Maternal pre-pregnancy body mass index and risk of preterm birth: a collaboration using large routine health datasets.

BACKGROUND: Preterm birth (PTB) is a leading cause of child morbidity and mortality. Evidence suggests an increased risk with both maternal underweight and obesity, with some studies suggesting underweight might be a greater factor in spontaneous PTB (SPTB) and that the relationship might vary by parity. Previous studies have largely explored established body mass index (BMI) categories. Our aim was to compare associations of maternal pre-pregnancy BMI with any PTB, SPTB and medically indicated PTB (MPTB) among nulliparous and parous women across populations with differing characteristics, and to identify the optimal BMI with lowest risk for these outcomes. METHODS: We used three UK datasets, two USA datasets and one each from South Australia, Norway and Denmark, together including just under 29 million pregnancies resulting in a live birth or stillbirth after 24 completed weeks gestation. Fractional polynomial multivariable logistic regression was used to examine the relationship of maternal BMI with any PTB, SPTB and MPTB, among nulliparous and parous women separately. The results were combined using a random effects meta-analysis. The estimated BMI at which risk was lowest was calculated via differentiation and a 95% confidence interval (CI) obtained using bootstrapping. RESULTS: We found non-linear associations between BMI and all three outcomes, across all datasets. The adjusted risk of any PTB and MPTB was elevated at both low and high BMIs, whereas the risk of SPTB was increased at lower levels of BMI but remained low or increased only slightly with higher BMI. In the meta-analysed data, the lowest risk of any PTB was at a BMI of 22.5 kg/m2 (95% CI 21.5, 23.5) among nulliparous women and 25.9 kg/m2 (95% CI 24.1, 31.7) among multiparous women, with values of 20.4 kg/m2 (20.0, 21.1) and 22.2 kg/m2 (21.1, 24.3), respectively, for MPTB; for SPTB, the risk remained roughly largely constant above a BMI of around 25-30 kg/m2 regardless of parity. CONCLUSIONS: Consistency of findings across different populations, despite differences between them in terms of the time period covered, the BMI distribution, missing data and control for key confounders, suggests that severe under- and overweight may play a role in PTB risk.

Co-occurrence of Periodontitis and Diabetes-Related Complications.

Periodontitis is a common finding among people with diabetes mellitus (DM) and has been cited as a DM complication. Whether and how periodontitis relates to other diabetes-related complications has yet to be explored. This study aims to examine the clustering of periodontitis with other diabetes-related complications and explore pathways linking diabetes-related complications with common risk factors. Using data from participants with DM across 3 cycles of the National Health and Nutrition Examination Survey (NHANES) (n = 2,429), we modeled direct and indirect pathways from risk factors to diabetes-related complications, a latent construct comprising periodontitis, cardiovascular diseases, proteinuria, and hypertension. Covariates included age, sex, socioeconomic status (SES), smoking, physical activity, healthy diet, alcohol consumption, hemoglobin A1c (HbA1c), dyslipidemia, and body mass index (BMI). Sensitivity analyses were performed considering participants with overweight/obesity and restricting the sample to individuals without DM. Periodontitis clustered with other diabetes complications, forming a latent construct dubbed diabetes-related complications. In NHANES III, higher HbA1c levels and BMI, older age, healthy diet, and regular physical activity were directly associated with the latent variable diabetes-related complications. In addition, a healthy diet and BMI had a total effect on diabetes-related complications. Although sex, smoking, dyslipidemia, and SES demonstrated no direct effect on diabetes-related complications in NHANES III, a direct effect was observed using NHANES 2011-2014 cycles. Sensitivity analysis considering participants with overweight/obesity and without DM showed consistent results. Periodontal tissue breakdown seems to co-occur with multiple diabetes-related complications and may therefore serve as a valuable screening tool for other well-known diabetes-related complications.

Appetite stimulation with cannabis-based medicine and methods for assessment of glomerular filtration in older patients with medical illness: A study protocol.

