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Objective To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. Design A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting Fourteen Swedish hospitals during 2016-2018. Population Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. Methods Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures The cost per gained life year and per gained QALY. Results The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was euro4108 in the IOL group (n = 1373) and euro4037 in the expectant management group (n = 1373), with a mean difference of euro71 (95% CI -euro232 to euro379). The ICER for IOL compared with expectant management was euro545 per life year gained and euro623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.

Objective To investigate whether polycystic ovary syndrome (PCOS) is associated with increased risk of stillbirth and whether any such association is linked to PCOS with a severe hyperandrogenic profile. Design Nationwide register-based cohort study. Setting Sweden. Population The cohort consisted of women giving birth to singleton infants in 1997–2015. All women with a diagnosis of PCOS in the period 1997–2017 and a randomly selected reference group of women without PCOS diagnosis were included. PCOS with a severe hyperandrogenic profile was defined as a PCOS diagnosis with at least two dispensations of prescribed anti-androgens during 2005–2017. Methods The risk of stillbirth in women with PCOS was estimated through multiple logistic regression, using women without PCOS as a reference. Risks were expressed as adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs), adjusted for maternal age, parity, body mass index, type-1 diabetes, educational level and country of birth. Main outcome measures Stillbirth, at ≥22 weeks of gestation in 2008–2015 and at ≥28 weeks of gestation in 1997–2007. Results Compared with women without PCOS (n = 241 750), women with PCOS (n = 41 851) had a 50% increased risk of stillbirth (aOR 1.50, 95% CI 1.28–1.77). The incidence of stillbirth in women with PCOS was particularly increased at term. Women with PCOS and a severe hyperandrogenic profile (n = 13 713) did not have a stronger association with stillbirth than women with PCOS who did not have such a profile. Conclusions PCOS is associated with stillbirth and should be considered as a possible risk factor in antenatal care. Further research is warranted to investigate possible causal mechanisms. Authors in thesis list of papers: Valgeirsdottir H, Kallak TK, Sundström-Poromaa I, Jonsson M, Stephansson O, Roos N, Lindström L, Wikström AK

Introduction Uterine rupture is an obstetric emergency associated with maternal and neonatal morbidity. The main risk factor is a prior cesarean section, with rupture occurring in subsequent labor. The aim of this study was to assess the risk of uterine rupture by labor duration and labor management. Material and methods This is a Swedish register-based cohort study of women who underwent labor in 2013-2018 after a primary cesarean section (n = 20 046). Duration of labor was the main exposure, calculated from onset of regular labor contractions and birth; both timepoints were retrieved from electronic medical records for 12 583 labors, 63% of the study population. Uterine rupture was calculated as events per 1000 births at different timepoints during labor. Risk estimates for uterine rupture by labor duration, induction of labor, use of oxytocin and epidural analgesia were calculated using Poisson regression, adjusted for maternal and birth characteristics. Estimates were presented as adjusted rate ratios (ARR) with 95% confidence intervals (CI). Results The prevalence of uterine rupture was 1.4% (282/20 046 deliveries). Labor duration was 9.88 hours (95% CI 8.93-10.83) for women with uterine rupture, 8.20 hours (95% CI 8.10-8.31) for women with vaginal delivery, and 10.71 hours (95% CI 10.46-10.97) for women with cesarean section without uterine rupture. Few women (1.0/1000) experienced uterine rupture during the first 3 hours of labor. Uterine rupture occurred in 15.6/1000 births with labor duration over 12 hours. The highest risk for uterine rupture per hour compared with vaginal delivery was observed at 6 hours (ARR 1.20, 95% CI 1.11-1.30). Induction of labor was associated with uterine rupture (ARR 1.54, 95% CI 1.19-1.99), with a particular high risk seen in those induced with prostaglandins and no risk observed with cervical catheter (ARR 1.19, 95% CI 0.83-1.71). Labor augmentation with oxytocin (ARR 1.60, 95% CI 1.25-2.05) and epidural analgesia (ARR 1.63, 95% CI 1.27-2.10) were also associated with uterine rupture. Conclusions Labor duration is an independent factor for uterine rupture among women attempting vaginal delivery after cesarean section. Medical induction and augmentation of labor increase the risk, regardless of maternal and birth characteristics.

Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0 to 1 weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] versus 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] versus 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusion Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.

