Purpose
An increasing consumption of opioids has been reported. The primary aim of the present study was follow‐up of neurocognitive development in children exposed to analgesic opioids during ...pregnancy, using three different validated instruments to assess language and communication development at 5 years.
Methods
The Norwegian Mother and Child Cohort Study (MoBa) prospectively included pregnant women 1999 to 2008. Participants reported medication use at pregnancy week 17/18 and 30, and 6 months after birth. Children's language competence and communication skills at 5 years were reported by mothers on three different validated scales; The Ages and Stages Questionnaire (ASQ), The Speech and Language Assessment Scale (SLAS) and The Twenty Statements about Language‐Related Difficulties list (Language20Q).
Results
A total of 27 428 women with 33 407 singleton pregnancies were included. Use of analgesic opioids was reported in 584 pregnancies (1.7%). No associations between opioid use and lower language competence or communication skills were found. For ASQ, the OR of being in the lowest category vs the group with maximum mean score was 0.82 (95%CI 0.57, 1.17), for SLAS the OR of scoring worse than typical for age vs better than typical for age was 0.84 (0.61, 1.17) in children exposed to opioids in utero. For Language20Q using the best performance category as reference, the OR of scoring in the lower performance category was 0.57 (0.35, 0.91) with exposure to opioids.
Conclusion
Use of analgesic opioids in pregnant women does not seem to negatively affect language development or communication skills in children at 5 years.
Initial studies have indicated diabetes and obesity to be risk factors for hepatocellular carcinoma; but the association between other metabolic risk factors and primary liver cancer (PLC) has not ...been investigated. The metabolic syndrome and cancer project (Me‐Can) includes cohorts from Norway, Austria and Sweden with data on 578,700 subjects. We used Cox proportional hazard models to calculate relative risks (RRs) of PLC by body mass index (BMI), blood pressure and plasma levels of glucose, cholesterol and triglycerides as continuous standardized variables (z‐score with mean = 0 and standard deviation (SD) = 1) and their standardized sum of metabolic syndrome (MetS) z‐score. RRs were corrected for random error in measurements. During an average follow‐up of 12.0 years (SD = 7.8), 266 PLCs were diagnosed among cohort members. RR of liver cancer per unit increment of z‐score adjusted for age, smoking status and BMI and stratified by birth year, sex and sub‐cohorts, was for BMI 1.39 (95% confidence interval (CI) 1.24–1.58), mid blood pressure 2.08 (0.95–4.73), blood glucose 2.13 (1.55–2.94) cholesterol 0.62 (0.51–0.76) and serum triglycerides 0.85 (0.65–1.10). The RR per one unit increment of the MetS z‐score was 1.35 (1.12–1.61). BMI, glucose and a composite MetS score were positively and cholesterol negatively associated with risk of liver cancer.
Inconsistent results have been reported on the association between folic acid use in pregnancy and risk of GDM. The aim of this study was to estimate the association between folic acid use and GDM in ...two population-based Nordic cohorts. Two cohort studies were conducted using data from the national population registers in Norway (2005-2018, n = 791,709) and Sweden (2006-2016, n = 1,112,817). Logistic regression was used to estimate the associations between GDM and self-reported folic acid use and prescribed folic acid use, compared to non-users, adjusting for covariates. To quantify how potential unmeasured confounders may affect the estimates, E-values were reported. An exposure misclassification bias analysis was also performed. In Norwegian and Swedish cohorts, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for maternal self-reported folic acid use were 1.10 (1.06-1.14) and 0.89 (0.85-0.93), with E-values of 1.43 (1.31) and 1.50 (1.36), respectively. For prescribed folic acid use, ORs were 1.33 (1.15-1.53) and 1.56 (1.41-1.74), with E-values of 1.99 (1.57) and 2.49 (2.17), in Norway and Sweden respectively. The slightly higher or lower odds for GDM in self-reported users of folic acid in Norway and Sweden respectively, are likely not of clinical relevance and recommendations for folic acid use in pregnancy should remain unchanged. The two Nordic cohorts showed different directions of the association between self-reported folic acid use and GDM, but based on bias analysis, exposure misclassification is an unlikely explanation since there may still be differences in prevalence of use and residual confounding. Prescribed folic acid is used by women with specific comorbidities and co-medications, which likely underlies the higher odds for GDM.
