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We use a large and heterogeneous sample of the Danish population to investigate the importance of distributional preferences for behavior in a trust game and a public good game. We find robust evidence for the significant explanatory power of distributional preferences. In fact, compared to twenty-one covariates, distributional preferences turn out to be the single most important predictor of behavior. Specifically, subjects who reveal benevolence in the domain of advantageous inequality are more likely to pick the trustworthy action in the trust game and contribute more to the public good than other subjects. Since the experiments were spread out more than one year, our results suggest that there is a component of distributional preferences that is stable across games and over time.

One strategy for improving detection of fetal growth restriction (FGR) is developing biosensors identifying placental dysfunction as a leading pathogenesis for FGR. The aim of this pilot study was to investigate the performance of a biosensor specified to detect placental dysfunction by means of maternal arterial turbulence acoustics in a low-resource setting. A cohort of 147 singleton pregnant women were prospectively followed with double-blinded biosensor tests, sonographic estimation of fetal weight (EFW) and Doppler flow at 26–28, 32–34 and 37–39 weeks of pregnancy. Full term live births with recorded birth weights (BWs) and without major congenital malformations were included. Outcomes were defined as (A) a solitary biometric measure (BW &lt, 3rd centile) and as (B) a biometric measure and contributory functional measure (BW &lt, 10th centile and antenatally detected umbilical artery pulsatility index &gt, 95th centile). Data from 118 women and 262 antenatal examinations were included. Mean length of pregnancy was 40 weeks (SD ± 8 days), mean BW was 3008 g (SD ± 410 g). Outcome (A) was identified in seven (6%) pregnancies, whereas outcome (B) was identified in one (0.8%) pregnancy. The biosensor tested positive in five (4%) pregnancies. The predictive performance for outcome (A) was sensitivity = 0.29, specificity = 0.97, p = 0.02, positive predictive value (PPV) was 0.40 and negative predictive value (NPV) was 0.96. The predictive performance was higher for outcome (B) with sensitivity = 1.00, specificity = 0.97, p = 0.04, PPV = 0.20 and NPV = 1.00. Conclusively, these pilot-study results show future potential for biosensors as screening modality for FGR in a low-resource setting.

Context The mechanisms underlying Roux-en-Y gastric bypass (RYGB) surgery-induced weight loss and the immediate postoperative beneficial metabolic effects associated with the operation remain uncertain. Enteroendocrine cell (EEC) secretory function has been proposed as a key factor in the marked metabolic benefits from RYGB surgery. Objective To identify novel gut-derived peptides with therapeutic potential in obesity and/or diabetes by profiling EEC-specific molecular changes in obese patients following RYGB-induced weight loss. Subjects and Methods Genome-wide expression analysis was performed in isolated human small intestinal EECs obtained from 20 gut-biopsied obese subjects before and after RYGB. Targets of interest were profiled for preclinical and clinical metabolic effects. Results Roux-en-Y gastric bypass consistently increased expression levels of the inverse ghrelin receptor agonist, liver-expressed antimicrobial peptide 2 (LEAP2). A secreted endogenous LEAP2 fragment (LEAP238-47) demonstrated robust insulinotropic properties, stimulating insulin release in human pancreatic islets comparable to the gut hormone glucagon-like peptide-1. LEAP238-47 showed reciprocal effects on growth hormone secretagogue receptor (GHSR) activity, suggesting that the insulinotropic action of the peptide may be directly linked to attenuation of tonic GHSR activity. The fragment was infused in healthy human individuals (n = 10), but no glucoregulatory effect was observed in the chosen dose as compared to placebo. Conclusions Small intestinal LEAP2 expression was upregulated after RYGB. The corresponding circulating LEAP238-47 fragment demonstrated strong insulinotropic action in vitro but failed to elicit glucoregulatory effects in healthy human subjects.

Maternal vaccination is a promising strategy for preventing neonatal disease caused by group B

Objective To evaluate the risk of inducing RhD immunisation in pregnancies of RhD-negative mothers with an RhD-positive fetus undergoing chorionic villus samplings (CVS) or amniocenteses (AC). Design, setting and population Registry-based study in a Danish cohort which has not been given rhesus prophylaxis. Methods Data were retrieved from the Department of Clinical Immunology at Rigshospitalet. All RhD-negative women carrying an RhD-positive fetus with screen test results from weeks 8-12 and weeks 25-29 were linked to data from the Danish Fetal Medicine Database. Data were divided into cases where no invasive prenatal diagnostic procedure was performed, cases that had AC performed, and cases that had CVS performed. Main outcome measures A comparison of the proportion of women who developed RhD immunisation between the two screen tests. Results The cohort consisted of 10 085 women: 9353 had no invasive procedures performed, 189 had AC and 543 had CVS performed. No women were immunised spontaneously or due to the procedure between the first and second screen test in the group with no procedure performed, or in the AC group. One woman was immunised in the CVS group. When comparing the proportion of women who was immunised in the CVS group with the no invasive test group a non-significant difference was found (P = 0.055). Conclusion The RhD immunisation rate before gestational weeks 25-29 in RhD-negative women carrying an RhD-positive fetus is very low, even in women undergoing prenatal invasive testing without rhesus prophylaxis. Tweetable abstract The RhD immunisation rate during pregnancy is very low even in women undergoing prenatal invasive testing.