BACKGROUND AND AIM: Malnutrition in older patients is linked to poor appetite. Cannabis-based medicine may have orexigenic properties in older patients, but this has to our knowledge never been investigated. In older patients, uncertainty applies to the accuracy of estimated glomerular filtration rate (eGFR) based on creatinine, which is crucial for medication prescribing. In older patients with poor appetite, the study aims (1) to assess the efficacy of Sativex® (8.1-mg delta-9-tetrahydrocannabinol [THC] and 7.5-mg cannabidiol [CBD]) to stimulate appetite and (2) to compare the performance of various GFR-estimates and measured-GFR (mGFR) for determining gentamicin clearance utilizing population pharmacokinetic (popPK) modelling methods. METHODS AND OBJECTIVES: This study is composed of two substudies. Substudy 1 is an investigator-initiated single-center, double-blinded, randomized, placebo-controlled, superiority, cross-over study. Substudy 1 will recruit 17 older patients with poor appetite, who will also be invited to substudy 2. Substudy 2 is a single-dose pharmacokinetics study and will recruit 55 patients. Participants will receive Sativex® and placebo in substudy 1 and gentamicin with simultaneous measurements of GFR in substudy 2. The primary endpoints are as follows: Substudy 1-the difference in energy intake between Sativex® and placebo conditions; substudy 2- the accuracy of different eGFR equations compared to mGFR. The secondary endpoints include safety parameters, changes in the appetite hormones, total ghrelin and GLP-1 and subjective appetite sensations, and the creation of popPK models of THC, CBD, and gentamicin.

The clinical task force: Improving quality of medical students' internship.

Background: Up to 40% of young medical doctors feel that the internships prepared them insufficiently for the clinical work. This study investigated whether a Clinical Task Force (CTF) could improve internship quality. Methods: The CTF visited internship departments with a triple-targeted approach: first, departments pre-filled a self-evaluating questionnaire; secondly, CTF visited departments to discuss the self-evaluation and previous student evaluations; and thirdly, CTF and departments agreed on several quality-improving focus points to work on after the meeting. Focus points were followed-up after three and 12 months. The impact on internship quality was assessed with departments' student evaluation scores, number of completed focus points, and the effect of completed focus points on a range of learning parameters. The CTF learned several things along the way, that potentially could affect the quality of internships. A shortlist of these was provided to illustrate unmeasurable benefits. Results: The CTF met with 53 out of 60 eligible departments. The CTF and departments agreed upon 197 focus points of which 64% were completed. The three most frequent categories of focus points were Introduction of the students, The departments' evaluation percentage, and The departments' function as an educational site. The mean student evaluation scores did not change significantly, but the individual evaluation parameters changed significantly in two categories. It decreased in the category regarding the students' satisfaction with the clinical lecturers and the scheduled teaching and increased in the category regarding the percentage of students evaluating the department. Conclusion: The CTF's triple-targeted approach did not increase the mean student evaluation score significantly. For departments that completed the agreed focus points, one category increased and another decreased. However, the unmeasurable benefits illustrated that CTF was a good viable linking element between the faculty, departments, and students with the potential of improving other aspects of the quality of internships.

Acoustic tethering of microorganisms.

We show how to construct and apply a setup to acoustically tether and enable behavioral observations of individual microorganisms using simple laboratory equipment and a standard light microscope. We explore the capability of the setup with the freely swimming dinoflagellate Alexandrium minutum as the study organism. The setup allows us to tether cells in focus in the mid-plane of the sample chamber and make observations of individual organisms at high magnification without affecting their flagellar beat frequencies. We discuss the prospect of the method to explore appendage motion and swimming kinematics of other flagellates and ciliates, and we argue that the method will be applicable to a broad range of cell sizes and shapes.

Effects of mechanical ventilation versus apnea on bi-ventricular pressure-volume loop recording.

