Chemokine and cytokine profiles in preterm and term labor, in preterm prelabor rupture of the membranes, and in normal pregnancy.

The objective of this study was to investigate the immune mechanisms involved in preterm labor (PTL), preterm prelabor rupture of the membranes (PPROM), and normal pregnancies. The second objective was to explore immune profiles in PTL for association with early ( < 34 gestational weeks (gw)) or instant ( < 48 h) delivery. This prospective observational multi-center study included women with singleton pregnancies with PTL (n = 80) or PPROM (n = 40) before 34 gw, women with normal pregnancies scheduled for antenatal visits (n = 44), and women with normal pregnancies in active labor at term (n = 40). Plasma samples obtained at admission were analyzed for cytokine and chemokine quantification using a multiplex bead assay in order to compare the immune profiles between PTL, PPROM, and normal pregnancies. In PTL, CXCL1 and CCL17 were significantly higher compared to gestational age-matched women at antenatal visits, whereas for PPROM, CXCL1 and IL-6 were increased. Women in term labor had a more pronounced inflammatory pattern with higher levels of CXCL1, CXCL8, and IL-6 compared with PTL (p = 0.007, 0.003, and 0.013, respectively), as well as higher levels of CCL17, CXCL1 and IL-6 (all p < 0.001) compared with the women at antenatal visits. In PTL, CXCL8 was higher in women with delivery before 34 gw, whereas CXCL8, GM-CSF, and IL-6 were significantly higher in women with delivery within 48 h. To conclude, PTL and PPROM were associated with a complex pattern of inflammation, both involving Th17 (CXCL1) responses. Although further studies are needed, CXCL8, GM-CSF, and IL-6 may be potential candidates for predicting preterm birth in PTL.

Validation of the Appendicitis Inflammatory Response (AIR) score during pregnancy: A nested case-control study.

OBJECTIVES: Appendicitis poses diagnostic challenges. A correct diagnosis is important during pregnancy to avoid unnecessary surgery on the one hand and delayed surgery on the other hand, as both may negatively affect pregnancy outcomes. Clinical scores for risk-stratified management of suspected appendicitis are well established in adults but have not been validated during pregnancy. This nested case-control study evaluated the diagnostic accuracy of the Appendicitis Inflammatory Response (AIR) score and imaging during pregnancy. METHODS: By cross-linking national Swedish health registries from a defined geographical area, we identified a cohort of 154 women who underwent appendectomy for suspected appendicitis during pregnancy and a matched cohort of 232 pregnant women admitted for acute abdominal pain and suspected appendicitis but with a discharge diagnosis of nonspecific abdominal pain (NSAP). All variables were extracted from medical records. The diagnostic value of AIR score and imaging was estimated for patients with a final diagnosis of appendicitis compared with patients with negative appendectomy and NSAP patients. RESULTS: The final diagnoses for the operated patients were uncomplicated and complicated appendicitis in 49.4% and 26.6%, respectively, and negative appendectomy in 24.0%. Nearly half of all the patients underwent diagnostic imaging (41%), mainly by ultrasonography. The sensitivity and specificity of diagnostic imaging were 44.9% (95% CI 32.9%-57.4%) and 42.2% (95% CI 31.9%-53.1%), respectively. The area under the receiver operating characteristic curve of AIR score was 0.88 (95% CI 0.84-0.92) for all appendicitis and 0.90 (95% CI 0.84-0.95) for complicated appendicitis. The sensitivity for complicated appendicitis was 100% at a score of ≥4. The specificity for all appendicitis was 97% at a score of ≥9. CONCLUSIONS: The results of this study suggest that the AIR score may be a suitable diagnostic tool for risk stratification of pregnant women with abdominal pain and suspected appendicitis but further validation among pregnant women is needed.

Tafoxiparin, a novel drug candidate for cervical ripening and labor augmentation: results from 2 randomized, placebo-controlled studies.

