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For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

Ovarian hyperstimulation syndrome (OHSS) in patients on tamoxifen therapy is a rare but potentially serious complication. This patient underwent a laparoscopic unilateral salpingo-oophorectomy due to persistent pelvic pain and received a gonadotropin-releasing hormone (GnRH) agonist injection with normalisation of her oestradiol level, previously elevated to 956 pg/mL. Management options of OHSS include medical therapy with GnRH agonists or surgical intervention. Studies have shown that GnRH agonists can effectively normalise oestradiol levels and induce the resolution of cysts in these patients. Additionally, combined therapy with tamoxifen and GnRH agonists may reduce the risk of OHSS. Risk factors for OHSS during tamoxifen treatment include younger age and absence of chemotherapy. Monitoring of oestradiol levels and close clinical follow-up are essential in managing patients on tamoxifen therapy to prevent and promptly address OHSS.

Objectives Intercountry comparability between studies on medication use in pregnancy is difficult due to dissimilarities in study design and methodology. This study aimed to examine patterns and factors associated with medications use in pregnancy from a multinational perspective, with emphasis on type of medication utilised and indication for use. Design Cross-sectional, web-based study performed within the period from 1 October 2011 to 29 February 2012. Uniform collection of drug utilisation data was performed via an anonymous online questionnaire. Setting Multinational study in Europe (Western, Northern and Eastern), North and South America and Australia. Participants Pregnant women and new mothers with children less than 1 year of age. Primary and secondary outcome measures Prevalence of and factors associated with medication use for acute/short-term illnesses, chronic/long-term disorders and over-the-counter (OTC) medication use. Results The study population included 9459 women, of which 81.2% reported use of at least one medication (prescribed or OTC) during pregnancy. Overall, OTC medication use occurred in 66.9% of the pregnancies, whereas 68.4% and 17% of women reported use of at least one medication for treatment of acute/short-term illnesses and chronic/long-term disorders, respectively. The extent of self-reported medicated illnesses and types of medication used by indication varied across regions, especially in relation to urinary tract infections, depression or OTC nasal sprays. Women with higher age or lower educational level, housewives or women with an unplanned pregnancy were those most often reporting use of medication for chronic/long-term disorders. Immigrant women in Western (adjusted OR (aOR): 0.55, 95% CI 0.34 to 0.87) and Northern Europe (aOR: 0.50, 95% CI 0.31 to 0.83) were less likely to report use of medication for chronic/long-term disorders during pregnancy than non-immigrants. Conclusions In this study, the majority of women in Europe, North America, South America and Australia used at least one medication during pregnancy. There was a substantial inter-region variability in the types of medication used.

Abstract STUDY QUESTION What are the direct costs of assisted reproductive technology (ART), and how affordable is it for patients in low- and middle-income countries (LMICS)? SUMMARY ANSWER Direct medical costs paid by patients for infertility treatment are significantly higher than annual average income and GDP per capita, pointing to unaffordability and the risk of catastrophic expenditure for those in need. WHAT IS KNOWN ALREADY Infertility treatment is largely inaccessible to many people in LMICs. Our analysis shows that no study in LMICs has previously compared ART medical costs across countries in international dollar terms (US$PPP) or correlated the medical costs with economic indicators, financing mechanisms, and policy regulations. Previous systematic reviews on costs have been limited to high-income countries while those in LMICs have only focussed on descriptive analyses of these costs. STUDY DESIGN, SIZE, DURATION Guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA), we searched PubMed, Web of Science, Cumulative Index of Nursing and Allied Health Literature, EconLit, PsycINFO, Latin American & Caribbean Health Sciences Literature, and grey literature for studies published in all languages from LMICs between 2001 and 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS The primary outcome of interest was direct medical costs paid by patients for one ART cycle. To gauge ART affordability, direct medical costs were correlated with the GDP per capita or average income of respective countries. ART regulations and public financing mechanisms were analyzed to provide information on the healthcare contexts in the countries. The quality of included studies was assessed using the Integrated Quality Criteria for Review of Multiple Study designs. MAIN RESULTS AND THE ROLE OF CHANCE Of the 4062 studies identified, 26 studies from 17 countries met the inclusion criteria. There were wide disparities across countries in the direct medical costs paid by patients for ART ranging from USD2109 to USD18 592. Relative ART costs and GDP per capita showed a negative correlation, with the costs in Africa and South-East Asia being on average up to 200% of the GDP per capita. Lower relative costs in the Americas and the Eastern Mediterranean regions were associated with the presence of ART regulations and government financing mechanisms. LIMITATIONS, REASONS FOR CAUTION Several included studies were not primarily designed to examine the cost of ART and thus lacked comprehensive details of the costs. However, a sensitivity analysis showed that exclusion of studies with below the minimum quality score did not change the conclusions on the outcome of interest. WIDER IMPLICATIONS OF THE FINDINGS Governments in LMICs should devise appropriate ART regulatory policies and implement effective mechanisms for public financing of fertility care to improve equity in access. The findings of this review should inform advocacy for ART regulatory frameworks in LMICs and the integration of infertility treatment as an essential service under universal health coverage. STUDY FUNDING/COMPETING INTEREST(S) This work received funding from the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO). The authors declare no competing interests. TRIAL REGISTRATION NUMBER This review is registered with PROSPERO, CRD42020199312.

