Anders Engeland

Elucidating the risk of Parkinson's disease High expression of the α-synuclein gene ( SNCA ) is a risk factor for Parkinson's disease (PD), but certain drugs may mitigate this risk. Mittal et al. ran a small-molecule screen to identify compounds that regulate levels of SNCA expression and found that several β2-adrenoreceptor (β2AR) agonists reduced them (see the Perspective by Snyder). These compounds modulated epigenetic marks at the SNCA gene, effectively suppressing SNCA transcription. The authors looked at the pharmaceutical history of more than 4 million Norwegians over an 11-year period and found a reduced risk of PD among those that were taking one of the β2AR agonists for other medical problems. Science , this issue p. 891 ; see also p. 869

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.

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.).

Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04-1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08-1.15) for men and 1.06 (95% CI: 1.02-1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.

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.