BACKGROUND: Slow progression of labor is a common obstetrical problem with multiple associated complications. Tafoxiparin is a depolymerized form of heparin with a molecular structure that eliminates the anticoagulant effects of heparin. We report on 2 phase II clinical studies of tafoxiparin in primiparas. Study 1 was an exploratory, first-in-pregnant-women study and study 2 was a dose-finding study. OBJECTIVE: Study 1 was performed to explore the effects on labor time of subcutaneous administration of tafoxiparin before onset of labor. Study 2 was performed to test the hypothesis that intravenous treatment with tafoxiparin reduces the risk for prolonged labor after spontaneous labor onset in situations requiring oxytocin stimulation because of dystocia. STUDY DESIGN: Both studies were randomized, double-blind, and placebo-controlled. Participants were healthy, nulliparous females aged 18 to 45 years with a normal singleton pregnancy and gestational age confirmed by ultrasound. The primary endpoints were time from onset of established labor (cervical dilation of 4 cm) until delivery (study 1) and time from start of study treatment infusion until delivery (study 2). In study 1, patients at 38 to 40 weeks of gestation received 60 mg tafoxiparin or placebo daily as 0.4 mL subcutaneous injections until labor onset (maximum 28 days). In study 2, patients experiencing slow progression of labor, a prolonged latent phase, or labor arrest received a placebo or 1 of 3 short-term tafoxiparin regimens (initial bolus 7, 21, or 35 mg followed by continuous infusion at 5, 15, or 25 mg/hour until delivery; maximum duration, 36 hours) in conjunction with oxytocin. RESULTS: The number of participants randomized in study 1 was 263, and 361 were randomized in study 2. There were no statistically significant differences in the primary endpoints between those receiving tafoxiparin and those receiving the placebo in both studies. However, in study 1, the risk for having a labor time exceeding 12 hours was significantly reduced by tafoxiparin (tafoxiparin 6/114 [5%] vs placebo 18/101 [18%]; P=.0045). Post hoc analyses showed that women who underwent labor induction had a median (range) labor time of 4.44 (1.2-8.5) hours with tafoxiparin and 7.03 (1.5-14.3) hours with the placebo (P=.0041) and that co-administration of tafoxiparin potentiates the effect of oxytocin and facilitates a shorter labor time among women with a labor time exceeding 6 to 8 hours (P=.016). Among women induced into labor, tafoxiparin had a positive effect on cervical ripening in 11 of 13 cases (85%) compared with 3 of 13 participants (23%) who received the placebo (P=.004). For women requiring oxytocin because of slow progression of labor, the corresponding results were 34 of 51 participants (66%) vs 16 of 40 participants (40%) (P=.004). In study 2, tafoxiparin had no positive effects on the secondary endpoints when compared with the placebo. Except for injection-site reactions in study 1, adverse events were no more common for tafoxiparin than for the placebo among either mothers or infants. There were few serious or treatment-related adverse events. CONCLUSION: Subcutaneous treatment with tafoxiparin before labor onset (study 1) may be effective in reducing the labor time among women undergoing labor induction and among those requiring oxytocin for slow progression of labor. Moreover, tafoxiparin may have a positive effect on cervical ripening. Short-term, intravenous treatment with tafoxiparin as an adjunct to oxytocin in patients with labor arrest (study 2) did not affect labor time or other endpoints. Both studies suggest that tafoxiparin has a favorable safety profile in mothers and their infants.

Cumulative oxytocin dose in spontaneous labour - Adverse postpartum outcomes, childbirth experience, and breastfeeding.

