| 1. |
- Axelsson, Daniel, 1974-
(författare)
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Postpartum infections; prevalence, associated obstetric factors and the role of vitamin D
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Postpartum infections are a major cause of maternal mortality and morbidity worldwide. Breast infection, endometritis, urinary tract infection and wound infections are the most common postpartum infections and together they affect almost 20% of women after childbirth. Some risk factors for postpartum infections, for example cesarean section, have been relatively well studied, but other presumable risk factors are yet to be confirmed.The proportion of pregnant women who are overweight or obese is increasing in most parts of the world. Increased maternal body mass index (BMI) is associated with maternal and infant morbidity. The association between overweight / obesity and postpartum infections is incompletely understood. Vitamin D deficiency has in epidemiological studies been shown to increase the risk of various infections. Furthermore, vitamin D is an important factor in the human immune system. Concomitantly, vitamin D supplementation seems protective against some types of infections. Whether vitamin D deficiency is a risk factor for postpartum infections has not been studied.Material and Methods: In a population-based observational study using questionnaires, the prevalences of postpartum wound infections, endometritis, urinary tract infections and mastitis in the southeast region of Sweden were estimated (Paper I). All women giving birth in the region during one year (n=11 124) were asked to participate. Papers II and III were cohort studies based on all deliveries in Sweden during eight years (2005-2012). Data sources were the Swedish Medical Birth Register, the Swedish National Patient Register and the Swedish Prescribed Drugs Register. In paper II all term deliveries were included (n=795 072). Risk factors for postpartum wound infections, endometritis and urinary tract infection were evaluated. Paper III included all deliveries (n=841 780) and examined the impact of BMI on the risk of postpartum wound infections, endometritis and breast abscess after different modes of delivery. Infections were defined as the presence of applicable ICD-10 codes. The Mantel-Haenszel technique was used to calculate adjusted odds ratios. In paper IV the association between vitamin D deficiency and overall postpartum infectious morbidity was analyzed. Serum samples from the Pregnancy Biobank in Linköping, drawn at the time of delivery, were used to determine concentrations of 25-hydroxyvitamin D in 1397 women. ICD-10 codes were extracted from the women’s medical records. The prevalence of vitamin D deficiency was calculated and adjusted odds ratios for postpartum infections were estimated with multivariable logistic regression analysis.Results: More than one out of ten women in southeast Sweden reported wound infections; endometritis, urinary tract infection or mastitis postpartum and 7.5% reported antibiotic treatment for infection. Cesarean section was the strongest risk factor for wound infection, followed by obstetric anal sphincter injuries and episiotomy. For endometritis, the strongest risk factors were anemia, manual placental removal and emergency cesarean section. Urinary tract infection was associated with anemia, instrumental vaginal delivery and emergency cesarean section. There was a dose-dependent increased risk of postpartum infection with higher BMI. For morbidly obese women the risk of infection was over 50% higher than for normal weight women. The risk of endometritis after normal vaginal delivery increased the higher the BMI, as did the risk of wound infection after cesarean section, regardless of the type of cesarean section. For breast abscess, there was an inverse association with BMI.Vitamin D deficiency was present among almost 60% of pregnant women at the time of delivery. No association between vitamin D deficiency and postpartum infections was found.Conclusions: Every tenth Swedish woman acquired an infection postpartum and three quarters of them received antibiotics for infection. Anemia was an important risk factor for postpartum infection, and the strongest risk factor for endometritis and urinary tract infection. Strong efforts should be made to reduce blood loss during and after childbirth. This thesis confirmed cesarean section as a major risk factor for postpartum infection, especially wound infection. The risk increased if the woman was overweight or obese, regardless of whether it was a planned or an emergency cesarean section.Vitamin D deficiency was common among Swedish pregnant women, but it was not found to be associated with postpartum infections.
