Exposure to Per- and Polyfluoroalkyl Substances and Timing of Puberty in Norwegian Boys: Data from the Bergen Growth Study 2.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with endocrine-disruptive properties. Their impact on puberty in boys is unclear. In this cross-sectional study, we investigated the association between PFAS exposure and pubertal timing in 300 Norwegian boys (9-16 years), enrolled in the Bergen Growth Study 2 during 2016. We measured 19 PFAS in serum samples and used objective pubertal markers, including ultrasound-measured testicular volume (USTV), Tanner staging of pubic hair development, and serum levels of testosterone, luteinizing hormone, and follicle-stimulating hormone. In addition to logistic regression of single pollutants and the sum of PFAS, Bayesian and elastic net regression were used to estimate the contribution of the individual PFAS. Higher levels of the sum of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid (PFHxS) were associated with later pubertal onset according to USTV (age-adjusted odds ratio (AOR): 2.20, 95% confidence interval (CI): 1.29, 3.93) and testosterone level (AOR: 2.35, 95% CI: 1.34, 4.36). Bayesian modeling showed that higher levels of PFNA and PFHxS were associated with later pubertal onset by USTV, while higher levels of PFNA and perfluoroundecanoic acid (PFUnDA) were associated with later pubertal onset by testosterone level. Our findings indicate that certain PFAS were associated with delay in male pubertal onset.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

INTRODUCTION: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. MATERIAL AND METHODS: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. RESULTS: Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. CONCLUSIONS: Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.

Seasonal variability in body mass index, waist circumference, and skinfolds in Norwegian children.

OBJECTIVES: Studies have shown that children develop a higher body weight during summer months. This has been demonstrated repeatedly using the body mass index (BMI), but the effect of season on other weight-related anthropometric measurements is still unclear. METHODS: Measurements of height, weight, waist circumference (WC), triceps, and subscapular skinfolds (TSF and SSF), collected from September till May in a cross-sectional sample of 4-16-year-old children and adolescents (n = 4525) from the Bergen Growth Study 1 (BGS1). Differences in z-score by season were tested with linear models adjusted for age group and separately for sex. Overall differences were tested with a one-way between-group analysis of variance. RESULTS: The girls had higher BMIz (+0.12, p = .03) and WCz (+0.18, p = .002) in fall compared with spring. TSFz (-0.19, p < .001) and SSFz (-0.18, p < .001) were lower in winter in girls, and in boys both in fall (TSFz -0.10, p = .046; SSFz - 0.16, p < .001), and winter (TSFz -0.15, p = .004; SSFz -0.14, p = .003), when compared with spring. CONCLUSIONS: Seasonal variation was detected for all anthropometric measures, but differences in the direction of the effect between measures of global (BMI), central (WC) or subcutaneous (SF) adiposity suggest a more complex mechanism that needs further exploration.

Excess non-COVID-19 mortality in Norway 2020-2022.

BACKGROUND: Causes of death other than COVID-19 seem to contribute significantly to the excess mortality observed during the 2020-2022 pandemic. In this study, we explore changes in non-COVID-19 causes of death in Norway during the COVID-19 pandemic from March 2020 to December 2022. METHODS: We performed a population-based cross-sectional study on data from the Norwegian Cause of Death Registry. All recorded deaths from 1st January 2010 to 31st December 2022 were included. The main outcome measures were the number of deaths and age-standardised death rate (ASMR) per 100000 population from the major cause of death groups in 2020, 2021 and 2022. The predicted number of deaths and ASMRs were forecasted with a 95% prediction interval constructed from a general linear regression model based on the corresponding number of deaths and rates from the preceding ten prepandemic years (2010-2019). We also examined whether there were deviations from expected seasonality in the pandemic period based on prepandemic monthly data from 2010-2019. The cumulative number of deaths and ASMR were estimated based on monthly mortality data. RESULTS: There was significant excess mortality (number of deaths) in 2021 and 2022 for all causes (3.7% and 14.5%), for cardiovascular diseases (14.3% and 22.0%), and for malignant tumours in 2022 (3.5%). In terms of ASMR, there was excess mortality in 2021 and 2022 for all causes (2.9% and 13.7%), and for cardiovascular diseases (16.0% and 25,8%). ASMR was higher than predicted in 2022 for malignant tumours (2.3%). There were fewer deaths than predicted from respiratory diseases (except COVID-19) in 2020 and 2021, and from dementia in 2021 and 2022. From March 2020 to December 2022, there were cumulatively 3754 (ASMR 83.8) more non-COVID-19 deaths than predicted, of which 3453 (ASMR: 79.6) were excess deaths from cardiovascular disease, 509 (ASMR 4.0) from malignant tumours. Mortality was lower than predicted for respiratory diseases (-1889 (ASMR: -44.3)), and dementia (-530 (ASMR -18.5)). CONCLUSIONS: There was considerable excess non-COVID-19 mortality in Norway from March 2020 until December 2022, mainly due to excess cardiovascular deaths. For respiratory diseases and dementia, mortality was lower than predicted.