OBJECTIVES: This study aimed to determine the association between the total cumulative oxytocin dose during labour and adverse postpartum outcomes, childbirth experience and breastfeeding in term primiparous women with spontaneous onset of labour. STUDY DESIGN: A prospective observational multicentre study, including 1395 women with spontaneous labour, in seven hospitals in Southeast Sweden. Multivariable logistic regression (Crude Odds Ratios (OR) and adjusted OR (aOR) for relevant confounders) was used to analyze the association between oxytocin dose and postpartum outcomes. The exposure was the cumulative oxytocin dose during labour, classified in percentiles (<25th, 25-75th, >75th). The outcomes were occurrence of obstetric anal sphincter injury, postpartum haemorrhage (blood loss > 1000 ml), Apgar score < 7 at five minutes, umbilical cord arterial pH, postpartum bladder overdistension, exclusive breastfeeding at one week and three months, and the woman's perceived birth experience. RESULTS: Women receiving high amounts (>75th percentile, >4370 mU) of oxytocin infusion during labour had an increased risk of postpartum haemorrhage (OR 2.73 (1.78-4.19)), an overdistended bladder (OR 2.19 (1.11-4.31)), an infant with an Apgar score < 7 at five minutes (OR 2.89 (1.27-6.57)), a negative birth experience (OR 1.83 (1.25-2.69)), and a decreased chance of exclusive breastfeeding at one week (OR 0.63 (0.41-0.96)). After adjusting for confounders, all outcomes remained statistically significant except risk of low Apgar score and chance of exclusive breastfeeding. CONCLUSION: In women with high cumulative oxytocin dose during labour prompt, and prophylactic administration of uterotonics after delivery of the placenta should be considered to reduce the risk of postpartum haemorrhage. The risk for bladder overdistension can be reduced by implementing routines for observation for signs of bladder filling in the early postpartum period, as well as routine use of bladder scans post micturition to assess for successful bladder emptying. As women's birth experience have a major impact on their future mental health, should be routinely assessed postpartum, and support should be offered to women with negative experiences.

Complications 8 weeks after an obstetric second-degree perineal laceration in relation to body mass index.

INTRODUCTION AND HYPOTHESIS: How body mass index (BMI) affects pelvic floor function after a second-degree perineal laceration is unknown. The hypothesis of this study is that pelvic floor dysfunction and complications after an obstetric second-degree perineal laceration are more common in women with a higher BMI 8 weeks postpartum. METHODS: This register-based cohort study includes 10,876 primiparous women with an obstetric second-degree perineal laceration between 2014 and 2021. Data were retrieved from the Swedish Perineal Laceration Registry. Outcomes in relation to maternal BMI were urinary incontinence (UI), anal incontinence (AI) and common complications attributable to the laceration. Uni- and multivariate logistic regressions were used for comparison between normal weight (BMI < 24.9, reference), overweight (25.0-29.9) and obese (≥ 30) women. RESULTS: Multivariate analyses showed an increased risk for UI in both overweight and obese women compared to normal-weight women 8 weeks after a second-degree perineal laceration with an adjusted odds ratio (aOR) of 1.21 (CI 1.02-1.44) and 1.27 (CI 1.13-1.58) respectively. Overweight and obese women had a decreased risk for AI (aOR 0.81, CI 0.68-0.96; aOR 0.72, CI 0.57-0.90 respectively) compared with normal-weight women. No significant differences were found in the univariate analyses over BMI strata concerning complications after perineal laceration. CONCLUSIONS: Primiparous overweight and obese women report less AI and more UI than normal-weight women 8 weeks after a second-degree perineal laceration. No differences were found regarding complications. These findings are new and merit further study to find potential preventive factors and interventions after a second-degree perineal laceration.

The association between maternal vitamin D deficiency and postpartum hemorrhage and uterine atony.

INTRODUCTION: Postpartum hemorrhage is the leading cause of maternal morbidity and mortality worldwide. There are several known risk factors for postpartum hemorrhage related to pregnancy and delivery, but less evidence of predisposing factors. Recent research has shown that vitamin D deficiency may increase the risk of cesarean section due to dystocia, based on its effect on striated muscle as well as possible effect on the myometrium. Whether vitamin D deficiency increases the risk for postpartum hemorrhage and especially atonic hemorrhage is unknown. MATERIAL AND METHODS: This was a retrospective translational study. The study population included 1367 women in Sweden and the main exposure was the serum concentration of 25-hydroxylated vitamin D at time of delivery. The LIASON® 25 OH vitamin D total assay method was used for analyzing 25-hydroxylated vitamin D. Vitamin D insufficiency was defined as serum concentration <50 nmol/L and vitamin D deficiency as serum concentrations <25 nmol/L. Primary outcomes were postpartum hemorrhage and severe postpartum hemorrhage defined as bleeding ≥500 mL and ≥ 1000 mL, respectively 2 h after delivery. Secondary outcome was atonic postpartum hemorrhage. Crude and adjusted odds ratios were calculated with 95% confidence intervals using univariable and multivariable logistic regression. Three different adjustment methods were used, adjusting for maternal, obstetrical and neonatal confounders. RESULTS: Postpartum hemorrhage and severe postpartum hemorrhage afflicted 31.3% and 6.4% of the women, respectively. Rate of atonic postpartum hemorrhage was 21% in the whole population. Rate of vitamin D insufficiency and deficiency was 57%. Vitamin D insufficiency or deficiency was neither found to be associated with postpartum hemorrhage, nor with atonic postpartum hemorrhage. CONCLUSIONS: In this study, the vitamin D status of women at the time of delivery was not a predictor of postpartum hemorrhage overall or atonic postpartum hemorrhage.