A woman in her 20s was referred to a tertiary hospital emergency department for management of a migrating Implanon NXT. The Implanon was inserted 1 week prior by the patient’s general practitioner who was unable to palpate the Implanon after insertion and hence, ordered an ultrasound scan which showed an actively migrating Implanon in the left basilic vein. She had mild chest pain, and her physical examination, ECG and blood tests were unremarkable. A CT chest showed a 31 mm foreign body within the right lower lobar artery. The foreign body was removed by interventional radiology by accessing the right internal jugular vein under ultrasound guidance and inserting a 6 FR pig catheter into the pulmonary trunk. The position was confirmed with angiogram and the foreign body was removed using a goose neck snare. The patient was discharged the same day with no complications, and fell pregnant a few months afterwards.

ObjectivesTo investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery.DesignPopulation based prospective cohort study.SettingNorway, between 1999 and 2008.Participants70 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37 050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34 458 cases.Main outcome measuresAdjusted OR for preeclampsia and preterm delivery according to consumption of probiotic milk at three different time periods (before pregnancy, during early and late pregnancy).ResultsProbiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03).ConclusionsIn this observational study, we found an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. If future randomised controlled trials could establish a causal association between probiotics consumption and reduced risk of preeclampsia and preterm delivery, recommending probiotics would be a promising public health measure to reduce these adverse pregnancy outcomes.

ObjectivesEndometriosis is a chronic disease with no known cure. Persons affected by this disease often use complementary therapies such as dietary changes to reduce their symptoms, and so it is important to investigate whether and how these therapies affect endometriosis symptoms. The aim of this study was to explore how persons with endometriosis experienced their health after dietary changes.DesignSemi-structured qualitative interviews were conducted with 12 persons with endometriosis who had made individual dietary changes aimed at decreasing their endometriosis symptoms. The interviews were recorded and transcribed verbatim, and analysed using thematic analysis.SettingRegion Västra Götaland and the estern part of Central Sweden, Sweden.ParticipantsTwelve persons with endometriosis aged 28 to 44 were recruited from two Swedish endometriosis support forums on the Internet.ResultsParticipants experienced an increase in well-being and a decrease in symptoms following their dietary and lifestyle changes. They also felt that the dietary changes led to increased energy levels and a deeper understanding of how they could affect their health by listening to their body’s reactions. The participants understood that they could influence their symptoms through lifestyle changes. Support from family and friends was important in implementing and sustaining the dietary changes. However, the participants stressed the lack of support from healthcare professionals.ConclusionsThis study contributes to filling the knowledge gap about dietary strategies in endometriosis and lifestyle change as a method of alleviating suffering and increasing well-being. An important finding is that the participants experienced decreased symptoms and increased well-being after adopting an individually-adapted diet. Healthcare professionals should take their patients’ knowledge and experience into consideration, and allow patients to participate in their own care. Further research is necessary to give evidenced-based dietary advices in endometriosis.

IntroductionFollowing the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysisWomen with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18–32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children’s Abilities-Revised questionnaire.Ethics and disseminationThe Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.Trial registration numberMain sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

ObjectiveTo compare experiences of the second stage of labour in women randomised to assistance by one or by two midwives to reduce severe perineal trauma (SPT).DesignAnalysis of a secondary outcome within the Swedish Oneplus multicentre randomised trial.SettingFive obstetric units in Sweden between December 2018 and March 2020.ParticipantsInclusion criteria in the Oneplus trial were women opting for their first vaginal birth from gestational week 37+0 with a singleton pregnancy and a live fetus in the vertex presentation. Further inclusion criteria were language proficiency in Swedish, English, Arabic or Farsi. Exclusion criteria were multiple pregnancies, intrauterine fetal demise and planned caesarean section. Of the 3059 women who had a spontaneous vaginal birth, 2831 women had consented to participate in the follow-up questionnaire.InterventionsWomen were randomly assigned (1:1) to assistance by two midwives (intervention group) or one midwife (standard care) when reaching the second stage of labour.Outcome measuresData were analysed by intention to treat. Comparisons between intervention and standard care regarding experiences of the second stage of labour were evaluated with items rated on Likert scales. The Student’s t-test was used to calculate mean differences with 95% CIs.ResultsIn total 2221 (78.5%) women responded to the questionnaire. There were no statistically significant differences regarding women’s experiences of being in control, feelings of vulnerability or pain. Women randomised to be assisted by two midwives agreed to a lesser extent that they could handle the situation during the second stage (mean 3.18 vs 3.26, 95% CI 0.01 to 0.15). Conducted subgroup analyses revealed that this result originated from one of the study sites.ConclusionsThe intervention’s lack of impact on the experience of the second stage is of importance considering the reduction in SPT when being assisted by two midwives.Trial registration number NCT03770962.