Respiration changes intrathoracic pressure and lung volumes in a cyclic manner, which affect cardiac function. Invasive ventricular pressure-volume (PV) loops can be recorded during ongoing mechanical ventilation or in transient apnea. No consensus exists considering ventilatory mode during PV loop recording. The objective of this study was to investigate the magnitude of any systematic difference of bi-ventricular PV loop variables recorded during mechanical ventilation versus apnea. PV loops were recorded simultaneously from the right ventricle and left ventricle in a closed chest porcine model during mechanical ventilation and in transient apnea (n=72). Variables were compared by regression analyses. Mechanical ventilation versus apnea affected regression coefficients for important PV variables including right ventricular stroke volume (1.22, 95% CI [1.08-1.36], p=0.003), right ventricular ejection fraction (0.90, 95% CI [0.81-1.00], p=0.043) and right ventricular arterial elastance (0.61, 95%CI [0.55-0.68], p<0.0001). Right ventricular pressures and volumes were parallelly shifted with Y-intercepts different from 0. Few left ventricular variables were affected, mainly first derivatives of pressure (dP/dt(max): 0.96, 95% CI [0.92-0.99], p=0.016, and dP/dt(min): 0.92, 95% CI [0.86-0.99], p=0.026), which might be due to decreased heart rate in apnea (Y-intercept -6.88, 95% CI [-12.22; -1.54], p=0.012). We conclude, that right ventricular stroke volume, ejection fraction and arterial elastance were mostly affected by apnea compared to mechanical ventilation. The results motivate future standardization of respiratory modality when measuring PV relationships.

Pregnancy and risk of COVID-19: a Norwegian registry-linkage study.

OBJECTIVE: To compare the risk of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and contact with specialist healthcare services for coronavirus disease 2019 (COVID-19) between pregnant and non-pregnant women. POPULATION OR SAMPLE: All women ages 15-45 living in Norway on 1 March 2020 (n = 1 033 699). METHODS: We linked information from the national birth, patient, communicable diseases and education databases using unique national identifiers. MAIN OUTCOME MEASURE: We estimated hazard ratios (HR) among pregnant compared to non-pregnant women of having a positive test for SARS-CoV-2, a diagnosis of COVID-19 in specialist healthcare, or hospitalisation with COVID-19 using Cox regression. Multivariable analyses adjusted for age, marital status, education, income, country of birth and underlying medical conditions. RESULTS: Pregnant women were not more likely to be tested for or to a have a positive SARS-CoV-2 test (adjusted HR 0.99; 95% CI 0.92-1.07). Pregnant women had higher risk of hospitalisation with COVID-19 (HR 4.70, 95% CI 3.51-6.30) and any type of specialist care for COVID-19 (HR 3.46, 95% CI 2.89-4.14). Pregnant women born outside Scandinavia were less likely to be tested, and at higher risk of a positive test (HR 2.37, 95% CI 2.51-8.87). Compared with pregnant Scandinavian-born women, pregnant women with minority background had a higher risk of hospitalisation with COVID-19 (HR 4.72, 95% CI 2.51-8.87). CONCLUSION: Pregnant women were not more likely to be infected with SARS-CoV-2. Still, pregnant women with COVID-19, especially those born outside of Scandinavia, were more likely to be hospitalised. TWEETABLE ABSTRACT: Pregnant women are at increased risk of hospitalisation for COVID-19.

Experiences of grief-bereavement after a medically assisted death in Canada: Bringing death to life.

Medical assistance in dying (MAiD) legislation was passed in Canada in 2016, yet the bereavement experience of family and friends is not well understood. Using interpretive description, we interviewed nine bereaved individuals. The time before the assisted death seems most impactful-an experience of bringing death to life shapes bereavement after death. We identified themes that inform this grieving: (1) certainty of date/time of death-intensifies a parade of lasts, initiates a countdown and affords time to say good-bye; (2) active family engagement as planners supports sense-making; and (3) enacting MAiD as ceremony slows time to "digest" loss.

Systematic review and meta-analysis of the effect of pertussis vaccine in pregnancy on the risk of chorioamnionitis, non-pertussis infectious diseases and other adverse pregnancy outcomes.