Maternal obesity and the risk of postpartum infections according to mode of delivery.

OBJECTIVE: The aim of the present study was to assess the impact of different maternal Body Mass Index (BMI) classes on the risk of postpartum endometritis, wound infection, and breast abscess after different modes of delivery. Secondly to estimate how the risk of postpartum infection varies with different maternal BMI groups after induction of labor and after obstetric anal sphincter injuries. METHODS: A population-based observational study including women who gave birth during eight years (N = 841,780). Data were collected from three Swedish Medical Health Registers, the Swedish Medical Birth Register, the Swedish National Patient Register, and the Swedish Prescribed Drug Register. Outcomes were defined by ICD-10 codes given within eight weeks postpartum. The reference population was uninfected women. Odds ratios were determined using Mantel-Haenszel technique. Year of delivery, maternal age, parity and smoking in early pregnancy were considered as confounders. RESULTS: There was a dose-dependent relationship between an increasing maternal BMI and a higher risk for postpartum infections. Women in obesity class II and III had an increased risk for endometritis after normal vaginal delivery aOR 1.45 (95% CI: 1.29-1.63) and for wound infections after cesarean section aOR 3.83 (95% CI: 3.39-4.32). There was no difference in how maternal BMI affected the association between cesarean section and wound infection, regardless of whether it was planned or emergent. Women in obesity class II and III had a lower risk of breast abscess compared with normal-weight women, aOR 0.47 (95% CI: 0.38-0.58). The risk of endometritis after labor induction decreased with increasing maternal BMI. The risk of wound infection among women with an obstetrical sphincter injury decreased with increasing BMI. CONCLUSION: This study provides new knowledge about the impact of maternal BMI on the risk of postpartum infections after different modes of delivery. There was no difference in how BMI affected the association between cesarean section and wound infections, regardless of whether it was a planned cesarean section or an emergency cesarean section.

The association between maternal body mass index and serial plasma oxytocin levels during labor.

OBJECTIVE: To evaluate the association between maternal body mass index (BMI) and plasma oxytocin (OT) levels at different OT infusion rates in labor. METHODS: A prospective observational study analyzing serial plasma samples in laboring women with OT infusion. The women were categorized into three groups, women with non-obesity (BMI 18.5-29.9, n = 12), obesity (BMI 30.0-34.9, n = 13), and morbid obesity (BMI ≥ 35.0, n = 15). Plasma OT was analyzed using tandem mass spectrometry. RESULTS: Except for a low positive correlation between OT levels and BMI and significantly increased plasma OT levels in women with morbid obesity at the OT infusion rate of 3.3 mU/min, no significant differences in OT levels between the BMI groups were found. Further, the inter-individual differences in OT levels were large and no dose-dependent increase of OT levels was seen. CONCLUSIONS: Other factors than plasma OT levels may be more likely to determine the clinical response of OT infusion in women with obesity. Perhaps the observed clinical need and individual response would be a better predictor of plasma OT levels than a pre-determined OT infusion rate. The OT dosage guidelines for labor augmentation should be individualized according to clinical response rather than generalized. TRIAL REGISTRATION: Clinical trial registration: ClinicalTrials.gov ID NCT04093479.

Gestational diabetes mellitus and time in active labor: A population-based cohort study.

