Risk factors for and consequences of difficult fetal extraction in emergency caesarean section. A retrospective registry-based cohort study.

INTRODUCTION: This study aimed to assess risk factors for difficult fetal extraction in emergency caesarean sections, focusing on top-up epidural anesthesia compared to spinal anesthesia. Additionally, this study addressed consequences of difficult fetal extraction on neonatal and maternal morbidity. MATERIAL AND METHODS: This retrospective registry-based cohort study included 2,332 of 2,892 emergency caesarean sections performed with local anesthesia during 2010-2017. Main outcomes were analyzed by crude and multiple adjusted logistic regression providing odds ratios. RESULTS: Difficult fetal extraction was found in 14.9% of emergency caesarean sections. Risk-factors for difficult fetal extraction included top-up epidural anesthesia (aOR:1.37[95 %CI 1.04-1.81]), high pre-pregnancy BMI (aOR:1.41[95 %CI 1.05-1.89]), deep fetal descent (ischial spine: aOR:2.53[95 %CI 1.89-3.39], pelvic floor: aOR:3.11[95 %CI 1.32-7.33]), and anterior placental position (aOR:1.37[95 %CI 1.06-1.77]). Difficult fetal extraction was associated with increased risk of low umbilical artery pH 7.00-7.09 (aOR:3.50[95 %CI 1.98-6.15]) pH ≤ 6.99 (aOR:4.20[95 %CI 1.61-10.91]), five-minute Apgar score ≤ 6 (aOR:3.41[95 %CI 1.49-7.83]) and maternal blood loss (501-1,000 ml: aOR:1.65[95 %CI 1.27-2.16], 1,001-1,500 ml: aOR:3.24[95 %CI 2.24-4.67], 1,501-2,000 ml: aOR:3.94[95 %CI 2.24-6.94] and ≥ 2001 ml: aOR:2.76[95 %CI 1.12-6.82]). CONCLUSION: This study identified four risk factors for difficult fetal extraction in emergency caesarean section: top-up epidural anesthesia, high maternal BMI, deep fetal descent and anterior placental position. Additionally, difficult fetal extraction was associated with poor neonatal and maternal outcomes.

Incidence of persistent postpartum opioid use by mode of delivery: a 2016 cohort study of Danish women.

BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365 days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.

Adhesive bowel obstruction: Incidence, recurrence and 30-day mortality in Danish women 1984-2013 - A national cohort study.

BACKGROUND: Adhesive bowel obstruction is a serious complication to abdominal surgery. It is unknown whether incidence and mortality rates have changed as new surgical procedures were introduced. METHODS: In a nationwide cohort of Danish women from 1984 to 2013, incidence of adhesive bowel obstruction and 30 days mortality were presented as standardized rates. Impact of treatment was analyzed by Cox regression and recurrent disease characterized by Kaplan Meyer estimates. RESULTS: Incidence of adhesive bowel obstruction increased 50% among women with no prior abdominal surgery. These women had 3-5 times lower incidence than those with a surgical record. 30-day mortality rate was 13%, highest in patients treated non-operatively. The mortality declined in recent years. Recurrent disease had lower mortality rates compared to the first episode. CONCLUSIONS: The incidence of adhesive bowel obstruction increased during the last 30 years, mortality after the first episode is high, while recurrent disease shows declining mortality rates.

A randomized controlled trial of AMH-based individualized FSH dosing in a GnRH antagonist protocol for IVF.