BACKGROUND: Several countries have introduced maternal immunisation with pertussis vaccine to provide protection against pertussis in early infancy. There is increasing interest in non-specific effects of vaccines including that non-live vaccines may enhance susceptibility to non-targeted infections in females. Some studies have shown increased risk of chorioamnionitis among women receiving pertussis vaccine during pregnancy. We aimed to conduct a systematic review and meta-analysis of the effect of maternal pertussis immunisation on the risk of chorioamnionitis, as well as the secondary outcomes of non-pertussis infections in women, non-pertussis infections in infants, spontaneous abortion or stillbirth, maternal death and infant death. METHODS: We searched PubMed and Embase for articles published until January 14, 2021. We screened articles for eligibility and extracted data using Covidence. Quality was assessed using Cochrane RoB tool and Newcastle-Ottawa Scale. Data were imported into RevMan for pooling and conduction of a meta-analysis stratified by study type. Outcomes are presented as risk ratios. RESULTS: We identified 13 observational studies and six randomized controlled trials eligible for inclusion. We pooled data on chorioamnionitis from six observational studies and found maternal pertussis vaccine (mostly compared with other maternal immunizations with non-live vaccines) to be associated with an increased risk among the pertussis vaccinated women, RR = 1.27 [CI 95%: 1.14-1.42]. We found no difference in the analysis of our secondary outcomes of non-pertussis infections, spontaneous abortion or stillbirth and death. CONCLUSION: We found an increased risk of chorioamnionitis among women who received pertussis vaccine in pregnancy. The large number of women receiving pertussis vaccine during pregnancy, as well as the growing evidence of non-live vaccines causing increased susceptibility to infections, indicates a need for further randomised trials to assess potential adverse effects of maternal immunisation with pertussis-containing vaccines.

20 years of the European IVF-monitoring Consortium registry: what have we learned? A comparison with registries from two other regions.

STUDY QUESTION: How has the performance of the European regional register of the European IVF-monitoring Consortium (EIM)/European Society of Human Reproduction and Embryology (ESHRE) evolved from 1997 to 2016, as compared to the register of the Centres for Disease Control and Prevention (CDC) of the USA and the Australia and New Zealand Assisted Reproduction Database (ANZARD)? SUMMARY ANSWER: It was found that coherent and analogous changes are recorded in the three regional registers over time, with a different intensity and pace, that new technologies are taken up with considerable delay and that incidental complications and adverse events are only recorded sporadically. WHAT IS KNOWN ALREADY: European data on ART have been collected since 1997 by EIM. Data collection on ART in Europe is particularly difficult due to its fragmented political and legal landscape. In 1997, approximately 78.1% of all known institutions offering ART services in 23 European countries submitted data and in 2016 this number rose to 91.8% in 40 countries. STUDY DESIGN, SIZE, DURATION: We compared the changes in European ART data as published in the EIM reports (2001-2020) with those of the USA, as published by CDC, and with those of Australia and New Zealand, as published by ANZARD. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a retrospective analysis of the published EIM data sets spanning the 20 years observance period from 1997 to 2016, together with the published data sets of the USA as well as of Australia and New Zealand. By comparing the data sets in these three large registers, we analysed differences in the completeness of the recordings together with differences in the time intervals on the occurrence of important trends in each of them. Effects of suspected over- and under-reporting were also compared between the three registers. X2 log-rank analysis was used to assess differences in the data sets. MAIN RESULTS AND THE ROLE OF CHANCE: During the period 1997-2016, the numbers of recorded ART treatments increased considerably (5.3-fold in Europe, 4.6-fold in the USA, 3.0-fold in Australia and New Zealand), while the number of registered treatment modalities rose from 3 to 7 in Europe, from 4 to 10 in the USA and from 5 to 8 in Australia and New Zealand, as published by EIM, CDC and ANZARD, respectively. The uptake of new treatment modalities over time has been very different in the three registers. There is a considerable degree of underreporting of the number of initiated treatment cycles in Europe. The relationship between IVF and ICSI and between fresh and thawing cycles evolved similarly in the three geographical areas. The freeze-all strategy is increasingly being adopted by all areas, but in Europe with much delay. Fewer cycles with the transfer of two or more embryos were reported in all three geographical areas. The delivery rate per embryo transfer in thawing cycles bypassed that in fresh cycles in the USA in 2012, in Australia and New Zealand in 2013, but not yet in Europe. As a result of these changing approaches, fewer multiple deliveries have been reported. Since 2012, the most documented adverse event of ART in all three registers has been premature birth (<37 weeks). Some adverse events, such as maternal death, ovarian hyperstimulation syndrome, haemorrhage and infections, were only recorded by EIM and ANZARD. LIMITATIONS, REASONS FOR CAUTION: The methods of data collection and reporting were very different among European countries, but also among the three registers. The better the legal background on ART surveillance, the more complete are the data sets. Until the legal obligation to report is installed in all European countries together with an appropriate quality control of the submitted data the reported numbers and incidences should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The growing number of reported treatments in ART, the higher variability in treatment modalities and the rising contribution to the birth rates over the last 20 years point towards the increasing impact of ART. High levels of completeness in data reporting have been reached, but inconsistencies and inaccuracies still remain and need to be identified and quantified. The current trend towards a higher diversity in treatment modalities and the rising impact of cryostorage, resulting in improved safety during and after ART treatment, require changes in the organization of surveillance in ART. The present comparison must stimulate all stakeholders in ART to optimize surveillance and data quality assurance in ART. STUDY FUNDING/COMPETING INTEREST(S): This study has no external funding and all costs are covered by ESHRE. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Women's perceptions of fertility assessment and counselling 6 years after attending a Fertility Assessment and Counselling clinic in Denmark.

