The Norwegian PraksisNett: a nationwide practice-based research network with a novel IT infrastructure.

PURPOSE: Clinical research in primary care is relatively scarce. Practice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary care. In Norway, almost all 5.4 million inhabitants have access to a general practitioner (GP) through a patient-list system. This gives opportunity for a PBRN with reliable information about the general population. The aim of the current paper is to describe the establishment, organization and function of PraksisNett (the Norwegian Primary Care Research Network). MATERIALS AND METHODS: We describe the development, funding and logistics of PraksisNett as a nationwide PBRN. RESULTS: PraksisNett received funding from the Research Council of Norway for an establishment period of five years (2018-2022). It is comprised of two parts; a human infrastructure (employees, including academic GPs) organized as four regional nodes and a coordinating node and an IT infrastructure comprised by the Snow system in conjunction with the Medrave M4 system. The core of the infrastructure is the 92 general practices that are contractually linked to PraksisNett. These include 492 GPs, serving almost 520,000 patients. Practices were recruited during 2019-2020 and comprise a representative mix of rural and urban settings spread throughout all regions of Norway. CONCLUSION: Norway has established a nationwide PBRN to reduce hurdles for conducting clinical studies in primary care. Improved infrastructure for clinical studies in primary care is expected to increase the attractiveness for studies on the management of disorders and diseases in primary care and facilitate international research collaboration. This will benefit both patients, GPs and society in terms of improved quality of care.Key pointsPractice-based research networks (PBRNs) are research infrastructures to overcome hurdles associated with conducting studies in primary careImproved infrastructure for clinical studies in primary care is expected to increase the attractiveness for studies on the management of disorders and diseases in primary care and facilitate international research collaborationWe describe PraksisNett, a Norwegian PBRN consisting of 92 general practices including 492 GPs, serving almost 520,000 patientsAn advanced and secure IT infrastructure connects the general practices to PraksisNett and makes it possible to identify and recruit patients in a novel way, as well as reuse clinical dataPraksisNett will benefit both patients, GPs and society in terms of improved quality of careThis paper may inform and inspire initiatives to establish PBRNs elsewhere.

Why do doctors in Norway choose general practice and remain there? A qualitative study about motivational experiences.

Objective: To explore experiences motivating doctors to become and remain GPs.Design and contributors: Qualitative analysis of written responses from an open-ended question about motivational experiences posted on an internet discussion list for GPs in Norway. Texts from 25 contributors were analysed with Systematic Text Condensation, supported by theories about calling as motivation.Results: Analysis revealed numerous aspects of motivation to become and remain a general practitioner. Inspirations from early experiences and skilled role models had conveyed values and offered insight into a fascinating world of care, gratitude and respect. Close and continuous relationships with patients provided GPs with humbling experiences and learning moments. Contributors described how these encounters became rewarding sources of insight and mutual trust, improving interpersonal skills. Also, the extensive variety of tasks during the workday and the space for autonomy and independence was emphasised.Implications: Understanding motivational experiences influencing GPs' choice of medical career is necessary to develop strategies for recruitment and stability and contribute to prevention of burn-out and improper work-life balance. GPs' professional identities and commitments should be recognized and developed in dialogues between authorities and GPs to enhance communication, improve the structural frames of work environment and thereby sustainable recruitment.Key pointsGPs regard their choice of medical career as strongly influenced by motivational experiences in childhood, adolescence and as medical studentsRole models, diversity of work, feelings of being able to contribute and rewarding and continuous relationships with patients were mentioned to activate and maintain general practice commitmentKnowledge about motivational influences, professional identities and commitment for GPs is crucial for medical education and dialogue to promote general practice as a career choice and prevent dangers of work overload and burnout.

Do you recommend cancer screening to your patients? A cross-sectional study of Norwegian doctors.