ObjectiveTo determine survival and outcomes in infants born at 22–24 weeks of gestation in a centre with a uniformly active approach to management of extremely preterm infants.Study designSingle-centre retrospective cohort study including infants born 2006–2015. Short-term morbidities assessed included retinopathy of prematurity, necrotising enterocolitis, patent ductus arteriosus, intraventricular haemorrhage, periventricular malacia and bronchopulmonary dysplasia. Neurodevelopmental outcomes assessed included cerebral palsy, visual impairment, hearing impairment and developmental delay.ResultsTotal survival was 64% (143/222), ranging from 52% at 22 weeks to 70% at 24 weeks. Of 133 (93%) children available for follow-up at 2.5 years corrected age, 34% had neurodevelopmental impairment with 11% classified as moderately to severely impaired. Treatment-requiring retinopathy of prematurity, severe bronchopulmonary dysplasia, visual impairment and developmental delay correlated with lower gestational age.ConclusionsA uniformly active approach to all extremely preterm infants results in survival rates that are not distinctly different across the gestational ages of 22–24 weeks and more than 50% survival even in infants at 22 weeks. The majority were unimpaired at 2.5 years, suggesting that such an approach does not result in higher rates of long-term adverse neurological outcome.

The plastic component bisphenol A (BPA) impairs reproductive organ development in various experimental animal species. In birds, effects are similar to those caused by other xenoestrogens. Because of its endocrine disrupting activity, BPA is being substituted with other bisphenols in many applications. Using the chicken embryo model, we explored whether the BPA alternatives bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) can induce effects on reproductive organ development similar to those induced by BPA. Embryos were exposed in ovo from embryonic day 4 (E4) to vehicle, BPAF at 2.1, 21, 210, and 520 nmol/g egg, or to BPA, BPF, or BPS at 210 nmol/g egg and were dissected on embryonic day 19. Similar to BPA, BPAF and BPF induced testis feminization, manifested as eg testis-size asymmetry and ovarian-like cortex in the left testis. In the BPS-group, too few males were alive on day 19 to evaluate any effects on testis development. We found no effects by any treatment on ovaries or Müllerian ducts. BPAF and BPS increased the gallbladder-somatic index and BPAF, BPF and BPS caused increased embryo mortality. The overall lowest-observed-adverse-effect level for BPAF was 210 nmol/g egg based on increased mortality, increased gallbladder-somatic index, and various signs of testis feminization. This study demonstrates that the BPA replacements BPAF, BPF, and BPS are embryotoxic and suggests that BPAF is at least as potent as BPA in inducing estrogen-like effects in chicken embryos. Our results support the notion that these bisphenols are not safe alternatives to BPA.

Vaginal delivery may lead to levator ani muscle (LAM) injury or avulsion. Episiotomy may reduce obstetric anal sphincter injury in operative vaginal delivery, but may increase the risk of LAM injury. Our aim was to assess whether lateral episiotomy in vacuum extraction (VE) in primiparous women causes LAM injury.A prospective cohort study of 58 primiparous women with episiotomy nested within an ongoing multicenter randomized controlled trial of lateral episiotomy versus no episiotomy in VE (EVA trial) was carried out in Sweden. LAM injury was evaluated using 3D endovaginal ultrasound 6-12 months after delivery and Levator Ani Deficiency (LAD) score. Episiotomy scar properties were measured. Characteristics were described and compared using Chi-squared tests. We stipulated that if a lateral episiotomy cuts the LAM, ≥50% would have a LAM injury. Among those, ≥50% would be side specific. We compared the observed prevalence with a test of one proportion.Twelve (20.7%, 95% CI 10.9-32.9) of 58 women had a LAD (p0.001, compared with the stipulated 50%). Six (50.0%, 95% CI 21.1% to 78.9%) of 12 women had a LAD on the episiotomy side, including those with bilateral LAD (p = 1.00). Two (16.7%, 95% CI 2.1% to 48.4%) of 12 women had a LAD exclusively on the episiotomy side (p = 0.02).There was no excessive risk of cutting the LAM while performing a lateral episiotomy. LAD was not seen in women with episiotomies shorter than 18 mm.

Objectives: An increased risk of preterm birth (PTB) following a caesarean section (CS) in the second stage of labor has been demonstrated. We aimed to investigate the relationship between the station of the presenting fetal part and the surgical technique at first CS, and the risk of subsequent PTB.Study design: This was a cohort study of 11,850 women in Sweden, delivered by CS in 2001-2007 at any of 23 birth units, with a second delivery in 2001-2009. Clinical information was retrieved from electronic birth records linked to national health registers. The risk of subsequent PTB was analyzed by fetal station, defined as low (at or below the ischial spines) or high (above the ischial spines), and aspects of the surgical technique at index CS. Associations were explored with logistic regression and results are presented as odds ratios (ORs) with 95% confidence intervals (CIs), by type and severity (very early < 32 gestational weeks and moderate preterm 32-36 gestational weeks) of PTB. Multiple logistic regression included adjustments for maternal age, gestational age at first delivery, and inter-delivery interval.Results: Out of 11,850 women delivered by CS, 1,016 (8.6%) delivered preterm in their subsequent pregnancy. There was an increased likelihood of spontaneous PTB, but not with medically indicated PTB, after an index CS with the fetal presenting part at a low station (aOR 1.61, 95% CI 1.23-2.11). CS performed at a low station was associated with birth < 32 gestational weeks (aOR 1.73, 95% CI 1.05-2.84) and birth at 32-36 gestational weeks (aOR 1.29, 95% CI 1.00-1.65), compared with high fetal station. Thickness of the uterine wall, incision type, and closure of the uterus at index CS did not affect the risk.Conclusion: A primary CS at a low station was associated with a subsequent spontaneous PTB, but not medically indicated PTB. Surgical technique at index CS did not alter the risk.