STUDY QUESTION: What are women's perceptions and experience of fertility assessment and counselling 6 years after attending a Fertility Assessment and Counselling (FAC) clinic in Denmark? SUMMARY ANSWER: Women viewed the personalized fertility knowledge and advice they received as important aids to decision-making and they felt the benefits outweighed the risks of receiving personalized fertility information. WHAT IS KNOWN ALREADY: Many young people wish to become parents in the future. However, research demonstrates there is a gap in women's and men's knowledge of fertility and suggests they may be making fertility decisions based on inaccurate information. Experts have called for the development of interventions to increase fertility awareness so that men and women can make informed fertility decisions and achieve their family-building goals. Since 2011, the FAC clinic in Copenhagen, Denmark has provided personalized fertility assessment and guidance based on clinical examination and evaluation of individual risk factors. Available qualitative research showed that attending the FAC clinic increased fertility awareness and knowledge and was experienced as a catalyst for change (e.g. starting to conceive, pursuing fertility treatment, ending a relationship) in women 1-year post-consultation. STUDY DESIGN SIZE DURATION: The study was a 6-year follow-up qualitative study of 24 women who attended the FAC clinic between January and June 2012. All women were interviewed during a 2-month period from February to March 2018 at Rigshospitalet, their home or office, in Copenhagen, Denmark. Interviews were held in English and ranged between 60 and 94 min (mean 73 min). PARTICIPANTS/MATERIALS SETTING METHODS: Invitations to participate in an interview-based follow-up study were sent to 141 women who attended the FAC clinic in 2012. In total, 95 women read the invitation, 35 confirmed interest in participating and 16 declined to participate. Twenty-five interviews were booked and 24 interviews held. Interviews followed a semi-structured format regarding reasons for attending the FAC clinic, if/how their needs were met, and perceptions of fertility assessment and counselling. Data were analysed using thematic analysis. MAIN RESULTS AND THE ROLE OF CHANCE: At the follow-up interview, women were on average 39.5 years old. Ten were currently single or dating and 14 were married/cohabiting. All were childless when they attended the FAC clinic. At the follow-up interview, 21 women were parents (14 women with one child; 6 with two children; 1 with three children) and the remaining three women intended to have children in the future. The most common reason for originally attending the FAC clinic was to determine how long they could delay childbearing. Most of the women now believed their needs for attending had been met. Those who were dissatisfied cited a desire for more exact ('concrete') information as to their remaining years of fertility, although acknowledged that this was likely not realistic. Women stated that they had felt reassured as to their fertility status after attending the FAC clinic whilst receiving the message that they could not delay childbearing 'too long'. Women viewed personalized fertility knowledge as an important aid to decision-making but cautioned about developing a false sense of security about their fertility and chance of conceiving in the future based on the results. Although women were generally satisfied with their experience, they wished for more time to discuss options and to receive additional guidance after their initial meeting at the FAC clinic. LIMITATIONS REASONS FOR CAUTION: Participants were from a group of Danish women attending the FAC clinic and interviews were conducted in English, which means they are not representative of all reproductive-aged women. Nevertheless, the study group included a broad spectrum of women who achieved parenthood through different means (heterosexual/lesbian relationship, single parent with donor, co-parent) with various family sizes, and women who were currently childless. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides support for an individualized approach to fertility education, assessment and counselling provided at a time when the information is relevant to the individual and their current fertility decision-making. The findings suggest that although satisfied with their visit to the FAC clinic, the women wished for more information and guidance after this visit, suggesting that the current intervention may need to be expanded or new interventions developed to meet these additional needs. STUDY FUNDING/COMPETING INTERESTS: E.K. was funded by an ESHRE Travel/Training grant by ReproUnion, co-financed by the European Union, Interreg V OKS. J.B. reports that the risk evaluation form used at the Fertility Assessment Clinic was inspired by the Fertility Status Awareness Tool FertiSTAT that was developed at Cardiff University for self-assessment of reproductive risk. J.B. also reports personal fees from Merck KGaA, Merck AB, Theramex, Ferring Pharmaceuticals A/S and a research grant from Merck Serono Ltd outside the submitted work. A.N.A. has received personal fees from both Merck Pharmaceuticals and Ferring and grants from Roche Diagnostics outside the submitted work. The other authors report no conflicts of interest.

