Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

STUDY QUESTION: Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? SUMMARY ANSWER: Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. WHAT IS KNOWN ALREADY: Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. STUDY DESIGN, SIZE, DURATION: A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. LIMITATIONS, REASONS FOR CAUTION: This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. WIDER IMPLICATIONS OF THE FINDINGS: Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Paternal and maternal birthweight and offspring risk of macrosomia at term gestations: A nationwide population study.

BACKGROUND: There is a paucity of data on whether parents' macrosomia (birthweight ≥4500 g) status influences the risk of macrosomia in the offspring. The role of maternal overweight in the generational effect of macrosomia is not known. OBJECTIVE: To estimate the risk of macrosomia by parental birthweight at term and evaluate if this risk varied with maternal body mass index (BMI, kg/m2) early in pregnancy. METHODS: We used data from the Medical Birth Registry of Norway on all singleton term births (37-42 gestational weeks) during 1967-2017. The primary exposure was parental macrosomia, and the outcome was macrosomia in the second generation. The secondary exposure was maternal BMI. We used binomial regression to calculate relative risk (RR) with a 95% confidence interval. We assessed potential unmeasured confounding and selection bias using a probabilistic bias analysis and performed analyses with and without imputation for variables with missing values. RESULTS: The data included 647,957 singleton parent-offspring trios born at term. The prevalence of macrosomia was 3.2% (n = 41,396) in the parental generation and 4.0% (n = 25,673) in the offspring generation. Macrosomia in parents was associated with an increased risk of macrosomia in offspring, with the RR for both parents were born macrosomic being 6.53 (95% confidence interval [CI] 5.31, 8.05), only mother macrosomic 3.37 (95% CI 3.17, 3.57) and only father macrosomic RR 2.22 (95% CI 2.12, 2.33). These risks increased by maternal BMI in early pregnancy: if both parents were born macrosomic, 17% of infants were macrosomic among mothers with normal BMI. If both parents were macrosomic and the mothers were obese, 31% of offspring were macrosomic. Macrosomia-related adverse outcomes did not differ with parental macrosomia status. CONCLUSIONS: Parents' weight at birth and maternal BMI appear to be strongly associated with macrosomia in the offspring delivered at term gestations.

Prevalence and predictors of post-COVID-19 symptoms in general practice - a registry-based nationwide study.

BACKGROUND: With Norwegian national registry data, we assessed the prevalence of post-COVID-19 symptoms at least 3 months after confirmed infection, and whether sociodemographic factors and pre-pandemic health problems were risk factors for these symptoms. METHODS: All persons with a positive SARS-CoV-2 PCR test from February 2020 to February 2021 (exposed) were compared to a group without a positive test (unexposed) matched on age, sex, and country of origin. We used Cox regression to estimate hazard ratios (HR) for 18 outcome symptoms commonly described as post-COVID-19 related, registered by GPs. We compared relative risks (RR) for fatigue, memory disturbance, or shortness of breath among exposed and unexposed using Poisson regression models, assessing sex, age, education, country of origin, and pre-pandemic presence of the same symptom and comorbidity as possible risk factors, with additional analyses to assess hospitalisation for COVID-19 as a risk factor among exposed. RESULTS: The exposed group (N = 53 846) had a higher prevalence of most outcome symptoms compared to the unexposed (N = 485 757), with the highest risk for shortness of breath (HR 2.75; 95%CI 2.59-2.93), fatigue (2.08; 2.00-2.16) and memory disturbance (1.41;1.26-1.59). High HRs were also found for disturbance of smell/taste and hair loss, but frequencies were low. Concerning risk factors, sociodemographic factors were at large similarly associated with outcome symptoms in both groups. Registration of the outcome symptom before the pandemic increased the risk for fatigue, memory disturbance and shortness of breath after COVID-19, but these associations were weaker among exposed. Comorbidity was not associated with fatigue and shortness of breath in the COVID-19 group. For memory disturbance, the RR was slightly increased with the higher comorbidity score both among exposed and unexposed. CONCLUSION: COVID-19 was associated with a range of symptoms lasting more than three months after the infection.