Introduction: A revised intrapartum cardiotocography (CTG) classification was introduced in Sweden in 2017. The aims of the revision were to adapt to the international guideline published in 2015 and to adjust the classification of CTG patterns to current evidence regarding intrapartum fetal physiology. This study aimed to investigate adverse neonatal outcomes before and after implementation of the revised CTG classification. Material and Methods: A before-and-after design was used. Cohort I (n = 160 210) included births from June 1, 2014 through May 31, 2016 using the former CTG classification, and cohort II (n = 166 558) included births from June 1, 2018 through May 31, 2020 with the revised classification. Data were collected from the Swedish Pregnancy and Neonatal Registers. The primary outcome was moderate to severe neonatal hypoxic ischemic encephalopathy (HIE 2-3). Secondary outcomes were birth acidemia (umbilical artery pH

Despite reported high levels of contraception use in eSwatini, unplanned pregnancies are common. The aims of this study were to investigate prevalence and determinants of contraception use and unplanned pregnancies in a disadvantaged area in the Kingdom of eSwatini (Swaziland), and to investigate the association between unplanned pregnancies and antenatal care attendance.This cross-sectional study was conducted at the non-governmental organization Siphilile Maternal and Child Health in Matsapha, a peri-urban industrial area, using data from pre-existing client records. The sample included clients (n = 1436) registered during pregnancy or up to three months postpartum between August 2014 and April 2016. Contraception use before conception and unplanned pregnancies were analysed with logistic regression to find associations with socio-demographic factors and health care utilization.In this population, 59% (n = 737) stated to have used contraception before becoming pregnant. Teenagers and first-time mothers were less likely to have used contraception. Seventy percent (789/1124) of the pregnancies were unplanned. Older women (≥35 years) were less likely while teenagers and multiparas (≥3 children) were more likely to have an unplanned pregnancy. Women with unplanned pregnancies were less likely to attend the recommended number of antenatal care visits compared to women with planned pregnancies.The rate of unplanned pregnancies is high in this population, especially among teenagers. Family planning interventions need to focus on preconception care for teenagers to enable pregnancy planning including improved antenatal care attendance.

Introduction One in four women giving birth in Sweden is foreign-born. Immigrant status has been suggested as a risk factor for adverse perinatal outcomes. It is not known if infants to foreign-born women have an increased risk of severe birth asphyxia, or which factors might mediate such association. Material and methods A population-based cohort study of 726 730 live births at 36 weeks of gestation or more in Sweden in 2009-2015. The exposure was maternal country of birth, grouped according to the World Bank country classification: low-, lower-middle, upper-middle, and high-income economies. The main outcome was neonatal hypoxic ischemic encephalopathy (HIE). The outcome was estimated by severity and classified as non-hypothermia-treated HIE, representing mainly mild cases, and hypothermia-treated HIE, representing moderate to severe cases. A secondary outcome was low Apgar score at 5 minutes, defined as

Heritage management in Sweden has undergone a substantial transformation in recent decades. The process of monitoring and managing heritage information has become increasingly digital, relying on interconnected systems to monitor registered archaeological remains to manage investigations and contract archaeology excavations. This also has to work together with the digital systems of the County Administrative Boards that administer all permissions for excavations. Current developments deal with archiving and dissemination of reports, and documentation from fieldwork. Documentation of archaeological excavations has predominantly been digital for the past 20 years, which brings both possibilities and challenges in making sure the information will adhere to the FAIR Principles. This article outlines some of these developments and exemplifies the possibilities of reusing legacy data through the Urdar project.