During pregnancy, many women experience sleep problems and anxiety that require treatment. The long-term safety for the child of maternal benzodiazepine (BZD) and z-hypnotic use during pregnancy ...remains controversial.
We conducted a cohort and a sibling control study using data from the Norwegian Mother and Child Cohort Study. Data on use of BZD and z-hypnotics, internalizing and externalizing outcomes, and covariates were collected from mothers at gestational weeks 17 and 30 and when children were 0.5, 1.5, and 3 years of age. The total sample consisted of 71,996 children (19,297 siblings) at 1.5 years and 55,081 children (13,779 siblings) at 3 years. Short-term use was defined as use in one pregnancy period only. Long-term use was defined as use in two or more pregnancy periods. Linear full cohort random-effect and sibling-matched fixed-effect regression models were used to compare internalizing and externalizing behavior in children prenatally exposed compared to those unexposed in the full cohort of pregnancies accounting for family clusters, as well as within sibling clusters comparing pregnancies with discordant exposures. Propensity score (PS) adjustment included variables on indication for use (sleep problems, symptoms of anxiety and depression) and other potential confounding factors.
Long-term prenatal exposure to BZD or z-hypnotics was associated with increased internalizing behavior in crude cohort analyses and at age 1.5 years after PS adjustment in sibling-matched fixed-effect models β 0.60, 95% confidence interval 0.17-0.95. Analyses on specific drug groups showed that prenatal exposure to BZD-anxiolytics was associated with increased internalizing problems at both 1.5 years β 0.25, 0.01-0.49 and 3 years β 0.26, 0.002-0.52 while exposure to z-hypnotics was not associated with any adverse outcomes after adjustment.
The findings suggest a moderate association between BZD-anxiolytic exposure and child internalizing problems that is not likely due to stable familial confounding factors.
•Frail older individuals are not included in clinical trials of COVID-19 vaccination.•Previous studies have shown few local and systemic reactions among vaccinated older people; however, even mild ...adverse events following immunization could destabilize frail individuals.•There was no evidence of increased short-term mortality among vaccinated older individuals.•Short-term mortality was lower in the vaccinated group compared to the unvaccinated group, which could reflect a healthy-vaccinee effect.•Real-world studies give the possibility to monitor adverse effects of COVID-19 vaccination.
There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used.
In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from theNorwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group.
Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 95% CI: 0.24–0.31). Similar results were obtained in analyses stratified by use of health services and age group.
We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality.
Abstract Objectives To assess the impact of exposure misclassification on risk associations when using prescription databases as the source for drug exposure in pregnancy by applying results from a ...validation analysis of exposure classification. Study Design and Setting Linkage of data on 27,656 participants in the Norwegian Mother and Child Cohort Study (MoBa) with the Norwegian Prescription Database (NorPD). Exposure to selective serotonin reuptake inhibitors (SSRIs) was defined by dispensed drugs during pregnancy including different time windows before pregnancy. The validity of NorPD data was estimated using self-reported use in MoBa as the reference standard. We applied the results from the validation analysis on data from a Nordic study on SSRI use in pregnancy and risk of persistent pulmonary hypertension in the newborn. Results Sensitivity increased and specificity decreased when the time window in NorPD was expanded before pregnancy. Using the same time window as in the Nordic study (+90 days before pregnancy), for use in early pregnancy, the odds ratio (OR) corrected for misclassification was 2.6 compared with the OR of 1.6 in the Nordic study. Conclusion Expansion of the time window to include intervals before pregnancy can lead to lower specificity and underestimation of risk associations.