Investigating causal relations between sleep duration and risks of adverse pregnancy and perinatal outcomes: linear and nonlinear Mendelian randomization analyses.

BACKGROUND: Observational studies have reported maternal short/long sleep duration to be associated with adverse pregnancy and perinatal outcomes. However, it remains unclear whether there are nonlinear causal effects. Our aim was to use Mendelian randomization (MR) and multivariable regression to examine nonlinear effects of sleep duration on stillbirth (MR only), miscarriage (MR only), gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, preterm birth and low/high offspring birthweight. METHODS: We used data from European women in UK Biobank (N=176,897), FinnGen (N=~123,579), Avon Longitudinal Study of Parents and Children (N=6826), Born in Bradford (N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, N=14,584). We used 78 previously identified genetic variants as instruments for sleep duration and investigated its effects using two-sample, and one-sample nonlinear (UK Biobank only), MR. We compared MR findings with multivariable regression in MoBa (N=76,669), where maternal sleep duration was measured at 30 weeks. RESULTS: In UK Biobank, MR provided evidence of nonlinear effects of sleep duration on stillbirth, perinatal depression and low offspring birthweight. Shorter and longer duration increased stillbirth and low offspring birthweight; shorter duration increased perinatal depression. For example, longer sleep duration was related to lower risk of low offspring birthweight (odds ratio 0.79 per 1 h/day (95% confidence interval: 0.67, 0.93)) in the shortest duration group and higher risk (odds ratio 1.40 (95% confidence interval: 1.06, 1.84)) in the longest duration group, suggesting shorter and longer duration increased the risk. These were supported by the lack of evidence of a linear effect of sleep duration on any outcome using two-sample MR. In multivariable regression, risks of all outcomes were higher in the women reporting <5 and ≥10 h/day sleep compared with the reference category of 8-9 h/day, despite some wide confidence intervals. Nonlinear models fitted the data better than linear models for most outcomes (likelihood ratio P-value=0.02 to 3.2×10-52), except for gestational diabetes. CONCLUSIONS: Our results show shorter and longer sleep duration potentially causing higher risks of stillbirth, perinatal depression and low offspring birthweight. Larger studies with more cases are needed to detect potential nonlinear effects on hypertensive disorders of pregnancy, preterm birth and high offspring birthweight.

Health at age 17 in Norwegian adolescents: Mental and physical status in the national cohort born in 2001.

AIMS: We present self-reported data on physical and mental health at age 17 years from 82% of Norwegians born in 2001. METHODS: In Norway, the Armed Forces require that each resident who reaches the age of 17 years completes a self-administered declaration of health that is used for military selection. The declaration collects information on height and weight, various clinically diagnosed diseases, mental and behavioural disorders, and other health conditions where clinical diagnosis is not required. In 2018, there were 65,913 adolescents born in 2001 living in Norway, of whom 10,223 were exempt from completing the declaration; declarations were therefore sent to 55,690 participants. We included 54,132 participants who completed the declaration (response rate 97.2%): 27,220 male and 26,912 female respondents. RESULTS: We found that 18% of male and 28% of female respondents reported at least one clinically diagnosed disease, mental disorder or behavioural disorder. Among health condition where clinical diagnosis was not required, 19% of male and 37% of female respondents reported anxiety/depression affecting daily life and 10 versus 18% reported migraines/recurring headaches. The respondents probably represent the healthiest part of the total cohort of 17-year-old Norwegians because those who are exempt from completing the declaration are already considered unfit for military service. CONCLUSIONS: These data represent a rich resource for further research. Similar data exist for the birth cohorts in 1993-2003. We encourage further research that can help decision-makers identify areas of concern that should be targeted for interventions.

Influenza vaccination and risk for cardiovascular events: a nationwide self-controlled case series study.