Objective To develop a Core Outcome Set (COS) for treatment of perinatal depression. Design Systematic overview of outcomes reported in the literature and consensus development study. Setting International. Population Two hundred and twenty-two participants, mainly patients, healthcare professionals and researchers, representing 13 countries. Methods A systematic overview of outcomes reported in recently published research, a two-round Delphi survey and a consensus meeting at which the final COS was decided using modified nominal group technique. Main results In the literature search, 1772 abstracts were identified and evaluated, and 165 studies were finally included in the review. In all, 106 outcomes were identified and included in the Delphi survey. In all, 222 participants registered for the first round of the Delphi survey and 151 (68%) responded. In the second round, 123 (55%) participants responded. Thirteen participants attended the consensus meeting, where the following nine outcomes were agreed upon for inclusion in the final COS: self-assessed symptoms of depression, diagnosis of depression by a clinician, parent to infant bonding, self-assessed symptoms of anxiety, quality of life, satisfaction with intervention, suicidal thoughts, attempted or committed suicide, thoughts of harming the baby, and adverse events. Conclusions The relevant stakeholders prioritised outcomes and reached consensus on a COS comprising nine outcomes. We expect that this COS will contribute to the consistency and uniformity of outcome selection and reporting in future clinical trials involving treatment of perinatal depression. Tweetable abstract Development of a core outcome set regarding treatment for perinatal depression by @SBU_en. TWEETABLE ABSTRACT.

Background Identifying women at high risk for preeclampsia is essential for the decision to start treatment with prophylactic aspirin. Prediction models have been developed for this purpose, and these typically incorporate body mass index (BMI). As waist circumference (WC) is a better predictor for metabolic and cardiovascular outcomes than BMI in nonpregnant populations, we aimed to investigate if WC is a BMI-independent predictor for preeclampsia and if the addition of WC to a prediction model for preeclampsia improves its performance. Methods We used a population-based cohort of 4,696 women with WC measurements taken in the first trimester. The influence of WC on the risk of developing preeclampsia was evaluated by multivariable logistic regression. We generated receiver operating characteristic curves and calculated the area under the curve (AUC) to evaluate the usefulness of WC measurements for prediction of preeclampsia. Results Women who developed preeclampsia had greater early pregnancy WC than women who did not (85.8 ± 12.6 vs. 82.3 ± 11.3 cm, P < 0.001). The risk of preeclampsia increased with larger WC in a multivariate model, adjusted odds ratio 1.02 (95% confidence interval 1.01–1.03). However, when adding BMI into the model, WC was not independently associated with preeclampsia. The AUC value for preeclampsia prediction with BMI and the above variables was 0.738 and remained unchanged with the addition of WC to the model. Conclusions Large WC is associated with a higher risk of preeclampsia, but adding WC to a prediction model for preeclampsia that already includes BMI does not improve the model’s performance., Graphical Abstract Graphical Abstract

A wide variety of anthropogenic chemicals is detected in humans and wildlife and the health effects of various chemical exposures are not well understood. Early life stages are generally the most susceptible to chemical disruption and developmental exposure can cause disease in adulthood, but the mechanistic understanding of such effects is poor. Within the EU project EDC-MixRisk, a chemical mixture (Mixture G) was identified in the Swedish pregnancy cohort SELMA by the inverse association between levels in women at around gestational week ten with birth weight of their children. This mixture was composed of mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-ethylhexyl phthalate, mono-isononyl phthalate, triclosan, perfluorohexane sulfonate, perfluorooctanoic acid, and perfluorooctane sulfonate. In a series of experimental studies, we characterized effects of Mixture G on early development in zebrafish models. Here, we studied apoptosis and Wnt/β-catenin signaling which are two evolutionarily conserved signaling pathways of crucial importance during development. We determined effects on apoptosis by measuring TUNEL staining, caspase-3 activity, and acridine orange staining in wildtype zebrafish embryos, while Wnt/β-catenin signaling was assayed using a transgenic line expressing an EGFP reporter at β-catenin-regulated promoters. We found that Mixture G increased apoptosis, suppressed Wnt/β-catenin signaling in the caudal fin, and altered the shape of the caudal fin at water concentrations only 20–100 times higher than the geometric mean serum concentration in the human cohort. These findings call for awareness that pollutant mixtures like mixture G may interfere with a variety of developmental processes, possibly resulting in adverse health effects. Title in thesis list of papers: Increased apoptosis, reduced Wnt/β-catenin signaling, and altered tail development in zebrafish embryos exposed to a chemical mixture that has been inversely associated with birth weight in humans

