ABSTRACTProblemPreterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L‐arginine) in women with spontaneous PTB and term birth.Methods of the StudyThe study was based on data from the population‐based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra‐High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF‐R1 and TNF‐R2 and GDF‐15.ResultsWomen with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L‐Arginine (p = 0.03). In addition, inflammation marker, TNF‐R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP.ConclusionsThese findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB.

The exact biochemical mechanisms that initiate labor are not yet fully understood. Nitric oxide is a potent relaxant of uterine smooth muscles until labor starts, and its precursor is L‐arginine. Asymmetric (ADMA) and symmetric (SDMA) dimethylarginines, are potent NO‐inhibitors. However, arginines (dimethylarginines and L‐arginine) are scarcely studied in relation to labor and childbirth. We aimed to investigate arginines in women with spontaneous (SLVB) and induced (ILVB) term labor with vaginal birth and in women undergoing elective caesarean section (ECS).

Background Unplanned pregnancy is common, and although some research indicates adverse outcomes for the neonate, such as death, low birth weight, and preterm birth, results are inconsistent. The purpose of the present study was to investigate associated neonatal outcomes of an unplanned pregnancy in a Swedish setting. Methods We conducted a retrospective cohort study in which data from 2953 women were retrieved from the Swedish Pregnancy Planning Study, covering ten Swedish counties from September 2012 through July 2013. Pregnancy intention was measured using the London Measurement of Unplanned Pregnancy. Women with unplanned pregnancies and pregnancies of ambivalent intention were combined and referred to as unplanned. Data on neonatal outcomes: small for gestational age, low birth weight, preterm birth, Apgar score < 7 at 5 min, and severe adverse neonatal outcome defined as death or need for resuscitation at birth, were retrieved from the Swedish Medical Birth Register. Results The prevalence of unplanned pregnancies was 30.4%. Compared with women who had planned pregnancies, those with unplanned pregnancies were more likely to give birth to neonates small for gestational age: 3.6% vs. 1.7% (aOR 2.1, 95% CI 1.2–3.7). There were no significant differences in preterm birth, Apgar score < 7 at 5 min, or severe adverse neonatal outcome. Conclusions In a Swedish setting, an unplanned pregnancy might increase the risk for birth of an infant small for gestational age.

Objectives Unplanned pregnancies are common and associated with late initiation and inadequate antenatal care attendance, which may pose health risks to mother and child. How pregnancy planning relates to maternal health and delivery in Sweden, a country with free antenatal care and free abortion, has not been studied previously. Our aims were to study whether pregnancy planning was associated with antenatal care utilization and pregnancy outcomes in a Swedish setting. Methods Data for 2953 women, who answered a questionnaire when recruited at antenatal clinics in Sweden and later gave birth, was linked to the Swedish Medical Birth Register. The degree of pregnancy planning was estimated using the London Measure of Unplanned Pregnancy. Unplanned (comprising unplanned and ambivalent intention to pregnancy) was compared to planned pregnancy. Differences between women with unplanned and planned pregnancy intention and associated pregnancy outcomes were analyzed using Fisher’s exact test and logistic regression. Results There were 31% unplanned (2% unplanned and 29% ambivalent) pregnancies, whereas most woman (69%) reported their pregnancy to be planned. Women with an unplanned pregnancy enrolled later to antenatal care, but there was no difference in number of visits compared with planned pregnancy. Women with an unplanned pregnancy had higher odds to have induced labor (17% versus 13%; aOR 1.33 95% CI 1.06–1.67) and a longer hospital stay (41% versus 37%; aOR 1.21 95% CI 1.02–1.44). No associations were found between pregnancy planning and pregnancy-induced hypertension, gestational diabetes mellitus, preeclampsia, epidural analgesia use, vacuum extraction delivery, Caesarean section or sphincter rupture. Conclusions Unplanned pregnancy was associated with delayed initiation of antenatal care, higher odds for induction of labor and longer hospital stay, but not with any severe pregnancy outcomes. These findings suggest that women with an unplanned pregnancy cope well in a setting with free abortion and free health care.