BACKGROUND: US and European guidelines diverge on whether to vaccinate adults who are not at high risk for cardiovascular events against influenza. Here, we investigated the associations between influenza vaccination and risk for acute myocardial infarction, stroke and pulmonary embolism during the 2009 pandemic in Norway, when vaccination was recommended to all adults. METHODS: Using national registers, we studied all vaccinated Norwegian individuals who suffered AMI, stroke, or pulmonary embolism from May 1, 2009 through September 30, 2010. We defined higher-risk individuals as those using anti-diabetic, anti-obesity, anti-thrombotic, pulmonary or cardiovascular medications (i.e. individuals to whom vaccination was routinely recommended); all other individuals were regarded as having lower-risk. We estimated incidence rate ratios with 95% CI using conditional Poisson regression in the pre-defined risk periods up to 180 days following vaccination compared to an unexposed time-period, with adjustment for season or daily temperature. RESULTS: Overall, we observed lower risk for cardiovascular events following influenza vaccination. When stratified by baseline risk, we observed lower risk across all three outcomes in association with vaccination among higher-risk individuals. In this subgroup, relative risks were 0.72 (0.59-0.88) for AMI, 0.77 (0.59-0.99) for stroke, and 0.73 (0.45-1.19) for pulmonary embolism in the period 1-14 days following vaccination when compared to the background period. These associations remained essentially the same up to 180 days after vaccination. In contrast, the corresponding relative risks among subjects not using medications were 4.19 (2.69-6.52), 1.73 (0.91-3.31) and 2.35 (0.78-7.06). CONCLUSION: In this nationwide study, influenza vaccination was associated with overall cardiovascular benefit. This benefit was concentrated among those at higher cardiovascular risk as defined by medication use. In contrast, our results demonstrate no comparable inverse association with thrombosis-related cardiovascular events following vaccination among those free of cardiovascular medications at baseline. These results may inform the risk-benefit balance for universal influenza vaccination.

The demographics of assisted reproductive technology births in a Nordic country.

STUDY QUESTION: What are the socio-demographic characteristics of families in Norway who have children after assisted reproductive technology (ART), and have these characteristics changed over time? SUMMARY ANSWER: Parents who conceive through ART in Norway tend to be advantaged families, and their socio-demographic profile has not changed considerably over the period 1985-2014. WHAT IS KNOWN ALREADY: A small number of studies show that couples who conceive through ART tend to be socio-economically advantaged. STUDY DESIGN, SIZE, DURATION: Norwegian Population Register, the Medical Birth Register and the national data bases were linked to study all live births in Norway between 1985 and 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: The sample consisted of 1 757 768 live births. Simple bivariate analyses were performed to describe the socio-demographic characteristics of parents who conceived through ART and changes in these characteristics over the time period 1985-2014. We used linear probability models to estimate the association between parental income and giving birth after ART from 2000 to 2014, before and after adjustment for maternal age at delivery, education and area of residence. MAIN RESULTS AND THE ROLE OF CHANCE: Parents conceiving through ART were more likely to be older, with the highest levels of income and education, and married. Their socio-demographic profiles did not change considerably during the period 1985-2014. In the unadjusted model, parents belonging to the top income quartile were 4.2 percentage points more likely (95% CI: 4.1 to 4.3) to have conceived through ART than parents who belonged to the bottom income quartile. Adjustment for maternal age only partially reduced the income disparities (for the top income quartile by 35% (ß = 2.7 with 95% CI: 2.5 to 2.8)). Additional adjustment for maternal education, marital status and area of residence did not further attenuate the associations. LIMITATIONS, REASONS FOR CAUTION: The data does not enable us to tell whether the lower numbers of children conceived through ART amongst more disadvantaged individuals is caused by lower success rates with ART treatment, lower demand of ART services or barriers faced in access to ART. The study focuses on Norway, a context characterised by high subsidisation of ART services. WIDER IMPLICATIONS OF THE FINDINGS: Even though in Norway access to ART services is highly subsidised, the results highlight important and persisting social inequities in use of ART. The results also indicate that children born after ART grow up in resourceful environments, which will benefit their development and well-being. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by European Research Council agreement n. 803959 (to A.G.), by Economic and Social Research Council grant ES/M001660/1 and by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Risk conditions in children hospitalized with influenza in Norway, 2017-2019.

