Per Magnus

Self-selection and bias in a large prospective pregnancy cohort in Norway.

Self-selection in epidemiological studies may introduce selection bias and influence the validity of study results. To evaluate potential bias due to self-selection in a large prospective pregnancy cohort in Norway, the authors studied differences in prevalence estimates and association measures between study participants and all women giving birth in Norway. Women who agreed to participate in the Norwegian Mother and Child Cohort Study (43.5% of invited; n = 73 579) were compared with all women giving birth in Norway (n = 398 849) using data from the population-based Medical Birth Registry of Norway in 2000-2006. Bias in the prevalence of 23 exposure and outcome variables was measured as the ratio of relative frequencies, whereas bias in exposure-outcome associations of eight relationships was measured as the ratio of odds ratios. Statistically significant relative differences in prevalence estimates between the cohort participants and the total population were found for all variables, except for maternal epilepsy, chronic hypertension and pre-eclampsia. There was a strong under-representation of the youngest women (<25 years), those living alone, mothers with more than two previous births and with previous stillbirths (relative deviation 30-45%). In addition, smokers, women with stillbirths and neonatal death were markedly under-represented in the cohort (relative deviation 22-43%), while multivitamin and folic acid supplement users were over-represented (relative deviation 31-43%). Despite this, no statistically relative differences in association measures were found between participants and the total population regarding the eight exposure-outcome associations. Using data from the Medical Birth Registry of Norway, this study suggests that prevalence estimates of exposures and outcomes, but not estimates of exposure-outcome associations are biased due to self-selection in the Norwegian Mother and Child Cohort Study.

The prevalence of allergy to egg: a population-based study in young children.

Background: The aim of the present study was to estimate the prevalence of adverse reactions to egg, as population‐based prevalence estimates based on objective diagnostic procedures are lacking.

Predicting zygosity in Norwegian twin pairs born 1915–1960

Present addresses of 12,752 like‐sexed twin pairs born in the period 1915–1960 were identified. A questionnaire, concerning the similarity of pair members, was sent to all individuals. Responses were obtained from 83.7% of the subjects. The zygosity of 207 pairs was established by examination of genetic markers. By using discriminant analysis on the responses from this subgroup, functions were obtained for prediction of zygosity from questionnaire data. It was estimated that 2.4% of the pairs would be misclassified if the questionnaire responses from both pair members were used, and 3.9% if only the response from one of the twins was used. Accordingly, zygosity could be predicted with satisfactory reliability also for twin pairs where only one of the twins had responded. The predicted percentage of monozygotic (MZ) pairs among pairs where one or both twins had responded, was 39.4 (4,402/11,175). The percentage of MZ pairs was significantly lower (34.5) in death‐discordant pairs than in pairs in which both twins were alive (39.6). The zygosity questionnaire data are sufficient to adequately score twin pairs for zygosity in the great majority of cases.

Exposure to pets and atopy-related diseases in the first 4 years of life

Background: It is still unclear how early‐life exposure to pets is related to childrens risk of developing atopy‐related diseases. We estimated associations between early‐life exposure to pets and atopy‐related diseases at 0‐4 years of life in a cohort of Norwegian children.

The familial risk of endometriosis

Methods. A total of 563 patients with endometriosis were interviewed about endometriosis or adenomyosis in their mothers or sisters. Five hundred and twenty‐eight patients (94%) gave information about their relatives. Six patients were adopted and had no knowledge about their relatives. Among 522 patients were seven pairs of sisters, of which only one was included, giving a total of 515 cases. The control group consisted of 149 women without endometriosis documented at a recently diagnostic laparoscopy performed in connection with sterilization. The controls were likewise interviewed about their relatives, and none refused to give information. If a gynecological operation in a relative was reported, medical records were obtained (68%) or a description of the medical history was given by the proband. Results Endometriosis or adenomyosis was disclosed in 3.9% of mothers of cases and in 0.7% of mothers of controls, in 4.8% of sisters of cases and in 0.6% of sisters of controls. The relative risk of endometriosis in a first‐degree relative (expressed as odds ratio), was 7.2 (95% confidence interval 2.1, 24.3). Severe manifestations of endometriosis were found more often among patients with a positive family history than among those without (26% versus 12%, p < 0.01).