Surgery, gonadotropin-releasing hormone agonist downregulation and in vitro fertilisation in women with infertility and endometriomas.

INTRODUCTION: Tonsillectomy is one of the most common procedures in the field of ear, nose and throat procedures. In 2012, the annual incidence in Denmark was 129.4 per 100,000 inhabitants. A common complication is post-tonsillectomy haemorrhaging (PTH). The overall PTH rates vary widely among studies ranging from 0.5% to 33%. METHODS: This was a nationwide open-population, retrospective and registry-based cohort study in Danes who underwent tonsillectomy complicated by PTH in hospitals and private otorhinolaryngology (ORL) offices in the period from 1991 to 2012. RESULTS: In the 1991-2012 period, a total of 177,211 tonsillectomies were performed among which 9,221 had a registered PTH (rPTH) (5.2%). The annual incidence rate of rPTH increased from 3% in 1991 to 13% in 2012 (p less-than 0.05). Males aged 20-40 years had a significantly higher risk of rPTH with the highest increase in rPTH incidence rates from 9.0% in 1998 to 16.4% in 2012 (p less-than 0.05). Approx. 12% had a primary rPTH within the first 24 hours; the maximum incidence of rPTH was on day six (14%). CONCLUSIONS: The rate of rPTH increased from 1991 to 2012 in hospitals and in private ORL office settings alike. There was a significantly higher rate of rPTH in the age group of 20-40 years and a significant geographical difference in rPTH. The highest risk of rPTH was observed on the day of surgery and on day six. TRIAL REGISTRATION: The Danish Data Protection Agency (record number 2012-41-0158) approved this study. FUNDING: The Olga Bryde Nielsen Foundation and H. Skouby & E. Skouby's Foundation supported this study financially.

No effect of oral sucrose or IV glucose during exercise in phosphorylase b kinase deficiency.

This case report investigated exercise metabolism and the effect of oral sucrose and intravenous glucose supplementation in a 30-year-old, mildly affected man with muscle phosphorylase b kinase (PHK) deficiency caused by a novel c.586G>A mutation in the PHKA1 gene. Only 12 patients with PHK deficiency have been reported and it is unclear to what extent patients exhibit symptoms during exercise. Carbohydrate and fat metabolism were measured during 30 min of exercise at ∼ 70% of peak oxidative capacity using stabile isotope technique and signaling proteins and enzymes in the energy pathway were analyzed by Western blot. Results were compared to four healthy subjects. These studies show that neither oral nor intravenous glucose improved exercise tolerance in this patient with PHK deficiency. Despite Western blots indicated affected metabolism on protein level, systemic substrate turnover studies showed that carbohydrate and fatty acid oxidations were normal.

Follicular hormone dynamics during the midcycle surge of gonadotropins in women undergoing fertility treatment.

