Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study.

OBJECTIVES: To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort study (MoBa) (1999-2008). POPULATION: A total of 51 404 singleton pregnancies. METHODS: Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis. MAIN OUTCOME MEASURES: Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning. RESULTS: In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07-1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs. CONCLUSIONS: Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance. TWEETABLE ABSTRACT: Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression.

Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway.

OBJECTIVE: To examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. POPULATION: 45,266 women with 51,748 singleton pregnancies. METHODS: The association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. MAIN OUTCOME MEASURES: Children's language competence at age three measured by maternal report on a validated language grammar scale. RESULTS: Women reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and long-term symptoms, respectively. CONCLUSIONS: Prolonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect.

Metabolic risk factors and skin cancer in the Metabolic Syndrome and Cancer Project (Me-Can).

BACKGROUND: Little is known about the associations of metabolic aberrations with malignant melanoma (MM) and nonmelanoma skin cancer (NMSC). OBJECTIVES: To assess the associations between metabolic factors (both individually and combined) and the risk of skin cancer in the large prospective Metabolic Syndrome and Cancer Project (Me-Can). METHODS: During a mean follow-up of 12 years of the Me-Can cohort, 1728 (41% women) incident MM, 230 (23% women) fatal MM and 1145 (33% women) NMSC were identified. Most NMSC cases (76%) were squamous cell carcinoma (SCC) (873, 33% women). Hazard ratios (HRs) were estimated by Cox proportional hazards regression for quintiles and standardized z-scores (with a mean of 0 and SD of 1) of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and for a combined metabolic syndrome score. Risk estimates were corrected for random error in the measurements. RESULTS: Blood pressure per unit increase of z-score was associated with an increased risk of incident MM cases in men and women [HR 1·17, 95% confidence interval (CI) 1·04-1·31 and HR 1·18, 95% CI 1·03-1·36, respectively] and fatal MM cases among women (HR 2·39, 95% CI 1·58-3·64). In men, all quintiles for BMI above the reference were associated with a higher risk of incident MM. In women, SCC NMSC risk increased across quintiles for glucose levels (P-trend 0·02) and there was a trend with triglyceride concentration (P-trend 0·09). CONCLUSION: These findings suggest that mechanisms linked to blood pressure may be involved in the pathogenesis of MM. SCC NMSC in women could be related to glucose and lipid metabolism.

Coffee intake and oral-oesophageal cancer: follow-up of 389,624 Norwegian men and women 40-45 years.

BACKGROUND: The evidence on the relationship between coffee intake and cancer of the oral cavity and oesophagus is conflicting and few follow-up studies have been done. METHODS: A total of 389,624 men and women 40-45 years who participated in a national survey programme were followed with respect to cancer for an average of 14.4 years by linkage to the Cancer Registry of Norway. Coffee consumption at baseline was reported as a categorical variable (0 or <1 cup, 1-4, 5-8, 9+ cups per day). RESULTS: Altogether 450 squamous oral or oesophageal cancers were registered during follow-up. The adjusted hazard ratios with 1-4 cups per day as reference were 1.01 (95% confidence interval: 0.70, 1.47), 1.16 (0.93, 1.45) and 0.96 (0.71, 1.14) for 0 or <1 cup, 5-8 and 9+ cups per day, respectively. Stratification by sex, type of coffee, smoking status and dividing the end point into oral and oesophageal cancers gave heterogeneous and non-significant estimates. CONCLUSION: This study does not support an inverse relationship between coffee intake and incidence of cancer in the mouth or oesophagus, but cannot exclude a weak inverse relationship.

Metabolic syndrome and rare gynecological cancers in the metabolic syndrome and cancer project (Me-Can).

BACKGROUND: Risk factors for rare gynecological cancers are largely unknown. Initial research has indicated that the metabolic syndrome (MetS) or individual components could play a role. MATERIALS AND METHODS: The Metabolic syndrome and Cancer project cohort includes 288,834 women. During an average follow-up of 11 years, 82 vulvar, 26 vaginal and 43 other rare gynecological cancers were identified. Hazard ratios (HRs) were estimated fitting Cox proportional hazards regression models for tertiles and standardized z-scores [with a mean of 0 and a standard deviation (SD) of 1] of body mass index (BMI), blood pressure, glucose, cholesterol, triglycerides and MetS. Risk estimates were corrected for random error in the measurement of metabolic factors. RESULTS: The MetS was associated with increased risk of vulvar [HR 1.78, 95% confidence interval (CI) 1.30-2.41) and vaginal cancer (HR 1.87, 95% CI 1.07-3.25). Among separate MetS components, 1 SD increase in BMI was associated with overall risk (HR 1.43, 95% CI 1.23-1.66), vulvar (HR 1.36, 95% CI 1.11-1.69) and vaginal cancer (HR 1.79, 95% CI 1.30-2.46). Blood glucose and triglyceride concentrations were associated with increased risk of vulvar cancer (HR 1.98, 95% CI 1.10-3.58 and HR 2.09, 95% CI 1.39-3.15, respectively). CONCLUSION: The results from this first prospective study on rare gynecological cancers suggest that the MetS and its individual components may play a role in the development of these tumors.