Trends in overweight and obesity in Bergen, Norway, using data from routine child healthcare 2010-2022.

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.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy.

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.

Treatment and 30-Day Mortality after Myocardial Infarction in Prostate Cancer Patients: A Population-Based Study from Norway.

INTRODUCTION: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. METHODS: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. RESULTS: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04-0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61-0.97). CONCLUSION: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population.

Deep exploration of a CDKN1C mutation causing a mixture of Beckwith-Wiedemann and IMAGe syndromes revealed a novel transcript associated with developmental delay.

BACKGROUND: Loss-of-function mutations in CDKN1C cause overgrowth, that is, Beckwith-Wiedemann syndrome (BWS), while gain-of-function variants in the gene's PCNA binding motif cause a growth-restricted condition called IMAGe syndrome. We report on a boy with a remarkable mixture of both syndromes, with developmental delay and microcephaly as additional features. METHODS: Whole-exome DNA sequencing and ultra-deep RNA sequencing of leucocyte-derived and fibroblast-derived mRNA were performed in the family. RESULTS: We found a maternally inherited variant in the IMAGe hotspot region: NM_000076.2(CDKN1C) c.822_826delinsGAGCTG. The asymptomatic mother had inherited this variant from her mosaic father with mild BWS features. This delins caused tissue-specific frameshifting resulting in at least three novel mRNA transcripts in the boy. First, a splice product causing CDKN1C truncation was the likely cause of BWS. Second, an alternative splice product in fibroblasts encoded IMAGe-associated amino acid substitutions. Third, we speculate that developmental delay is caused by a change in the alternative CDKN1C-201 (ENST00000380725.1) transcript, encoding a novel isoform we call D (UniProtKB: A6NK88). Isoform D is distinguished from isoforms A and B by alternative splicing within exon 1 that changes the reading frame of the last coding exon. Remarkably, this delins changed the reading frame back to the isoform A/B type, resulting in a hybrid D-A/B isoform. CONCLUSION: Three different cell-type-dependent RNA products can explain the co-occurrence of both BWS and IMAGe features in the boy. Possibly, brain expression of hybrid isoform D-A/B is the cause of developmental delay and microcephaly, a phenotypic feature not previously reported in CDKN1C patients.

Parental income gradients in child and adolescent mortality: Norwegian trends over half a century.

BACKGROUND: Child mortality has declined rapidly over the last century in many high-income countries. However, little is known about the socio-economic differences in this decline and whether these vary across causes of death. METHODS: We used register data that included all Norwegian births between 1968 and 2010 (2.1 million), and we analysed how all-cause and cause-specific child (0-4 years) and adolescent (5-20 years) mortality rates vary with relative parental income the year before the birth. RESULTS: Child and adolescent all-cause mortality decreased with increasing parental relative income within all birth cohorts. Among children aged 0-4 years, the socio-economic gradient in all-cause mortality and in mortality due to external causes, sudden infant deaths and perinatal factors declined over the period, while there was no systematic decline in mortality from congenital malformations. Among children aged 5-20 years, the gradient did not weaken similarly, although there were indications of declines in the socio-economic gradient related to all-cause deaths and deaths because of suicides and other external causes. While the absolute differences in mortality declined over time, the relative differences remained stable. CONCLUSIONS: Although children of low-income parents still have elevated mortality, there has been a large reduction in child mortality in all socio-economic groups across 50 years for all causes combined and most of the groups of specific causes of death.