Changes in concentrations of intra-follicular hormones during ovulation are important for final oocyte maturation and endometrial priming to ensure reproductive success. As no human studies have investigated these changes in detail, our objective was to describe the dynamics of major follicular fluid (FF) hormones and transcription of steroidogenic enzymes and steroid receptors in human granulosa cells (GCs) during ovulation. We conducted a prospective cohort study at a public fertility clinic in 2016-2018. Fifty women undergoing ovarian stimulation for fertility treatment were included. From each woman, FF and GCs were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation, and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 h after OI. Follicular fluid concentrations of oestradiol, progesterone, androstenedione, testosterone, 17-hydroxyprogesterone, anti-Mullerian hormone, inhibin A and inhibin B were measured using ELISA assays, and a statistical mixed model was used to analyse differences in hormone levels between time points. Gene expression of 33 steroidogenic enzymes and six hormone receptors in GCs across ovulation were assessed by microarray analysis, and selected genes were validated by quantitative reverse transcription PCR. We found that concentrations of oestradiol, testosterone, progesterone, AMH, inhibin A and inhibin B (P < 0.001) and gene expression of 12 steroidogenic enzymes and five receptors (false discovery rate < 0.0001) changed significantly during ovulation. Furthermore, we found parallel changes in plasma hormones. The substantial changes in follicular hormone production during ovulation highlight their importance for reproductive success.

Clinical characteristics including cardiovascular and metabolic risk factors in adolescents with psoriasis.

BACKGROUND: Clinical studies on psoriasis in adolescents have mainly been performed in patients with severe psoriasis. Population-based studies of clinical characteristics and risk factors for later cardiovascular and metabolic disease in children and adolescents are lacking. OBJECTIVES: To examine the clinical characteristics of adolescents with psoriasis nested in a general population cohort. Furthermore, to investigate cardiovascular and metabolic risk factors in the adolescents with psoriasis compared to parentally predisposed and non-predisposed adolescents without psoriasis from the same birth cohort. METHODS: We identified adolescents with and without psoriasis using a nationwide general population birth cohort in Denmark. A clinical examination included skin inspection and scoring of psoriasis severity, completion of a questionnaire on psoriasis and comorbidities, physical measurements, and blood sampling. Participants also completed self-administered questionnaires on quality of life and mental health. RESULTS: We included 81 adolescents with psoriasis and 234 controls (110 with genetic predisposition for psoriasis and 124 without predisposition). Median age was 15.6 (13.5-18.5) years, and in those with active psoriasis, median Psoriasis Area and Severity Index score was 1.2 (0.1-11.4). The scalp was the most common site of psoriasis, both at debut and at time of examination. Diaper rash in infancy was more frequent in the psoriasis group. No significant differences regarding quality of life, anxiety and depression were found. More adolescents with psoriasis were obese (8.6% vs. 1.7%, P = 0.008), and physical measures of abdominal obesity were also significantly higher. HbA1c was significantly higher (31.55 vs. 30.81 mmol/mol, P = 0.048), while no differences were found for blood pressure, lipids or high-sensitivity C-reactive protein. In a subgroup analysis, this was evident in the non-predisposed psoriasis-free controls only. CONCLUSIONS: Overall, adolescents with psoriasis from this general population had mild disease. Still, early markers of cardiovascular and metabolic disease were elevated.

Oral contraceptive use and genital anomalies in sons. A Danish cohort study.

Exposure to exogenous sex hormones with estrogenic or anti-androgen properties may influence intrauterine development of male genitals. This population-based cohort study based on data from 44,408 live-born singleton sons in the Danish National Birth Cohort (DNBC) aimed to investigate whether maternal use of oral contraceptives prior to or during early pregnancy increase the risk of cryptorchidism or hypospadias. We found no consistent association between use of oral contraceptives and cryptorchidism or hypospadias, neither in those exposed any time four months prior to conception [cryptorchidism: adjusted Odds Ratio (aOR): 1.06 (95% CI: 0.91; 1.23), hypospadias: 0.74 (95% CI: 0.53; 1.03)] nor in those exposed any time during the first trimester of pregnancy [cryptorchidism: aOR: 0.93 (95% CI: 0.53; 1.62), hypospadias: 1.02 (95% CI: 0.32; 3.23)]. Despite relatively strong exposure levels from oral contraceptive use in pregnancy, this study revealed no evidence of an increased risk of either two genital malformations.