Background Systematic reviews often conclude low confidence in the results due to heterogeneity in the reported outcomes. A Core Outcome Set (COS) is an agreed standardised collection of outcomes for a specific area of health. The outcomes included in a COS are to be measured and summarized in clinical trials as well as systematic reviews to counteract this heterogeneity. Aim The aim is to identify, compile and assess final and ongoing studies that are prioritizing outcomes in the area of pregnancy and childbirth. Methods All studies which prioritized outcomes related to pregnancy and childbirth using consensus method, including Delphi surveys or consensus meetings were included. Searches were conducted in Ovid MEDLINE, EMBASE, PsycINFO, Academic Search Elite, CINAHL, SocINDEX and COMET databases up to June 2021. For all studies fulfilling the inclusion criteria, information regarding outcomes as well as population, method, and setting was extracted. In addition, reporting in the finalized studies was assessed using a modified version of the Core Outcome Set–STAndards for Reporting. Results In total, 27 finalized studies and 42 ongoing studies were assessed as relevant and were included. In the finalized studies, the number of outcomes included in the COS ranged from 6 to 51 with a median of 13 outcomes. The majority of the identified COS, both finalized as well as ongoing, were relating to physical complications during pregnancy. Conclusion There is a growing number of Core Outcome Set studies related to pregnancy and childbirth. Although several of the finalized studies follow the proposed reporting, there are still some items that are not always clearly reported. Additionally, several of the identified COS contained a large number (n > 20) outcomes, something that possibly could hinder implementation. Therefore, there is a need to consider the number of outcomes which may be included in a COS to render it optimal for future research.

Gao, K.; Tian, J.; Wu, Y.; Mei, P.; Zhang, Z.; Jonsson, M., and Brandt, I., 2021. Induction of cytochrome P4501 genes by various inducers in rainbow trout (Oncorhynchus mykiss). Journal of Coastal Research, 37(1), 143–148. Coconut Creek (Florida), ISSN 0749-0208.Juvenile rainbow trout is widely found in various aquatic systems, such as freshwater, coastal, and marine habitats all over the world. Expression patterns of the cytochrome P4501 (CYP1) genes exposed to various stressors in such fish could be informative and useful in biomonitoring. In the present study, the induction of CYP1 in rainbow trout by indigo, humic acid (HA), and benzo(a)pyrene (BaP) was studied through a 12-hour exposure experiment by using rainbow trout as an experimental object. First, 7-ethoxyresorufin O-deethylase (EROD) activity and CYP1 expression levels in fish exposed to different concentrations of indigo were analyzed. The EROD activities in fish gills were greatly affected by the concentration of indigo (1, 18, 50, and 80 nM). The expression level of CYP1A1 and CYP1A3 in gills was higher compared with CYP1B1 and CYP1Cs. Second, the gill EROD activity and CYP1 mRNA expressions levels were compared when induced by indigo, HA, and BaP at the same concentration (1 nM). Results indicated that rainbow trout were sensitive to all three inducers. Among them, the HA affected CYP1A1 and CYP1A3 most obviously. CYP1A, as an important biomarker, was more sensitive than CYP1B and CYP1C to those inducers. The observed effects of the different CYP1 inducers could provide a useful tool for monitoring of AhR-active pollutants in the aquatic environment.

Unplanned pregnancies constitute a major health problem globally carrying negative social, economic and health consequences for individuals and families. In this study, we explored the underlying causes and implications of this phenomenon in Eswatini, a country with high rates of unplanned pregnancy. Three focus group discussions were conducted in January 2018 with female health workers called mentor mothers, chosen because they offer a twofold perspective, being both Swati women and health workers in socially and economically disadvantaged settings. Using inductive thematic analysis, we identified five sub-themes and an overarching theme called 'the perpetuating cycle of unplanned pregnancy' in the data. A social-ecological model was used to frame the results, describing how factors at the individual, relationship, societal and community levels interact to influence unplanned pregnancy. In this setting, factors such as perceived low self-esteem as well as poor conditions in the community drove young women to engage in transactional relationships characterised by abuse, gender inequality and unprotected sex, resulting in unplanned pregnancy. These pregnancies led to neglected and abandoned children growing up to become vulnerable, young adults at risk of becoming pregnant unintendedly, thus creating an iterative cycle of unplanned childbearing.

INTRODUCTION The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes. MATERIAL AND METHODS This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes. RESULTS Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (

Objective: To identify antepartum and intrapartum risk factors for neonatal seizures in the absence of hypoxic ischemic encephalopathy (HIE).Methods: Population-based case-control study. Of 98 484 ...

INTRODUCTION There is a paucity of data on the impact of organ injury on long-term outcomes after a hysterectomy for benign indications. The aim of this study was to investigate fistula formation and patient-reported long-term health outcomes after organ injury at the time of a hysterectomy. MATERIAL AND METHODS This was a population-based study of 22 538 women undergoing a hysterectomy between 2000 and 2014 in Sweden. Their medical history, characteristics of their surgery, and patient-reported outcomes were retrieved from Swedish national health and quality registers. Predictors for fistula formation were investigated with logistic regression and are presented as odds ratios with a 95% CI. RESULTS Fistulas were reported in 7% of women with organ injuries, compared with 0.4% of those without organ injuries (adjusted odds ratio 15.29 [9.81-23.85]). Laparotomy and postoperative infection were associated with postoperative fistulas. Most of the women reported having better health 1 year after the hysterectomy, but 7% of those with organ injuries and 24% of those with fistulas reported deteriorated health, compared with 2% of women without injuries. CONCLUSIONS Organ injury at the time of hysterectomy is associated with the development of fistulas involving the female genital tract and increases the proportion of women reporting deteriorated health 1 year after surgery.