Maternal vaccination, resulting in transfer of protective IgG across the placenta, represents a promising strategy to prevent neonatal disease caused by group B Streptococcus (GBS). The prototype vaccine GBS-NN, a fusion protein consisting of the N-terminal domains of the alpha-like protein (Alp) family members AlphaC and Rib, has been shown to display a good safety profile and to elicit a strong antibody response against the intact GBS-NN protein in a randomized placebo-controlled double-blind phase 1 trial in healthy adult women. Here we show that the vaccinees achieve robust IgG and IgA responses against both AlphaC and Rib and that vaccination additionally gives rise to antibodies against the heterotypic Alp family members Alp1-3. Responses against the heterotypic N-domains were more variable between subjects and correlated strongly with levels of pre-existing antibodies. Postvaccination sera mediated opsonophagocytic killing that correlated strongly with IgG but not IgM responses elicited by the vaccine. These sera also consistently prevented bacterial invasion of human cervical epithelial cells. Like the vaccine-induced response, naturally acquired IgG against the N-domains of AlphaC and Rib was dominated by the IgG1 subclass. Consistent with the enhanced ability of IgG1 to cross the placenta, naturally acquired IgG against both domains accumulated in neonatal relative to maternal blood, as assessed in a separate group of non-vaccinated pregnant women and their babies.

We present a new type of field experiment to investigate ethnic prejudice in the workplace. Our design allows us to study how potential discriminators respond to changes in the cost of discrimination. We find that ethnic discrimination is common but highly responsive to the “price of prejudice,” i.e., to the opportunity cost of choosing a less productive worker on ethnic grounds. Discriminators are on average willing to forego 8 percent of their earnings to avoid a coworker of the other ethnic type. The evidence suggests that animus rather than statistical discrimination explains observed behavior. (JEL C93, J15, J24, J31, J71)

OBJECTIVE: To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones.METHODS: The present retrospective study took place in an anechoic chamber facility at Aalborg University, Aalborg, Denmark, in 2012, and included pregnant participants aged 18-40 years with a singleton pregnancy at 32-36 weeks and a parity of 0-2. Abdominal Doppler ultrasonography was performed bilaterally on the uterine arteries. Subsequently, in the same positions, sound recordings were performed with microphones. The derived raw sound signal was separated into two frequency ranges, and characterized accordingly.RESULTS: The mean pregnancy length among 25 participants was 33.6 ± 2.0 weeks. The pulsatility index of the uterine artery was 0.67 ± 0.24. All 50 recordings displayed the first and second maternal heart sounds (frequency 25-100 Hz), and in 17 of 50 recordings, maternal vascular murmurs (frequency 200-800 Hz) were present. The average pulse wave velocity between the maternal aortic valve and the uterine artery was estimated to be 6.6 ± 1.5 m/s.CONCLUSION: Maternal vascular murmurs in the frequency range of 200-800 Hz were identified as a possible marker of abnormal uteroplacental blood flow, and provide a means to measure the arterial pulse wave velocity.

This article explores how different visitors experience the performances, promotions and each other at Denmark's most visited agricultural fair. Visitors acknowledge differences between urban and rural visitors but no tension or conflict. Embodied knowledge and tactile experiences seem like the most legitimate way to understand agriculture from the perspective of both rural-urban and farming/non-farming visitors, and they are also a key thematic focus in this article. Some performances even provide the visitor with a sense of trust in agriculture which, temporarily at least, can mitigate concerns about the overall food production system. Making sense of the activities at the fair seems to be achieved through embodied experiences as well as broader cultural identifications relating to and integrating images and experiences of landscapes, people and animals and their interaction. The results of this article should thus contribute to the sociological body of work trying to make sense of the changing meanings and roles of agriculture and farmers to the general public, as well as provide insights into how such meanings are created and maintained both inside and outside of the event.

Dopamine-producing tyrosine hydroxylase (TH) neurones in the hypothalamic arcuate nucleus (ARC) have recently been shown to be involved in ghrelin signalling and body weight homeostasis. In the present study, we investigate the role of the intracellular regulator RhoA in hypothalamic TH neurones in response to peripheral hormones. Diet-induced obesity was found to be associated with increased phosphorylation of TH in ARC, indicating obesity-associated increased activity of ARC TH neurones. Mice in which RhoA was specifically knocked out in TH neurones (TH-RhoA-/- mice) were more sensitive to the orexigenic effect of peripherally administered ghrelin and displayed an abolished response to the anorexigenic hormone leptin. When TH-RhoA-/- mice were challenged with a high-fat high-sucrose (HFHS) diet, they became hyperphagic and gained more body weight and fat mass compared to wild-type control mice. Importantly, lack of RhoA prevented development of ghrelin resistance, which is normally observed in wild-type mice after long-term HFHS diet feeding. Patch-clamp electrophysiological analysis demonstrated increased ghrelin-induced excitability of TH neurones in lean TH-RhoA-/- mice compared to lean littermate control animals. Additionally, increased expression of the orexigenic hypothalamic neuropeptides agouti-related peptide and neuropeptide Y was observed in TH-RhoA-/- mice. Overall, our data indicate that TH neurones in ARC are important for the regulation of body weight homeostasis and that RhoA is both a central effector in these neurones and important for the development of obesity-induced ghrelin resistance. The obese phenotype of TH-RhoA-/- mice may be a result of increased sensitivity to ghrelin and decreased sensitivity to leptin, resulting in increased food intake.

We use a large and heterogeneous sample of the Danish population to investigate the importance of distributional preferences for behavior in a public good game and a trust game. We find robust evidence for the significant explanatory power of distributional preferences. In fact, compared to twenty-one covariates, distributional preferences turn out to be the single most important predictor of behavior. Specifically, subjects who reveal benevolence in the domain of advantageous inequality contribute more to the public good and are more likely to pick the trustworthy action in the trust game than other subjects. Since the experiments were spread out more than one year, our results suggest that there is a component of distributional preferences that is stable across games and over time.

