Body mass index z-scores in the first 2 years of life were associated with adverse metabolic and anthropometric outcomes at 3 years of age.

AIM: We investigated associations between body mass index (BMI) z-scores for children aged 0-2 years and the BMI z-scores, body fat percentage and metabolic risk factors at 3 years of age. METHODS: This was a secondary analysis of the Lifestyle in Pregnancy and Offspring randomised controlled trial, carried out at two university hospitals in Denmark. It comprised 149 mothers with BMI ≥30 kg/m2 who did or did not receive a lifestyle intervention during pregnancy and a reference group of 97 mothers with normal-weight, with follow-up of their 3-year-old offspring. The children in these three groups were pooled for the data analyses, due to similar characteristics between groups. The BMI z-scores were calculated at 5 weeks, 5 months and 1, 2 and 3 years, using Danish reference groups. Their anthropometrics and metabolic outcomes were examined at 3 years of age. RESULTS: BMI z-scores at 5 months to 2 years were associated with BMI z-scores and body fat percentage at 3 years of age and BMI z-scores were not associated with metabolic risk factors at 3 years. CONCLUSION: BMI z-scores from 5 weeks of age were associated with adverse anthropometric outcomes but not with metabolic risk factors at 3 years of age.

High-Sensitivity Cardiac Troponin I Enhances Preeclampsia Prediction Beyond Maternal Factors and the sFlt-1/PlGF Ratio.

BACKGROUND: Preeclampsia shares numerous risk factors with cardiovascular diseases. Here, we aimed to assess the potential utility of high-sensitivity cardiac troponin I (hs-cTnI) values during pregnancy in predicting preeclampsia occurrence. METHODS: This study measured hs-cTnI levels in 3721 blood samples of 2245 pregnant women from 4 international, prospective cohorts. Three analytical approaches were used: (1) a cross-sectional analysis of all women using a single blood sample, (2) a longitudinal analysis of hs-cTnI trajectories in women with multiple samples, and (3) analyses of prediction models incorporating hs-cTnI, maternal factors, and the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio. RESULTS: Women with hs-cTnI levels in the upper quarter had higher odds ratios for preeclampsia occurrence compared with women with levels in the lower quarter. Associations were driven by preterm preeclampsia (odds ratio, 5.78 [95% CI, 2.73-12.26]) and remained significant when using hs-cTnI as a continuous variable adjusted for confounders. Between-trimester hs-cTnI trajectories were independent of subsequent preeclampsia occurrence. A prediction model incorporating a practical hs-cTnI level of detection cutoff (≥1.9 pg/mL) alongside maternal factors provided comparable performance with the sFlt-1/PlGF ratio. A comprehensive model including sFlt-1/PlGF, maternal factors, and hs-cTnI provided added value (cross-validated area under the receiver operator characteristic, 0.78 [95% CI, 0.73-0.82]) above the sFlt-1/PlGF ratio alone (cross-validated area under the receiver operator characteristic, 0.70 [95% CI, 0.65-0.76]; P=0.027). As assessed by likelihood ratio tests, the addition of hs-cTnI to each prediction model significantly improved the respective prediction model not incorporating hs-cTnI, particularly for preterm preeclampsia. Net reclassification improvement analyses indicated that incorporating hs-cTnI improved risk prediction predominantly by correctly reclassifying women with subsequent preeclampsia occurrence. CONCLUSIONS: These exploratory findings uncover a potential role for hs-cTnI as a complementary biomarker in the prediction of preeclampsia. After validation in prospective studies, hs-cTnI, alongside maternal factors, may either be considered as a substitute for angiogenic biomarkers in health care systems where they are sparce or unavailable, or as an enhancement to established prediction models using angiogenic markers.

Gender bias in shared decision-making among cancer care guidelines: A systematic review.