Maternal microchimerism may arise in the offspring during pregnancy, and may be favorable or unfavorable. Additionally, maternal cells present in umbilical cord blood used for stem cell transplantation may affect the outcome after transplantation. The aim of this study was to evaluate the cellular subset and frequency of maternal cells in umbilical cord blood following vaginal deliveries and elective Cesarean sections where the umbilical cord clamping time was measured. A total of 44 healthy women with normal pregnancies were included in the study. Of these, 24 delivered vaginally and 20 by elective Cesarean sections. In the fresh umbilical cord blood, cellular subsets of CD3+ (T-cells), CD19+ (B-cells), CD33+ (myeloid cells), CD34+ (hematopoietic progenitor cells) and CD56+ (natural killer cells) cells were isolated and DNA extracted. A single-nucleotide polymorphism unique to the mother was identified and maternal microchimerism in the different cellular fractions was detected using quantitative real-time polymerase chain reaction with a sensitivity of 0.01%. Overall, 5 out of the 44 (11%) umbilical cord blood samples contained maternal microchimerism. The positive fractions were total DNA (whole blood, n = 3), CD34+ ( n = 1), CD56+ ( n = 1) and CD34+/CD56+ ( n = 1). Overall, four of the five (80%) positive samples were from Cesarean sections and one was from a vaginal delivery. The conclusion from this study is that maternal microchimerism in umbilical cord blood is not a common phenomenon but includes both lymphoid and hematopoietic progenitor lineages.

Antifungal azoles are widely used in medicine, agriculture, and material protection and several antifungal azoles have been found in environmental samples. Although these compounds were designed to inhibit fungal enzymes such as lanosterol-14-demethylase (cytochrome P450 (CYP) 51), it is well established that the inhibitory actions of azoles are not specific for fungal CYP isozymes. We refined a gill filament assay to determine the inhibition of CYP1, measured as reduced 7-ethoxyresorufin-O-deethylase (EROD) activity, in rainbow trout (Oncorhynchus mykiss) gill tissue ex vivo. The advantage of this method is that both induction and inhibition of EROD are performed ex vivo. Among thirteen azoles studied, the five that caused the strongest inhibition of gill EROD activity at a concentration of 5 μM were selected for concentration–response assessment. These compounds (bifonazole, clotrimazole, imazalil, miconazole, and prochloraz) showed IC50 values ranging from 0.1 to 1.5 μM. CYP19 (aromatase) inhibition was measured using microsomes from rainbow trout brains. Concentration-response curves for CYP19 inhibition were determined for letrozole, bifonazole, clotrimazole, imazalil, miconazole and prochloraz, which gave IC50 values ranging from 0.02 to 3.3 μM. It was further found that mixtures of the five most potent azoles reduced both CYP1 and 19 catalytic activity in an additive fashion (IC50 = 0.7 μM and 0.6 μM, in the respective assay). Bifonazole (IC50 = 0.1 μM) is not previously known to inhibit CYP1 activity. The additive inhibition of CYP1 and CYP19 catalytic activity is an important finding of the present study. We conclude that this additive action of azoles could mediate adverse impacts on CYP regulated physiological functions in environmentally exposed fish.

OBJECTIVE: The aim of the study was to evaluate the association between abdominal adhesions at the time of gynaecologic surgery and a history of caesarean delivery, and to investigate obstetric fac ...

Bisphenol A (BPA) and phthalate diesters are ubiquitous environmental contaminants. While these compounds have been reported as reproductive toxicants, their effects may partially be attributed to metabolites. The aim of this study was to examine reproductive organ development in chicken embryos exposed to the BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP; 100 µg/g egg) or a human-relevant mixture of 4 phthalate monoesters (85 µg/g egg). The mixture was designed within the EU project EDC-MixRisk based upon a negative association with anogenital distance in boys at 21 months of age in a Swedish pregnancy cohort. Chicken embryos were exposed in ovo from an initial stage of gonad differentiation (embryonic day 4) and dissected two days prior to anticipated hatching (embryonic day 19). No discernible effects were noted on reproductive organs in embryos exposed to the mixture. MBP-treated males exhibited retention of Müllerian ducts and feminization of the left testicle, while MBP-administered females displayed a diminished the left ovary. In the left testicle of MBP-treated males, mRNA expression of female-associated genes was upregulated while the testicular marker gene SOX9 was downregulated, corroborating a feminizing effect by MBP. Our results demonstrate that MBP, but not the phthalate monoester mixture, disrupts both male and female reproductive organ development in an avian embryo model.