INTRODUCTION: In high-income countries the majority of pregnancies have a good outcome, and many adverse obstetric outcomes rarely occur. This makes demonstrating clinically relevant and statistically significant effects of new interventions a challenge. The objective of the study was to report incidences of important obstetric outcomes and to calculate sample sizes for tentative studies.MATERIAL AND METHODS: The study was a registry-based study. Data were retrieved from the Danish Medical Birth Registry and included all deliveries in Denmark from 2008 to 2015. The total population included 465 919 deliveries. The study population comprised intended vaginal deliveries with a single fetus in cephalic presentation at term (n=381 567). Incidences were reported for 20 outcomes considering the relevance for the patients and the severity of the outcomes. We calculated the sample sizes required in tentative obstetric studies to detect risk reductions of 25% and 50%, for tests at the 5% level, using a power of 80% and 90%. For the randomized controlled trials we calculated the sample size required for comparing two proportions with equal-sized groups, while for the cohort study we calculated the sample size also required for two proportions but with unequal sized groups. Outcome measures for sample size calculation were: neonatal mortality, Apgar score RESULTS: The incidence of neonatal mortality, Apgar score CONCLUSIONS: Most obstetric outcomes occur rarely; thus, very large sample sizes are required to achieve adequate statistical power in randomized controlled trials. Multicenter studies, international collaborations or alternative study designs to randomized controlled trials could be considered. This article is protected by copyright. All rights reserved.

INTRODUCTION Studies indicate an association between errors in cardiotocography (CTG) management and hypoxic brain injuries among newborns. Continuing professional education is recommended. We aimed to examine whether the implementation of a national interprofessional CTG education program in Denmark was associated with a decrease in risk of fetal hypoxia measured by umbilical cord pH

Congenital heart diseases (CHDs) are reported in 0.8% of newborns. Numerous factors influence cardiovascular development and CHD prevalence, and possibly also development of cardiovascular disease later in life. However, known factors explain the probable etiology in only a fraction of patients. Past large-scale population-based studies have made invaluable contributions to the understanding of cardiac disease, but none recruited participants prenatally and focused on the neonatal period. The Copenhagen Baby Heart Study (CBHS) is a population-based study of the prevalence, spectrum, and prognosis of structural and functional cardiac abnormalities. The CBHS will also establish normal values for neonatal cardiac parameters and biomarkers, and study prenatal and early childhood factors potentially affecting later cardiovascular disease risk. The CBHS is an ongoing multicenter, prospective study recruiting from second trimester pregnancy (gestational weeks 18–20) (expected n = 25,000). Information on parents, pregnancy, and delivery are collected. After birth, umbilical cord blood is collected for biochemical analysis, DNA purification, and biobank storage. An echocardiographic examination, electrocardiography, and post-ductal pulse oximetry are performed shortly after birth. Infants diagnosed with significant CHD are referred to a specialist or admitted to hospital, depending on CHD severity. CBHS participants will be followed prospectively as part of specific research projects or regular clinical follow-up for CHD. CBHS design and methodology are described. The CBHS aims to identify new mechanisms underlying cardiovascular disease development and new targets for prevention, early detection, and management of CHD and other cardiac diseases presenting at birth or developing later in life.

This reflection piece addresses and dismantles five myths strongly associated with the food cultures of yesteryears in most developed countries. The myths are: (1) The decline of the family meal; (2) The myth of the happy (nuclear) family eating together; (3) The “kitchen illiterate” children of today; (4) Danish and northern European consumers low food expenditure as something solely negative; (5) Good tasting and fresh food products as something belonging to the past and never to be found in industrialized agriculture. The main reasons the authors of this reflection piece address and dismantle these five myths are to facilitate change in our present food culture and systems without necessary resorting to an overt idealization of our foods and food habits of the “good old days,” while also steering clear of the many myths concerning the supposed decline of our present food culture.

Objective To define learning objectives for a national cardiotocography (CTG) education program based on expert consensus. Design A three-round Delphi survey. Population and setting One midwife and one obstetrician from each maternity unit in Denmark were appointed based on CTG teaching experience and clinical obstetric experience. Methods Following national and international guidelines, the research group determined six topics as important when using CTG: fetal physiology, equipment, indication, interpretation, clinical management, and communication/responsibility. In the first Delphi round, participants listed one to five learning objectives within the predefined topics. Responses were analyzed by a directed approach to content analysis. Phrasing was modified in accordance with Bloom's taxonomy. In the second and third Delphi rounds, participants rated each objective on a five-point relevance scale. Consensus was predefined as objectives with a mean rating value of ≥3. Main outcome measures A prioritized list of CTG learning objectives. Results A total of 42 midwives and obstetricians from 21 maternity units were invited to participate, of whom 26 completed all three Delphi rounds, representing 18 maternity units. The final prioritized list included 40 objectives. The highest ranked objectives emphasized CTG interpretation and clinical management. The lowest ranked objectives emphasized fetal physiology. Mean ratings of relevance ranged from 3.15 to 5.00. Conclusions National consensus on CTG learning objectives was achieved using the Delphi methodology. This was an initial step in developing a valid CTG education program. A prioritized list of objectives will clarify which topics to emphasize in a CTG education program.