Purpose: To assess the association between height and risk of cancer and cancer death. Methods: The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants ...from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model. Results: During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06–1.09), and in men, HR 1.04 (95 % CI 1.03–1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11–1.24), and in men HR 1.12 (95 % CI 1.08–1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01–1.16), and in men, HR 1.03 (95 % CI 1.01–1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00–1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07–1.30). All these associations were independent of body mass index. Conclusion: Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.
Obesity is associated with an increased risk of esophageal adenocarcinoma (EAC) and a decreased risk of esophageal squamous cell carcinoma (ESCC). However, little is known about the risk of EAC and ...ESCC related to other metabolic risk factors. We aimed to examine the risk of EAC and ESCC in relation to metabolic risk factors, separately and combined in a prospective cohort study.
The Metabolic Syndrome and Cancer cohort includes prospective cohorts in Austria, Norway and Sweden, with blood pressure, lipids, glucose and BMI available from 578 700 individuals. Relative risk (RR) for EAC and ESCC was calculated using Cox's proportional hazards analysis for metabolic risk factors categorized into quintiles and transformed into z-scores. The standardized sum of all z-scores was used as a composite score for the metabolic syndrome (MetS).
In total, 324 histologically verified cases of esophageal cancer were identified (114 EAC, 184 ESCC and 26 with other histology). BMI was associated with an increased risk of EAC (RR 7.34 (95% confidence interval, 2.88-18.7) top versus bottom quintile) and negatively associated with the risk of ESCC (RR 0.38 (0.23-0.62)). The mean value of systolic and diastolic blood pressure (mid blood pressure) was associated with the risk of ESCC (RR 1.77 (1.37-2.29)). The composite MetS score was associated with the risk of EAC (RR 1.56 (1.19-2.05) per one unit increase of z-score) but not ESCC.
In accordance with previous studies, high BMI was associated with an increased risk of EAC and a decreased risk of ESCC. An association between high blood pressure and risk of ESCC was observed but alcohol consumption is a potential confounding factor that we were not able to adjust for in the analysis. The MetS was associated with EAC but not ESCC. However this association was largely driven by the strong association between BMI and EAC. We hypothesize that this association is more likely to be explained by factors directly related to obesity than the metabolic state of the MetS, considering that no other metabolic factor than BMI was associated with EAC.
ObjectivesThe objective was to prospectively examine potential differences in the risk of first cardiovascular disease (CVD) events between South Asians and Europeans living in Norway and New ...Zealand, and to investigate whether traditional risk factors could explain any differences.MethodsWe included participants (30–74 years) without prior CVD in a Norwegian (n=16 606) and a New Zealand (n=129 449) cohort. Ethnicity and cardiovascular risk factor information was linked with hospital registry data and cause of death registries to identify subsequent CVD events. We used Cox proportional hazards regression to investigate the relationship between risk factors and subsequent CVD for South Asians and Europeans, and to calculate age-adjusted HRs for CVD in South Asians versus Europeans in the two cohorts separately. We sequentially added the major CVD risk factors (blood pressure, lipids, diabetes and smoking) to study their explanatory role in observed ethnic CVD risk differences.ResultsSouth Asians had higher total cholesterol (TC)/high-density lipoprotein (HDL) ratio and more diabetes at baseline than Europeans, but lower blood pressure and smoking levels. South Asians had increased age-adjusted risk of CVD compared with Europeans (87%–92% higher in the Norwegian cohort and 42%–75% higher in the New Zealand cohort) and remained with significantly increased risk after adjusting for all major CVD risk factors. Adjusted HRs for South Asians versus Europeans in the Norwegian cohort were 1.57 (95% CI 1.19 to 2.07) in men and 1.76 (95% CI 1.09 to 2.82) in women. Corresponding figures for the New Zealand cohort were 1.64 (95% CI 1.43 to 1.88) in men and 1.39 (95% CI 1.11 to 1.73) in women.ConclusionDifferences in TC/HDL ratio and diabetes appear to explain some of the excess risk of CVD in South Asians compared with Europeans. Preventing dyslipidaemia and diabetes in South Asians may therefore help reduce their excess risk of CVD.
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