Background The process of delivery entails potentially traumatic events in which the mother or child becomes injured or dies. Midwives and obstetricians are sometimes responsible for these events and can be negatively affected by them as well as by the resulting investigation or complaints procedure (clinical negligence). Objective To assess the self-reported exposure rate of severe events among midwives and obstetricians on the delivery ward and the cumulative risk by professional years and subsequent investigations and complaints. Design Cross-sectional survey. Participants Members of the Swedish Association of Midwives (SFB) and the Swedish Society of Obstetrics and Gynaecology (SFOG). Methods A questionnaire covering demographic characteristics, experiences of self-reported severe events on the delivery ward, and complaints of medical negligence was developed. Potential consequences of the complaint was not reported. A severe event was defined as: 1) the death of an infant due to delivery-related causes during childbirth or while on the neonatal ward; 2) an infant being severely asphyxiated or injured at delivery; 3) maternal death; 4) very severe or life threatening maternal morbidity; or 5) other stressful events during delivery, such as exposure to violence or aggression. Results The response rate was 39.9% (n=1459) for midwives and 47.1% (n=706) for obstetricians. Eighty-four percent of the obstetricians and almost 71% of responding midwives had experienced one or more self-reported severe obstetric event with detrimental consequences for the woman or the new-born. Fourteen percent of the midwives and 22.4% of the obstetricians had faced complaints of medical negligence from the patient or the family of the patient. Conclusions A considerable proportion of midwives and obstetricians will, in the course of their working life, experience severe obstetric events in which the mother or the new-born is injured or dies. Preparedness for such exposure should be part of the training, as should managerial and peer support for those in need. This could prevent serious consequences for the health care professionals involved and their subsequent careers.

BackgroundPostpartum depression (PPD) is a common disorder after childbirth. The strongest known predictors are a history of depression and/or a history of PPD. However, for a significant proportion of women, PPD constitutes their first depressive episode. This study aimed to gain further insight into the risk factors for PPD in first time mothers without previous psychiatric contact.MethodsWomen delivering in Uppsala University Hospital, Sweden, from May 2006 to June 2007, were asked to participate and filled out questionnaires five days and six weeks postpartum, containing inter alia the Edinburgh Postnatal Depression Scale (EPDS). Univariate logistic regression models, as well as a path analysis, were performed to unveil the complex interplay between the study variables.ResultsOf the 653 participating primiparas, 10.3% and 6.4% reported depressive symptoms (EPDS ≥ 12 points) five days and six weeks postpartum, respectively. In the path analysis, a positive association between anxiety proneness and depressive symptoms at five days and six weeks postpartum was identified. For depressive symptoms six weeks after delivery, additional risk factors were detected, namely depressive symptoms five days postpartum and subjective experience of problems with the baby. Caesarean section and assisted vaginal delivery were associated with fewer depressive symptoms at 6 six weeks postpartum.ConclusionsIdentification of anxiety proneness, delivery mode and problems with the baby as risk factors for self-reported depressive symptoms postpartum in this group of primiparas can be important in helping health care professionals identify women at increased risk of affective disorders in the perinatal period, and provide a base for early intervention.

Objective: To investigate the maternal complications associated with cesarean section (CS) in the extremely preterm period according to the gestational week (GW) and to indication of delivery. Study design: This is a retrospective case-referent study with a review of medical records of women who delivered at 22–27 weeks of gestation (n=647) at two level III units in Sweden. For abdominal delivery, gestational length was stratified into 22–24 (n=105) and 25–27 (n=301) weeks. For comparison, data on women who underwent a CS at term were identified in a register-based database. Results: The rate of CS in extremely preterm births was 62.8%. There was no difference in the complication rates, but types of incisions other than the low transverse incision were required more often at 22–24 (18.1%) weeks than at 25–27 GWs (9.6%) (P=0.02). Major maternal complications occurred in 6.6% compared with 2.1% in the extremely preterm and term CS, respectively (P Conclusions: Almost two-thirds of the births at 22–27 GWs had an abdominal delivery. No increase in short-term morbidity was observed at 22–24 weeks compared to 25–27 weeks. CS performed extremely preterm had more major complications recorded than cesarean at term. The complications are driven by the underlying maternal condition.