Objective To investigate associations between mode of delivery and subsequent reproductive outcomes. Design Cohort study. Population Women with term singleton live births from 1987 to 2009. Setting Denmark, birth registration data. Methods Women with a first singleton delivery after 37 weeks were followed until the end of 2010, from a first birth to include subsequent live births. We used Cox's proportional hazards model stratified by parity to compare the likelihood for subsequent delivery according to mode of delivery at first and later births, estimating maternal age effects and lag time to next delivery. Main outcome measure Likelihood of a subsequent live-born child by previous delivery mode. Results We identified 642 052 women with a first delivery. Compared with women with a non-instrumental vaginal delivery, delivering a child by elective cesarean section implied a 23% (95% CI 0.76–0.787) decreased likelihood for subsequent delivery. Emergency cesarean section meant 16% fewer (95% CI 0.84–0.85), and vaginal instrumental delivery 4% fewer subsequent deliveries (95% CI 0.95–0.96). Hazard ratios were largely unchanged after controlling for parity and year of birth. Small age-trends were seen, with hazard ratios affected by maternal age at birth. Delivery mode at first birth affected marginally the time lag until next birth. Conclusions Fecundity, measured as likelihood of a successive live-born child, varied with mode of delivery at the first and also subsequent births. A first or later delivery by cesarean section implied decreased likelihood of subsequent delivery compared with women with a first vaginal birth.

We experimentally manipulate agents' information regarding the rationality of others in a setting in which previous studies have found irrationality to be present, namely the asset market experiments introduced by Smith et al. (1988) . Recent studies suggest that mispricing in such markets may be an artefact of confusion, which can be reduced by training subjects to understand the diminishing fundamental value. We reconsider this view, and propose that when it is made public knowledge that training has occurred, this may also reduce uncertainty over the behavior of others and facilitate the formation of common expectations. Our design disentangles the direct effect of training from the indirect effect of its public knowledge, and our results demonstrate a distinct and statistically significant effect of public knowledge over and above that of training alone.

Objective To investigate the effect on fetal growth of treatment with oral beta-blockers during pregnancy in women with congenital or acquired heart disease. Design Historical matched cohort study. Setting Centre for Pregnant Women with Heart Disease, Copenhagen University Hospital, Denmark. Population A cohort of 175 women with heart disease, grouped according to beta-blocker treatment, and a cohort of 627 women from the overall population matched on seven birthweight-determining factors. Methods Differences between groups were tested by simple descriptive statistics and assessed using standard hypothesis tests. Associations were estimated by correlational analysis and multivariable regression. Main outcome measure Proportion of infants born small for gestational age (SGA). Results More of the infants exposed to beta-blockers were SGA compared with non-exposed infants (29.4 versus 15.3%; P

SummarySuboptimal adherence to pharmacological treatment of asthma and chronic obstructive pulmonary disease (COPD) has adverse effects on disease control and treatment costs. The reasons behind non-adherence revolve around patient knowledge/education, inhaler device convenience and satisfaction, age, adverse effects and medication costs. Age is of particular concern given the increasing prevalence of asthma in the young and increased rates of non-adherence in adolescents compared with children and adults. The correlation between adherence to inhaled pharmacological therapies for asthma and COPD and clinical efficacy is positive, with improved symptom control and lung function shown in most studies of adults, adolescents and children. Satisfaction with inhaler devices is also positively correlated with improved adherence and clinical outcomes, and reduced costs. Reductions in healthcare utilisation are consistently observed with good adherence; however, costs associated with general healthcare and lost productivity tend to be offset only in more adherent patients with severe disease, versus those with milder forms of asthma or COPD. Non-adherence is associated with higher healthcare utilisation and costs, and reductions in health-related quality of life, and remains problematic on an individual, societal and economic level. Further development of measures to improve adherence is needed to fully address these issues.

Objective To assess possible associations between the size of labor units and the frequency of approved obstetric claims. Design A nationwide retrospective descriptive study. Setting Denmark. Population All patients seeking financial compensation due to obstetric injuries occurring between 1995 and 2009. Methods In all, 1440 anonymized obstetrics claims were reviewed; 1326 were included in the study. Information regarding the annual number of deliveries for each place of injury was retrieved from the National Birth Registry. Main outcome measures Obstetric injuries approved by the Danish Patient Insurance Association categorized by labor unit size. Results The overall approval rate for submitted claims was 39.7%. Large labor units (3000–3999 deliveries/year) were found to have a lower approval rate (34.2%), compared with very large (≥4000 deliveries/year, 38.6%), intermediate (1000–2999 deliveries/year, 41.7%), and small (

We aimed to examine whether cardiotocography (CTG) knowledge, interpretation skills and decision-making measured by a written assessment were associated with size of maternity unit, years of obstetric work experience and healthcare professional background.A national cross-sectional study in the setting of a CTG teaching intervention involving all 24 maternity units in Denmark. Participants were midwives (n = 1260) and specialists (n = 269) and residents (n = 142) in obstetrics and gynecology who attended a 1-day CTG course and answered a 30-item multiple-choice question test. Associations between mean test score and work conditions were analyzed using multivariable robust regression, in which the three variables were mutually adjusted.Participants from units with3000 deliveries/year scored higher on the test than participants from units with1000 deliveries/year (3000-3999 deliveries/year: mean difference 0.8, p0.0001;4000 deliveries/year: mean difference 0.5, p = 0.006). Participants with15 years of work experience scored higher than participants with15 years of experience (15-20 years of experience: mean difference - 0.6, p = 0.007;20 years experience: mean difference - 0.9, p0.0001). No differences were detected concerning professional background.CTG knowledge, interpretation skills and decision-making measured by a written assessment were positively associated with working in large maternity units and having15 years of obstetric work experience. This might indicate a challenge in maintaining CTG skills in small units and among experienced staff but could also reflect different levels of motivation, test familiarity and learning culture. Whether the findings are transferable to the clinical setting was not examined.

