Ingvil Krarup Sørbye

Pre-eclampsia affects 2–8% of all pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality. A randomised trial in South Africa suggested metformin used to treat preterm pre-eclampsia (26–32 weeks’ gestation) may prolong pregnancy by 7 days compared with standard care. However, this finding was borderline significant and requires validation in higher-resource settings and in diverse populations. Here, we present a Nordic multicentre trial protocol designed to evaluate whether extended-release metformin can prolong gestation in women with preterm pre-eclampsia. Pre-eclampsia Intervention 4 trial is a phase III, double-blind, multicentre randomised controlled trial conducted in Sweden, Norway and Finland aiming to investigate whether metformin can prolong gestation in preterm pre-eclampsia. A total of 294 women between 22+0 and 33+6 weeks of gestation with pre-eclampsia and planned to undergo expectant management will be enrolled. Participants are randomised to receive one gram of extended-release metformin or matching placebo three times daily. The primary outcome is prolongation of gestation defined as time from randomisation to birth. Secondary outcomes include length of neonatal hospital stay and neonatal birth weight. Adverse events will be reported in line with current clinical trial guidelines. All efficacy analyses will be conducted according to the intention-to-treat principle. The trial is conducted in accordance with Good Clinical Practice, as defined by the International Council for Harmonisation. The protocol, including amendments, was approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency in accordance with national legislation, and authorised for Finland and Norway through the Clinical Trials Information System in accordance with the EU Clinical Trials Regulation. Results will be disseminated at international conferences and published in peer-reviewed journals and communicated via popular science outlets, media, patient organisations and the trial website: https://www.preeclampsiaresearch.com/pi-trials. NCT06033131.

Migration status and socioeconomic factors may influence access to and provision of gynaecological surgical care. However, evidence from European settings remains limited. This study aimed to examine disparities in surgical approach and indications for hysterectomy by migration status, while adjusting for education and income, among women with benign gynaecological conditions in Norway. We conducted a nationwide register-based cohort study using data from the Norwegian Patient Registry, including all women who underwent hysterectomy for benign indications in Norway between 2008 and 2020 (n = 38 913). Surgical approach was categorized as laparoscopic, vaginal, or open abdominal. Multinomial logistic regression was used to estimate odds ratios (OR), 95% confidence intervals (CI) and absolute risk difference for laparoscopic and vaginal hysterectomy compared with open surgery, adjusting for demographic, clinical, and socioeconomic factors. The frequency of surgical indications was assessed by migration status and regional group of birth. Migrants had lower odds of undergoing laparoscopic hysterectomy (OR 0.66, 95% CI: 0.57–0.77) and vaginal hysterectomy (OR 0.60, 95% CI: 0.49–0.75), compared with open surgery. Higher income was associated with increased odds of laparoscopic hysterectomy, with a stronger association observed among migrants. Migrants had lower proportions of hysterectomies performed due to genital prolapse and higher proportions due to fibroid compared with Norwegian-born women. Migration status is associated with surgical approach and hysterectomy indications, suggesting inequities in minimally invasive surgery despite Norway’s universal health coverage. These findings highlight the need for efforts to ensure equitable surgical care in gynaecology.

Introduction Presently, more than one in four births in high-income countries undergo labour induction. Induction of labour is an independent risk factor for adverse obstetric outcomes, including high rates of operative delivery. Two drugs, hyoscine butylbromide and sodium bicarbonate, have been used in labour to facilitate cervical dilation and prevent uterine lactate accumulation. However, no previous randomised trial has systematically studied the separate and combined effects of these drugs in women with induction of labour. Methods and analysis The Safe Induction of Labour Trial (SAINT) study will assess the efficacy of oral sodium bicarbonate and intravenous hyoscine butylbromide on facilitating spontaneous (ie, non-operative) delivery in nulliparous participants with induction of labour. We present a 2×2 factorial design where three active treatment arms are compared with double-placebo. Participants are recruited at 10 delivery departments across Norway. Treatment will start on diagnosis of established labour with a maximum of three consecutive doses 4 hours apart. Approximately 5100 women will be screened to achieve 3000 participants randomly assigned to study intervention. Statistical analyses The primary outcome of spontaneous delivery will be analysed using binary logistic regression. Results will be presented as marginal adjusted risk differences between each of the three active treatment groups and the double-placebo group. Ethics and dissemination The SAINT study is approved by the Regional Committee for Medical and Health Research Ethics, the European Union Clinical Trials Information System, the Norwegian Medical Products Agency and Institutional Review Boards. Results will be disseminated in peer-reviewed journals and communications to congresses. Trial registration number Clinical Trials: NCT05719467. EudraCT/EUCT: 2021-000392-37/2024-511848-55-00.