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study.

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974-2007, initially aged 20-50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13-1.20), 1.20 (1.14-1.27), 1.26 (1.19-1.34) and 1.09 (0.96-1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01-1.04), 1.03 (1.00-1.05), 1.03 (1.00-1.06) and 0.99 (0.92-1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women.

Long-term risk of tuberculosis among immigrants in Norway.

BACKGROUND: Two-thirds of the tuberculosis (TB) cases in Norway were discovered among immigrants. Some cases were discovered at arrival, but many develop the disease several years post-migration. Knowledge about how long after migration to Norway TB were discovered will enable us to better target preventive measures including preventive therapy. This study examines the long-term risk of TB among immigrants in Norway. METHODS: All non-Nordic immigrants who arrived in Norway between 1986 and 2002, as registered by the Norwegian Directorate of Immigration, were followed-up. Their TB status was determined from the National Tuberculosis Registry. Observation period for TB cases was calculated from the date of arrival in Norway to TB registration. For persons without TB, it was calculated from the date of arrival in Norway to the date of emigration from Norway, date of death, or until end of follow-up (December 31, 2002). RESULTS: For immigrants from Africa and Asia, the TB rates were 190 and 80 per 100,000 person-years (PY), respectively, at 7 years post-migration. For immigrants from Somalia, Pakistan, Vietnam, and the former Yugoslavia, the rates were 520, 160, 210, and 40 per 100 000 PY respectively, at 7 years post-migration. These rates were 7 to 90 times higher than the crude TB incidence for Norway. This increased risk applies to both genders, pulmonary and extra-pulmonary sites. CONCLUSION: These results indicate the need for health personnel to be aware that immigrants remain at high risk of TB many years post-migration. Screening for TB on arrival should be strengthened, and preventive therapy for those with recent TB infection should be considered.

Tuberculosis in Norway by country of birth, 1986-1999.

OBJECTIVE: To estimate the standardised incidence ratio (SIR) of TB among the foreign-born in Norway. METHOD: The expected number of TB cases was calculated by applying the sex- and age-specific incidence rates for those born in Norway to the corresponding foreign-born population. The SIR was measured as the ratio between observed and expected number of cases. RESULTS: The expected number of TB cases was between zero and three for all selected countries; the observed number of cases was significantly higher. The SIR was highest for Africa (160, 95%CI 144-175) and lowest for USA/Canada (0.4, 95%CI 0.1-1.0). It was 883 for Somalia (95%CI 775-991), 122 for Vietnam (95%CI 106-139), 119 for Pakistan (95%CI 105-134), 115 for the Philippines (95%CI 91-144) and 49 for former Yugoslavia (95%CI 40-57). The SIR for all the foreign-born was 21 (95%CI 20-22), giving a population attributable risk of 38%. It was highest in the age group 15-39 years (95, 95%CI 89-101), and lowest for those 65 years and older (3, 95%CI 2.1-3.3). The SIR for extrapulmonary TB was also high in those aged 15-39 years (159, 95%CI 146-173). CONCLUSION: SIRs for TB differ by country and continent of birth. Understanding local epidemiology and immigration patterns will help better target prevention efforts.

Body mass index and cardiovascular mortality at different levels of blood pressure: a prospective study of Norwegian men and women.