Premature birth increases a child's risk of cerebral palsy and death. The aim of this work is to investigate the association between treatment with magnesium sulphate during premature deliveries and infants' cerebral palsy and mortality through a meta-analysis of observational studies. A comprehensive search of the Cochrane Library, EMBASE and the PubMed database from their inceptions to 1 October, 2010 using the keywords 'magnesium sulphate, children/infant/pre-term/premature and cerebral palsy/mortality/morbidity/adverse effects/outcome' identified 11 reports of observational studies. Two authors working independently extracted the data. A meta-analysis of the data found an association between magnesium sulphate treatment and a significantly reduced risk of mortality (RR 0.73; 95% CI 0.61-0.89) and cerebral palsy (OR 0.64; 95% CI 0.47-0.89). Antenatal treatment with magnesium sulphate during premature deliveries seems to be associated with health benefits for the infants. The effective dose and timing, however, is not defined and given the lack of mechanistic understanding of the effect of MgSO(4), a reasonable alternative is a large-scale pragmatic clinical trial.

BACKGROUND: The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. STUDY DESIGN AND METHODS: This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. RESULTS: Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. CONCLUSIONS: Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

To explore positive aspects of family life after extremely premature childbirth, thereby supplementing current literature on long-term family outcome. Semi-structured, qualitative research interviews were analysed according to the editing strategy described by Miller and Crabtree. Denmark, Europe. Nine fathers and 11 mothers of 14 children born before 28 completed weeks of gestation at a tertiary centre were interviewed when their children were 7–10 years old. Whereas developmental delay, functional limitations, family burden, and parental distress are commonly used outcome measures, experiences of another nature were reported in the lives of survivors and their parents in our study. Thus, in spite of periods of deep distress and fear, periods of concern and anxiety and for some parents a workload far beyond average, parents’ descriptions of their children’s trajectories were also characterised by a perception of improvement and progress. Likewise, all parents reported much love and joy from child rearing. The value of these results may lie in the perspective they add to the interpretation of current research, the inspiration they may lend to future research on family outcome, as well as the balance they may offer in the information provided to parents of premature children.

The transplacental passage of monomethylphtalate (mMP) and mono (2-ethylhexyl) phthalate (mEHP) was studied using an ex vivo placental perfusion model with simultaneous perfusion of fetal and maternal circulation in a single cotyledon. Umbilical cord blood and placental tissue collected both before and after perfusion were also analyzed. Placentas were obtained immediately after elective cesarean section and dually perfused in a recirculation system. mMP or mEHP was added to maternal perfusion medium to obtain concentrations at 10 and 25 μg/L, respectively. The placental transfer was followed analyzing samples from fetal and maternal perfusion media by liquid chromatography–mass spectrometry–mass spectrometry (LC-MS-MS). Four perfusions with mMP indicated a slow transplacental transfer, with a fetomaternal ratio (FM ratio) of 0.30 ± 0.03 after 150 min of perfusion. Four perfusions with mEHP indicated a very slow or nonexisting placental transfer. mEHP was only detected in fetal perfusion media from two perfusions, giving rise to FM ratios of 0.088 and 0.20 after 150 min of perfusion. Detectable levels of mMP, mEHP, monoethylphthalate (mEP), and monobutylphthalate were found in tissue. Higher tissue levels of mMP after perfusions with mMP compared to perfusions with mEHP suggest an accumulation of mMP during perfusion. No tendency for accumulation of mEHP was observed during perfusions with mEHP compared to perfusions with mMP. Detectable levels of mEHP and mEP were found in umbilical cord plasma samples. mMP and possibly other short-chained phthalate monoesters in maternal blood can cross the placenta by slow transfer, whereas the results indicate no placental transfer of mEHP. Further studies are recommended.

Fetal exposure to phthalates may be associated with adverse reproductive effects, including cryptorchidism and decreased semen quality. Information about human placental transfer is needed to qualify the hypotheses. A dual recirculating placenta perfusion system to monitor concentrations of eight phthalate monoesters in fetal and maternal perfusates was established. In addition to perfusate background measures of phthalate monoesters, the concentrations in umbilical cord plasma and placenta tissue were measured. Monomethyl phthalate (mMP), monoethyl phthalate (mEP), monobutyl phthalate (mBP), and mono (2-ethyl-hexyl) phthalate (mEHP) were detected in both maternal and fetal perfusate, demonstrating a release of compounds from tissue or blood to perfusates. The distribution of compounds between perfusate, umbilical cord plasma, and tissue was in accordance with the physical-chemical properties of the compounds. Results from the present study of compounds residing in the tissue are essential before studying human transplacental transfer, storage, and metabolism of selected phthalate monoesters.