INTRODUCTION: Women with gestational diabetes mellitus (GDM) have higher rates of adverse perinatal outcomes compared with women without GDM, including an increased risk for having labor induced and for cesarean section. The findings from previous studies analyzing duration of labor in women with GDM are contradictory. The aim of the study was to evaluate the impact of GDM on time in spontaneous and induced active labor. MATERIAL AND METHODS: This was a population-based cohort study including 247 524 primiparous women who gave birth to a singleton fetus with cephalic presentation, ≥34+0 (completed gestational weeks + additional days) between January 2014 and May 2020 in Sweden. Data was obtained from the Swedish Pregnancy Register. Time in active labor was compared between women with GDM and without GDM with a spontaneous labor onset or induction of labor using Kaplan Meier survival analysis and Cox regression analysis. RESULTS: Women with GDM had significantly longer time in active labor, both with a spontaneous onset and induction of labor compared to women without GDM. Women with GDM had a decreased chance of vaginal delivery at a certain time-point compared to women without GDM, with adjusted hazard ratio of 0.92 (0.88-0.96) and 0.83 (0.76-0.90) for those with spontaneous onset and induction of labor, respectively. Women with GDM had increased risk for time in active labor ≥12 h both in spontaneous labor onset (adjusted odds ratio 1.14 [1.04-1.25]) and in induction of labor (adjusted odds ratio 1.55 [1.28-1.87]). CONCLUSIONS: Women with GDM seem to spend a longer time in active labor, both in spontaneous and induced active labor compared to women without GDM. To be able to individualize care intrapartum, there is a need for more studies demonstrating the impact of hyperglycemia during pregnancy on outcomes during childbirth.

Student-led clinic cervical cancer screening-medical students' views on progression of learning, quality of Pap smears and women´s experiences of the visit - a mixed methods study.

BACKGROUND: Student-led clinics (SLC) have been described, but not in gynecology. Gynecology is a subject typically covered in the last terms of medical training, however it includes few opportunities for students to tackle all phases of a consultation and a shortage of opportunities to perform gynecological examinations. Therefore, we started a student-led clinic for cervical cancer screening (SLC-CCS) in Linköping, Sweden and aimed to evaluate students' views on the progression of learning, the quality of the Papanicolaou (Pap) smear, and women´s experiences of the visit, using mixed methodology. METHODS: The implementation of the SLC-CCS is described in detail. Students (n = 61) taking part in the SLC-CCS between January and May 2021 were invited to participate in a follow-up discussion (n = 24) focused around four themes: attitudes and expectations prior to participation, experiences of the patient encounter, organization of the placement, and reflections on and suggestions for further development of the placements. The group meetings were conducted in Swedish, recorded, transcribed verbatim and subjected to a qualitative, descriptive thematic analysis. Thematic analysis is considered an appropriate method of analysis for seeking to understand experiences, thoughts, or behaviors across a data set. The proportion of Pap smears lacking cells from the squamous epithelium during the study period was compared with data from the same clinic before the SLC-CCS started. A validated questionnaire on women's experience of the Pap smear visit was provided. Answers were compared between women who had the Pap smear taken by a student or a healthcare provider. RESULTS: Three different themes were generated: growing confidence in the clinical situation, embodied awareness of variation in anatomy, doubting accuracy of one's own performance. The percentage of Pap smears lacking cells from the squamous epithelium were equal (2%) during the study period compared to the period before the SLC-CCS started (p = 0.28). No difference was found in the satisfaction index between the women examined by a student, those examined by a healthcare provider, or women who did not know who the examiner was (p = 0.112). CONCLUSIONS: The students expressed a growing confidence in the clinical situation and there was high satisfaction from the women. The quality of the Pap smears taken by the students was equal to the quality of those taken by the health care staff. All these findings indicate that high patient safety was maintained during this activity support the recommendation to include SLC-CCS as part of the medical training.

Prominent epigenetic and transcriptomic changes in CD4+ and CD8+ T cells during and after pregnancy in women with multiple sclerosis and controls.

BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4+ and CD8+ T cells are implicated in MS pathogenesis as being key regulators of inflammation and brain lesion formation. Although Tcells are prime candidates for the pregnancy-associated improvement of MS, the precise mechanisms are yet unclear, and in particular, a deep characterization of the epigenetic and transcriptomic events that occur in peripheral T cells during pregnancy in MS is lacking. METHODS: Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4+ and CD8+ T cells samples. Differential analysis and network-based approaches were used to analyze the global dynamics of epigenetic and transcriptomic changes. RESULTS: Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets. CONCLUSION: This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4+ and CD8+ T cells during pregnancy in MS. Our findings indicate that pregnancy induces profound changes in peripheral T cells, in both MS and healthy controls, which are associated with the modulation of inflammation and MS activity.