STUDY OBJECTIVE: The study investigated the joint effect of body mass index and systolic blood pressure on cardiovascular and total mortality. DESIGN: This was a prospective cohort study. The main outcome measures were age adjusted mortality and relative risks estimated from survival models. SETTING: The population of the city of Bergen, Norway. PARTICIPANTS: Subjects were 21,145 men and 30,330 women aged 30-79 years at the time of examination in 1963. MAIN RESULTS: Both cause specific and all cause mortality increased with systolic blood pressure within each category of body mass index. Stroke mortality was not significantly associated with body mass index when adjusted for systolic blood pressure in either age group of men or women. Coronary heart disease mortality increased on average 30% per 5 kg/m2 increase in body mass index in men and women aged 30-59 years at baseline. Adjusted for systolic blood pressure, the relative risks were reduced to 1.20 (95% confidence interval (CI) 1.12, 1.29) in men and 1.10 (95% CI 1.03, 1.18) in women. They were similar at each level of systolic blood pressure. For coronary heart disease mortality in men and women aged 60-79 years at measurement a negative interaction between body mass index and systolic blood pressure was suggested in the first five years. Excluding the first five years, adjusted relative risks per 5 kg/m2, were 1.05 (95% CI 0.96, 1.15) in men and 1.11 (95% CI 1.04, 1.17) in women in the older age group. There was an upturn in cardiovascular mortality at low levels of body mass index in both age groups of women, but not in men. CONCLUSIONS: Hypertension is an important risk factor for cardiovascular and all cause mortality even in the obese. Body mass index is generally a weak predictor of cardiovascular mortality in this population. It is a stronger risk factor of coronary death in men when measured at a younger age. Thin people with hypertension are not at particularly high risk of death from coronary heart disease compared with their obese counterparts, except possibly in the first few years after measurement in the elderly. Being underweight is associated with increased risk of death from all cardiovascular causes in women, but not in men.

Cost and health consequences of reducing the population intake of salt.

STUDY OBJECTIVE: The aim was to estimate health and economic consequences of interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g per person in the Norwegian population. Health promotion (information campaigns), development of new industry food recipes, declaration of salt content in food and taxes on salty food/subsidies of products with less salt, were possible interventions. DESIGN: The study was a simulation model based on present age and sex specific mortality in Norway and estimated impact of blood pressure reductions on the risks of myocardial infarction and stroke as observed in Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure (range 1-4) was assumed through the actual interventions. The cost of the interventions in themselves, welfare losses from taxation of salty food/subsidising of food products with little salt, cost of avoided myocardial infarction and stroke treatment, cost of avoided antihypertensive treatment, hospital costs in additional life years and productivity gains from reduced morbidity and mortality were included. RESULTS: The estimated increase in life expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost of the interventions was minus $118 millions (that is, cost saving) in the base case. Sensitivity analyses indicate that the interventions would be cost saving unless the systolic blood pressure reduction were less than 2 mm Hg, productivity gains were disregarded or the welfare losses from price interventions were high. CONCLUSION: Population interventions to reduce the intake of salt are likely to improve the population's health and save costs to society.

Cod liver oil consumption, smoking, and coronary heart disease mortality: three counties, Norway.

It has been hypothesized that omega-3 fatty acid consumption may lessen the adverse effect of smoking on coronary heart disease (CHD) risk. Thus, we explored whether cod liver oil consumption was protective of coronary heart disease in a cohort of men and women participating in a cardiovascular disease screening in Norway. The study population was aged 35-54 at the time of the baseline screening conducted by the National Health Screening Service of Norway in 1977-1983. Of 56,718 age-eligible men and women, 52,138 participated, of whom 42,612 (82%) completed a dietary questionnaire. Cod liver oil use was reported by 12.5%. At baseline, cod liver oil users had lower triglycerides, adjusting for age, body mass index, time since last meal and income (p < or = .05). As of December 1992, 639 and 118 CHD deaths were observed among the men and women, respectively. Overall, we observed no effect of cod liver oil consumption reported at baseline and CHD mortality in Cox Proportional Hazards analyses [Hazard Ratio (HR) = 1.0 (0.8-1.3)]. In analyses, stratified by smoking status, never smokers and current smokers showed non-significant beneficial associations between cod liver oil use and CHD mortality (HR = 0.7, 95% CI = 0.4-1.5; and HR = 0.8, 95% CI = 0.6-1.2, respectively). However, among former smokers a non-significant excess risk of CHD mortality was associated with cod liver oil use (HR = 1.6, 95% CI = 0.9-2.6). Smokers, regardless of their cod liver oil use were at a substantially higher risk for CHD mortality relative to non-smokers. Omega-3 fatty acid supplementation, as practiced in this cohort, provided no significant benefits to CHD risk among study participants.

Rose angina predicts 23-year coronary heart disease mortality in women and men aged 40-49 years.