Background Since 2007 the Danish Health and Medicines Authority has advised total alcohol abstinence from the time of trying to conceive and throughout pregnancy. The prevalence of binge drinking among pregnant Danish women has nevertheless been reported to be up to 48 % during early pregnancy. Since the introduction of the recommendation of total abstinence, no studies have examined pre-pregnancy lifestyle and reproductive risk factors associated with this behaviour in a Danish context. The aims of this study were therefore to describe the prevalence of weekly alcohol consumption and binge drinking in early pregnancy among women living in the capital of Denmark. Secondly to identify pre-pregnancy lifestyle and reproductive risk factors associated with binge drinking during early pregnancy. Methods Data were collected from September 2012 to August 2013 at the Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark. Self-reported information on each woman’s socio-demographic characteristics, medical history, and lifestyle factors including alcohol habits was obtained from an electronic questionnaire filled out as part of the individual medical record. Descriptive analysis was conducted and multivariate logistic regression analysis was used to assess the potential associated risk factors (adjusted odds ratio (aOR)). Results Questionnaires from 3,238 women were included. A majority of 70 %, reported weekly alcohol consumption before pregnancy. The prevalence decreased to 3 % during early pregnancy. The overall proportion of women reporting binge drinking during early pregnancy was 35 % (n = 1,134). The following independent risk factors for binge drinking in early pregnancy were identified: lower degree of planned pregnancy, smoking and alcohol habits before pregnancy ((1 unit/weekly aOR 4.48, CI: 3.14 - 6.40), (2–7 units aOR 10.23, CI: 7.44-14.06), (≥8 units aOR 33.18, CI: 19.53-56.36)). Multiparity and the use of assisted reproductive technology were associated with lower odds of binge drinking in early pregnancy. Conclusion The prevalence of weekly alcohol consumption decreased considerably during early pregnancy compared with pre-pregnancy levels. Nevertheless one third of the pregnant women engaged in binge drinking. Identification of risk factors for this behaviour renders it possible not only to design prevention strategies, but also to target those most at risk. Electronic supplementary material The online version of this article (doi:10.1186/s12884-015-0757-z) contains supplementary material, which is available to authorized users.

We examined the association between exposure to seafood intake during two periods of pregnancy on the one hand and risks of preterm delivery and postterm delivery on the other. In a prospective cohort of 8729 pregnant Danish women, we assessed frequency of fish meals during the first and second trimester of pregnancy by questionnaires completed around gestation weeks 16 and 30, respectively. When fish intake was based solely on intake reported for the early period of pregnancy, mean gestation length was shorter by 3.91 (95% CI: 2.24-5.58) days and odds of preterm delivery were increased 2.38 (1.23-4.61) times in those who never consumed fish (n = 308) vs. those who consumed both fish as main meal and fish in sandwiches at least once per week (n = 785). These measures were similar when fish intake was based solely on intake reported for mid-pregnancy. In the subgroup of women reporting same intake in the two trimesters, those who never consumed fish (n = 165) had 8.57 (5.46-11.7) days shorter mean gestation and 19.6 (2.32-165) times increased odds of preterm delivery, compared to high fish consumers (n = 127); odds of elective and postterm delivery were reduced by a factor 0.33 (0.11-1.02) and 0.34 (0.12-0.95), respectively, in zero fish consumers. All analyses were adjusted for potential confounding by factors such as maternal smoking, height, and prepregnant weight. We conclude that never consuming fish in the first two trimesters of pregnancy was an extremely strong risk factor for preterm delivery but was also associated with reduced risks of elective delivery and postterm delivery.

Background. Cigarette smoking has been considered a risk factor for spontaneous abortion, but conclusions from many studies may be impaired by methodological problems. Studies are required that use data on smoking habits collected before knowledge about outcome of pregnancy and in which adjustment is made for potential confounders. Methods. All Danish-speaking pregnant women booking for delivery at the Department of Obstetrics and Gynecology, Aarhus University Hospital, from September 1989 to August 1996 were invited to participate in the study ( n = 24 608 pregnancies, including 321 spontaneous abortions and 100 induced abortions). Information about smoking habits before pregnancy and during the first trimester was obtained from self-administered questionnaires before the knowledge about pregnancy outcome. Information about spontaneous and induced abortions was obtained from the Danish National Patient Registry. We used Cox regression analyses with delayed entry (left truncation) for analyses, and hazard...

In Europe, an increasing number of women have bariatric surgery; therefore, obstetricians are likely to encounter these patients. We report a 22-year-old woman, who had previously undergone uncomplicated laparoscopic Roux-en-Y gastric bypass. She was admitted with severe abdominal pain at 35 weeks of gestation. A cesarean section with delivery of a healthy baby in combination with an exploratory laparotomy was performed. Internal herniation was suspected, but not identified during surgery. Three days later she died of a severely gangrenous small bowel secondary to internal herniation. This fatal case illustrates a potential complication and difficulties in the management of pregnant women who have undergone Roux-en-Y gastric bypass. In these women, observation and investigations based on a multidisciplinary approach are vital if abdominal pain develops, with involvement of intestinal surgeons experienced in bariatric surgery, as well as radiologists with specific knowledge of relevant imaging procedures.

This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining “normal tissue” versus “pathologic lesions.” A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact “trophoblastic vacuolization,” which is believed to represent dilated transtrophoblastic channels, was reproducible and significantly correlated to the perfusion marker “fetal leakage.” In longer perfusions, microscopy of the perfused cotyledon revealed bacteria in the fetal vessels. This finding led to an adjustment in the perfusion protocol with addition of antibiotics to the medium. In the “normal” tissue, certain lesions were very frequent and showed only fair or poor interobserver agreement. Revised minimum criteria for these lesions were defined and found reproducible. This study has emphasized the value of pathologic examination as a supplement in placental perfusion models. Examination of the perfused cotyledon for trophoblastic vacuolization is recommended as an additional quality marker in perfusion models. The study also underlines the need for exact definitions of abnormality in frequent placental lesions.