Key outcomes in childbirth: Development of a perinatal core outcome set for management of labor and delivery at or near term.

INTRODUCTION: Consistency and relevance of perinatal outcome measures are necessary basics for obstetric research, audit, and clinical counseling. Still, there is an unwarranted variation in reported perinatal outcomes, which impairs research synthesis, validity, and implementation, as well as clinical benchmarking and longitudinal comparisons. The aim of this study was to develop a short-term perinatal (fetal and neonatal) Core Outcome Set to be used in research and quality assurance of management of labor and delivery at or near term. MATERIAL AND METHODS: The methods were guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. The project was prospectively registered on July 2, 2020 in the Core Outcome Measures in Effectiveness Trials (COMET) data base (reference number 1593). A list of potential outcomes was created based on a systematic review of studies evaluating interventions for peripartum management at or near term (≥34 weeks of gestation), including decisions regarding timing and type of onset of labor, intrapartum care, and mode of delivery. The list was entered into a two-round Delphi survey with predefined consensus criteria. Participants (n = 67) included clinicians, researchers, lay persons with experience of childbirth (patient representatives), and other stakeholders. A consensus meeting was held to reach a final agreement. RESULTS: Response rates were 82.1% (55/67) and 92.7% (51/55) for the first and second Delphi rounds, respectively. In total, 17 outcomes were included in the final core outcome set, reflecting mortality, health or morbidity, including asphyxia, central nervous system status, infection, neonatal resuscitation and admission, breastfeeding and mother-infant interaction, operative delivery due to fetal distress, as well as birthweight and gestational age. Two of these outcomes were suggested by patient representatives. CONCLUSIONS: The Swedish Perinatal Core Outcome Set (SPeCOS) study involved a broad circle of relevant stakeholders and reached consensus on a minimal set of perinatal outcomes that should be collected and reported in a standardized way in all future studies on management of labor and delivery at or near term, regardless of the specific population or condition studied. This could improve obstetric research, evidence synthesis, uptake, implementation, and adherence, as well as clinical practice, audit, and comparisons in childbirth care.

Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures. Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk. Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Body mass index and complications after obstetric anal sphincter injury, 8 weeks postpartum.

INTRODUCTION AND HYPOTHESIS: The impact of body mass index (BMI) on pelvic floor recovery after an obstetric anal sphincter injury (OASI) is unclear. The aim of this study was to evaluate the hypothesis that urinary incontinence (UI) and anal incontinence (AI) are more common in overweight and obese women than in normal-weight women 8 weeks postpartum in women with OASI. METHODS: A population-based cohort study including 6,595 primiparous women, with an OASI, delivered between 2014 and 2019. Exposure and questionnaire data were retrieved from the Swedish Perineal Laceration Registry. Uni- and multivariate analyses were used to compare normal-weight (BMI ≤24.9, reference), overweight (25.0-29.9), and obese (≥ 30) women with regard to UI and AI at 8 weeks post-partum. RESULTS: Multivariate analyses showed an increased risk for urinary incontinence (OR 1.54, 95% CI 1.27-1.87) among overweight women as well as among obese women (OR 1.72, 95% CI 1.32-2.24). In contrast to our hypothesis, both overweight women (OR 0.68, 95% CI 0.56-0.83) and obese women (OR 0.65, 95% CI 0.49-0.87) were at a decreased risk for any gas and/or faecal incontinence after adjustment to possible confounding factors. The absolute rate of AI was 40.1% among normal-weight women, 34.2% among overweight women, and 29.1% in the obese group. CONCLUSIONS: Urinary incontinence is more common, whereas AI is less common among overweight and obese women than in primiparous women with a BMI <24.9, 8 weeks after an OASI. The new finding, that overweight women report less AI than normal-weight women, merits further study.

Physical Activity, Body Composition, and Cardiometabolic Health during Pregnancy: A Compositional Data Approach.