BACKGROUND: Norwegian children are more frequently hospitalized with influenza than adults. Little is known about the characteristics of these children. Our aim was to investigate the presence of pre-existing risk conditions and to determine the duration of influenza hospitalizations in children during two influenza seasons. METHODS: The Norwegian Patient Registry holds data on all hospitalized patients in Norway. We included all patients younger than 18 years hospitalized with a diagnosis of influenza during the influenza seasons 2017-18 and 2018-19. Pre-existing risk conditions for influenza were identified by ICD-10 diagnoses in the Norwegian Patient Registry. In addition, information on asthma diagnoses were also retrieved from the Norwegian Registry for Primary Health Care. To estimate the prevalence of risk conditions in the child population, we obtained diagnoses on all Norwegian children in a two-year period prior to each influenza season. We calculated age-specific rates for hospitalization and risk for being hospitalized with influenza in children with risk conditions. RESULTS: In total, 1013 children were hospitalized with influenza during the two influenza seasons. Children younger than 6 months had the highest rate of hospitalization, accounting for 13.5% of all admissions (137 children). Hospitalization rates decreased with increasing age. Among children hospitalized with influenza, 25% had one or more pre-existing risk conditions for severe influenza, compared to 5% in the general population under 18 years. Having one or more risk conditions significantly increased the risk of hospitalization, (Odds Ratio (OR) 6.1, 95% confidence interval (CI) 5.0-7.4 in the 2017-18 season, and OR 6.8, 95% CI 5.4-8.4 in the 2018-19 season). Immunocompromised children and children with epilepsy had the highest risk of hospitalization with influenza, followed by children with heart disease and lung disease. The average length of stay in hospital were 4.6 days, and this did not differ with age. CONCLUSION: Children with pre-existing risk conditions for influenza had a higher risk of hospitalization for influenza. However, most children (75%) admitted to hospital with influenza in Norway during 2017-2019 did not have pre-existing risk conditions. Influenza vaccination should be promoted in particular for children with risk conditions and pregnant women to protect new-borns.

Hospitalization following influenza infection and pandemic vaccination in multiple sclerosis patients: a nationwide population-based registry study from Norway.

Patients with multiple sclerosis (MS) are at increased risk of infections and related worsening of neurological function. Influenza infection has been associated with increased risk of various neurological complications. We conducted a population-based registry study to investigate the risk of acute hospitalization of MS patients in relation to influenza infection or pandemic vaccination in Norway. The entire Norwegian population in the years 2008-2014 was defined as our study population (N = 5,219,296). Information on MS diagnosis, influenza infection and vaccination were provided by Norwegian national registries. The self-controlled case series method was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CI) in defined risk periods. 6755 MS patients were identified during the study period. Average age at first registration of an MS diagnosis was 51.8 years among men and 49.9 years among females (66.9%). The IRR for emergency hospitalization among MS patients the first week after an influenza diagnosis was 3.4 (95% CI 2.4-4.8). The IRR was 5.6 (95% CI 2.7-11.3) after pandemic influenza, and 4.8 (95% CI 3.1-7.4) after seasonal influenza. Pandemic vaccination did not influence risk of hospitalization [IRR within the first week: 0.7 (95% CI 0.5-1.0)]. Among MS patients, influenza infection was associated with increased risk for acute hospitalization while no increased risk was observed after pandemic vaccination. Influenza vaccination could prevent worsening of MS-related symptoms as well as risk of hospitalization.