Denne artikel handler om sammenhængen mellem kortisol-niveau hos moderen under graviditeten og barnets risiko for overvægt gennem barndommen og i teenageårene. Artiklen bygger på en hypotese om, at eksponering for moderens stress under graviditeten kan påvirke det ufødte barns udvikling af sit hormonsystem, så barnet gennem opvæksten vil være mere tilbøjelig til at tage på i vægt. Resultaterne viser overordnet, at de fleste overvægtige børn var født af mødre med et højt kortisol-niveau under graviditeten. Disse fund var signifikante hos overvægtige børn i aldersgruppen 2-6 år og 12-16 år, hvis mødre havde haft et højt kortisol-niveau under 2. trimester. Studiet bygger på data fra fødselskohorten ”Aarhus Birth Cohort”, hvor 655 mødre to gange under graviditeten afleverede en spyt-prøve morgen og aften i årene 1989-1991. Data for børnenes højde og vægt er siden indsamlet hos praktiserende læger og skolesundhedsplejersker. INTRODUCTION: Animal and human studies suggest that programing of the hypothalamic-pituitary-adrenal (HPA) axis may be involved in the development of obesity, but human studies of biological indicators of HPA axis activity are lacking. We studied the association between levels of the stress hormone cortisol during pregnancy and overweight offspring during childhood into adolescence.METHODS: Salivary samples from 655 Danish pregnant women with singleton pregnancies (1989-1991) were collected once in the morning and once in the evening in their second and third trimester. We followed the offspring from two to 16 years of age with at least one measurement of height and weight, and classified their body mass index into overweight and normal weight. The adjusted relative difference in median salivary cortisol (with 95% confidence interval (CI)) during pregnancy (the four samples), in second and third trimester (morning and evening samples) between overweight and normal weight offspring was estimated. Furthermore, the adjusted median ratio between morning and evening maternal salivary cortisol level was estimated for normal weight and overweight children. All the analyses were stratified into the equal age groups: 2-6, 7-11, and 12-16 years.RESULTS: We found non-significant higher maternal cortisol levels during pregnancy in offspring that were overweight at the age of 2-6, 7-11 and 12-16 years than in normal weight peers; adjusted relative difference in median salivary cortisol 11% (95% CI: -2; 25), 6% (95% CI: -7; 20), and 9% (95% CI: -4; 24), respectively. A statistically significantly higher level of maternal cortisol was found in the second trimester in 2-6-year-old and 12-16-year-old overweight offspring; relative difference 19% (95% CI: 3; 37), and 20% (95% CI: 3; 41), respectively. The median ratio between morning and evening maternal salivary cortisol level was similar for overweight and normal weight children; e.g. at age 2-6 years in third trimester 4.31 (95% CI: 4.05; 4.60)nmol/l and 4.28 (95% CI: 3.60; 5.09)nmol/l, respectively (P=0.93).CONCLUSION: Our findings suggest a relatively consistent association between pregnancy cortisol levels and overweight offspring, especially in the second trimester.

Background: Chronic obstructive pulmonary disease (COPD) guidelines emphasize the importance of patient education to improve quality of life and avoid exacerbations. Longitudinal evaluations of structured management of COPD in primary care are lacking. Aim: To evaluate the impact of primary care asthma/COPD clinics on exacerbations, hospitalizations, and associated costs in COPD. Methods: This population-based, retrospective, observational study, linking primary care medical records data to mandatory Swedish national registries, included patients with COPD from 76 primary healthcare centers (1999-2009). A questionnaire on access to an asthma/COPD clinic was retrospectively answered. Propensity score matching was performed at index (COPD diagnosis) by center type (with and without an asthma/COPD clinic). Poisson regression was used to compare the yearly rate of exacerbations (hospitalization, emergency visits, or prescription for oral steroids or antibiotics) and COPD-related prescriptions at the centers. An economic analysis was performed from the Swedish healthcare perspective using 2011 unit costs and the incremental cost-effectiveness ratio was calculated. Results: The study included 21,361 patients (mean age, 68.0 years; 53% female). Access to asthma/COPD clinics increased from 34% to 85% during the study period. Patients at primary healthcare centers with asthma/COPD clinics had 27% fewer exacerbations (0.71 vs. 0.98) and 37% fewer hospitalizations annually (0.36 vs. 0.58) (p < 0.0001). Asthma/COPD clinics reduced the annual cost of medication and healthcare contacts by 37% (SEK 52,892 [(sic)5858] to SEK 33,410 [(sic)3700] per patient). Conclusions: Patients at primary healthcare centers with asthma/COPD clinics experienced fewer COPD exacerbations and hospitalizations, and overall treatment costs were substantially reduced. ClinicalTrials.gov identifier: NCT01146392. (C) 2014 The Authors. Published by Elsevier Ltd.

We present a new type of field experiment to investigate ethnic prejudice in the workplace. Our design allows us to study how potential discriminators respond to changes in the cost of discrimination. We find that ethnic discrimination is common but remarkably responsive to the "price of prejudice", i.e. to the opportunity cost of choosing a less productive worker on ethnic grounds. In addition, we find that the standard theory of statistical discrimination fails to explain observed choices, and that taking ethnic prejudice into account helps to predict the incidence of discrimination.

The objectives of the study were to identify factors associated with utilisation of antenatal care facilities in a rural population in South India. A community-based, cross-sectional questionnaire study of 30 randomly selected areas was used. A total of 1254 women (95%) had at least one antenatal care visit. The median number of visits was four. High utilisation of antenatal care facilities was associated with low parity and adverse obstetrical history, short distance to healthcare facilities and literacy. It was concluded that antenatal care coverage was high. Information about the above few aspects can be used to target women who are at risk of getting inadequate antenatal care.