PURPOSE: The aim of this study was to examine the cross-sectional and longitudinal associations of 24-h movement behaviors (sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA)) with body composition and cardiometabolic health in i) early and ii) late pregnancy (gestational weeks 14 and 37). METHODS: This observational study utilized cross-sectional ( n = 273) and longitudinal data ( n = 242) from the HealthyMoms trial. Time spent in movement behaviors over seven consecutive 24-h periods (ActiGraph wGT3x-BT accelerometer), body composition (Bod Pod), and cardiometabolic health indicators (glucose levels, homeostatic model for insulin resistance (HOMA-IR), systolic and diastolic blood pressure, metabolic syndrome (MetS) score) were measured in early and late pregnancy. RESULTS: In early pregnancy, reallocating time to MVPA from LPA, SB, and sleep was associated with lower MetS score (adjusted γ = -0.343, P = 0.002). Correspondingly, reallocating time to LPA from SB and sleep in early pregnancy was associated with lower body weight (adjusted γ = -5.959, P = 0.047) and HOMA-IR (adjusted γ = -0.557, P = 0.031) at the same time point. Furthermore, reallocating time to LPA from SB and sleep in early pregnancy was associated with lower fat mass index (adjusted γ = -0.668, P = 0.028), glucose levels (adjusted γ = -0.315, P = 0.006), HOMA-IR (adjusted γ = -0.779, P = 0.004), and MetS score (adjusted γ = -0.470, P = 0.027) in late pregnancy. The changes in behaviors throughout pregnancy were not associated with body weight, body composition, and MetS score in late pregnancy. CONCLUSIONS: Our results demonstrated that increasing LPA or MVPA while reducing SB and sleep was associated with lower weight and more favorable cardiometabolic health in early pregnancy. In contrast, LPA in early pregnancy seems to be a stimulus of enough intensity to improve body composition and cardiometabolic health indicators in late pregnancy.

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3rd trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved. In this study, we used the highly sensitive and specific proximity extension assay technology to perform protein profiling analysis of 92 inflammation-related proteins in MS patients (n=15) and healthy controls (n=10), longitudinally sampled before, during, and after pregnancy. Differential expression analysis was performed using linear models and p-values were adjusted for false discovery rate due to multiple comparisons. Our findings reveal gradual dynamic changes in plasma proteins that are most prominent during the 3rd trimester while reverting post-partum. Thus, this pattern reflects the disease activity of MS during pregnancy. Among the differentially expressed proteins in pregnancy, several proteins with known immunoregulatory properties were upregulated, such as PD-L1, LIF-R, TGF-ß1, and CCL28. On the other hand, inflammatory chemokines such as CCL8, CCL13, and CXCL5, as well as members of the tumor necrosis factor family, TRANCE and TWEAK, were downregulated. Further in-depth studies will reveal if these proteins can serve as biomarkers in MS and whether they are mechanistically involved in the disease amelioration and worsening. A deeper understanding of the mechanisms involved may identify new treatment strategies mimicking the pregnancy milieu.

Maternal childbirth experience and time in labor: a population-based cohort study.

A negative childbirth experience may have long term negative effects on maternal health. New international guidelines allow a slower progress of labor in the early active phase. However, a longer time in labor may influence the childbirth experience. In this population-based cohort study including 26,429 women, who gave birth from January 2016 to March 2020, the association between duration of different phases of active labor and childbirth experience was studied. The women assessed their childbirth experience by visual analogue scale (VAS) score. Data was obtained from electronic medical records. The prevalence of negative childbirth experience (VAS 1-3) was 4.9%. A significant association between longer duration of all labor phases and a negative childbirth experience was found for primi- and multipara. The adjusted odds ratio (aOR (95%CI)) of negative childbirth experience and longer time in active labor (above the 90th percentile) in primipara was 2.39 (1.98-2.90) and in multipara 2.23 (1.78-2.79). In primi-and multipara with duration of labor ≥ 12 h or ≥ 6 h the aOR (95%CI) of negative childbirth experience were 2.22 (1.91-2.58) and 1.91 (1.59-2.26) respectively. It is of great importance to identify and optimize the clinical care of women with longer time in labor to reduce the risk of negative childbirth experience and associated adverse long-term effects.

