Abstract
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.
IMPORTANCE: Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. OBJECTIVE: To evaluate the risks of neonatal ...adverse events after exposure to COVID-19 vaccination during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. EXPOSURE: Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. MAIN OUTCOMES AND MEASURES: Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. RESULTS: Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio aOR, 0.78 95% CI, 0.61-0.99), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 95% CI, 0.55-0.96), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 95% CI, 0.50-0.91). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. CONCLUSIONS AND RELEVANCE: In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.
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.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
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.
Aim
The Norwegian Action Plan for a Healthier Diet (2017–2021) set the target that 25% of infants should be exclusively breastfed for 6 months by 2022. Our aim was to determine trends in the ...prevalence and duration of breastfeeding in the municipality of Bergen.
Methods
Data on breastfeeding status in 2010–2018 were extracted from a standardised electronic medical record kept by public child health centres and recorded as exclusive, partial or none, at 6 weeks and 6 months of age.
Results
We found that 28,503 and 26,735 infants attended the 6‐week and 6‐month consultations, respectively. The prevalence of any breastfeeding was 92.0% at 6 weeks and 78.0% at 6 months with no trend over time between 2010 and 2018. The prevalence of exclusive breastfeeding at 6 weeks was 73.9% and stable over time, but it declined at 6 months, from 28.1% in 2010 to 11.1% in 2014 and remained stable thereafter.
Conclusion
During 2010–2018, the prevalence of any and exclusive breastfeeding at 6 weeks and any breastfeeding at 6 months was stable. Exclusive breastfeeding at 6 months declined halfway through the study period, to a stable, but low, prevalence of 11.1% by 2014.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The Bergen Growth Study 2 (BGS2) aims to characterise somatic and endocrine changes in healthy Norwegian children using a novel methodology.
A cross-sectional sample of 1285 children aged 6-16 years ...was examined in 2016 using novel objective ultrasound assessments of breast developmental stages and testicular volume in addition to the traditional Tanner pubertal stages. Blood samples allowed for measurements of pubertal hormones, endocrine disruptive chemicals, and genetic analyses.
Ultrasound staging of breast development in girls showed a high degree of agreement within and between observers, and ultrasound measurement of testicular volume in boys also showed small intra- and interobserver differences. The median age was 10.4 years for Tanner B2 (pubertal onset) and 12.7 years for menarche. Norwegian boys reached a pubertal testicular volume at a mean age of 11.7 years. Continuous reference curves for testicular volume and sex hormones were constructed using the LMS method.
Ultrasound-based assessments of puberty provided novel references for breast developmental stages and enabled the measurement of testicular volume on a continuous scale. Endocrine z-scores allowed for an intuitive interpretation of changing hormonal levels during puberty on a quantitative scale, which, in turn, provides opportunities for further analysis of pubertal development using machine-learning approaches.
Full text
Available for:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Aim Trends in childhood overweight, obesity and severe obesity have been lacking in Norway. This study assessed pre‐pandemic trends from 2010 to 2019 and evaluated differences in prevalence ...during the 2020–2022 pandemic years. Methods Routine height and weight measurements from child and school health centres were extracted retrospectively from children aged 2, 4, 6, 8 and 13 years. Overweight, obesity and severe obesity was classified according to the International Obesity Task Force cut‐offs. Pre‐pandemic trends were estimated using linear regression. The prevalence during the pandemic was compared to the 95% prediction interval of this model. Results We obtained 181 527 body mass index measurements on 78 024 children (51.0% boys). There was a decrease in the prevalence of overweight including obesity from 2010 to 2019 in boys and this was statistically significant at 4 and 13 years of age. We found no significant trends in girls during this period. During the pandemic, the prevalence of overweight including obesity exceeded the prediction intervals for boys aged 4, 6, and 8 years, and for 6‐year‐old girls. Conclusion From 2010–2019, overweight including obesity plateaued in girls and decreased in boys but increased during the pandemic among prepubertal boys. Routine healthcare data is useful for estimating the prevalence of different weight status.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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.
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).
The increased BMI in metformin-exposed children might indicate a potential risk of inferior cardiometabolic health. Implications for adult health cannot be excluded.
The Research Council of Norway, Novo Nordisk Foundation, St Olavs University Hospital, and the Norwegian University of Science and Technology.
Introduction
Population‐based studies about the consequences of SARS‐CoV‐2 infection (COVID‐19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems.
...Material and methods
This study examines pregnant women with COVID‐19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS‐CoV‐2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID‐19‐related.
Results
In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID‐19. The risk of admission due to COVID‐19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID‐19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID‐19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID‐19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported.
Conclusions
The risk of admission due to COVID‐19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID‐19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
PDF