BACKGROUND: In cancer care, the promotion and implementation of shared decision-making in clinical practice guidelines (CPG) and consensus statements may have potential differences by gender. OBJECTIVE: To systematically analyse recommendations concerning shared decision-making in CPGs and consensus statements for the most frequent cancers exclusively among males (prostate) and females (endometrial). SEARCH STRATEGY: We prospectively registered the protocol at PROSPERO (ID: RD42021241127). MEDLINE, EMBASE, Web of Science, Scopus and online sources (8 guideline databases and 65 professional society websites) were searched independently by two reviewers, without language restrictions. INCLUSION CRITERIA: CPGs and consensus statements about the diagnosis or treatment of prostate and endometrial cancers were included from January 2015 to August 2021. DATA EXTRACTION AND SYNTHESIS: Quality assessment deployed a previously developed 31-item tool and differences between the two cancers analysed. MAIN RESULTS: A total of 176 documents met inclusion criteria, 97 for prostate cancer (84 CPGs and 13 consensus statements) and 79 for endometrial cancer (67 CPGs and 12 consensus statements). Shared decision-making was recommended more often in prostate cancer guidelines compared to endometrial cancer (46/97 vs. 13/79, 47.4% vs. 16.5%; p < .001). Compared to prostate cancer guidelines (mean 2.14 items, standard deviation 3.45), compliance with the shared-decision-making 31-item tool was lower for endometrial cancer guidelines (mean 0.48 items, standard deviation 1.29) (p < .001). Regarding advice on the implementation of shared decision-making, it was only reported in 3 (3.8%) endometrial cancer guidelines and in 16 (16.5%) prostate cancer guidelines (p < .001). DISCUSSION AND CONCLUSIONS: We observed a significant gender bias as shared decision-making was systematically more often recommended in the prostate compared to endometrial cancer guidelines. These findings should encourage new CPGs and consensus statements to consider shared decision-making for improving cancer care regardless of the gender affected. PATIENT OR PUBLIC CONTRIBUTION: The findings may inform future recommendations for professional associations and governments to update and develop high-quality clinical guidelines to consider patients' preferences and shared decision-making in cancer care.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes.

OBJECTIVE: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition. METHODS: Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls. RESULTS: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia. CONCLUSION: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.

Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight.

OBJECTIVE: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester. METHODS: We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28-30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval. RESULTS: Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22-2.70) mmHg higher SBP and 1.04 (0.07-2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05-5.25) mmHg higher SBP and 1.94 (0.42-3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance. CONCLUSION: GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.

The COVIDPregDK Study: A national survey on pregnancy during the early COVID-19 pandemic in Denmark.

AIM: We aimed to describe the aim, data collection and content from a survey completed among pregnant women during the first peak of the COVID-19 pandemic in Denmark. METHODS: The declaration of the COVID-19 pandemic in early 2020 challenged pregnant women's mental well-being due to a concern for their unborn child and their need for healthcare services through pregnancy and birth. To explore how the COVID-19 pandemic and the intensified measures such as the lockdown of Denmark impacted pregnant women's well-being and mental health, we conducted a questionnaire survey in the spring of 2020 when the COVID-19 pandemic was at its first peak, and the consequences for pregnant women and the unborn child were very uncertain. All women residing in Denmark and registered with an ongoing pregnancy on 24 April 2020 were invited to participate. The questionnaire included background information, variables on COVID-19 symptoms and validated batteries of questions on loneliness, anxiety, stress, quality of life, meditation and prayers. Additional questions were included to examine concerns related to pregnancy and childbirth during the pandemic. COHORT CHARACTERISTICS: Almost 18,000 women answered the questionnaire, which represents 60% of all invited women who experienced a national lockdown for the first time. Their median age was 30 years, and they were more likely to be multiparous. CONCLUSIONS: Data from the COVIDPregDK Study will enable us to gain valuable knowledge on how the pandemic, the intensified measures from the health authorities and the national lockdown affected pregnant women's mental health and their concerns during the COVID-19 pandemic.

Validation of the Danish version of the Second Victim Experience and Support Tool.

OBJECTIVE: Health-care professionals (HCPs) who are involved in an unanticipated adverse patient event, a medical error or a patient-related injury can become second victims. Being a second victim can lead to various symptoms, affecting the well-being of HCPs and possible turnover intentions or absenteeism. An increasing number of hospitals have implemented a second-victim support programme. To achieve unique insights into what works and what does not work in second-victim support programmes, HCPs' perceptions are needed. The aim of this study was to translate the Second Victim Experience and Support Tool (SVEST) into Danish and test the psychometric properties of the Danish version (D-SVEST). METHODS: The SVEST self-administered questionnaire was translated into Danish following the World Health Organization's guidelines. Assessments of the content validity, construct validity and internal consistency were performed based on 171 participants. RESULTS: The study demonstrated that the D-SVEST is content valid and fits the a priori defined structure. Yet, four items revealed unacceptable factor loadings (<0.4) and item-rest correlations <0.3. All Cronbach's alpha estimates for these five dimensions exceeded 0.70. The dimensions on colleague and institutional support did not contribute to the validity. CONCLUSIONS: In conclusion, the D-SVEST is considered relevant and valid for measuring second-victim experiences and the adequacy of support resources. However, we recommend a modification of items 9 and 25 to enhance the measurement scale in a Danish context. The D-SVEST can be used by health-care management at Danish hospitals.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Vitamin D levels were significantly higher during and after lifestyle intervention in pregnancy: A randomized controlled trial.