Heritable and reversible changes in gene expression can occur without alterations in DNA sequence largely dependent upon the position of a gene within an accessible (euchromatic) chromatin environment. This position effect variegation in Drosophila and S. pombe, and higher order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group (e.g. histone deacetylases (HDACs), protein phosphatases) and enhancer E(var) group (e.g. ATP-dependent nucleosome remodeling proteins). Higher order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin and histone tails in turn serve as platforms for recruitment of signaling modules that include non-histone proteins such as HP1 and NuRD. As the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also target non-histone substrates, a mechanism is in place by which epigenetic regulatory processes can affect the function of these alternate substrates. The nuclear receptor (NR) superfamily consists of conserved modular transcriptional regulators. Herein, we review the functional properties of nuclear receptors regulated by their direct acetylation including ligand-dependent activation, cellular growth and apoptosis.

Background: Vulvodynia is defined as vulvar pain for at least 3 months without a clear cause. To the best of our knowledge, there are no trials investigating the effects of internet treatment using CBT (Cognitive behavioural therapy) treatment with Acceptance and Commitment Therapy (ACT) components for women with vulvodynia. The aim of this study is to examine the effects of such a guided internet-based intervention on provoked vulvar pain during the waiting period before clinical treatment. Methods: We will randomise 52 patients to either guided internet-based intervention with CBT with (ACT) components or no intervention during the waiting period for treatment as usual. Online assessments are conducted at baseline, posttreatment, and at follow-up after 9 months. The primary outcome measure is provoked vulvar pain. Secondary outcomes are depression, anxiety, sexual function, and quality of life. Linear-mixed effect models will be used to assess the effect of the internet-based intervention on vulvar pain, pain acceptance, depression, anxiety, sexual function, and quality of life over time, by applying the intention-to-treat approach. Continuous data will be analysed with general linear models using intention-to-treat and also per protocol approaches to assess the effects of the intervention at different time points. Ordinal and binary data will be analysed with Mann Whitney's test, Fischer's exact test and multivariate logistic regression, respectively. Discussion: As a randomised controlled trial with short- and long-term follow-up points, the EMBLA study intends to provide a novel and better understanding regarding the treatment of vulvodynia and the role of internet-based treatment as a complement to standard care for women suffering from vulvodynia. The effects of vulvodynia on pain, sexual function, quality of life, depression, and anxiety are investigated. The study's results are expected to be of value in the planning of clinical care in the medical area. High dropout rates and technical difficulties associated with using the platform are common in similar studies. Trial registration number: NCT02809612

BACKGROUND:Internet-based ACT (Acceptance and commitment therapy) treatment may improve accessibility and reduce stigma related to seeking health care, but there are a lack of studies investigating internet-based treatment using ACT principles for women with vulvodynia. AIM:The aim of this study was to investigate the effects of an internet-based treatment of pain during intercourse for women with provoked vulvodynia compared with no intervention during the waiting period before clinical treatment. METHODS:A multicenter randomized controlled trial was conducted during 2016 to 2020, in which 99 participants were included. Participants were randomized to either a 6 week guided internet-based treatment using ACT principles or usual care. Data were collected at baseline, 6 weeks after baseline, and approximately 10 months after baseline. OUTCOMES:Pain-related (pain during intercourse, tampon test, impact of pain on sexual function) and pain behavior-related outcomes (attempts at intercourse, sexual activities besides intercourse, willingness to perform the tampon test, chronic pain acceptance questionnaire) were used as outcomes. RESULTS:Treatment was efficacious in what concerns pain during intercourse and pain acceptance. Less pain during intercourse among women in the intervention group was observed at both post-treatment (primary endpoint, P = .01, Cohen's d = 1.4, 95% CI = 0.33, 2.4), and follow-up (P = .04). Absolut mean difference between groups for pain during intercourse at post-treatment was -2.84, (95 % CI = -4.91, -0.78), and -1.58 at follow-up, (95 % CI = -3.17, 0.02), where the intervention group rated less pain than controls. No differences between groups over time were found for tampon test measures or impact of pain on sexual function. There was a significant difference between groups at all timepoints indicating fewer attempts at intercourse among participants in the intervention group. At post-treatment, women who underwent internet-based treatment reported higher pain acceptance and a rise in activity engagement compared with the control group. CLINICAL IMPLICATIONS:There is an indication that internet-based treatment could be incorporated into clinical practice as a complement to clinical treatment. STRENGTHS & LIMITATIONS:Study strengths included using several forms of recruitment and an intervention built by different professions with long experience of treating patients with vulvodynia. High dropout rate was a limitation of this study. CONCLUSION:Internet-based treatment may have an impact on pain during intercourse and positive effects on pain acceptance. However, conclusions must be drawn with caution due to the small sample size. Engström AH, Bohm-Starke N, Kullinger M, et al. Internet-based Treatment for Vulvodynia (EMBLA) - A Randomized Controlled Study. J Sex Med 2022;19:319-330.