STUDY QUESTION: Does an individualized serum anti-Müllerian hormone (AMH) based FSH dosing algorithm used in a GnRH antagonist protocol increase the proportion of patients with an intended number of oocytes (5-14) retrieved compared with a standard regimen? SUMMARY ANSWER: The AMH-based individualized algorithm did not increase the proportion of patients with an intended oocyte retrieval. WHAT IS KNOWN ALREADY: Individualizing treatment for ovarian stimulation by serum AMH or antral follicle count can theoretically improve the ratio between benefits and risks. Current data suggest that there may be a reduced risk of ovarian hyperstimulation syndrome (OHSS), but without improved pregnancy or live birth rates. Only two randomized controlled trials (RCTs) have examined the potential of AMH-based algorithms to optimize the FSH dosing in ovarian stimulation. STUDY DESIGN SIZE DURATION: A dual-center open-label investigator-driven RCT was conducted between January 2013 and November 2016. Eligibility was assessed in 269 women and 221 were randomized 2:1 between individualized and standard dosing groups. Women with pretreatment serum AMH > 24 pmol/L had 100 IU/day of recombinant FSH (rFSH); AMH 12-24 pmol/L had 150 IU/day of rFSH, and AMH < 12 pmol/L had maximal stimulation with corifollitropin 100 or 150 mg depending on bodyweight ±60 kg. The standard group had 150 IU/day of rFSH irrespective of pretreatment AMH. All patients followed the GnRH-antagonist protocol.The sample size calculation assumed that individualized dosing by AMH would reduce the proportion of unintended oocyte yield (outside the 5-14 range) by 50%, from 35 to 17.5%. In a 2:1 randomization this required 216 patients: 144 in the individualized and 72 patients in the standard group (80% power, 5% significance). PARTICIPANTS/MATERIALS SETTING METHODS: All women had a presumed ovulatory normal menstrual cycle, were aged 25-38 years, weighed < 75 kg, had pretreatment AMH 4-40 pmol/L, did their first IVF or ICSI cycle and had two ovaries accessible to oocyte retrieval. Recruitment was conducted from both participating sites. Women were excluded if diagnosed with anovulatory polycystic ovary syndrome, endometriosis grade III/IV, hydrosalpings on ultrasound, recurrent miscarriages (≥3), FSH > 12 IU/L or major medical disorders. MAIN RESULTS AND THE ROLE OF CHANCE: After randomization 149 women were allocated to the individualized group and 72 to the standard group. The primary outcome of women with an intended (5-14) number of oocytes retrieved was similar in the individualized (n = 105) versus the standard (n = 55) rFSH treatment group (72% [95% CI 64-79%] versus 78% [95% CI 67-86%], respectively, P = 0.68, between group standardized mean difference (SMD) -6%, 95% CI: -19-8%). In the high AMH stratum of the individualized group, significantly more women (n = 13) had an unintended low number of oocytes (<5) retrieved (38% [95% CI: 23-55%]) compared with the standard group (6% [95% CI 0.3-24%], P = 0.029, between group SMD 32%, 95% CI: 9-56%). Conversely, in the low pretreatment AMH stratum, individualized dosing using corifollitropin reduced the proportion of unintended low responders to 24% (95% CI: 12-40%) compared with 47% (95% CI: 26-69%) in the standard group, P = 0.10, between group SMD -23% (95% CI: -54-8%). OHSS was diagnosed in four women (two in each study arm), and all cases were mild. Daily luteal phase questionnaire reporting showed similar wellbeing in terms of abdominal distention, abdominal pain, dyspnea and occurrence of bleeding between groups. The cumulative live birth rate per started cycle was similar (32 and 35%) comparing the individualized with the standard group. LIMITATIONS REASONS FOR CAUTION: This study was powered for showing differences only in the distribution of oocyte retrieval when comparing individualized and standard groups, therefore additional results should be viewed with caution. In addition, there was a change of AMH assay halfway through the study period and the possibility that corifollitropin being introduced to a subgroup of the intervention has introduced confounding cannot be ruled out. WIDER IMPLICATIONS OF FINDINGS: In the expected high responder AMH stratum, 100 IU/day is an insufficient rFSH dose in a high proportion of patients. Further research might explore the 125 IU/day dose for the high AMH segment. STUDY FUNDING/COMPETING INTERESTS: None for the submitted work. ICMJE declared personal interests for two of the authors. TRIAL REGISTRATION NUMBER: EUDRACT registration number: 2012-004969-40. TRIAL REGISTRATION DATE: 27 November 2012. DATE OF FIRST PATIENT'S ENROLLMENT: 10 January 2013.

Are Danish doctors comfortable teaching in English?

BACKGROUND: From 2012-2015, the Departments of Obstetrics and Gynecology and of Pediatrics at the University of Copenhagen conducted a project, "Internationalization at Home ", offering clinical teaching in English. The project allowed international students to work with Danish speaking students in a clinical setting. Using semi-quantitative questionnaires to 89 clinicians about use of English and need for training, this paper considers if Danish clinical doctors are prepared to teach in English. RESULTS: The majority self-assessed their English proficiency between seven and eight on a 10 unit visual analogue scale, with 10 equivalent to working in Danish, while 15 % rated five or less. However, one-fourth found teaching and writing in English to be twice as difficult than in Danish, and 12 % rated all teaching tasks in English at four or less compared to Danish. The self-assessed need for additional English skills was perceived low. CONCLUSION: Teaching in English was rated as 30 % more difficult than in Danish, and a significant subgroup of doctors had difficulties in all forms of communication in English, resulting in challenges when introducing international students in non-native English speaking medical departments.

Prospective multi-centre randomised trial comparing induction of labour with a double-balloon catheter versus dinoprostone.