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| 2. |
- Ginstman, Charlotte, 1975-
(författare)
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Contraception in women with obesity with special reference to gastric bypass surgery
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The prevalence of obesity is increasing worldwide. The treatment of morbid obesity is dominated by bariatric surgery, for example Roux-en-Y gastric bypass (RYGB) surgery. If other contraceptive options are available, women with obesity should not be prescribed combined hormonal contraceptives due to the obesity-related increased risk of venous thromboembolism. Women are advised not to become pregnant during the first 12-18 months after RYGB surgery. There is a lack of knowledge of what type of contraceptive methods women with obesity are prescribed and whether they experience more or different side effects compared to normal-weight women. It is not known if the absorption and pharmacokinetic profile of progestins are affected by RYGB. The aim of this thesis was to investigate the pattern of contraceptive use in women with obesity, what type of contraceptive counselling was given to women in relation to RYGB, and whether the pharmacokinetics of two different progestins were affected by RYGB surgery.Material and Methods: Paper I is a retrospective cohort study analysing the patterns of contraceptive prescription, adverse effects, duration of treatment, reasons for discontinuation and bleeding pattern in 371 women with obesity compared with 744 normal-weight women. Medical records were scrutinised from 1 Jan 2010 until 31 Dec 2014. Paper II is based on a questionnaire sent to 987 women who had undergone RYGB during 2010. The questionnaire concerned preoperative and present contraceptive use, contraceptive counselling in relation to surgery and what type of recommendations they had received regarding pregnancy after RYGB. Papers III and IV are experimental studies investigating the pharmacokinetics of desogestrel (etonogestrel) and levonorgestrel in relation to RYGB.Results and conclusions: The most commonly prescribed contraceptive method for women with obesity was the progestin-only pill but many women with obesity were prescribed combined hormonal contraceptives despite the current recommendations of cautious prescription of oestrogen-containing methods. There were no differences in adherence to contraceptive method between women with obesity and normal-weight women. Despite the uncertainties regarding absorption, almost 10 % of women continued using oral contraceptives after RYGB. Nearly 40% were not aware of the recommendation to avoid pregnancy in the first year after RYGB and almost one third did not use any contraception during this period. This could be due to a lack of information or that the women did not retain the given information to avoid pregnancy. We found no clinically significant differences in the steady state pharmacokinetics of desogestrel before compared with after RYGB, or in single dose pharmacokinetics of levonorgestrel in women with BMI< 30 having undergone RYGB compared with BMI-matched non-operated women. This suggests that oral contraceptives containing desogestrel and levonorgestrel might be used after RYGB surgery.
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| 3. |
- Hellberg, Sandra, 1986-
(författare)
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Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement.The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment.The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells.This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
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| 4. |
- Kilander, Helena, 1976-
(författare)
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Contraceptive counselling in abortion care
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Improving women’s knowledge about contraception, and their access to contraceptive methods, is central in order to strengthen their sexual and reproductive rights at the time of an abortion. Contraceptive counselling aims to support women’s reproductive control and prevent unintended pregnancies (UPs). It is unclear, however, how to provide contraceptive counselling and how to organise services at the time of an abortion, in order to achieve this.Aim: The overall aim was to study women’s choices and use of contraceptive methods post-abortion. The research also aimed to describe contraceptive counselling in the context of an abortion from women’s and health professionals’ (HP’s) perspectives. Initial studies informed subsequent improvement efforts, also evaluated in the thesis, regarding contraceptive counselling and services at the time of an abortion.Design and Methods: The studies in this thesis involve both quantitative (studies I and IV) and qualitative (studies II–IV) methods, performed at six departments in southeast Sweden. Study I had a quantitative and longitudinal design. The medical records of women (n=987) were reviewed regarding women’s choice of contraceptive method at the index abortion and the odds of repeat abortion within three to four years. Studies II and III were qualitative interview studies, in which 13 women (study II) and 21 healthcare professionals (HPs) (study III) described their experiences of contraceptive counselling at the time of an abortion. The interviews were analysed using interpretive phenomenology (study II) and conventional content analysis (study III). Study IV was a case study regarding a qualitative improvement collaborative (QIC), designed to improve contraceptive counselling and services. Three multi-professional teams involved in abortion care participated in the QIC and two women provided user-experience input. Both qualitative and quantitative data were collected and analysed.Results: The findings of the thesis are organised into three themes: I) Women and HPs described contraceptive counselling at the time of an abortion as an often - complex meeting. There was scepticism about contraceptive methods and limited receptivity to information among women. Respectful counselling facilitated women’s choice of contraceptive method even if they were sceptical and found the situation emotionally charged. II) Women’s choices, need for guidance and access to the contraceptive methods was described in the second theme. Choice of oral contraceptives (OC) dominated. Overall, 25% of the women experienced repeat abortion during followup. Women who chose long-acting reversible contraception (LARC) experienced fewer repeat abortions compared to women who chose OC. Both women and HPs reported barriers in access to LARC post-abortion. III) In a Quality Improvement Collaborative (QIC), two volunteering women provided user-experience input. HPs participating in this QIC reported strengthened skills in counselling and enhanced ability to evaluate their performance. Despite the team’s prediction that they would reach the QIC goal that ≥50% of women would start LARC within 30 days post-abortion, and the fact that a majority of the women in QIC units chose LARC, none of the teams managed to reach the goal, primarily due to insufficient capacity for timely initiation of LARC.Conclusion: The findings suggest that women need respectful counselling and guidance at the time of an abortion. Access to a range of contraceptive methods, particularly LARC, is important to prevent repeat UPs. There is room for further improvement in offering coordinated and timely access for women who choose LARC, and to evaluate counselling, in the present settings.