INTRODUCTION: Vitamin D deficiency is common in pregnancy, especially in obese women. Lifestyle intervention could potentially result in higher levels of vitamin D. We therefore aimed to study the effect of lifestyle intervention during pregnancy on serum levels of 25-hydroxyvitamin D (25(OH)D). MATERIAL AND METHODS: A total of 360 obese women were randomized before gestational age 14 weeks to lifestyle intervention (diet and exercise) or routine clinical follow up (controls). Clinical outcomes and levels of 25(OH)D were determined three times: At gestational age 12-15 weeks (baseline), gestational age 28-30 weeks and 6 months postpartum. RESULTS: A total of 304 (84%) women completed the intervention study and 238 (66%) attended postpartum follow up. Vitamin D levels were similar in the two groups at baseline. At gestational age 28-30 weeks and 6 months postpartum, 25(OH)D levels were significantly higher in the intervention group than in controls (75.6 vs 66.8 nmol/L, P = 0.009) and (54.8 vs 43.1 nmol/L, P = 0.013), respectively. Concurrently, vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was less frequent in the intervention group than in controls: 15 vs 25% (P = 0.038) at gestational age 28-30 and 45 vs 63% (P = 0.011) 6 months postpartum, respectively. CONCLUSIONS: Lifestyle intervention during pregnancy was associated with significantly increased vitamin D levels in late pregnancy and postpartum compared with controls.

Safety and Efficacy of Tocolytics for the Treatment of Spontaneous Preterm Labour.

BACKGROUND: Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Attempts to reduce the burden may be proactive using biochemical or biophysical prediction and preventative measures. If these efforts fail, then the approach may have to be reactive using tocolytics to inhibit spontaneous preterm labour. OBJECTIVE: We have reviewed the evidence concerning the safety and efficacy of various classes of tocolytic agents. RESULTS: The evidence to support the use of magnesium sulfate or nitric oxide donors as a tocolytic is poor. Compared to placebo or no treatment, there is evidence to support the efficacy of calcium channel blockers (mainly nifedipine), prostaglandin synthetase inhibitors (mainly indomethacin and sulindac), oxytocin receptor antagonists (mainly atosiban) and ß2-agonists (mainly ritodrine, terbutaline, salbutamol and fenoterol). Maternal safety concerns have reduced the use of ß2-agonists. Fetal safety and gestational age restrictions have largely condemned prostaglandin synthetase inhibitors to second-line therapy. First-line therapy in Europe and other parts of the world outside the USA and Australia is limited to calcium channel blockers and oxytocin receptor antagonists. With respect to efficacy, atosiban and nifedipine are similar, but the robustness of the evidence favours atosiban. With respect to safety, atosiban is clearly the safest tocolytic as there are fetomaternal concerns with nifedipine, particularly in high daily doses. CONCLUSION: The perfect tocolytic that is uniformly effective and safe does not exist. Cost, licensing and informed consent are considerations involved in the choice. Efforts continue to develop and introduce other or better agents, including novel compounds such as progesterone, PGF2α antagonists and statins.

Lifestyle Intervention in Danish Obese Pregnant Women With Early Gestational Diabetes Mellitus According to WHO 2013 Criteria Does Not Change Pregnancy Outcomes: Results From the LiP (Lifestyle in Pregnancy) Study.

OBJECTIVE: To study effects of lifestyle intervention on metabolic and clinical outcomes in obese women fulfilling the World Health Organization (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) in early gestation. RESEARCH DESIGN AND METHODS: Secondary analysis of data from the Lifestyle in Pregnancy (LiP) study, a lifestyle randomized controlled trial in 304 pregnant women with BMI ≥30 kg/m2. Early GDM (week 12-15) was diagnosed according to modified WHO 2013 GDM criteria: fasting venous plasma glucose ≥5.1 mmol/L and/or 2-h capillary blood glucose (CBG) ≥8.5 mmol/L (75-g oral glucose tolerance test [OGTT]). Women with treated GDM fulfilling local Danish GDM criteria (2-h CBG ≥9.0 mmol/L) (n = 16) and women with normal OGTT (n = 198) were excluded. RESULTS: Of 90 women with early GDM, 36 received lifestyle intervention and 54 standard care. All were Caucasian, and median age was 29 years (interquartile range 27-33) and BMI 34.5 kg/m2 (32.3-38.1). All baseline characteristics were similar in the lifestyle intervention and standard care groups. At gestational week 28-30, the women in the lifestyle intervention group had significantly higher fasting total cholesterol and fasting LDL. All other metabolic parameters including measurements of glucose, insulin, and HOMA of insulin resistance were similar. There were more planned cesarean sections in the lifestyle intervention group (22.2 vs. 5.6%), but all other obstetric outcomes were similar. CONCLUSIONS: Lifestyle intervention in obese women fulfilling WHO 2013 GDM criteria in early pregnancy was not effective in improving obstetric or metabolic outcomes. Future studies should focus on interventions starting prepregnancy.