OBJECTIVE: To determine the long-term coronary heart disease (CHD) mortality in women and men with symptoms, according to the Rose Angina Questionnaire at a relatively young age. DESIGN: Cohort study with the baseline survey conducted during 1974-8. Information on symptoms was collected by a short, three-item version of the Rose Angina Questionnaire. Participants were re-invited to a similar survey five years later and followed for mortality throughout 2000. SETTING: Three counties in Norway (the Norwegian Counties Study). PARTICIPANTS: 16 616 men and 16 265 women aged 40-49 years and denying CHD in 1974-8. MAIN OUTCOME MEASURE: CHD mortality during 23 years. RESULTS: By the end of follow-up 1316 men (7.9%) and 310 women (1.9%) had died from CHD, including 16% (66/406) of men and 4% (24/563) of women with Rose angina in 1974-8. Rose angina implied an elevated mortality from CHD with adjusted hazard ratios 1.50 (95% CI 1.16 to 1.93) in men and 1.98 (95% CI 1.30 to 3.02) in women. According to calculations based on the Cox model these increases in risk are similar to those associated with elevations of total cholesterol by 1.8 mmol/l (men) and 2.5 mmol/l (women) or elevations of systolic blood pressure by 21 mm Hg (men) or 31 mm Hg (women). CONCLUSIONS: Angina symptoms in ages as low as 40-49 years were associated with elevated long-term CHD mortality in Norwegian women and men. This indicates that the three-item version of the Rose Angina Questionnaire, although a screening tool rather than a diagnostic test, adds information on undiagnosed CHD in both sexes.

A comparison of Poisson regression models fitted to multiway summary tables and Cox's survival model using data from a blood pressure screening in the city of Bergen, Norway.

Multiplicative models for the association between blood pressure and coronary heart disease mortality in 5201 men aged 40-49 years at time of examination were compared. Piecewise exponential models fitted to summary tables formed by cross-classification by three systolic and three diastolic blood pressure groups, two age groups and three time intervals gave results close to the Cox model for continuous data. The parametric integrated baseline hazard functions estimated from grouped data were close to Breslow's nonparametric estimate in the Cox model.

Blood pressure and twenty-year mortality in the city of Bergen, Norway.

A blood pressure survey was carried out in 1963 in the city of Bergen, Norway. The relation between 20-year mortality and blood pressure in 52,064 participants aged 30-89 years at examination was analyzed. Increased blood pressure was related to increased mortality from coronary heart disease, stroke, and all causes in all age groups except the oldest, where a more irregular pattern was present. The relative risks decreased with age at screening, while the absolute increase in mortality with increasing blood pressure was greatest in persons aged 60-69 or 70-79 years at screening. A log-linear relation between systolic blood pressure and coronary heart disease and stroke mortality was seen in both men and women. An upturn in total mortality at low systolic blood pressures was suggested in the groups aged 60 years or more at screening. An upturn, or leveling off, was also seen at low diastolic blood pressures for total deaths and stroke deaths in both men and women.

Mortality from stroke, coronary heart disease and all causes related to blood pressure and length of follow-up.

Measurements of blood pressure in 52,064 men and women in the city of Bergen, Norway, who were 30 to 89 years in 1963, have been related to mortality occurring in different intervals of the follow-up period from 1963 throughout 1983. Blood pressure measurements obtained on one occasion were highly predictive of both coronary heart disease, stroke and all-cause mortality several years after measurements. The relative risk of stroke mortality associated with blood pressure varied little in the first ten to fifteen years, but the predictive power was clearly lower in the last five years of follow-up. The relative risk of death from coronary heart disease was stable in the whole period of follow-up. The risk curves relating coronary heart disease mortality to diastolic blood pressure in men and women aged 60-79 years at screening had the same shape in the first five years as in the rest of the follow-up. No J-shaped association was seen in either time interval.

The negligible influence of premarital cohabitation on marital fertility in current Danish cohorts, 1975.

This paper studies the influence of premarital cohabitation on marital fertility by applying life table methods to data for cohorts of Danish women born in 1926-1955, collected in retrospective interviews made in 1975. For each five-year cohort, the data have been analyzed by duration of marriage or by duration since previous birth, for women who had no reported births before marriage. Our main empirical results are: (a) that women who married at age 15-19 had higher rates of marital first and second births than those married at ages 20-24, and (b) that premarital cohabitation had very little influence on births of these two first orders in our data.

Income, educational level and body height.