OBJECTIVE: Guidelines for cancer screening have been debated and are followed to varying degrees. We wanted to study whether and why doctors recommend disease-specific cancer screening to their patients. DESIGN: Our cross-sectional survey used a postal questionnaire. The data were examined with descriptive methods and binary logistic regression. SETTING: We surveyed doctors working in all health services. PARTICIPANTS: Our participants comprised a representative sample of Norwegian doctors in 2014/2015. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is whether doctors reported recommending their patients get screening for cancers of the breast, colorectum, lung, prostate, cervix and ovaries. We examined doctors' characteristics predicting adherence to the guidelines, including gender, age, and work in specialist or general practice. The secondary outcomes are reasons given for recommending or not recommending screening for breast and prostate cancer. RESULTS: Our response rate was 75% (1158 of 1545). 94% recommended screening for cervical cancer, 89% for breast cancer (both established as national programmes), 42% for colorectal cancer (upcoming national programme), 41% for prostate cancer, 21% for ovarian cancer and 17% for lung cancer (not recommended by health authorities). General practitioners (GPs) adhered to guidelines more than other doctors. Early detection was the most frequent reason for recommending screening; false positives and needless intervention were the most frequent reasons for not recommending it. CONCLUSIONS: A large majority of doctors claimed that they recommended cancer screening in accordance with national guidelines. Among doctors recommending screening contrary to the guidelines, GPs did so to a lesser degree than other specialties. Different expectations of doctors' roles could be a possible explanation for the variations in practice and justifications. The effectiveness of governing instruments, such as guidelines, incentives or reporting measures, can depend on which professional role(s) a doctor is loyal to, and policymakers should be aware of these different roles in clinical governance.

Variations in serum concentrations of selected organochlorines among delivering women in Argentina. The EMASAR study.

The EMASAR study is the first study to describe the body burden of OCs in Argentinian women after delivery. In total, 698 maternal serum samples from Salta (n = 498) and Ushuaia (n = 200) were collected in 2011-2012 and analyzed for a total of 7 polychlorinated biphenyls (PCBs) and 12 pesticide-related compounds. Only 11 of the compounds had detection rates above 60% in one or both places. Compared with Ushuaian women, those from Salta exhibited higher lipid-adjusted concentrations of p,p'-DDE, p,p'-DDT, ß-HCH, and PCB 118 (p ≤ 0.003), with no differences in concentrations of PCB 153 and 138. After controlling for age, parity and heritage (born in the province or migrated there from other regions of Argentina), concentrations of p,p'-DDE, p,p'-DDT, ß-HCH and all PCBs were significantly higher in Salta natives compared with Ushuaia natives or migrants (p ≤ 0.010). No variations between native and migrated Ushuaian women were observed other than for PCB 153 (6.1 versus 8.6 µg kg-1 lipid, p = 0.022). Age was generally associated positively with the body burden of nearly all OCs and parity negatively so, with p,p'-DDD, o,p'-DDT, and o,p'-DDD residues and α-HCH in Ushuaia being the exceptions. The regional differences in OC concentrations are explained by contrasting domestic sources, historical and current uses, industrial emissions, dietary patterns and lifestyle factors, as well as long-range-transport. The relatively high PCB 118/PCB 180 ratio observed for both Argentinian communities likely reflects the use of technical mixtures with congener-specific composition. In a comprehensive comparison with other countries, the Argentinian OC concentrations were mostly in the lower range. It is concluded that a latitude effect equivalent to that operative in the Arctic region seems unlikely.

What happens when the doctor denies a patient's request? A qualitative interview study among general practitioners in Norway.

OBJECTIVE: To explore general practitioners (GPs') experiences from consultations when a patient's request is denied, and outcomes of such incidents. DESIGN AND PARTICIPANTS: We conducted a qualitative study with semi-structured individual interviews with six GPs in Norway. We asked them to tell about experiences from specific encounters where they had refused a patient's request. The texts were analysed with Systematic Text Condensation, a method for thematic cross-case analysis. MAIN OUTCOME MEASURES: Accounts of experiences from consultations when GPs refused their patients' requests. RESULTS: Subjects of dispute included clinical topics like investigation and treatment, certification regarding welfare benefits and medico-legal issues, and administrative matters. The arguments took different paths, sometimes settled by reaching common ground but more often as unresolved disagreement with anger or irritation from the patient, sometimes with open hostility and violence. The aftermath and outcomes of these disputes lead to strong emotional impact where the doctors reflected upon the incidents and sometimes regretted their handling of the consultation. Some long-standing and close patient-doctor relationships were injured or came to an end. CONCLUSIONS: The price for denying a patient's request may be high, and GPs find themselves uncomfortable in such encounters. Skills pertaining to this particular challenge could be improved though education and training, drawing attention to negotiation of potential conflicts. Also, the notion that doctors have a professional commitment to his or her own autonomy and to society should be restored, through increased emphasis on core professional ethics in medical education at all levels.