Urine exosomes from healthy and hypertensive pregnancies display elevated level of α-subunit and cleaved α- and γ-subunits of the epithelial sodium channel-ENaC.

Preeclampsia is characterized by hypertension, proteinuria, suppression of plasma renin-angiotensin-aldosterone, and impaired urine sodium excretion. Aberrantly filtered plasmin in urine may activate proteolytically the γ-subunit of the epithelial sodium channel (ENaC) and promote Na+ reabsorption and urine K+ loss. Plasma and urine was sampled from patients with preeclampsia, healthy pregnant controls and non-pregnant women, and from patients with nephrostomy catheters. Aldosterone concentration, urine plasminogen, and protein were determined. Exosomes were isolated by ultracentrifugation. Immunoblotting was used to detect exosome markers; γ-ENaC (two different epitopes within the inhibitory peptide tract), α-ENaC, and renal outer medullary K-channel (ROMK) and compared with human kidney cortex homogenate. Urine total plasmin(ogen) was significantly increased in preeclampsia, plasma and urine aldosterone was higher in pregnancy compared to non-pregnancy, and the urine Na/K ratio was lower in preeclampsia compared to healthy pregnancy. Exosome markers ALIX and AQP-2 were stably associated with exosomes across groups. Exosomal α-ENaC-subunit migrated at 75 kDa and dominantly at 50 kDa and was significantly elevated in pregnancy. In human kidney cortex tissue and two of four pelvis catheter urine, ~90-100 kDa full-length γ-ENaC was detected while no full-length γ-ENaC but 75, 60, and 37 kDa variants dominated in voided urine exosomes. There was no difference in γ-ENaC protein abundances between healthy pregnancy and preeclampsia. ROMK was detected inconsistently in urine exosomes. Pregnancy and preeclampsia were associated with increased abundance of furin-cleaved α-ENaC subunit while γ-subunit appeared predominantly in cleaved form independently of conditions and with a significant contribution from post-renal cleavage.

Public health benefits of hair-mercury analysis and dietary advice in lowering methylmercury exposure in pregnant women.

AIMS: To evaluate whether a public health intervention using focused dietary advice combined with a hair-mercury analysis can lower neurotoxic methylmercury exposure among pregnant women without decreasing their overall intake of seafood. METHODS: A total of 146 pregnant women were consecutively recruited from the antenatal clinic at a Danish university hospital at their initial ultrasound scan. Dietary advice was provided on avoiding methylmercury exposure from large predatory fish and a hair sample from each participant was analysed for mercury, with the results being communicated shortly thereafter to the women. A dietary questionnaire was filled in. Follow-up three months later included a dietary questionnaire and a repeat hair-mercury analysis. RESULTS: In the follow-up group, 22% of the women had hair-mercury concentrations above a safe limit of 0.58 µg/g at enrolment, decreasing to 8% three months later. Average hair-mercury concentrations decreased by 21%. However, the total seafood intake remained at the same level after three months. CONCLUSIONS: Increased exposure to methylmercury among pregnant women is an important public health concern in Denmark. The observed lowering of hair-mercury concentrations associated with dietary advice corresponds to a substantial public health benefit that probably makes such an intervention highly profitable.

The treatment of bacterial vaginosis in pregnancy with clindamycin to reduce the risk of infection-related preterm birth: a response to the Danish Society of Obstetrics and Gynecology guideline group's clinical recommendations.

Preterm birth is the major cause of perinatal mortality and morbidity worldwide. Infection/inflammation is responsible for a significant percentage of preterm birth, particularly at early gestations. A recent clinical recommendation by a guidelines group of the Danish Society of Obstetrics and Gynecology advised against the use of clindamycin for the treatment of bacterial vaginosis in pregnancy to reduce the risk of spontaneous preterm birth based on lack of evidence of efficacy. We believe that the evidence for the use of clindamycin for this indication is robust and that this recommendation was reached erroneously on the basis of flawed inclusion criteria: the inclusion of an unpublished study with poorly diagnosed bacterial vaginosis and the exclusion of an important pivotal study on the use of clindamycin in early pregnancy for the prevention of preterm birth. Had these errors been corrected, the conclusions would have been different.