Evaluating national guidelines for monitoring early growth using routinely collected data in Bergen, Norway.

AIMS: The overarching aim of this study was to evaluate the Norwegian guidelines for growth monitoring using routinely collected data from healthy children up to five years of age. We analysed criteria for both status (size for age) and change (centile crossing) in growth. METHODS: Longitudinal data were obtained from the electronic health record (EHR) at the well-baby clinic for 2130 children included in the Bergen growth study 1 (BGS1). Measurements of length, weight, weight-for-length, body mass index (BMI) and head circumference were converted to z-scores and compared with the World Health Organization (WHO) growth standards and the national growth reference. RESULTS: Using the WHO growth standard, the proportion of children above +2SD was generally higher than the expected 2.3% for all traits at birth and for length at all ages. Crossing percentile channels was common during the first two years of life, particularly for length/height. By the age of five years, 37.9% of the children had been identified for follow-up regarding length/height, 33% for head circumference and 13.6% for high weight-for-length/BMI. CONCLUSIONS: The proportion of children beyond the normal limits of the charts is higher than expected, and a surprisingly large number of children were identified for rules concerning length or growth in head circumference. This suggests the need for a revision of the current guidelines for growth monitoring in Norway.

Trends in the prevalence of breastfeeding up to 6 months of age using structured data from routine child healthcare visits.

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.

Deep phenotyping of pubertal development in Norwegian children: the Bergen Growth Study 2.

BACKGROUND: The Bergen Growth Study 2 (BGS2) aims to characterise somatic and endocrine changes in healthy Norwegian children using a novel methodology. SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A nationwide school fruit and vegetable policy and childhood and adolescent overweight: A quasi-natural experimental study.

BACKGROUND: School free fruit and vegetable (FFV) policies are used to promote healthy dietary habits and tackle obesity; however, our understanding of their effects on weight outcomes is limited. We assess the effect of a nationwide FFV policy on childhood and adolescent weight status and explore heterogeneity by sex and socioeconomic position. METHODS AND FINDINGS: This study used a quasi-natural experimental design. Between 2007 and 2014, Norwegian combined schools (grades 1-10, age 6 to 16 years) were obligated to provide FFVs while elementary schools (grades 1-7) were not. We used 4 nationwide studies (n = 11,215 children) from the Norwegian Growth Cohort with longitudinal or cross-sectional anthropometric data up to age 8.5 and 13 years to capture variation in FFV exposure. Outcomes were body mass index standard deviation score (BMISDS), overweight and obesity (OW/OB), waist circumference (WC), and weight to height ratio (WtHR) at age 8.5 years, and BMISDS and OW/OB at age 13 years. Analyses included longitudinal models of the pre- and post-exposure trajectories to estimate the policy effect. The participation rate in each cohort was >80%, and in most analyses <4% were excluded due to missing data. Estimates were adjusted for region, population density, and parental education. In pooled models additionally adjusted for pre-exposure BMISDS, there was little evidence of any benefit or unintended consequence from 1-2.5 years of exposure to the FFV policy on BMISDS, OW/OB, WC, or WtHR in either sex. For example, boys exposed to the FFV policy had a 0.05 higher BMISDS (95% CI: -0.04, 0.14), a 1.20-fold higher odds of OW/OB (95% CI: 0.86, 1.66) and a 0.3 cm bigger WC (95% CI: -0.3, 0.8); while exposed girls had a 0.04 higher BMISDS (95% CI: -0.04, 0.13), a 1.03 fold higher odds of OW/OB (95% CI: 0.75, 1.39), and a 0-cm difference in WC (95% CI: -0.6, 0.6). There was evidence of heterogeneity in the policy effect estimates at 8.5 years across cohorts and socioeconomic position; however, these results were inconsistent with other comparisons. Analysis at age 13 years, after 4 years of policy exposure, also showed little evidence of an effect on BMISDS or OW/OB. The main limitations of this study are the potential for residual confounding and exposure misclassification, despite efforts to minimize their impact on conclusions. CONCLUSIONS: In this study we observed little evidence that the Norwegian nationwide FFV policy had any notable beneficial effect or unintended consequence on weight status among Norwegian children and adolescents.