Seasonal and pandemic influenza during pregnancy and risk of fetal death: A Norwegian registry-based cohort study.

Previous studies of fetal death with maternal influenza have been inconsistent. We explored the effect of maternal influenza-like illness (ILI) in pregnancy on the risk of fetal death, distinguishing between diagnoses during regular influenza seasons and the 2009/2010 pandemic and between trimesters of ILI. We used birth records from the Medical Birth Registry of Norway to identify fetal deaths after the first trimester in singleton pregnancies (2006-2013). The Norwegian Directorate of Health provided dates of clinical influenza diagnoses by primary-health-care providers, whereas dates of laboratory-confirmed influenza A (H1N1) diagnoses were provided by the Norwegian Surveillance System for Communicable Diseases. We obtained dates and types of influenza vaccinations from the Norwegian Immunisation Registry. Cox proportional-hazards regression models were fitted to estimate hazard ratios (HRs) of fetal death, with associated 95% confidence intervals (CIs), comparing women with and without an ILI diagnosis in pregnancy. There were 2510 fetal deaths among 417,406 eligible pregnancies. ILI during regular seasons was not associated with increased risk of fetal death: adjusted HR = 0.90 (95% CI 0.64-1.27). In contrast, ILI during the pandemic was associated with substantially increased risk of fetal death, with an adjusted HR of 1.75 (95% CI 1.21-2.54). The risk was highest following first-trimester ILI (adjusted HR = 2.28 [95% CI 1.45-3.59]). ILI during the pandemic-but not during regular seasons-was associated with increased risk of fetal death in the second and third trimester. The estimated effect was strongest with ILI in first trimester.

Probability and outcomes of second pregnancy after HELLP syndrome in the first: A population-based registry study.

INTRODUCTION: Some studies have suggested that women may avoid further pregnancies after experiencing a pregnancy affected by a hypertensive disorder. Large population-based studies are needed to better understand the outcomes of later pregnancies among women who have a history of hypertensive disorders of pregnancy. The aims of the study were to assess outcomes of the second pregnancy and second delivery rate among women experiencing Hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome in their first pregnancy. MATERIAL AND METHODS: This population-based registry study included all women with a first delivery registered in the Medical Birth Registry of Norway from 1999 to 2014 (n = 418 897). Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for adverse outcomes of the second delivery and the probability of no second delivery among women with HELLP syndrome in first pregnancy compared with women without HELLP syndrome. We also compared outcomes in the first and second pregnancies among women with HELLP syndrome in first. RESULTS: HELLP syndrome occurred in 0.24% of first pregnancies (n = 1006). Among women with HELLP syndrome in their first pregnancy, adverse outcomes were substantially less frequent in the second pregnancy: preterm deliveries declined from 56.0% to 14.2%, and small for gestational age from 6.6% to 2.8%. More than 75% had no hypertensive disorder in their second pregnancy. Still, compared with women without a history of HELLP syndrome, ORs for adverse outcomes in second pregnancies were increased: preterm birth (OR 3.7, 95% CI 2.8-4.8), small for gestational age (OR 2.7, 95% CI 1.6-4.8), perinatal death (OR 3.1, 95% CI 1.4-7.0), placental abruption (OR 4.2, 95% CI 1.8-9.4) and hypertensive complication (OR 8.3, 95% CI 6.7-10.3). HELLP syndrome did not influence the probability of a second delivery. CONCLUSIONS: Among women with HELLP syndrome in their first pregnancy, the occurrence of adverse pregnancy outcomes was substantially reduced in the second pregnancy. However, compared with unaffected women, they were still at greater risk of pregnancy complications.

Deaths after confirmed SARS-CoV-2 in Norway. / Dødsfall etter påvist SARS-CoV-2 i Norge.