Introduction: In response to the increasing rates of induction of labor (IOL), outpatient IOL has emerged as a potential approach to enhance women's satisfaction while reducing costs and staffing requirements. There is a growing interest in oral misoprostol as an outpatient IOL method, particularly in the Nordic region. This study aims to evaluate the clinical outcomes and feasibility of implementing IOL with oral misoprostol as an outpatient procedure.Material and Methods: This multicenter, prospective cohort study is part of the Labor Induction Inpatient and Outpatient (LINO) project (ClinicalTrials.gov Identifier: NCT04746248). Women with low‐risk pregnancies undergoing IOL with oral misoprostol were offered outpatient treatment as an alternative to the standard inpatient approach. The primary outcome was the proportion of births and adverse events occurring before or within 30 min after admission, comparing outpatient and inpatient groups. Secondary outcomes included maternal and neonatal safety and efficacy endpoints.Results: During the study period, 212 women were included in the study: 123 (58.0%) in the outpatient group and 89 (42.0%) in the inpatient group. No births occurred before admission to the hospital or within the first 30 min after admission. Adverse events were rare, and there were no significant differences in safety outcomes between the groups. The duration from hospital admission to giving birth was significantly shorter among women in the outpatient group as compared to the inpatient group (12.3 h vs. 28.1 h, p = 0.001). In the outpatient group, 76.4% of the women completed the misoprostol treatment as outpatients.Conclusions: In this study of 212 women undergoing IOL with oral misoprostol, we found similar safety outcomes between women who chose outpatient IOL and those who chose inpatient IOL. The outpatient group had significantly shorter hospital stays before giving birth, and more than three in four women in the outpatient group completed the misoprostol treatment as outpatients. While larger studies are needed to draw definitive conclusions, our study suggests that implementing oral misoprostol in an outpatient IOL protocol may represent a safe and feasible alternative.

Introduction: Women with cardiovascular disease may be at increased risk of hypertensive disorders of pregnancy (HDP). We aimed to: (1) Investigate the occurrence of HDP in a cohort of pregnant women with cardiovascular disease and compare it with the occurrence in the general population. (2) Assess the association between maternal cardiovascular risk and risk of HDP.Material and methods: We reviewed clinical data on a cohort of 901 pregnancies among 708 women with cardiovascular disease who were followed at the National Unit for Pregnancy and Heart Disease and gave birth at Oslo University Hospital between 2003 and 2018. The exposure under study was maternal cardiovascular risk, classified as low, moderate, or high based on a modified classification by the World Health Organization. The main outcome of interest was HDP, which included pre‐eclampsia and gestational hypertension. The proportion of HDP cases in the general population in the same period was extracted from the Medical Birth Registry of Norway. We used logistic regression to estimate crude and adjusted odds ratios (OR) of HDP, with associated 95% confidence intervals (CIs), for women with moderate‐ and high cardiovascular risk compared to women with low risk.Results: The occurrence of HDP in the study cohort was 12.1% (95% CI: 10.0%–14.4%) and varied between 8.7% (95% CI: 6.5%–11.3%) in the low‐risk group, 15.7% (95% CI: 11.1%–21.4%) in the moderate‐risk group, and 22.2% (95% CI: 15.1%–30.8%) in the high‐risk group. By contrast, the nationwide occurrence of HDP was 5.1% (95% CI: 5.1%–5.2%). In the study cohort, the proportions of pregnancies with gestational hypertension and pre‐eclampsia were similar (6.3% and 5.8%, respectively). Compared to pregnancies with low cardiovascular risk, the adjusted OR of HDP was 2.04 (95% CI: 1.21–3.44) in the moderate‐risk group and 2.99 (95% CI: 1.73–5.18) in the high‐risk group.Conclusions: The occurrence of hypertensive disease of pregnancy in the study cohort was more than doubled compared to the general population in Norway. The risk of HDP increased with maternal cardiovascular risk group. We recommend taking into account maternal cardiovascular risk group when assessing risk and prophylaxis of HDP.