VITAMIN D SUPPLEMENTATION AND REDUCED RISK OF PREECLAMPSIA IN NULLIPAROUS WOMEN

Background: A recent study showed that nulliparous women who develop preeclampsia had low concentrations of vitamin D in serum sampled in midpregnancy. The aim of the present study was to estimate the association between intake of vitamin D during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study. Methods: Participating women answered questionnaires at gestational week 15 (general health questionnaire), at week 22 (food frequency questionnaire), and at week 30 (general health questionnaire). Pregnancy outcomes were obtained from the Medical Birth Registry. Nutrient intake was calculated from foods and dietary supplements. We estimated relative risks as odds ratios, and controlled for confounding with multiple logistic regression. Results: The odds ratio of preeclampsia for women with a total vitamin D intake of 15–20 &mgr;g/d compared with less than 5 &mgr;g/d was 0.76 (95% confidence interval = 0.60–0.95). Considering only the intake of vitamin D from supplements, we found a 27% reduction in risk of preeclampsia (OR = 0.73 [0.58–0.92]) for women taking 10–15 &mgr;g/d as compared with no supplements. No association was found between intake of vitamin D from the diet alone and the occurrence of preeclampsia. Conclusions: These findings are consistent with other reports of a protective effect of vitamin D on preeclampsia development. However, because vitamin D intake is highly correlated with the intake of long chain n-3 fatty acids in the Norwegian diet, further research is needed to disentangle the separate effects of these nutrients.

Interior surface materials in the home and the development of bronchial obstruction in young children in Oslo, Norway.

OBJECTIVES This study assessed the role of polyvinyl chloride (PVC) plastics and textile materials in the home in the development of bronchial obstruction during the first 2 years of life. METHODS The study was a matched pair case-control study based on a cohort of 3754 newborns in Oslo in 1992 and 1993 who were followed up for 2 years. The case group consisted of 251 children with bronchial obstruction; the control group was matched one-to-one for date of birth. RESULTS In conditional logistic regression analysis, the risk of bronchial obstruction was related to the presence of PVC flooring (adjusted odds ratio [OR] = 1.89; 95% confidence interval [CI] = 1.14, 3.14) and textile wall materials (adjusted OR = 1.58; 95% CI = 0.98, 2.54). The reference category was wood or parquet flooring and painted walls and ceiling. Further analysis revealed an exposure-response relationship between the assessed amount of PVC and other plasticizer-containing surface materials and the risk of bronchial obstruction. CONCLUSIONS This study provides new evidence of the role of PVC and textile wall materials in the development of bronchial obstruction in young children.

Day Care Centers and Respiratory Health

Objective. To estimate the effects of the type of day care on respiratory health in preschool children. Methods. A population-based cross-sectional study of Oslo children born in 1992 was conducted at the end of 1996. A self-administered questionnaire inquired about day care arrangements, childrens health, environmental conditions, and family characteristics (n = 3853; response rate, 79%). Results. In logistic regression controlling for confounding, children in day care centers had more often nightly cough (adjusted odds ratio, 1.89; 95% confidence interval, 1.34–2.67), and blocked or runny nose without common cold (1.55; 1.07–1.61) during the past 12 months compared with children in home care. Poisson regression analysis showed an increased risk of the common cold (incidence rate ratio, 1.21; 1.12–1.30) and otitis media (1.48; 1.22–1.80), and the attributable proportion was 17.4% (95% confidence interval, 10.7–23.1) for the common cold and 32.4% (18.0–44.4) for otitis media. Early starting age in the day care center increased the risk of developing recurrent otitis media. Also the lifetime risk of doctor-diagnosed asthma was higher in children who started day care center attendance during the first 2 years of life. Conclusions. Attendance to day care centers increases the risk of upper respiratory symptoms and infections in 3- to 5-year-old children. The starting age seems to be an important determinant of recurrent otitis media as well as asthma. The effect of day care center attendance on asthma is limited to age up to 2 years. This effect is most likely mediated via early respiratory tract infections that are substantially more common in children in day care centers compared with children in home care.

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.).

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.