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| 5. |
- Malmborg, Agota, 1979-
(författare)
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Happy with the method? : Sexual function changes in young women using contraception
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sexuality and contraception are closely linked topics. In theory, hormonal contraception use might affect female sexual function in both positive and negative directions. Some women experience and report adverse sexual function changes while they use hormonal contraception while others report no or positive changes. Questions of causality, the potential mechanisms of action, and how to counsel women reporting adverse changes have been a matter of debate but scientific consensus is lacking on the answers.Material and Methods: The first study was a cross-sectional study with 1851 women, aged 22, 25 and 28 years, who answered a questionnaire regarding contraception use, positive and negative side effects, contraceptive counselling, and aspects of sexual function. The second study was a randomised double-blind placebo-controlled multicentre clinical trial. In this study we compared 102 women who used a combined oral contraceptive with 100 women who took placebo, regarding sexual function scores evaluated with the Mc Coy Female Sexuality Questionnaire. We measured testosterone level changes in serum and hair as a secondary outcome. The third study was a qualitative study in which we explored women’s experiences of the negative effects of hormonal contraceptive use on sexual function. We interviewed 24 selected women who had reported previous experiences of adverse sexual function changes while using a hormonal contraceptive method.Results and Conclusions: Young Swedish women who used hormonal contraception, reported a negative change in sexual desire more than twice as often as women who used hormone-free contraceptive methods. A similar difference was seen between users of the levonorgestrel-intrauterine system compared with users of the copper-intrauterine device.The experience of an adverse sexual desire effect, which the women thought was due to contraceptive use, was a strong predictive factor for reconsideration of the contraceptive method.We found no change in the total score of sexual function during the use of a combined oral contraceptive compared with placebo. Sexual interest and lubrication which were two aspects of the total sexual function, were found to be negatively associated with the use of the tested combined oral contraceptive. Changes were small however, and the clinical relevance of these findings is therefore unclear. Furthermore, lubrication change did not persist following adjustment for change in self-rated depression scores.The biologically active fraction of testosterone embedded in hair did not decrease during combined oral contraceptive treatment and no reliable associations were found between the induced serum testosterone level decrease and sexual desire changes. Women reporting negative sexual function effects while using hormonal contraception, described lubrication difficulties and decreased sexual desire associated with both contraceptive use and parts of the menstrual cycle. Associations became obvious with time and experience and consequently contraceptive choice became easier with age, experience, and better understanding, all of which we concluded could be facilitated by a responsive contraceptive counsellor.Our findings indicate the need for further evaluation of sexual function changes in the selected group of women who seem to be susceptible to the use of hormonal contraceptives.
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| 6. |
- Sundell, Micaela, 1989-
(författare)
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Epidemiological and Clinical Aspects of Hormonal Contraception and Menopausal Hormone Therapy in Women
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The main indications for therapy with female sex hormones are contraception and menopausal hormone therapy (MHT). The aim of this thesis was to investigate the use of hormonal contraception and MHT in different populations of women in Sweden, 2000–2021. The use of contraception in women with obesity was studied. The use of MHT in Sweden over time was studied and different run-in periods were validated to define an incident MHT user. We also investigated the risk of pulmonary embolism (PE) in women using MHT, including considerations regarding administration form, treatment duration and type of progestin used. Women with premature or early menopause after bilateral oophorectomy were studied with regard to dispensed MHT.Material and Methods: The studies were based on different data sources including electronical medical records, national mandatory health registers, and a national quality register (GynOp). The use of MHT over time was studied using defined daily doses (DDD) per 1,000 women per day, one-year prevalence and incidence proportion. The definition of an incident drug user was validated by calculating the predictive value of different run-in periods.Results: The most prescribed contraceptive method in women with obesity was progestin-only pills (44%), but 21% were prescribed combined hormonal contraceptives contrary to Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within one year, compared with normal weight women. The use of MHT decreased significantly after the turn of the century. In the 50–54 years age interval, the dispensed amount decreased from 282 DDD/1,000 women per day in 2000, to 77 in 2006. It then stabilised around 50 DDD/1,000 women per day during 2010 to 2017. The one-year prevalence followed the same pattern, with a plateau 2010–2016. From 2017, an increase in MHT dispensations was observed. A run-in period of 18 months had a PV of 88% in the 50 to 54 years age group and was found to be suitable and reliable for defining incident users of MHT at the ages close to menopause. The risk of PE was significantly increased in users of oral MHT, but not transdermal. The risk was highest in first-ever users (OR 2.32; 95% CI, 1.34–4.00) and was considerably lower in women who may have used MHT previously (OR 1.38; 95% CI, 1.01–1.89). 69% of all women with a bilateral oophorectomy had at least one dispensation of MHT within one year after surgery. Within this treated group the estimated treatment time constituted 63% of the remaining time to natural menopause.Conclusions: Progestin-only pills was the most prescribed contraceptive method in women with obesity, but many women with obesity were prescribed combined hormonal contraceptives contrary to clinical guidelines. The use of MHT decreased significantly after the turn of the century, but has increased since 2017 in the age groups close to menopause. The classifications used for prevalent and incident drug use are of importance to the results. The risk of pulmonary embolism is increased in users of oral but not transdermal MHT. There seems to be a significant undertreatment with hormone therapy in women with premature, surgical menopause.
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