Background: Prolonged labor is a common condition associated with maternal and perinatal complications. The standard treatment with oxytocin for augmentation of labor increases the risk of adverse outcomes. Hyoscine butylbromide is a spasmolytic drug with few side effects shown to shorten labor when used in a general population of laboring women. However, research on its effect on preventing prolonged labor is lacking. We aimed to assess the effect of hyoscine butylbromide on the duration of labor in nulliparous women showing early signs of slow labor. Methods and findings: In this double-blind randomized placebo-controlled trial, we included 249 nulliparous women at term with 1 fetus in cephalic presentation and spontaneous start of labor, showing early signs of prolonged labor by crossing the alert line of the World Health Organization (WHO) partograph. The trial was conducted at Oslo University Hospital in Norway from May 2019 to December 2021. One hundred and twenty-five participants were randomized to receive 1 ml hyoscine butylbromide (Buscopan) (20 mg/ml), while 124 received 1 ml sodium chloride intravenously. Randomization was computer-generated, with allocation concealment by opaque sequentially numbered sealed envelopes. The primary outcome was duration of labor from administration of the investigational medicinal product (IMP) to vaginal delivery, which was analyzed by Weibull regression to estimate the cause-specific hazard ratio (HR) of vaginal delivery between the 2 treatment groups, with associated 95% confidence interval (CI). A wide range of secondary maternal and perinatal outcomes were also evaluated. Time-to-event outcomes were analyzed by Weibull regression, whereas continuous and dichotomous outcomes were analyzed by median regression and logistic regression, respectively. All main analyses were based on the modified intention-to-treat (ITT) set of eligible women with signed informed consent receiving either of the 2 treatments. The follow-up period lasted during the postpartum hospital stay. All personnel, participants, and researchers were blinded to the treatment allocation. Median (mean) labor duration from IMP administration to vaginal delivery was 401 (440.8) min in the hyoscine butylbromide group versus 432.5 (453.6) min in the placebo group. We found no statistically significant association between IMP and duration of labor from IMP administration to vaginal delivery: cause-specific HR of 1.00 (95% CI [0.77, 1.29]; p = 0.993). Among 255 randomized women having received 1 dose of IMP, 169 women (66.3%) reported a mild adverse event: 75.2% in the hyoscine butylbromide group and 57.1% in the placebo group (Pearson’s chi-square test: p = 0.002). More than half of eligible women were not included in the study because they did not wish to participate or were not included upon admission. The participants might have represented a selected group of women reducing the external validity of the study. Conclusions: One intravenous dose of 20 mg hyoscine butylbromide was not found to be superior to placebo in preventing slow labor progress in a population of first-time mothers at risk of prolonged labor. Further research is warranted to answer whether increased and/or repeated doses of hyoscine butylbromide might have an effect on duration of labor. Trial registration: ClinicalTrials.gov (NCT03961165) EudraCT (2018-002338-19)

Introduction: Labor induction rates have increased over the last decades, and in many high‐income countries, more than one in four labors are induced. Outpatient management of labor induction has been suggested in low‐risk pregnancies to improve women's birth experiences while also promoting a more efficient use of healthcare resources. The primary aim of this paper was to assess the proportion of women in a historical cohort that would have been eligible for outpatient labor induction with oral misoprostol. Second, we wanted to report safety outcomes and assess efficacy outcomes for mothers and infants in pregnancies that met the criteria for outpatient care.Material and methods: Criteria for outpatient labor induction with oral misoprostol were applied to a historical cohort of women with induction of labor at two Norwegian tertiary hospitals in the period January 1, through July 31, 2021. The criteria included low‐risk women with an unscarred uterus expecting a healthy, singleton baby in cephalic position at term. The primary outcome was the proportion of women eligible for outpatient labor induction. Secondary outcomes included reasons for ineligibility and, for eligible women, safety and efficacy outcomes.Results: Overall, 29.7% of the 1320 women who underwent labor induction in a singleton term pregnancy met the criteria for outpatient labor induction. We identified two serious adverse events that potentially could have occurred outside the hospital if the women had received outpatient care. The mean duration from initiation of labor induction to administration of the last misoprostol was 22.4 h. One in 14 multiparous women gave birth within 3 h after the last misoprostol dose.Conclusions: In this historical cohort, three in ten women met the criteria for outpatient management of labor induction with oral misoprostol. Serious adverse events were rare. The average time span from the initiation of labor induction to the last misoprostol was nearly 24 h. This suggests a potential for low‐risk women with an induced labor to spend a substantial period of time at home before labor onset. However, larger studies testing or evaluating labor induction with oral misoprostol as an outpatient procedure are needed to draw conclusions.