Suggested Cut-Off Values for Vitamin D as a Risk Marker for Total and Cardiac Death in Patients with Suspected Acute Coronary Syndrome.

BACKGROUND: Several studies have demonstrated an association between low vitamin D levels and cardiovascular risk. Vitamin D cut-off levels are still under debate. OBJECTIVES: To assess two cut-off levels, 40 and 70 nmol/L, respectively, for vitamin D measured as 25-hydroxyvitamin D in chest pain patients with suspected acute coronary syndrome. METHODS: We investigated 1853 patients from coastal-Norway and inland Northern-Argentina. A similar database was used for pooling of data. Two-year follow-up data including all-cause mortality, cardiac death, and sudden cardiac death in the total patient population were analyzed, applying univariate and multivariable analysis. RESULTS: Two hundred fifty-five patients with known vitamin D concentrations died. In the multivariable analysis, there was a decrease in total mortality above a cut-off level of 40 nmol/L and a decrease in cardiac death above a cut-off level of 70 nmol/L [HRs of 0.66 (95% CI, 0.50-0.88), p = 0.004 and 0.46 (95% CI, 0.22-0.94), p = 0.034, respectively]. CONCLUSION: Vitamin D cut-off levels of 40 and 70 nmol/L were related to total mortality and cardiac death, respectively.

Borderline Values of Troponin-T and High Sensitivity C-Reactive Protein Did Not Predict 2-Year Mortality in TnT Positive Chest-Pain Patients, Whereas Brain Natriuretic Peptide Did.

BACKGROUND: Troponin-T (TnT), high-sensitive C-reactive protein (hsCRP), and Brain Natriuretic Peptide (BNP) have been shown to be independent prognostic indicators of total and cardiac death during short- and long-term follow-up. METHODS: We investigated prospectively the prognostic value of admission samples of TnT, hsCRP, and BNP in 871 chest-pain patients from South-Western Norway and 982 patients from Northern Argentina, based on a similar protocol and database setup. Follow-up was 2 years for the pooled population. The prognostic value of the selected biomarkers was investigated in quartiles of 239 patients with TnT values greater than 0.01 and up to and including 0.1 ng/mL, with continuous TnT as a potential confounder. RESULTS: After 24 months, 69 patients had died, of whom 38 died from cardiac causes. In the selected range of TnT, this biomarker was not significantly different between patients who died and survived (mean 0.0452 and 0.0457, p = 0.887). The BNP levels were significantly higher among patients dying than in long-term survivors [340 (142-656) versus 157 (58-367) pg/mL (median, 25 and 75% percentiles), p < 0.001]. In a multivariable Cox regression model for death within 2 years, the hazard ratio (HR) for BNP in the highest quartile (Q4) as compared to the lowest (Q1) was significantly related to total mortality [HR 2.84 (95% confidence interval (CI), 1.13-7.17)], p = 0.027, in addition to age (p ≤ 0.001) and hypercholesterolemia (p = 0.043). For cardiac death, the HR for BNP was 5.18 (95% CI, 1.06-25.3), p = 0.042. Several other variables (age, congestive heart failure, ST elevation myocardial infarction, and study country) were also significantly related to cardiac death. In a multivariable Cox regression model, hsCRP rendered no significant prognostic information for all-cause mortality (p = 0.089) or for cardiac mortality (p = 0.524). CONCLUSION: In patients with borderline TnT values (greater than 0.01 and up to and including 0.1 ng/mL), this biomarker as well as hsCRP did not render prognostic information, whereas BNP was found to be a strong prognostic indicator of 2-year total and cardiac mortality.

GPs' negotiation strategies regarding sick leave for subjective health complaints.