BACKGROUND: Advanced age is the most important risk factor for death as a result of COVID-19, but there is a dearth of knowledge regarding the impact of chronic diseases. Using health registry data, we describe the disease profiles of persons who died after a confirmed infection with SARS-CoV-2 during the first three months of the pandemic in Norway. MATERIAL AND METHOD: Data from the specialist health service (Norwegian Patient Registry, NPR) and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) were linked to information on positive tests for SARS-CoV-2 from the Norwegian Surveillance System for Communicable Diseases (MSIS) and on deaths from the National Population Register. The data retrieval included the Norwegian population as of 1 March 2020 with data for confirmed infections, hospitalisations and deaths until 31 May 2020. RESULTS: Of 8 412 persons with a confirmed SARS-CoV-2 infection, altogether 244 (2.9 %) died, whereof 133 (55 %) were men. Among those with a confirmed infection, the proportion who died varied from 0.2 % (age < 60 years) to 52 % (age ≥ 90 years). Altogether 92 (38 %) patients died in hospital. 25 (16 %) of those who died elsewhere had previously been hospitalised for COVID-19. The proportion with no registered chronic disease was 39 % in the age group < 70 years and 26 % in the age group ≥ 70 years. The disease distribution varied between those patients who had died in and outside of hospital, especially for diagnoses of diabetes, renal failure and dementia. INTERPRETATION: Among those who had a SARS-CoV-2 infection confirmed during the first three months of the pandemic in Norway, only a small proportion died. The majority of those who died were 70 years or older and had at least one chronic disease, but the disease profile varied between patients who died in and outside of hospital. Health registry data can help provide a better overview of and advice to risk groups in the population during an ongoing pandemic.

Maternal history of miscarriages and measures of fertility in relation to childhood asthma.

BACKGROUND: It remains unclear what underlies the greater risk of asthma reported among children conceived by assisted reproductive technologies (ART). OBJECTIVE: Our aim was to clarify the role of parental subfertility and unmeasured confounding on the association between ART and childhood asthma, and to examine the possibility for common mechanisms underlying parental subfertility and miscarriages influencing asthma pathogenesis. METHODS: We used data from national Norwegian health registries (n=474 402) and the Norwegian Mother and Child Cohort Study (MoBa) (n=75 797). We used log-linear regression to estimate overall associations, and fixed-effects logistic regression to estimate associations within siblings. RESULTS: ART offspring had greater asthma risk, the adjusted relative risk (aRR) was 1.20 (95% CI 1.09 to 1.32) in the registry-based cohort, and 1.42 (95% CI 1.14 to 1.76) in MoBa. The sibling analysis yielded similar associations, although the CI included the null value. The elevated asthma risk among ART offspring was attenuated when they were compared with spontaneously conceived offspring with time to conception >12 months, aRR 1.22 (95% CI 0.95 to 1.57). Asthma risk also increased with maternal history of early miscarriages (≤12 weeks), with an aRR of 1.07 (95% CI 1.03 to 1.11) for one, aRR 1.18 (95% CI 1.10 to 1.26) for two and aRR 1.24 (95% CI 1.12 to 1.37) for three or more. CONCLUSION: Our findings indicate that both parental subfertility and characteristics related to the ART procedure itself might increase offspring asthma risk, although this needs to be confirmed in future studies, and further suggest that common mechanisms underlying parental subfertility and recurrent miscarriages might influence offspring asthma pathogenesis.

Association of Household Income With Life Expectancy and Cause-Specific Mortality in Norway, 2005-2015.