Previous research in our laboratory showed that acetaminophen (ACE) induced embryonic mortality and abnormalities in zebrafish. Here, we examined the dose response of ACE (0.05–50 μg L−1) in zebrafish embryos. Concentrations as low as 0.1 μg L−1 significantly increased abnormalities, and all test concentrations significantly increased mortality rates. In mammals, ACE inhibits cyclooxygenase (COX) enzymes to decrease prostaglandin production. Here we report COX activity and expression of the cox-1, cox-2a, and cox-2b genes in zebrafish embryos. COX activity was significantly inhibited by specific mammalian cox-1 (SC-560) and cox-2 (DuP-697) inhibitors in unexposed and ACE-exposed embryos. COX activity declined with development time. Maternal transcripts of all cox genes were found at 1 -h post fertilization and embryonic expression began in gastrulation or early segmentation. Co-exposure of ACE and prostaglandin E2 abolished the ACE-induced effects. This strongly supports that ACE elicits embryo toxicity in zebrafish though the same molecular mechanism of action of their therapeutic effects in mammals.

Objective To evaluate if induction of labour at 41 weeks improves perinatal and maternal outcomes in women with a low risk pregnancy compared with expectant management and induction of labour at 42 weeks. Design Multicentre, open label, randomised controlled superiority trial. Setting 14 hospitals in Sweden, 2016-18. Participants 2760 women with a low risk uncomplicated singleton pregnancy randomised (1:1) by the Swedish Pregnancy Register. 1381 women were assigned to the induction group and 1379 were assigned to the expectant management group. Interventions Induction of labour at 41 weeks and expectant management and induction of labour at 42 weeks. Main outcome measures The primary outcome was a composite perinatal outcome including one or more of stillbirth, neonatal mortality, Apgar score less than 7 at five minutes, pH less than 7.00 or metabolic acidosis (pH 12 mmol/L) in the umbilical artery, hypoxic ischaemic encephalopathy, intracranial haemorrhage, convulsions, meconium aspiration syndrome, mechanical ventilation within 72 hours, or obstetric brachial plexus injury. Primary analysis was by intention to treat. Results The study was stopped early owing to a significantly higher rate of perinatal mortality in the expectant management group. The composite primary perinatal outcome did not differ between the groups: 2.4% (33/1381) in the induction group and 2.2% (31/1379) in the expectant management group (relative risk 1.06, 95% confidence interval 0.65 to 1.73; P=0.90). No perinatal deaths occurred in the induction group but six (five stillbirths and one early neonatal death) occurred in the expectant management group (P=0.03). The proportion of caesarean delivery, instrumental vaginal delivery, or any major maternal morbidity did not differ between the groups. Conclusions This study comparing induction of labour at 41 weeks with expectant management and induction at 42 weeks does not show any significant difference in the primary composite adverse perinatal outcome. However, a reduction of the secondary outcome perinatal mortality is observed without increasing adverse maternal outcomes. Although these results should be interpreted cautiously, induction of labour ought to be offered to women no later than at 41 weeks and could be one (of few) interventions that reduces the rate of stillbirths. Trial registration Current Controlled Trials ISRCTN26113652 .

Delayed labour progress is common in nulliparous women, often leading to caesarean section despite augmentation of labour with synthetic oxytocin.High- or low-dose oxytocin can be used for augmentation of delayed labour, but evidence for promoting high-dose is weak. Aim To ascertain the effect on caesarean section rate of high-dose versus low-dose oxytocin for augmentation of delayed labour in nulliparous women. Methods Multicentre parallel double-blind randomised controlled trial (ClinicalTrials.gov: NCT01587625) in six labour wards in Sweden. Healthy nulliparous women at term with singleton cephalic fetal presentation, spontaneous labour onset, confirmed delay in labour and ruptured membranes (n=1351) were randomised to labour augmentation with either high-dose (6.6 mU/minute) or low-dose (3.3 mU/minute) oxytocin infusion.1295 women were included in intention-to-treat analysis (high-dose n=647; low-dose n=648). Caesarean section rates did not differ between groups (12.4% and 12.3%, 95% Confidence Interval -3.7 to 3.8). Women with high-dose oxytocin had: shorter labours (-23.4min); more uterine tachysystole (43.2% versus 33.5%); similar rates of instrumental vaginal births, with more due to fetal distress (43.8% versus 22.7%) and fewer due to failure to progress (39.6% versus 58.8%). There were no differences in neonatal outcomes.Our study could not confirm results of two systematic reviews indicating, with weak evidence, that use of high-dose oxytocin was associated with lower frequency of caesarean section.We found no advantages for routine use of high-dose oxytocin in the management of delay in labour. Low-dose oxytocin regimen is recommended to avoid unnecessary events of tachysystole and fetal distress.