Objective To assess possible association between the incidence of approved claims for severe and fatal obstetric injuries and delivery volume in Denmark. Design and setting A nationwide panel study of labor units. Population Claimants seeking financial compensation due to injuries occurring in labor units in 1995–2012. Methods Exposure information regarding the annual number of deliveries per labor unit was retrieved from the Danish National Birth Register. Outcome information was retrieved from the Danish Patient Compensation Association. Exposure was categorized in delivery volume quintiles as annual volume per labor unit: (10–1377), (1378–2016), (2017–2801), (2802–3861), (3862–6659). Main outcome measures Five primary measures of outcome were used. Incidence rate ratios of (A) Submitted claims, (B) Approved claims, (C) Approved severe injury claims (120% degree of disability), (D) Approved fatal injury claims, and (C+D) Combined. Results 1 151 734 deliveries in 51 labor units and 1872 submitted claims were included. The incidence rate ratios of approved claims overall, of approved fatal injury claims, and of approved severe and fatal injuries combined increased significantly with decreasing annual delivery volume. Face value incidence rate ratios of approved severe injuries increased with decreasing labor unit volume, but the association did not reach statistical significance. Conclusion High volume labor units appear associated with fewer approved and fewer fatal injury claims compared with units with less volume. The findings support the development towards consolidation of units in Denmark. A suggested option would be to tailor obstetric patient safety initiatives according to the delivery volume of individual labor units.

Background. The aim of the study was to describe changes in smoking habits among Danish pregnant women during an eight-year period in relation to changes in sociodemographic and lifestyle factors. Methods. From 1989 to 1996 all pregnant women attending routine antenatal care at the Department of Gynecology and Obstetrics at Aarhus University Hospital who completed an inclusion questionnaire were invited to participate in the present study (n=27,194). They were asked to complete two additional questionnaires during pregnancy. Apart from smoking habits. these questionnaires provided information on medical and obstetric history together with information on sociodemographic and other lifestyle variables. Results. The proportion of pregnant smokers decreased from 34% (95% Cl: 32%-36%) in 1989 to 21% (95% CI: 19%-22%) in 1996 (p

The neonatal Fc receptor (FcRn) directs the transfer of maternal immunoglobulin G (IgG) antibodies across the placenta and thus provides the fetus and newborn with passive protective humoral immunity. Pathogenic maternal IgG antibodies will also be delivered via the placenta and can cause alloimmunity, which may be lethal. A novel strategy to control pathogenic antibodies would be administration of a nondestructive IgG antibody blocking antigen binding while retaining binding to FcRn. We report on 2 human IgG3 antibodies with a hinge deletion and a C131S point mutation (IgG3ΔHinge) that eliminate complement activation and binding to all classical Fcγ receptors (FcγRs) and to C1q while binding to FcRn is retained. Additionally, 1 of the antibodies has a single point mutation in the Fc (R435H) at the binding site for FcRn (IgG3ΔHinge:R435H). We compared transplacental transport with wild-type IgG1 and IgG3, and found transport across trophoblast-derived BeWo cells and ex vivo placenta perfusions with hierarchies as follows: IgG3ΔHinge:R435H>wild-type IgG1≥IgG3ΔHinge and IgG3ΔHinge:R435H=wild-type IgG1=wild-type IgG3>>>IgG3ΔHinge, respectively. Collectively, IgG3ΔHinge:R435H was transported efficiently from the maternal to the fetal placental compartment. Thus, IgG3ΔHinge:R435H may be a good candidate for transplacental delivery of a nondestructive antibody to the fetus to combat pathogenic antibodies.

Background Maternal immunization against KEL1 of the Kell blood group system can have serious adverse consequences for the fetus as well as the newborn baby. Therefore, it is important to determine the phenotype of the fetus to predict whether it is at risk. We present data that show the feasibility of predicting the fetal KEL1 phenotype using next-generation sequencing (NGS) technology. Study Design and Methods The KEL1/2 single-nucleotide polymorphism was polymerase chain reaction (PCR) amplified with one adjoining base, and the PCR product was sequenced using a genome analyzer (GAIIx, Illumina); several millions of PCR sequences were analyzed. Results The results demonstrated the feasibility of diagnosing the fetal KEL1 or KEL2 blood group from cell-free DNA purified from maternal plasma. Conclusion This method requires only one primer pair, and the large amount of sequence information obtained allows well for statistical analysis of the data. This general approach can be integrated into current laboratory practice and has numerous applications. Besides DNA-based predictions of blood group phenotypes, platelet phenotypes, or sickle cell anemia, and the determination of zygosity, various conditions of chimerism could also be examined using this approach. To our knowledge, this is the first report focused on antenatal blood group determination using NGS.

Background During pregnancy women are at increased risk of severe complications to influenza infection, including death of mother or fetus, especially if chronic comorbid medical conditions such as diabetes mellitus are present. Case presentation A 36 years old Caucasian pregnant woman with type 1 diabetes underwent mechanical ventilation in gestation week 27 for severe respiratory failure due to influenza and pneumonia. For three weeks during and following her most severe illness, fetal growth could not be detected and the umbilical flows and amniotic fluid volumes were affected too. The possibility of preterm delivery and extracorporeal membrane oxygenation (ECMO) treatment were considered, however the patient and her fetus recovered gradually on conservative treatment. Under close surveillance the pregnancy continued until term, with delivery of an infant with appropriate weight for gestational age. Conclusion Preterm delivery and decreased birth weight were reported for women with antepartum pneumonia. Mechanical ventilation and ECMO treatment for severe respiratory failure in pregnancy are life threatening conditions and have been associated with preterm delivery. It remains uncertain if delivery improves the respiratory status of a critically ill woman, and the fetal condition is likely to improve, if the maternal condition is stabilized. Severe respiratory insufficiency requiring mechanical ventilation in a diabetic pregnant woman with influenza was successfully treated conservatively. Despite clear signs of impaired fetal condition in the acute phase, watchful waiting resulted in delivery of a normal weight infant at term.