This randomised controlled study compared the efficacy of double-balloon catheter versus vaginal prostaglandin E2 (dinoprostone) for induction of labour. In total, 825 pregnant women with cephalic presentation and an unfavourable cervix undergoing induction for conventional indications were randomised to double-balloon or vaginal dinoprostone (3 mg) groups. There was a significantly higher failure rate for labour induction in the balloon group (relative risk: 1.25, 95% confidence interval [CI]: 1.02-1.49). Median induction time was 27.3 h in the balloon group and 29.8 h in the dinoprostone group (difference not significant). After 24 h, 55.3% had given birth in the balloon group versus 54.3% in the dinoprostone group. Additional oxytocin stimulation was used more often in the balloon (46%) compared with that in the dinoprostone (34%) (relative risk: 1.34 (95%CI 1.16 -1.54) group. Caesarean section rates and neonatal outcome were similar. Overall, the two methods for induction were comparable with regard to efficacy and safety.

Combined hormonal contraception and risk of venous thromboembolism within the first year following pregnancy. Danish nationwide historical cohort 1995-2009.

Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15-49 during the period of 1995-2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.

Drinking pattern and mortality in Danish nurses.

BACKGROUND/OBJECTIVE: Moderate alcohol consumption has beneficial effects on survival. Sex differences, however, have been suggested implying less beneficial effect among women. We examined the impact of alcohol consumed on weekdays and at weekends, respectively, on risk of death among women. SUBJECTS AND METHODS: At baseline in 1993, a total of 17 772 female members of the Danish Nurse Association completed questionnaires on alcohol intake and other lifestyle factors. The influence of alcohol intake on risk of death was analyzed using Cox proportional hazard model. RESULTS: Alcohol intake of 1-3 drinks per week was associated with the lowest risk of death. Intake above six drinks per weekend (Friday through Sunday) increased risk of death from all causes by 3% for each additional drink consumed per weekend (corresponding to an increased risk by 9% per drink per weekend day). Consumption of one or more drinks per weekday (Monday, Tuesday, Wednesday or Thursday) increased risk by 4% for each additional drink consumed per day. CONCLUSIONS: The results indicated an increasing risk of death for intake above six drinks per weekend and of one or more drinks per weekday.

The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.

UNLABELLED: Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. OBJECTIVE: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. METHODS: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. RESULTS: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found. CONCLUSION: We found an increased risk of ischaemic heart disease associated with early removal of the ovaries that might be reduced with HT. The present study need confirmation from other studies but suggests that early ovariectomised women could benefit from HT.

Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study.

OBJECTIVE: To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors. DESIGN: Prospective observational study. SETTING: Denmark. PARTICIPANTS: 19 898 nurses aged 45 and over completing a questionnaire on lifestyle and use of hormone replacement therapy in 1993. MAIN OUTCOME MEASURES: All cases of death and incident cases of ischaemic heart disease and myocardial infarction until the end of 1998. RESULTS: Current users of hormone replacement therapy smoked more, consumed more alcohol, had lower self rated health, but were slimmer and had a lower prevalence of diabetes than never users. In current users compared with never users, hormone replacement therapy had no protective effect on ischaemic heart disease (hazard ratio 1.2, 0.9 to 1.7) or myocardial infarction (1.0, 0.6 to 1.7), whereas current users with diabetes had an increased risk of death (3.2, 1.4 to 7.5), ischaemic heart disease (4.2, 1.4 to 12.5), and myocardial infarction (9.2, 2.0 to 41.4) compared with never users with diabetes. CONCLUSION: Hormone replacement therapy showed no protective effect on ischaemic heart disease, but there was a significantly increased risk of death from all causes and ischaemic heart disease among women with diabetes.

The influence of hormone replacement therapy on the aging-related change in cognitive performance. Analysis based on a Danish cohort study.

OBJECTIVE: A maintenance and/or improvement of cognitive performance with postmenopausal hormone replacement therapy (HRT) is biological plausible. The objectives of this study were to analyze the impact of HRT on aging-related changes in cognitive performances, and to assess whether women who choose HRT have better cognitive performance prior to HRT. METHODS: Data derives from a longitudinal sub-cohort of women participating in a large survey of the general adult population-The Danish MONICA (MONItoring CArdiovascular risk factors) Study. Main variables for analyses come from neuropsychological examination consisting of 28 cognitive parameters collected in 1982-1983 and again in 1993-1994, by a computer-aided test technique, the Cognitive Function Scanner((R)). The final analyses comprised 126 'never users', 40 'current users' at follow-up, and 30 'future users' of HRT (women who started HRT during the observation period subsequent to baseline registration). RESULTS: 'Current users' of HRT at follow-up showed a less pronounced decline in cognitive performance compared to 'never users' in one of six parameters for concentration ability and two of eight parameters for visuomotor function. 'Future users' of HRT had better cognitive performance at baseline compared to 'never users' in long-term visual memory, concentration, and reaction time. 'Future users' of HRT were more precise but spent more time in the tests for visuomotor function than 'never users'. CONCLUSION: HRT-treated women show a postponed aging-related decline in cognitive functioning, partly in concentration and partly in visuomotor function. However, women who choose HRT have better cognitive performance prior to the treatment.