Importance: Examining causes of death and making comparisons across countries may increase understanding of the income-related differences in life expectancy. Objectives: To describe income-related differences in life expectancy and causes of death in Norway and to compare those differences with US estimates. Design and Setting: A registry-based study including all Norwegian residents aged at least 40 years from 2005 to 2015. Exposures: Household income adjusted for household size. Main Outcomes and Measures: Life expectancy at 40 years of age and cause-specific mortality. Results: In total, 3 041 828 persons contributed 25 805 277 person-years and 441 768 deaths during the study period (mean [SD] age, 59.3 years [13.6]; mean [SD] number of household members per person, 2.5 [1.3]). Life expectancy was highest for women with income in the top 1% (86.4 years [95% CI, 85.7-87.1]) which was 8.4 years (95% CI, 7.2-9.6) longer than women with income in the lowest 1%. Men with the lowest 1% income had the lowest life expectancy (70.6 years [95% CI, 69.6-71.6]), which was 13.8 years (95% CI, 12.3-15.2) less than men with the top 1% income. From 2005 to 2015, the differences in life expectancy by income increased, largely attributable to deaths from cardiovascular disease, cancers, chronic obstructive pulmonary disease, and dementia in older age groups and substance use deaths and suicides in younger age groups. Over the same period, life expectancy for women in the highest income quartile increased 3.2 years (95% CI, 2.7-3.7), while life expectancy for women in the lowest income quartile decreased 0.4 years (95% CI, -1.0 to 0.2). For men, life expectancy increased 3.1 years (95% CI, 2.5-3.7) in the highest income quartile and 0.9 years (95% CI, 0.2-1.6) in the lowest income quartile. Differences in life expectancy by income levels in Norway were similar to differences observed in the United States, except that life expectancy was higher in Norway in the lower to middle part of the income distribution in both men and women. Conclusions and Relevance: In Norway, there were substantial and increasing gaps in life expectancy by income level from 2005 to 2015. The largest differences in life expectancy between Norway and United States were for individuals in the lower to middle part of the income distribution.

Preeclampsia and Hypertension During Pregnancy in Areas with Relatively Low Levels of Traffic Air Pollution.

Objectives Air pollution exposure may contribute to the development of preeclampsia and hypertension during pregnancy. However, the evidence for such a relation is still limited. We investigated the associations between exposure for moderate to low levels of air pollution during pregnancy and preeclampsia and gestational hypertension in selected urban and county areas of Norway. Methods This study used a sub-group of 17,533 women in the Norwegian Mother and Child Cohort Study. Air pollution levels at residential addresses were estimated using land use regression models and back-extrapolated to the period of each pregnancy. Information on preeclampsia and gestational hypertension were obtained from the Medical Birth Registry of Norway and information on lifestyle factors was collected from questionnaires completed by the women during pregnancy. Results Moderate mean levels of NO2 (13.6 ± 6.9 µg/m3) at residential address during pregnancy were not associated with preeclampsia and pregnancy hypertension. We found no statistically significant associations per 10 µg/m3 change in NO2 exposure and preeclampsia (adjusted OR 0.89, 95% CI 0.74, 1.08) or hypertension during pregnancy (adjusted OR 0.91, 95% CI 0.78, 1.06). Conclusions for Practice In this large Norwegian pregnancy cohort, we found no statistically significant associations for moderate to low levels of pregnancy NO2 exposure and preeclampsia or hypertension during pregnancy.

General practice consultations and use of prescription drugs after changes to school absence policy. / Legesøkning og legemiddeluttak etter innføring av nye fraværsregler.

BACKGROUND: New rules for absence with stricter requirements for documentation were introduced in upper secondary schools in the autumn of 2016. We investigated the use of general practice services and dispensing of prescription drugs among 16 ­ 18-year-olds in the autumn of 2016 and compared this with equivalent figures for the period 2013 ­ 15. MATERIAL AND METHOD: We retrieved information on consultations in general practice (GP) and dispensing of prescription drugs to 15 ­ 18-year-olds in the period 2013 ­ 16 from the Directorate of Health's system for control and payment of health reimbursements (KUHR) and the Norwegian Prescription Database respectively. The number of consultations and dispensing of drugs were compared to previous years using Poisson regression (reference year 2015). The incidence rate ratio (IRR) was used as an outcome measure. RESULTS: The number of GP consultations for 16 ­ 18-year-olds was 30 % higher in the autumn of 2016 than in the autumn of 2015 (IRR 1.30, 95 % confidence interval (CI) 1.29 ­ 1.31). In the same period, the dispensing of drugs to this age group increased by 8 % (IRR 1.08, 95 % CI 1.08 ­ 1.09). Among the diagnosis groups, respiratory tract infections had the largest increase (IRR 2.21, 95 % CI 2.17 ­ 2.25). The largest increase in drug dispensing was found for remedies for coughs and colds (IRR 1.73, 95 % CI 1.65 ­ 1.80). INTERPRETATION: The increase in consultations in general practice and dispensing of drugs to 16 ­ 18-year-olds coincided in time with the introduction of new rules for absence from school. We hold it to be highly likely that the changes were caused by the stricter rules for documentation of absence from school.

