screen time (p = 0.032), more regular breakfast eating (p = 0.023), higher intake of sugar sweetened soda (p = 0.036), and lower intake of vegetables than girls (p = 0.011). By contrast, physical activity level and intake of fruit and berries did not differ between genders. CONCLUSIONS: Male treatment-seeking adolescents with severe obesity had a more unfavorable set of metabolic and behavioral risk factors for cardiovascular disease than girls. Our results indicate that lifestyle behavioral markers should be thoroughly assessed in both genders, and possible gender-related differences in risk profile should be taken into account in future treatment programs.

Reference Ranges for Head Circumference in Ethiopian Children 0-2 Years of Age.

BACKGROUND: Head circumference (HC) charts are important for early detection of hydrocephalus during childhood. In low-income countries where population-based HC charts are rarely available, hydrocephalus occurs more commonly than in developed countries, and is usually not diagnosed early enough to prevent severe brain damage. This applies to Ethiopia as well. The World Health Organization (WHO) has provided standard HC charts advocated for global use, but recent studies cast doubts whether these charts are equally applicable in various populations. The aim of the study was therefore to establish reference ranges for early childhood HC in Ethiopia. METHODS: In this prospective, observational cross-sectional study, measurements of HC were collected from healthy children of different ethnicities between birth and 24 months, in health centers situated in 5 Ethiopian cities. Reference ranges for HC were estimated using the LMS method and compared with those recommended by WHO. RESULTS: A total of 4019 children were included. Overall, 6.7% of boys and 7.1% of girls were above the +2 standard deviation (SD) of the WHO reference ranges, whereas the corresponding figures below -2 SD were 2.8% and 2.1%. Similarly, the +2 SD lines of the Ethiopian reference curves were considerably higher than those of the WHO growth standards, whereas the median and -2 SD lines were more comparable. CONCLUSIONS: Ethiopian HC reference ranges for children from birth to 24 months of age were found to differ significantly from those established by WHO and should correspondingly be considered as the first choice for screening for hydrocephalus in that population.

TV viewing and obesity among Norwegian children: the importance of parental education.

AIM: To analyse the effect of lifestyle factors on the prevalence of overweight and obesity in 6-15-year-old Norwegian children. METHODS: Questionnaire data on lifestyle factors (sedentary behaviour, activity and eating habits) and prevalence numbers of overweight and obesity based on measured height and weight were analysed using multinomial logistic regression in a sample of 2281 children included in the Bergen Growth Study. RESULTS: More screen time increased the risk of overweight (odds ratio (OR): 1.25; p = 0.02) and obesity (OR: 1.12; p = 0.02) as did the presence of a TV in the child's bedroom (OR: 1.26 (overweight), OR: 1.81 (obese); p = 0.04). The obese children reported less sugar intake than the not overweight children (OR: 0.58; p = 0.01). Higher parental education was associated with less screen time (p = 0.02), lower frequency of TV in the child's bedroom (p = 0.001), more sports (p = 0.005), as well as eating more fruit and vegetables, less sweets, soft drinks and fast food, and more regular meals (for all, p < 0.03). CONCLUSION: Indicators of sedentary lifestyle, such as screen time and the presence of a TV in the child's bedroom, were associated with overweight and obesity in Norwegian schoolchildren. Higher parental education was generally associated with less obesogenic lifestyle.

[Trichorhinophalangeal syndrome--clinical presentation and genetics]. / Trikorhinofalangealt syndrom--klinisk presentasjon og genetikk.

BACKGROUND: The trichorhinophalangeal syndrome (TRPS) is a hereditary, skeletal dysplasia which has a characteristic clinical presentation and is classified in types 1, 2 and 3, based on phenotype and genotype. Typical findings may be mild and many patients probably remain undiagnosed. MATERIAL AND METHODS: The paper is based on four case reports and provides a short review of the condition. RESULTS: Our four patients all have typical facial features, such as a large nose and thin upper lip, thin hair and short curved fingers with characteristic radiological findings. The condition is autosomal dominant and caused by a mutation in the TRPS1 gene, which codes a gene-regulating protein involved in development of hair and modulation of chondrocytes. The diagnosis can be based on clinical findings, but DNA-analysis can be of help in unclear situations. Two of our patients were diagnosed from clinical and radiological findings, but for the two others genetic examinations were done as well. There is no causal treatment, but the diagnosis can give patients an explanation of their problems, and genetic counseling for the patient and family can be offered. Orthopedic surgery and cosmetic aids are valuable for many. INTERPRETATION: In an increasingly technified medical daily life, the clinical view is still the most important tool in diagnosing patients with this condition.