OBJECTIVES: To explore general practitioners' (GPs') specific negotiation strategies regarding sick-leave issues with patients suffering from subjective health complaints. DESIGN: Focus-group study. SETTING: Nine focus-group interviews in three cities in different regions of Norway. PARTICIPANTS: 48 GPs (31 men, 17 women; age 32-65), participating in a course dealing with diagnostic practice and assessment of sickness certificates related to patients with subjective health complaints. RESULTS: The GPs identified some specific strategies that they claimed to apply when dealing with the question of sick leave for patients with subjective health complaints. The first step would be to build an alliance with the patient by complying with the wish for sick leave, and at the same time searching for information to acquire the patient's perspective. This position would become the basis for the main goal: motivating the patient for a rapid return to work by pointing out the positive effects of staying at work, making legal and moral arguments, and warning against long-term sick leave. Additional solutions might also be applied, such as involving other stakeholders in this process to provide alternatives to sick leave. CONCLUSIONS AND IMPLICATIONS: GPs seem to have a conscious approach to negotiations of sickness certification, as they report applying specific strategies to limit the duration of sick leave due to subjective health complaints. This give-and-take way of handling sick-leave negotiations has been suggested by others to enhance return to work, and should be further encouraged. However, specific effectiveness of this strategy is yet to be proven, and further investigation into the actual dealings between doctor and patients in these complex encounters is needed.

In utero preeclampsia exposure, milk intake and pubertal development.

Cord blood insulin-like growth factor-1 (IGF-1) concentrations are lower in preeclamptic (PE) than normotensive (NT) pregnancies. PE offspring have increased risk of cardiovascular disease and decreased risk of some cancers including breast. We examined the effects of PE exposure in utero, infant feeding and childhood diet at 3-5 years on IGF-1 and breast development in 194 female offspring who were followed from birth until follow-ups at 10.8 and 12.9 years. Diet was not associated with serum IGF-1 levels at 10.8 years. PE exposure was associated with reduced odds of thelarche at 10.8 years only among exclusively breastfed girls. Milk, butter and ice cream consumption at 3-5 years was inversely related to the OR of breast development at 10.8 years. Child's weight and maternal overweight were positively associated with breast development at 10.8 years; child's height and weight were positively associated with breast development at 12.9 years.

Vitamin d predicts all-cause and cardiac mortality in females with suspected acute coronary syndrome: a comparison with brain natriuretic Peptide and high-sensitivity C-reactive protein.

Vitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 ± 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33-0.93), 0.29 (95% CI 0.15-0.55), and 0.13 (95% CI 0.06-0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS.

Socioeconomic assessment and impact of social security on outcome in patients admitted with suspected coronary chest pain in the city of salta, Argentina.

Low socioeconomic status is associated with increased mortality from coronary heart disease. We assessed total mortality, cardiac death, and sudden cardiac death (SCD) in relation to socioeconomic class and social security in 982 patients consecutively admitted with suspected coronary chest pain, living in the city of Salta, northern Argentina. Patients were divided into three socioeconomic classes based on monthly income, residential area, and insurance coverage. Five-year follow-up data were analyzed accordingly, applying univariate and multivariate analyses. At follow-up, 173 patients (17.6%) had died. In 92 patients (9.4%) death was defined as cardiac, of whom 59 patients (6.0%) were characterized as SCD. In the multivariate analysis, the hazard ratios (HRs) for all-cause and cardiac mortality in the highest as compared to the lowest socioeconomic class were 0.42 (95% confidence interval (CI), 0.22-0.80), P = 0.008, and 0.39 (95% CI, 0.15-0.99), P = 0.047, respectively. Comparing patients in the upper socioeconomic class to patients without healthcare coverage, HRs were 0.46 (95% CI, 0.23-0.94), P = 0.032, and 0.37 (95% CI, 0.14-1.01), P = 0.054, respectively. In conclusion, survival was mainly tied to socioeconomic inequalities in this population, and the impact of a social security program needs further attention.

Omega-3 index and prognosis in acute coronary chest pain patients with a low dietary intake of omega-3.