Preconception leisure-time physical activity and family history of stroke and myocardial infarction associate with preterm delivery: findings from a Norwegian cohort.

BACKGROUND: Preterm birth poses short and long-term health consequences for mothers and offspring including cardiovascular disease sequelae. However, studies evaluating preexisting family history of cardiovascular disease and risk factors, such as physical activity, as they relate prospectively to risk of delivering preterm are lacking. OBJECTIVES: To evaluate whether preconception past-year weekly leisure-time physical activity or a family history of stroke or of myocardical infarction prior to age 60 years in first degree relatives associated, prospectively, with preterm delivery. DESIGN: Cohort study. Baseline data from Cohort Norway (1994-2003) health surveys were linked to the Medical Birth Registry of Norway for identification of all subsequent births (1994-2012). Logistic regression models provided odds ratios (OR) and 95% confidence intervals (CI) for preterm delivery (< 37 weeks gestation); multinomial logistic regression provided OR for early preterm (< 34 weeks) and late preterm (34 through to end of 36 weeks gestation) relative to term deliveries. RESULTS: Mean (SD) length of time from baseline health survey participation to delivery was 5.6 (3.5) years. A family history of stroke associated with a 62% greater risk for late preterm deliveries (OR 1.62; CI 1.07-2.47), while a family history of myocardial infarction associated with a 66% greater risk of early preterm deliveries (OR 1.66; CI 1.11-2.49). Sensitivity analyses, removing pregnancies complicated by hypertensive disorders of pregnancy, diabetes mellitus, and stillbirth deliveries, gave similar results. Preconception vigorous physical activity of three or more hours relative to less than 1 h per week associated with increased risk of early preterm delivery (OR 1.52; 95% CI 1.01-2.30), but not late or total preterm deliveries. Light physical activity of three or more hours per week relative to less activity prior to pregnancy was not associated with early, late, or total preterm deliveries. CONCLUSIONS: Results suggest that family history of cardiovascular disease may help identify women at risk for preterm delivery. Further, research is needed regarding preconception and very early pregnancy vigorous physical activity and associated risks.

Exposures during the prepuberty period and future offspring's health: evidence from human cohort studies†.

Emerging evidence suggests that exposures in prepuberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father's exposed to tobacco smoking or overweight that started in prepuberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of prepuberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during prepuberty plays a role for grand-offspring's health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring's health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multigeneration data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male prepuberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research, and biological plausibility, all support the notion that exposures in the prepuberty of males may influence the phenotype of future offspring.

Growth in children conceived by ART.