Aims: The aim was to study pregnancy outcomes in women with coarctation of the aorta (CoA) and associations to hypertensive disorders of pregnancy. Maternal morbidity and mortality are higher in women with heart disease and pre-eclampsia. Chronic hypertension, frequently encountered in CoA, is a risk factor for pre-eclampsia. Methods and results: Clinical data from the National Unit for Pregnancy and Heart Disease database was reviewed for pregnant women with CoA from 2008 to 2021. The primary outcome was hypertensive pregnancy disorders. The secondary outcomes were other cardiovascular, obstetric, and foetal complications. Seventy-six patients were included, with a total of 87 pregnancies. Seventeen (20%) patients were treated for chronic hypertension before pregnancy. Fifteen (20%) patients developed pre-eclampsia, and 5 (7%) had pregnancy-induced hypertension. Major adverse cardiac events developed in four (5%) patients, with no maternal or foetal mortality. Maternal age at first pregnancy [odds ratio (OR) 1.37], body mass index before first pregnancy (OR 1.77), and using acetylsalicylic acid from the first trimester (OR 0.22) were statistically significantly associated with pre-eclampsia. At follow-up (median) 8 years after pregnancy, 29 (38%) patients had anti-hypertensive treatment, an increase of 16% compared to pre-pregnancy. Five (7%) patients had progression of aorta ascendens dilatation to >40 mm, seven (9%) had an upper to lower systolic blood pressure gradient >20 mmHg, and six (8%) had received CoA re-intervention. Conclusion: Pre-eclampsia occurred in 20% of women with CoA in their first pregnancy. All pre-eclamptic patients received adequate anti-hypertensive treatment. All CoA patients were provided multi-disciplinary management, including cardiologic follow-up, to optimize maternal–foetal outcomes.

Background: First-time mothers are prone to prolonged labor, defined as the crossing of partograph alert or action lines. Prolonged labor may occur among as many as one out of five women, and is associated with a range of adverse birth outcomes. Oxytocin is the standard treatment for prolonged labor, but has a narrow therapeutic window, several adverse effects and limited efficacy. Despite poor evidence, labor wards often use antispasmodic agents to treat prolonged labor. The antispasmodic drug butylscopolamine bromide (Buscopan^®) may shorten duration of labor, but studies on prevention of prolonged labor are lacking. In this randomized double-blind placebo-controlled clinical trial, we aim to evaluate the effect of butylscopolamine bromide on duration of labor in first-time mothers showing first signs of slow labor progress by crossing the World Health Organization partograph alert line. Methods and analysis: The study is a single center study at Oslo University Hospital, Oslo, Norway. We will recruit 250 primiparous women with spontaneous labor start at term. Women are included in the first stage of labor if they show signs of slow labor progress, defined as the crossing of the partograph alert line with a cervical dilation between 3–9 cm. Participants are randomized 1:1 to either 20 mg intravenous butylscopolamine bromide or intravenous placebo (1 mL sodium chlorine 9 mg/mL). We considered a mean difference of 60 minutes in labor duration clinically relevant. The primary outcome is duration of labor from the provision of the investigational medicinal product to vaginal delivery. The secondary outcomes include change in labor pain, use of oxytocin augmentation, delivery mode, and maternal birth experience. The primary data for the statistical analysis will be the full analysis set and will occur on completion of the study as per the prespecified statistical analysis plan. The primary outcome will be analyzed using Weibull regression, and we will treat cesarean delivery as a censoring event.

Introduction: A greater risk of obstetric anal sphincter injury has been reported among African migrants in several host countries compared with the general population. To what degree female genital mutilation/cutting affects this risk is not clear. In infibulated women, deinfibulation prevents anal sphincter injury. Whether the timing of deinfibulation affects the risk, is unknown. This study aimed to investigate the risks of anal sphincter injury associated with female genital mutilation/cutting and timing of deinfibulation in Norway, and to compare the rates of anal sphincter injury in Somali‐born women and the general population.Material and methods: In a historical cohort study, nulliparous Somali‐born women who had a vaginal birth in the period 1990–2014 were identified by the Medical Birth Registry of Norway and data collected from medical records. Exposures were female genital mutilation/cutting status and deinfibulation before labor, during labor or no deinfibulation. The main outcome was obstetric anal sphincter injuries.Results: Rates of obstetric anal sphincter injury did not differ significantly by female genital mutilation/cutting status (type 1–2: 10.2%, type 3: 11.3%, none: 15.2% P = 0.17). The total rate of anal sphincter injury was 10.3% compared to 5.0% among nulliparous women in the general Norwegian population. Women who underwent deinfibulation during labor had a lower risk than women who underwent deinfibulation before labor (odds ratio 0.48, 95% confidence interval 0.27–0.86, P = 0.01).Conclusions: The high rate of anal sphincter injury in Somali nulliparous women was not related to type of female genital mutilation/cutting. Deinfibulation during labor protected against anal sphincter injury, whereas deinfibulation before labor was associated with a doubled risk. Deinfibulation before labor should not be routinely recommended during pregnancy.