BACKGROUND: The omega-3 index (eicosapentaenoic acid + docosahexaenoic acid) content in red blood cell membranes has been suggested as a novel risk marker for cardiac death. Objective. To assess the ability of the omega-3 index to predict all-cause mortality, cardiac death and sudden cardiac death following hospitalization with an acute coronary syndrome (ACS), and to include arachidonic acid (AA) in risk assessment. MATERIAL AND METHODS: The omega-3 index was measured in 572 consecutive patients (median 63 years and 59% males) admitted with chest pain and suspected ACS in an inland Northern Argentinean city with a dietary habit that was essentially based on red meat and a low intake of fish. Clinical endpoints were collected during a 5-year follow-up period, median 3.6 years, range 1 day to 5.5 years. Stepwise Cox regression analysis was employed to compare the rate of new events in the quartiles of the omega-3 index measured at inclusion. Multivariable analysis was performed. RESULTS: No statistical significant differences in baseline characteristics were noted between quartiles of the omega-3 index. The median of the adjusted omega-3 index was 3.6%. During the follow-up period, 100 (17.5%) patients died. Event rates were similar in all quartiles of the omega-3 index, with no statistical significant differences. AA added no prognostic information. CONCLUSION: In a population with a low intake of fish and fish oils, the adjusted omega-3 index did not predict fatal events following hospitalization in patients with acute chest pain and suspected ACS.

Serum 25(OH)D is a 2-year predictor of all-cause mortality, cardiac death and sudden cardiac death in chest pain patients from Northern Argentina.

BACKGROUND: Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. METHODS: We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. RESULTS: There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19-0.73), p = 0.004, 0.23 (95% CI, 0.08-0.67), p = 0.007, and 0.32 (95% CI, 0.11-0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10-0.54), p = 0.001, 0.18 (95% CI, 0.05-0.60), p = 0.006 and 0.25 (95% CI, 0.07-0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. CONCLUSION: Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. TRIAL REGISTRATION: ClinicalTrials.gov NCT01377402.

B-type natriuretic peptide and high sensitive C-reactive protein predict 2-year all cause mortality in chest pain patients: a prospective observational study from Salta, Argentina.

BACKGROUND: Several mechanisms are involved in the pathophysiology of the Acute Coronary Syndrome (ACS). We have addressed whether B-type natriuretic peptide (BNP) and high-sensitive C-reactive protein (hsCRP) in admission samples may improve risk stratification in chest pain patients with suspected ACS. METHODS: We included 982 patients consecutively admitted with chest pain and suspected ACS at nine hospitals in Salta, Northern Argentina. Total and cardiac mortality were recorded during a 2-year follow up period. Patients were divided into quartiles according to BNP and hsCRP levels, respectively, and inter quartile differences in mortality were statistically evaluated applying univariate and multivariate analyses. RESULTS: 119 patients died, and the BNP and hsCRP levels were significantly higher among these patients than in survivors. In a multivariable Cox regression model for total death and cardiac death in all patients, the hazard ratio (HR) in the highest quartile (Q4) as compared to the lowest quartile (Q1) of BNP was 2.32 (95% confidence interval (CI), 1.24-4.35), p = 0.009 and 3.34 (95% CI, 1.26-8.85), p = 0.015, respectively. In the TnT positive patients (TnT > 0.01 ng/mL), the HR for total death and cardiac death in Q4 as compared to Q1 was 2.12 (95% CI, 1.07-4.18), p = 0.031 and 3.42 (95% CI, 1.13-10.32), p = 0.029, respectively.The HR for total death for hsCRP in Q4 as compared to Q1 was 1.97 (95% CI, 1.17-3.32), p = 0.011, but this biomarker did not predict cardiac death (p = 0.21). No prognostic impact of these two biomarkers was found in the TnT negative patients. CONCLUSION: BNP and hsCRP may act as clinically useful biomarkers when obtained at admission in a population with suspected ACS.

Pubertal development in daughters of women with pre-eclampsia.