Introduction. Swedish national guidelines for pregnancy dating were published in 2010. Follow-up is needed to assess adherence and to identify whether any clinical topics are not covered in the gui ...

To assess associations between discrepancy of pregnancy dating methods and adverse pregnancy, delivery, and neonatal outcomes, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for discrepancy categories among all singleton births from the Medical Birth Register (1995–2010) with estimated date of delivery (EDD) by last menstrual period (LMP) minus EDD by ultrasound (US) −20 to +20 days. Negative/positive discrepancy was a fetus smaller/larger than expected when dated by US (EDD postponed/changed to an earlier date). Large discrepancy was <10th or >90th percentile. Reference was median discrepancy ±2 days. Odds for diabetes and preeclampsia were higher in pregnancies with negative discrepancy, and for most delivery outcomes in case of large positive discrepancy (+9 to +20 days): shoulder dystocia [OR 1.16 (95% CI 1.01–1.33)] and sphincter injuries [OR 1.13 (95% CI 1.09–1.17)]. Odds for adverse neonatal outcomes were higher in large negative discrepancy (−4 to −20 days): low Apgar score [OR 1.18 (95% CI 1.09–1.27)], asphyxia [OR 1.18 (95% CI 1.11–1.25)], fetal death [OR 1.47 (95% CI 1.32–1.64)], and neonatal death [OR 2.19 (95% CI 1.91–2.50)]. In conclusion, especially, large negative discrepancy was associated with increased risks of adverse perinatal outcomes.

Historically, pregnancy dating has been based on self-reported information on the first day of the last menstrual period. In the 1970s, ultrasound biometry was introduced as an alternative for pregnancy dating and is now the leading method in Nordic countries. The use of ultrasound led to a reduction of post-term births and fewer inductions, and is considered more precise than last menstrual period-based methods for pregnancy dating. Nevertheless, differences in early growth and specific situations, such as maternal obesity, can render its estimates less precise, leading to gestational age misclassification. Clinical implications of ultrasound dating include effect on timely induction in case of post-term pregnancies, treatment with corticosteroids in cases of anticipated preterm delivery and decision on viability in cases of extreme prematurity. Furthermore, gestational age misclassification may influence the numbers and the magnitude of some adverse perinatal outcomes, closely related to gestational age, which are recorded in the Nordic birth registers.

Historically, pregnancy dating has been based on self-reported information on the first day of the last menstrual period. In the 1970s, ultrasound biometry was introduced as an alternative for pregnancy dating and is now the leading method in Nordic countries. The use of ultrasound led to a reduction of post-term births and fewer inductions, and is considered more precise than last menstrual period-based methods for pregnancy dating. Nevertheless, differences in early growth and specific situations, such as maternal obesity, can render its estimates less precise, leading to gestational age misclassification. Clinical implications of ultrasound dating include effect on timely induction in case of post-term pregnancies, treatment with corticosteroids in cases of anticipated preterm delivery and decision on viability in cases of extreme prematurity. Furthermore, gestational age misclassification may influence the numbers and the magnitude of some adverse perinatal outcomes, closely related to gestational age, which are recorded in the Nordic birth registers.

Gestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. We identified all singleton births ( n = 1 201 679) recorded in the Swedish Medical Birth Register in 1995–2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. Women with a body mass index >40 kg/m 2 had the highest odds for large negative discrepancies (−9 to −20 days) [odds ratio (OR) 2.16, 95% CI 2.01–2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9 kg/m 2 or <18.5 kg/m 2 , a history of gestational diabetes, female fetus, shorter stature (<−1 SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20 days) were associated with male fetus (OR 1.80, 95% CI 1.77–1.83), age ≥30 years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. Several maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

INTRODUCTION:Gestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. MATERIAL AND METHODS:We identified all singleton births (n = 1 201 679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. RESULTS:Women with a body mass index >40 kg/m2 had the highest odds for large negative discrepancies (-9 to -20 days) [odds ratio (OR) 2.16, 95% CI 2.01-2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9 kg/m2 or <18.5 kg/m2 , a history of gestational diabetes, female fetus, shorter stature (<-1 SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20 days) were associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age ≥30 years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. CONCLUSIONS:Several maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

Assessing gestational age by ultrasound can introduce a systematic bias due to sex differences in early growth.