Upper secondary school leaving celebrations and final exams - consultations in general practice and emergency care. / Russefeiring og eksamenstid ­ bruk av fastlege og legevakt.

BACKGROUND: Increased use of antibiotics and a higher rate of injury in May for 19-year-olds have been described earlier. We examined whether 19-year-olds also demonstrate greater use of general practitioner services at the time of russefeiring ­ celebrations in connection with completion of upper secondary school. MATERIAL AND METHOD: The study is based on data from the Directorate of Health's system for the control and payment of reimbursements to healthcare providers (KUHR) for all consultations in the general practitioner services for age group 18 ­ 20 years in the period 2012 ­ 15. The number of consultations per month and age group were analysed using Poisson regression, with 19-year-olds in March as a reference group. The incidence rate ratio (IRR) was the outcome measure. RESULTS: All calendar years showed a sharp increase in the number of consultations among 19-year-olds in May in all calendar years compared with other calendar months and the cohorts above and below. The incidence rate ratio for consultations with GPs and emergency departments was 1.40 (95 % confidence interval (CI) 1.38 ­ 1.41) and 2.07 (95 % CI 2.02 ­ 2.13). The increase was greatest for respiratory infections (IRR 3.64, 95 % CI 3.55 ­ 3.73). The incidence rate ratio for injuries was 1.21 (95 % CI 1.16 ­ 1.27). The increase commenced in the three weeks before 17 May (Constitution Day) and persisted in the following two weeks. INTERPRETATION: The sharp increase in the number of consultations for 19-year-olds in the general practitioner services is associated timewise with celebrations in connection with completion of upper secondary school (russefeiring). More frequent contact with these services lasts well into the ensuing examination period.

Risk of Guillain-Barré syndrome after exposure to pandemic influenza A(H1N1)pdm09 vaccination or infection: a Norwegian population-based cohort study.

Vaccinations and infections are possible triggers of Guillain-Barré syndrome (GBS). However, studies on GBS after vaccinations during the influenza A(H1N1)pmd09 pandemic in 2009, show inconsistent results. Only few studies have addressed the role of influenza infection. We used information from national health data-bases with information on the total Norwegian population (N = 4,832,211). Cox regression analyses with time-varying covariates and self-controlled case series was applied. The risk of being hospitalized with GBS during the pandemic period, within 42 days after an influenza diagnosis or pandemic vaccination was estimated. There were 490 GBS cases during 2009-2012 of which 410 cases occurred after October 1, 2009 of which 46 new cases occurred during the peak period of the influenza pandemic. An influenza diagnosis was registered for 2.47% of the population and the vaccination coverage was 39.25%. The incidence rate ratio of GBS during the pandemic peak relative to other periods was 1.46 [95% confidence interval (CI) 1.08-1.98]. The adjusted hazard ratio (HR) of GBS within 42 days after a diagnosis of pandemic influenza was 4.89 (95% CI 1.17-20.36). After pandemic vaccination the adjusted HR was 1.11 (95% CI 0.51-2.43). Our results indicated that there was a significantly increased risk of GBS during the pandemic season and after pandemic influenza infection. However, vaccination did not increase the risk of GBS. The small number of GBS cases in this study warrants caution in the interpretation of the findings.