STUDY QUESTION: Is the growth pattern of children conceived by ART different compared to naturally conceived children. SUMMARY ANSWER: Both ART and underlying parental subfertility may contribute to differences in early childhood growth between children conceived with and without the use of ART. WHAT IS KNOWN ALREADY: Children conceived by ART weigh less and are shorter at the time of delivery. The extent to which differences in growth according to mode of conception persist during childhood, and the role of underlying parental subfertility, remains unclear. STUDY DESIGN, SIZE, DURATION: We conducted a prospective study population-based study. We studied 81 461 children participating in the Norwegian Mother, Father and Child Cohort Study (MoBa) and 544 113 adolescents screened for military conscription. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conception by ART as registered in the Medical Birth Registry. We compared maternally reported length/height and weight among children in MoBa from mid-pregnancy to age 7 according to mode of conception using mixed-effects linear regression. Differences in self-reported height and weight at 17 years of age at screening for military conscription were assessed with linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: At birth, children conceived by ART were shorter (boys -0.3 cm; 95% CI, -0.5 to -0.1), girls -0.4 cm; 95% CI, -0.5 to -0.3) and lighter (boys -113 grams; 95% CI, -201 to -25, girls -107 grams; 95% CI, -197 to -17). After birth, children conceived by ART grew more rapidly, achieving both greater height and weight at age 3. Children conceived by ART had a greater height up to age 7, but did not have a greater height or weight by age 17. Naturally conceived children of parents taking longer time to conceive had growth patterns similar to ART children. Children born after frozen embryo transfer had larger ultrasound measures and were longer and heavier the first 2 years than those born after fresh embryo transfer. LIMITATIONS, REASONS FOR CAUTIONS: Selection bias could have been introduced due to the modest participation rate in the MoBa cohort. Our reliance on self-reported measures of length/height and weight could have introduced measurement error. WIDER IMPLICATIONS OF THE FINDINGS: : Our findings provide reassurance that offspring conceived by ART are not different in height, weight or BMI from naturally conceived once they reach adolescence. STUDY FUNDING/COMPETING INTEREST(S): Research Council of Norway; Medical Research Council; National Institute of Environmental Health Sciences. The authors have no competing interest. TRIAL REGISTRATION NUMBER: N/A.

COVID-19 in pregnancy-characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries.

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.

Associations of age, body mass index and biochemical parameters with brain morphology in patients with anorexia nervosa.

OBJECTIVE: Accumulating evidence shows that patients with anorexia nervosa (AN) have globally reduced brain mass, including lower cortical volume and thickness, which largely normalizes following weight restoration. The underlying mechanisms for these processes are unknown, and how age and severity of emaciation are associated with brain morphology in AN is poorly understood. We investigated associations of age, body mass index (BMI) and biochemical parameters with brain morphology among patients in treatment. METHOD: We included 85 patients (94% female) aged 12-48 (mean = 23) years with quality controlled magnetic resonance imaging (MRI) data. T1-weighted MRI images, clinical characteristics and biochemical parameters were retrospectively collected from hospital records. Brain morphology was measured using FreeSurfer, and associations investigated using regression models and correlations. RESULTS: Controlling for BMI, age showed significant associations with brain morphology generally concordant with typical brain developmental patterns. Controlling for age, BMI showed significant positive associations with cortical volume and thickness. There were no significant interaction effects between age and BMI. None of the biochemical parameters correlated significantly with brain morphology. CONCLUSION: Our findings suggest the presence of typical neurodevelopmental patterns in AN. Importantly, we showed that severity of emaciation is related to brain morphology reductions, underscoring the importance of weight restoration.

Does a history of cardiovascular disease or cancer affect mortality after SARS-CoV-2 infection? / Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BACKGROUND: Cardiovascular disease and cancer have been described as possible risk factors for COVID-19 mortality. The purpose of this study was to investigate whether a history of cardiovascular disease or cancer affects the risk of dying after a COVID-19 diagnosis in Norway. MATERIAL AND METHOD: Data were compiled from the Norwegian Surveillance System for Communicable Diseases, the Norwegian Cardiovascular Disease Registry and the Cancer Registry of Norway. Univariable and multivariable regression models were used to calculate both relative and absolute risk. RESULTS: In the first half of 2020, 8 809 people tested positive for SARS-CoV-2 and 260 COVID-19-associated deaths were registered. Increasing age, male sex (relative risk (RR): 1.5; confidence interval (CI): 1.2-2.0), prior stroke (RR: 1.5; CI: 1.0-2.1) and cancer with distant metastasis at the time of diagnosis (RR: 3.0; CI: 1.1-8.2) were independent risk factors for death after a diagnosis of COVID-19. After adjusting for age and sex, myocardial infarction, atrial fibrillation, heart failure, hypertension, and non-metastatic cancer were no longer statistically significant risk factors for death. INTERPRETATION: The leading risk factor for death among individuals who tested positive for SARS-CoV-2 was age. Male sex, and a previous diagnosis of stroke or cancer with distant metastasis were also associated with an increased risk of death after a COVID-19 diagnosis.