Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.

INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4). CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.

The variation in free 25-hydroxy vitamin D and vitamin D-binding protein with season and vitamin D status.

PURPOSE: Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP. METHODS: Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated. RESULTS: The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = -0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = -0.095; P = 0.027). CONCLUSIONS: Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.

Urinary free cortisol and androgens in the population-Hormone interactions and the relationship with body composition and bone status.

OBJECTIVE: Abnormal secretion of thyroid hormones, growth hormone, cortisol and androgens influences body composition. We hypothesised that higher cortisol excretion, in combination with higher androgen and IGF-I concentrations, had a synergistic, favourable effect on body mass and bone. DESIGN, PATIENTS AND METHODS: This was a cross-sectional study on a population sample of 290 women and 93men. The mean age was 65.4±7.2yearsinwomen and 59.7±10.0yearsinmen. Body composition was assessed with bioimpedance, and skeletal health with calcaneal quantitative ultrasound and fracture rate. The influence of urinary free cortisol (UFC), serum DHEAs (women), testosterone (men), free T4andIGF-I on the outcome was studied with regression analyses adjusted for age and body mass index. RESULTS: In women, higher concentrations of UFC, DHEAs, IGF-I and lower free T4, were associated with higher fat-free mass. Only a higher UFC concentration was associated with favourable calcaneal measurements. In men, higher testosterone was associated with higher fat-free mass and lower fat mass. Higher IGF-I concentration, but not UFC, was independently associated with higher fat-free mass in men. Interaction analyses did not reveal any additive effects of hormones on body composition or bone in either sex. In both men and women, only age was associated with osteoporotic fractures. CONCLUSION: Serum concentrations of androgens together with IGF-I were positively associated with body composition in both sexes. Urinary cortisol was positively associated with fat-free mass and bone status in women only. Increasing age, but not hormones, was the major determinant of osteoporotic fractures in this population sample.

The association between urinary cortisol excretion and cardiovascular risk factors, bone status and quality of life in the population.

OBJECTIVE: Patients with glucocorticoid excess have increased cardiovascular risk, decreased bone mineral density and impaired quality of life (QoL). The aim of this study was to evaluate the association between urinary cortisol excretion and cardiovascular risk factors, bone status and QoL in the population. We hypothesized that higher cortisol excretion was associated with adverse cardiovascular risk profile, worse skeletal health and QoL. DESIGN, PATIENTS AND METHODS: This was a cross-sectional study including a population sample (n=348), aged 38-77years. The mean age in women was 64.0±8.5years (n=276) and 60.3±10.2years in men (n=72). The metabolic syndrome, body composition measured with bioimpedance, calcaneal quantitative ultrasound, fractures and QoL evaluated with the Nottingham Health Profile, Psychological General Well-Being (PGWB) and the Short Form 36 (SF-36) were studied. Urinary free cortisol (UFC) was measured using radioimmunoassay. RESULTS: UFC was higher in men (230±120nmol/L) compared to women (153±71; P<0.001) and decreased with increasing age (P<0.001). In a regression analysis, after adjustment for gender, age and body mass index, higher UFC was associated with higher fat-free mass (P<0.01), favourable calcaneal bone measurements (P<0.05), better general health measured with PGWB (P<0.01) and SF-36 (P=0.001) and tended to be negatively associated with the metabolic syndrome (P=0.07). CONCLUSION: In contrast to our hypothesis, UFC in the upper physiological range was associated with a favourable cardiovascular risk profile, bone measures and QoL.

Normocalcaemic, vitamin D-sufficient hyperparathyroidism - high prevalence and low morbidity in the general population: A long-term follow-up study, the WHO MONICA project, Gothenburg, Sweden.

OBJECTIVE: There is limited knowledge about the natural history of normocalcaemic, vitamin D-sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity. DESIGN: Cross-sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: A random population of 608 men and women, age 25-64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient). MEASUREMENTS: A serum intact parathyroid hormone (S-PTH) ≥60 ng/l was considered as HPT, S-calcium 2·15-2·49 mmol/l as normocalcaemia and S-25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17-year follow-up. RESULTS: The prevalence of nHPT was 2·0% in 1995 (age 25-64) and 11·0% in 2008 (age 38-79). S-PTH was positively correlated with age and BMI. After adjustment for these variables, a high S-PTH level (≥60 ng/l) at follow-up was associated with previously low S-25(OH)D, high osteocalcin, S-PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow-up. CONCLUSIONS: This small random population study showed that nHPT was common, 11% at follow-up. Only one individual developed mild hypercalcaemia in 13 years. Previous S-PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end-points was seen over a 17-year period.

Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort.

To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 blood donors (60 % men; mean age 41 ± 13 years) and 75 thrombocyte donors (92 % men, aged 46 ± 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (r S = 0.326; p < 0.001). During January-March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July-September in 11 and 50 % (p < 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values <75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D <50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.

Secular trends in sex hormones and fractures in men and women.

OBJECTIVE: To study secular trends in sex hormones, anthropometry, bone measures and fractures. DESIGN: A random population sample was studied twice and subjects of similar age group were compared 13 years apart. METHODS: X-ray-verified fractures were retrieved from a random population sample of 2400 men and women (participants 1616=67%) aged 25-64 years from the WHO, MONICA Project in Gothenburg, Sweden, in 1995 and 2008. Fasting serum hormones and calcaneal ultrasound were measured in every fourth subject. In fertile women, measurements were performed on cycle day interval 7-9. RESULTS: In 2008, men had lower serum free testosterone than men of similar age in 1995 (P<0.001). Body composition, physical activity and fracture incidence were similar. In women, hormone replacement therapy (HRT) was lower in 2008, 7 vs 28% (P<0.0001), as was serum oestradiol, although use of tranquilisers and leisure time physical activity were higher. In 2008, the fracture incidence was higher in postmenopausal women, 29 vs 17% (P<0.001), and vertebral crush had increased from 8 to 19% of all fractures (P=0.031). Serum cholesterol and triglycerides were lower in all subjects in 2008 compared with that in 1995. CONCLUSIONS: Secular trends were observed with lower serum testosterone in men in 2008, but no effect was seen on the fracture incidence of these fairly young men. In postmenopausal women in 2008, there was a higher fracture incidence along with more vertebral compressions. Lower HRT use, lower serum oestradiol and higher fall risk exposure due with more tranquilisers and leisure time physical activity in 2008 may explain the results.