OBJECTIVE: To compare clinical signs of puberty onset in daughters of pre-eclampsia and normotensive pregnancies. DESIGN: Population based follow-up study. METHODS: In a cohort of 120 daughters of pre-eclampsia pregnancies and 203 daughters of pregnancies without pre-eclampsia, pubic hair growth and breast development were assessed at 11, 12 and 13 years of age by Tanner scores and by self-assessment. RESULTS: Compared to the normotensive group, pubic hair growth (pubarche) more often preceded breast development (thelarche) (risk ratio (RR) 2.3, 95% CI 1.3 to 4.1) and thelarche less often preceded pubarche (RR 0.8, 95% CI 0.7 to 1.0) in daughters of pre-eclampsia pregnancies. Adjustment for birth weight and body mass index in early adolescence did not substantially influence these results, but increasing severity of pre-eclampsia strengthened the differences. CONCLUSIONS: Pubarche tends to precede thelarche in daughters of pre-eclampsia pregnancies compared to daughters of normotensive pregnancies. This may reflect a stronger androgenic influence in daughters of pre-eclampsia pregnancies at the beginning of puberty.

Considerations made by the general practitioner when dealing with sick-listing of patients suffering from subjective and composite health complaints.

OBJECTIVES: To explore GPs' considerations in decision-making regarding sick-listing of patients suffering from SHC. DESIGN: Qualitative analysis of data from nine focus-group interviews. SETTING: Three cities in different regions of Norway. Participants. A total of 48 GPs (31 men, 17 women; aged 32-65) participated. The GPs were recruited when invited to a course dealing with diagnostic practice and assessment of sickness certificates related to patients with composite SHCs. RESULTS: Decisions on sick-listing patients with SHCs were regarded as a very challenging task. Trust in the patient's own story and self-judgement was deemed crucial, but many GPs missed hard evidence of illness and loss of function. Several factors that might influence decision-making were identified: the patients' ability to present their story to evoke sympathy, the GP's prior knowledge of the patient, and the GPs' own experience as a patient and their tendency to avoid conflicts. The approach to the task of sick-listing differed from patient-led cooperation to resistant confrontation. CONCLUSION AND IMPLICATIONS: Issuing sickness certification in patients with composite health complaints is considered challenging and burdensome. It is seen as mainly patient-driven, and the decisions vary according to GPs' attitudes, beliefs, and personalities. Guiding the GPs to a more focused awareness of the decision process should be considered.

Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data.

BACKGROUND: Preeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia. METHODS: Three haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata. RESULTS: We found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33). CONCLUSION: Our findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.

Preeclampsia and adiponectin in cord blood.

AIMS: To compare cord blood concentrations of total adiponectin in the offspring of pregnancies with and without preeclampsia. METHODS: Using a Luminex analyzer, cord blood adiponectin was measured in 182 singleton pregnancies with preeclampsia and compared to adiponectin measured in 511 singleton pregnancies without preeclampsia. RESULTS: Adiponectin levels in cord blood increased with increasing gestational age, but overall, crude levels were similar in pregnancies with and without preeclampsia. However, in pregnancies with early delivery (weeks 32-36), and in pregnancies with delivery after spontaneous contractions, adiponectin levels were higher in the preeclampsia group. CONCLUSION: In preterm pregnancies and in pregnancies with spontaneous contractions, adiponectin levels in cord blood were higher in the preeclampsia group than in pregnancies without preeclampsia, maybe reflecting the need to optimize energy in preeclampsia.

Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies.

OBJECTIVE: To compare blood pressure (BP) in adolescence (11-12 years) among the offspring of preeclamptic and normotensive pregnancies. METHOD: SBP and DBP of 181 girls and boys born after pregnancies with preeclampsia were measured and compared with the BP of 356 age-matched girls and boys of normotensive pregnancies. The association of preeclampsia with later BP was adjusted for perinatal information, anthropometric factors at follow-up, and maternal BP and BMI. RESULTS: In the preeclampsia group, SBP in early adolescence was higher than in the normotensive group (115.3 vs. 113.5 mmHg, P = 0.03), but there was no difference in DBP (66.4 vs. 65.3 mmHg, P = 0.10). After adjustment for maternal body mass and BP, the difference in SBP was largely attenuated. CONCLUSION: The higher SBP among adolescent offspring of preeclamptic pregnancies could be mediated by maternal body mass or BP, factors that are positively associated with the risk of preeclampsia in pregnancy.