Anders Engeland

Body Mass Index in Adolescence in Relation to Cause-specific Mortality: A Follow-up of 230,000 Norwegian Adolescents

The prevalence of obesity in childhood and adolescence has increased worldwide. Long-term effects of adolescent obesity on cause-specific mortality are not well specified. The authors studied 227,000 adolescents (aged 14-19 years) measured (height and weight) in Norwegian health surveys in 1963-1975. During follow-up (8 million person-years), 9,650 deaths were observed. Cox proportional hazards regression was used to compare cause-specific mortality among individuals whose baseline body mass index (BMI) was below the 25th percentile, between the 75th and 84th percentiles, and above the 85th percentile in a US reference population with that of individuals whose BMI was between the 25th and 75th percentiles. Risk of death from endocrine, nutritional, and metabolic diseases and from circulatory system diseases was increased in the two highest BMI categories for both sexes. Relative risks of ischemic heart disease death were 2.9 (95% confidence interval (CI): 2.3, 3.6) for males and 3.7 (95% CI: 2.3, 5.7) for females in the highest BMI category compared with the reference. There was also an increased risk of death from colon cancer (males: 2.1, 95% CI: 1.1, 4.1; females: 2.0, 95% CI: 1.2, 3.5), respiratory system diseases (males: 2.7, 95% CI: 1.4, 5.2; females: 2.5, 95% CI: 1.4, 4.8), and sudden death (males: 2.2, 95% CI: 1.2, 4.3; females: 2.7, 95% CI: 1.1, 6.6). Adolescent obesity was related to increased mortality in middle age from several important causes.

Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries

Objective To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs. Design Population based cohort study using data from the national health registers. Setting Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007. Participants More than 1.6 million infants born after gestational week 33. Main outcome measures Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs. Results Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0). Conclusions The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

Obesity in Adolescence and Adulthood and the Risk of Adult Mortality

Background: There are few long-term follow-up data on the relation between body mass index (BMI) in adolescence and in adulthood, and between adolescent BMI and adult mortality. The present study explores these relations. Methods: In Norwegian health surveys during 1963–1999, height and weight were measured for 128,121 persons in a standardized way both in adolescence (age 14–19 years) and 10 or more years later. Persons were followed for an average of 9.7 years after the adult measurement. Cox proportional hazard regression models were used to study the association between adolescent and adult BMI and mortality. Results: The odds ratio of obesity (BMI ≥30) in adulthood increased steadily with BMI in adolescence, from 0.2 for low BMI up to 16 for very high BMI. Very high adolescent BMI was associated with 30–40% higher adult mortality compared with medium BMI. Adjusting for adult BMI explained most of the association of adolescent obesity and mortality, especially among men. Adjustment for smoking did not change the results. Conclusions: Obesity in adolescence tends to persist into adulthood. Adolescent obesity is also connected to excess mortality, but this excess seems to be explained mostly by obesity in adulthood. High BMI in adolescence seems to be predictive of both adult obesity and mortality.

Height, body mass index, and prostate cancer: a follow-up of 950 000 Norwegian men

The present study explored body mass index (BMI), height, and risk of prostate cancer in a large Norwegian cohort of 950 000 men aged 20–74 years, whose height and weight were measured in a standardised way in the period 1963–1999. These were followed for an average of 21 years. The Cox proportional hazard models were used in the analyses. During follow-up, 33 300 histologically verified cases of prostate cancer were registered. The risk of prostate cancer increased by both BMI and height. The magnitude of the increase by BMI was modest, the relative risk (RR) of obese men (BMI⩾30) compared with normal weighted was 1.09 (95% CI: 1.04–1.15). However, the RR at age 50–59 years was 1.58 (95% CI: 1.29–1.94) in men being obese at about age 45 years compared with normal weighted men. The tallest men had an RR of 1.72 (95% CI: 1.46–2.04) compared with the shortest men. The overall effect of BMI on the incidence of prostate cancer was modest. The larger effect found in men aged 50–59 years might partly explain the previous inconsistent findings.

Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination

BACKGROUND During the 2009 influenza A (H1N1) pandemic, pregnant women were at risk for severe influenza illness. This concern was complicated by questions about vaccine safety in pregnant women that were raised by anecdotal reports of fetal deaths after vaccination. METHODS We explored the safety of influenza vaccination of pregnant women by linking Norwegian national registries and medical consultation data to determine influenza diagnosis, vaccination status, birth outcomes, and background information for pregnant women before, during, and after the pandemic. We used Cox regression models to estimate hazard ratios for fetal death, with the gestational day as the time metric and vaccination and pandemic exposure as time-dependent exposure variables. RESULTS There were 117,347 eligible pregnancies in Norway from 2009 through 2010. Fetal mortality was 4.9 deaths per 1000 births. During the pandemic, 54% of pregnant women in their second or third trimester were vaccinated. Vaccination during pregnancy substantially reduced the risk of an influenza diagnosis (adjusted hazard ratio, 0.30; 95% confidence interval [CI], 0.25 to 0.34). Among pregnant women with a clinical diagnosis of influenza, the risk of fetal death was increased (adjusted hazard ratio, 1.91; 95% CI, 1.07 to 3.41). The risk of fetal death was reduced with vaccination during pregnancy, although this reduction was not significant (adjusted hazard ratio, 0.88; 95% CI, 0.66 to 1.17). CONCLUSIONS Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis. Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.).

Height and body mass index in relation to total mortality

Background. The relation between body mass index (BMI) and mortality is not clear in the literature. An inverse relation between height and mortality has been suggested. We explore these relations in a very large cohort in Norway. Methods. We studied two million men and women, age 20–74 years, who were measured during 1963–2000. These persons were followed for an average of 22.1 years. We used Cox proportional hazard models in the analyses. Also, the optimal BMI (the BMI at the time of measurement that was subsequently related to the lowest mortality) was estimated. Results. Over the study period, 723,000 deaths were registered. The relative risk of death by BMI showed a J- or U-shaped curve, with the lowest rates of death at BMI between 22.5 and 25.0. In men, the optimal BMI increased from 21.6 when measured at age 20–29 to 24.0 when measured at age 70–74. In women, the optimal BMI was consistently higher, increasing from 22.2 to 25.7. Mortality decreased with increased height in men; in women, mortality decreased with height only up to heights of about 160–164 cm and then increased among the tallest women. Conclusions. The relation between BMI and mortality was J- or U-shaped, with the “optimal” BMI varying by age and sex. Height was inversely related to mortality in men and in women up to a height of 165 cm.

Prescription drug use among fathers and mothers before and during pregnancy. A population‐based cohort study of 106 000 pregnancies in Norway 2004–2006

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Mothers are using medicines during pregnancies; the extent varies across the world and is generally difficult to compare. In this registry-based study, we examined more than 100,000 Norwegian pregnancies and described the drug prescription pattern of both fathers and mothers around conception and during pregnancy (mothers). WHAT THIS STUDY ADDS In every trimester of pregnancy, about 30% of the mothers was dispensed a drug. The total drug exposure did not seem to diminish throughout pregnancy. One-quarter of the fathers was dispensed drugs during the last 3 months prior to conception. AIMS The primary aim of this study was to describe the use of prescribed drugs in both mothers and fathers before and during pregnancy in Norway. METHODS This population-based cohort study was based on data retrieved from the Medical Birth Registry of Norway and the Norwegian Prescription Database. These registries cover the entire population of Norway. Information on >100,000 births during 2004-2006 in the birth registry was linked to prescription data. Prescriptions issued to mothers just prior to, during and after the pregnancies as well as prescriptions to fathers just prior to conception were identified. RESULTS Among mothers, 83% were prescribed drugs during the period 3 months prior to estimated conception until 3 months after giving birth. The mothers who received drugs were prescribed on average 3.3 different Anatomical Therapeutic Chemical (ATC) codes (range 1-38). During pregnancy, 57% were prescribed drugs. In the first trimester, 33% of mothers were dispensed drugs, while the figure was 29% for mothers in the last trimester. Among fathers, 25% used prescribed drugs during the 3 months prior to conception, with on average 1.9 different ATC codes (range 1-22). CONCLUSION Large proportions of both fathers and mothers were dispensed drugs prior to conception or during pregnancy. While there is a high awareness of the issues involved in maternal drug use in pregnancy, possible teratogenic effects of drug use in fathers shortly before conception should be further explored.