The relation between adult body height and two socio-economic factors (income and educational level) was studied in a large, ethnically homogenous population. In the period 1980-1983 all persons aged 40-54 years (born 1926-1941) in two Norwegian counties were invited to a cardiovascular screening. Ninety per cent (or 38162 persons) of those invited attended and had their height measured. Information concerning income and education was available at an individual level from the 1980 national census. Strong, positive relations were found between mean body height and the socio-economic factors, relations that probably are due to conditions during growth influencing both height, attained education and income abilities. The difference between highest and lowest educational class was 3.3 cm in men and 3.2 cm in women, and between highest and lowest income group 3.5 cm in men and 4.2 cm in women. These differences could not be explained by the strong cohort effect of increasing height in the successive birth cohorts from 1926 to 1941 which also was evident. It should be emphasized that height only could explain a small fraction of the variance in the socio-economic factors and is thus not a usable indicator of an individual's socio-economic status. However, it might contribute with important information concerning social inequalities in groups or population.

[Chronic low back pain in 40-year olds in 12 Norwegian counties]. / Kroniske korsryggssmerter hos 40-åringer i 12 norske fylker.

In this study, a questionnaire and a short interview were used to estimate the prevalence of chronic low back pain alone and low back pain together with other musculo-skeletal pains among 40-year-old women and men in 12 Norwegian counties (a total of 67,338 persons). On average 2.4% of men and 1.7% of women had only chronic low back pain, while 5.7% of men and 9.2% of women in addition had other pains as well. Persons with low back pain only were approximately equally distributed across the counties. Greater variations across the counties and between the sexes were found in persons with additional pain. The duration of the pain did not vary significantly between the sexes or across the counties, but the duration was on average two years longer in cases of multi-cause pain. Reduced capacity for work because of pain was approximately equally distributed between the sexes and the groups. More women than men were unable to do their daily work. About one third in both groups (more men than women) had been absent from work because of pain during the last year. More women than men in both groups received national insurance benefits. Persons with only low back pains were approximately equally represented across all levels of education and regardless of marital status, while people with multi-cause pain were overrepresented among those with low levels of education and among the divorced.

Prognosis in cardiac pacing. A comparison between patients with atrioventricular block and sick sinus syndrome.

The prognosis of 64 patients with atrioventricular (AV) block among 128 consecutive patients, 65 males and 63 females, treated with permanent pacemakers, was compared with that of 56 patients with sick sinus syndrome (SSS) during a mean observation period of 32.5 months. A poor survival rate was found in patients with known coronary heart disease (CHD) compared to those with isolated conduction defect (ICD). Among patients with CHD, a higher mortality was found in patients with AV block than in those with SSS (58 vs. 24%). Likewise, among patients with ICD the mortality in AV block was higher than in SSS (31 vs. 15%). Regression analysis showed a mortality excess in AV block vs. SSS (p=0.02), males vs. females (p=0.04). The mortality excess in patients with CHD vs. ICD was significant (p=0.01). It is concluded that the increased mortality rate in patients with AV block is related to widespread myocardial damage, this being especially pronounced in patients with CHD.

Reliability of the Reflotron in the determination of cholesterol.

Measurements of total cholesterol in the field by means of the Reflotron dry-chemistry system (capillary blood) were compared to total cholesterol obtained by a standardized conventional wet-chemistry method in a clinico-chemical laboratory (serum). A total of 1200 people participated in the study. Two identical Reflotron machines were used. In the first period of the study an excellent agreement was found between Reflotron measurements of a reference serum provided by the manufacturer (mean, 4.99 mmol/l; CV, 1.8%) and the stated value (4.97 mmol/l). In the rest of the study higher values and greater variation were found with the Reflotron (mean, 5.32 mmol/l; CV 5.2%). Clearly the Reflotron measurements in the latter period of study were not reliable. In the period with stable instruments most of the values obtained at the two Reflotron machines differed from each other by less than 10%, with a mean difference of 0.08 mmol/l. Reflotron (both machines) and wet-chemistry measurements agreed well for the first 500 participants in the study (mean difference, Reflotron-wet-chemistry, -0.008 mmol/l; 95% confidence interval, -0.035 to 0.019 mmol/l; correlation, 0.967). In this period most Reflotron values differed from wet-chemistry values by less than 9% below to 9% above. With the next 200 participants the Reflotron gave on average slightly higher values than wet-chemistry measurements. The coefficients of variation for measurement variation were higher for Reflotron that for wet-chemistry even in the period with stable instruments. In all parts of the study period a lower HDL-cholesterol level was associated with larger differences between total cholesterol determined by Reflotron and wet-chemistry.