Validation of hospital discharge diagnoses for hypertensive disorders of pregnancy.

INTRODUCTION: A correct diagnosis of preeclampsia and gestational hypertension is important for treatment and epidemiological studies. Changes in diagnostic criteria and underreporting in certain subsets of patients may hamper validity of the diagnoses. MATERIALS AND METHODS: We validated the discharge diagnoses of preeclampsia and gestational hypertension, which are reported to the Danish National Patient Registry, in a cohort of 2163 pregnant women by retrospective evaluation of electronic hospital data. RESULTS: A preeclampsia discharge diagnosis was found in 113 (5.2%) of the participants. After validation, significantly more patients fulfilled criteria for diagnosis of preeclampsia (n = 163, 7.5%, p = 0.002); more had severe preeclampsia, 14 (0.6%) vs. 70 (3.2%), p < 0.001 and gestational hypertension, 62 (2.9%) vs. 46 (2.1%), p = 0.12. The diagnostic sensitivity for preeclampsia by discharge diagnosis was 55.8%; severe preeclampsia 18.6%; gestational hypertension 39.1%. Corresponding positive predictive values were 80.5, 92.9 and 29.0%. Misclassification occurred in 4.3, 2.7 and 3.3%, respectively. Misclassification was more prevalent in obese compared to lean women (10% vs. 3.6%, p < 0.0001). CONCLUSIONS: Discharge diagnoses substantially underestimated the prevalence of preeclampsia, especially severe preeclampsia. Misclassification was most common in obese preeclamptic women. These findings depict the limitations associated with the direct use of discharge diagnoses of hypertensive disorders in pregnancy for research purposes.

Blame and guilt - a mixed methods study of obstetricians' and midwives' experiences and existential considerations after involvement in traumatic childbirth.

INTRODUCTION: When complications arise in the delivery room, midwives and obstetricians operate at the interface of life and death, and in rare cases the infant or the mother suffers severe and possibly fatal injuries related to the birth. This descriptive study investigated the numbers and proportions of obstetricians and midwives involved in such traumatic childbirth and explored their experiences with guilt, blame, shame and existential concerns. MATERIAL AND METHODS: A mixed methods study comprising a national survey of Danish obstetricians and midwives and a qualitative interview study with selected survey participants. RESULTS: The response rate was 59% (1237/2098), of which 85% stated that they had been involved in a traumatic childbirth. We formed five categories during the comparative mixed methods analysis: the patient, clinical peers, official complaints, guilt, and existential considerations. Although blame from patients, peers or official authorities was feared (and sometimes experienced), the inner struggles with guilt and existential considerations were dominant. Feelings of guilt were reported by 36-49%, and 50% agreed that the traumatic childbirth had made them think more about the meaning of life. Sixty-five percent felt that they had become a better midwife or doctor due to the traumatic incident. CONCLUSIONS: The results of this large, exploratory study suggest that obstetricians and midwives struggle with issues of blame, guilt and existential concerns in the aftermath of a traumatic childbirth.

Prostasin and matriptase (ST14) in placenta from preeclamptic and healthy pregnant women.

OBJECTIVE: Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, and aldosterone. Regulated activity of tissue serine proteases, prostasin, and matriptase is necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia is associated with low prostasin expression in placenta and spillover of prostasin into urine across the defect glomerular barrier. METHODS: In a cross-sectional study, 20 healthy pregnant women and 20 patients suspected of preeclampsia were included. Plasma and urine was obtained before delivery, and placental biopsies were taken immediately after delivery (mean gestational age: control 39 and preeclampsia 38 weeks). RESULTS: Patients with preeclampsia displayed lower levels of aldosterone in plasma and in spot urine normalized for creatinine (P = 0.0001). Prostasin, matriptase, hepatocyte growth factor activator inhibitor type 1 (HAI-1) and 2, and nexin-1 mRNA abundances were not different in placental tissue between groups. Prostasin mRNA in placenta correlated directly with nexin-1 and HAI-1 mRNA, but not with matriptase mRNA. Plasma prostasin and placental homogenate prostasin and nexin-1 protein levels did not differ between groups. Activated, arginine 614 (Arg614)-cleaved matriptase was not detectable in placentas. Western blotting showed significant elevated levels of prostasin in urine from preeclamptic patients that correlated with urine albumin. Placenta and plasma prostasin did not correlate to aldosterone or placental weight. CONCLUSION: Preeclampsia is not associated with altered prostasin in placenta or plasma at term, but with increased prostasin in urine. An impact of prostasin-matriptase on placental development is likely to be at the level of activity and not protein abundance.