Smoking habits and risk of cancers other than lung cancer: 28 years' follow-up of 26,000 Norwegian men and women.

The impact of tobacco smoking on lung cancer risk has been investigated thoroughly since the 1950s, but other types of cancer also have been associated with smoking. In the present study, the aim was to explore the variation in risk connected with cigarette, cigar, and pipe smoking of suspected smoking-associated cancers other than lung cancer. Data were obtained from a survey of a random sample of the Norwegian population. A self-administered mailed questionnaire, which included questions about smoking habits, was completed by 26,000 men and women in 1965 (response rate: 76 percent). The cohort was followed from 1966 through 1993, including registration of all incident cancer cases. A dose-response relationship of cigarette smoking to the risk of urinary bladder cancer and cancers of the upper digestive and respiratory tract was observed. For the latter forms of cancer, a dose-response relationship of pipe smoking also was observed. In cancer of the pancreas, a stronger association between cigarette smoking and cancer risk was observed when the analysis was confined to histologically confirmed cases only. Current cigarette smokers at baseline had a significantly higher risk of cervical cancer than those who never smoked cigarettes. In cancers of the stomach, colon, rectum, breast, corpus uteri, ovary, and prostate, and in leukemia, no association between smoking and cancer risk was observed.

Cohort Profile: Cohort of Norway (CONOR)

A number of large population-based cardiovascular surveys have been conducted in Norway since the beginning of the 1970s. The surveys were carried out by the National Health Screening Service in cooperation with the universities and local health authorities. All surveys comprised a common set of questions, standardized anthropometric and blood pressure measurements and non-fasting blood samples that were analysed for serum lipids at the Ulleval Hospital Laboratory. These surveys provided considerable experience in conducting large-scale population-based surveys, thus an important background for the Cohort of Norway (CONOR). In the late 1980s the Research Council of Norway established a programme in epidemiology. This also gave stimulus to the idea of establishing a cohort including both core survey data and stored blood samples. In the early 1990s, all universities, the National Health Screening Service, The National Institute of Public Health and the Cancer Registry discussed the possibility of a national representative cohort. The issue of storing blood samples for future analyses raised some concern and it was discussed in the parliament. In 1994, the Ministry of Health appointed the Steering Committee for the CONOR collaboration. In 1994–95, the fourth round of the Tromso Study was conducted, and became the first survey to provide data and blood samples for CONOR. During the years 1994–2003, a number of health surveys that were carried out in other counties and cities also provided similar data for the network. So far, 10 different surveys have provided data and blood samples for CONOR (Figure 1). The administrative responsibility for CONOR was given to the Norwegian Institute of Public Health (NIPH) in 2002. The CONOR collaboration is currently a research collaboration between the NIPH and the Universities of Bergen, Oslo, Tromso and Trondheim.

Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam

BACKGROUND Despite the high prescription rate of benzodiazepine-like hypnotics (z-hypnotics), there is limited information on the road traffic accident risk associated with the use of these drugs. We wanted to investigate whether filling a prescription for zopiclone or zolpidem was associated with increased risk of road traffic accidents at a national population level. Nitrazepam and flunitrazepam were used as comparator drugs. METHOD All Norwegians 18-69 years (3.1 million) were followed-up from January 2004 until the end of September 2006. Information on prescriptions, road traffic accidents and emigration/death was obtained from three Norwegian population-based registries. The first week after the hypnotics had been dispensed was considered to be the exposure period. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of accidents in the exposed person-time to the incidence of accidents in the unexposed person-time. RESULTS During exposure, 129 accidents were registered for zopiclone, 21 for zolpidem, 27 for nitrazepam and 18 for flunitrazepam. The SIRs were (SIR for all ages and both sexes combined; 95% CI): z-hypnotics (zopiclone+zolpidem) 2.3; 2.0-2.7, nitrazepam 2.7; 1.8-3.9 and flunitrazepam 4.0; 2.4-6.4. The highest SIRs were found among the youngest users for all hypnotics. CONCLUSIONS This study found that users of hypnotics had a clearly increased risk of road traffic accidents. The SIR for flunitrazepam was particularly high.