Labor dystocia and oxytocin augmentation before or after six centimeters cervical dilatation, in nulliparous women with spontaneous labor, in relation to mode of birth.

BACKGROUND: The effects of diagnosing and treating labor dystocia with oxytocin infusion at different cervical dilatations have not been fully evaluated. Therefore, we aimed to examine whether cervical dilatation at diagnosis of dystocia and initiation of oxytocin infusion at different stages of cervical dilatation were associated with mode of birth, obstetric complications and women's birthing experience. METHODS: A retrospective cohort study, including 588 nulliparous term women with spontaneous onset of labor and dystocia requiring oxytocin augmentation. The study population was divided into three groups according to cervical dilatation at diagnosis of dystocia and initiation of oxytocin-infusion (≤ 5 cm, 6-10 cm, fully dilated) with mode of birth as the primary outcome. Secondary outcomes were obstetrical and neonatal complications and women´s experience of childbirth. Statistical comparison between groups using Chi-square and ANOVA was performed. The risk of operative birth (cesarean section and instrumental birth) was assessed using binary logistic regression with suitable adjustments (maternal age, body mass index and risk assessment on admission to the labor ward). RESULTS: The cesarean section rate differed between the groups (p < 0.001); 12% in the ≤ 5 cm group, 6% in the 6-10 cm group and 0% in the fully dilated group. There was no increased risk for operative birth in the ≤ 5 cm group compared to the 6-10 cm group, adjusted OR 1.28 95%CI (0.78-2.08). The fully dilated group had a decreased risk of operative birth (adjusted OR 0.48 95%CI (0.27-0.85). The rate of a negative birthing experience was high in all groups (28.5%, 19% and 18%) but was only increased among women in the ≤ 5 cm group compared with the 6-10 cm group, adjusted OR 1.76 95%CI (1.05-2.95). CONCLUSIONS: Although no difference in the risk of operative birth was found between the ≤ 5 cm and 6-10 cm cervical dilatation-groups, the cesarean section rate was highest in women with dystocia requiring oxytocin augmentation at ≤ 5 cm cervical dilatation. This might indicate that oxytocin augmentation before 6 cm cervical dilatation could be contra-productive in preventing cesarean sections. Further, the increased risk of negative birth experience in the ≤ 5 cm group should be kept in mind to improve labor care.

Clinical-pathological features in placentas of pregnancies with SARS-CoV-2 infection and adverse outcome: case series with and without congenital transmission.

OBJECTIVE: To correlate clinical outcomes to pathology in SARS-CoV-2 infected placentas in stillborn and live-born infants presenting with fetal distress. DESIGN: Retrospective, observational. SETTING: Nationwide. POPULATION: Five stillborn and nine live-born infants from 13 pregnant women infected with SARS-CoV-2 seeking care at seven different maternity units in Sweden. METHODS: Clinical outcomes and placental pathology were studied in 14 cases (one twin pregnancy) of maternal SARS-CoV-2 infection with impaired fetal outcome. Outcomes were correlated to placental pathology in order to investigate the impact of virus-related pathology on the villous capillary endothelium, trophoblast and other cells. MAIN OUTCOME MEASURES: Maternal and fetal clinical outcomes and placental pathology in stillborn and live-born infants. RESULTS: Reduced fetal movements were reported (77%) and time from onset of maternal COVID-19 symptoms to signs of fetal distress among live-born infants was 6 (3-12) days and to diagnosis of stillbirth 11 (2-25) days. Two of the live-born infants died during the postnatal period. Signs of fetal distress led to emergency caesarean section in all live-born infants with umbilical cord blood gases and low Apgar scores confirming intrauterine hypoxia. Five stillborn and one live-born neonate had confirmed congenital transmission. Massive perivillous fibrinoid deposition, intervillositis and trophoblast necrosis were associated with SARS-CoV-2 placental infection and congenital transmission. CONCLUSIONS: SARS-CoV-2 can cause rapid placental dysfunction with subsequent acute fetal hypoxia leading to intrauterine fetal compromise. Associated placental pathology included massive perivillous fibrinoid deposition, intervillositis and trophoblast degeneration.