| 1. |
- Axfors, Cathrine
(författare)
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Anxious personality traits in pregnant women : Associations with postpartum depression, delivery complications and health care use
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anxious personality traits, including those encompassed by negative emotionality (neuroticism) and the tendency to worry about close relationships (attachment anxiety) during pregnancy were the focus of this thesis. The overall aim was to examine perinatal correlates of these characteris-tics in terms of psychiatric and obstetric health as well as antenatal care (ANC).Papers I-II were part of a large population-based project on pregnant women in Uppsala in 2009-2012 (n=2160). Papers III-IV adjoined participants from several projects in 2005-2011, on oral contraceptive use, infertility, induced abortion, premenstrual mood disorder, and perina-tal depression (n=2819). The participants reported on the Swedish universities Scales of Per-sonality for neuroticism (papers II-IV) and the Attachment Style Questionnaire (ASQ) for attachment anxiety (papers I-II). The participants also answered the Edinburgh Postnatal De-pression Scale on depressive symptoms (paper II). In paper III, information on obstetric com-plications for primiparous women with singleton pregnancies (n=1969) was extracted from Swedish national health registers. In paper IV, ANC use was derived from medical records of obstetric low-risk women residing in Uppsala (n=1052).The ASQ had similar psychometric properties in pregnant women (n=1631) as in previous reports (paper I). In non-depressed pregnant women (n=1431), the combination of neuroticism and attachment anxiety was the best risk indicator of postpartum depressive symptoms (paper II). Whereas high neuroticism was not related to obstetric complications (paper III), it was associated with higher use of ANC (paper IV).Summarized, this thesis illustrates how anxious personality traits may predispose for post-partum depression and higher use of ANC in the absence of obstetric complications. Future development of these findings should be to evaluate individual and societal benefits of a greater emphasis on psychological support in ANC.
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| 2. |
- Bränn, Emma, 1988-
(författare)
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Biomarkers for Peripartum Depression : Focusing on aspects of the immune system and the metabolome
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripartum depression is a common, multifactorial, and potentially devastating disease among new mothers. A biological marker for peripartum depression would facilitate early detection, better understanding of the pathophysiology, and identification of targets for treatment. Evidence is growing for a potential role of the immune system in depression outside the peripartum period. Major adaptations of the immune system occur during pregnancy, justifying the search for immunological markers for peripartum depression. The immune system is very complex and dynamic during pregnancy, complicating the study of associations with depression. The metabolome is also affected by pregnancy and is linked to the immune system via, e.g., the microbiota. Hence, metabolomic profiling could increase the understanding of peripartum depression. This thesis aimed to explore inflammatory markers and metabolic profiles in the peripartum period, in order to discover possible biomarkers, and to increase the understanding of the pathophysiology of peripartum depression.All studies were conducted within the Biology, Affect, Stress, Imaging, and Cognition (BASIC) study. The Edinburgh Postnatal Depression Scale and the Mini International Neuropsychiatric Interview were used to assess depressive symptoms. Multiplex Proximity Extension assays were used to analyze inflammatory markers in pregnancy and postpartum. Luminex Bio-Plex Pro Human Cytokine Assays were used to analyze cytokine levels across the peripartum period, and gas chromatography-mass spectrometry metabolomics were used for metabolic profiling. No marker was discriminative enough to be used on its own as a biomarker for peripartum depression. However, several inflammatory markers (such as STAM-BP, TRANCE, HGF, IL-18, FGF-23, and CXCL1) were identified as possible candidates for more advanced diagnostic algorithms. The results further pointed towards the importance of adaptation of the immune system during pregnancy and postpartum, where levels of cytokines such as VEGF-A might have an important role in antenatal and postpartum depression. The results even highlight the importance of examination timing. Lastly, the metabolic profiling suggested different subgroups of women with postpartum depressive symptoms, supporting theories of peripartum depression being a heterogeneous disease in need of subgroup definition.
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| 3. |
- Cato, Karin, 1977-
(författare)
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Breastfeeding – Initiation, duration, attitudes and experiences
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to increase knowledge about factors that influence breastfeeding initiation and duration, as well as about women’s attitudes towards breastfeeding during pregnancy.The first two studies were a part of the UPPSAT project, a population-based cohort study conducted in Uppsala, Sweden. The women answered questionnaires five days, six weeks and six months postpartum, including questions on breastfeeding initiation and duration. Eight hundred and seventy-nine women and 679 women were included in the first study (Paper I) and second study (Paper II), respectively. The third study (Paper III) was part of the BASIC study, a large cohort following women from pregnancy and up to one year postpartum. In BASIC, the women completed web-questionnaires, and 1217 women participated during mid-pregnancy and postpartum. The fourth study (Paper IV) was part of a qualitative project, “Narratives of breastfeeding”, and included 11 women, interviewed individually in late pregnancy.The prevalence of the hands-on approach was 38%. Women who received the hands-on approach were more likely to report a negative experience of the first breastfeeding session (Paper I). Seventy-seven percent of the women reported exclusive breastfeeding up to, at least, two months postpartum. Being a first-time mother, reporting emotional distress during pregnancy, and giving birth by cesarean section were factors independently associated with exclusive breastfeeding lasting less than two months postpartum (Paper II). Women with depressive symptoms during pregnancy who breastfed for the first time later than two hours postpartum had the highest odds of not breastfeeding exclusively at six weeks postpartum (Paper III). When pregnant women thought about their future breastfeeding, they were balancing between social norms and personal desires (Paper IV).These results can help to develop clinical practice to improve women’s experience of the first breastfeeding session. Additionally, the results may facilitate identifying women in need for targeted support, in order to promote longer exclusive breastfeeding duration. By acknowledging pregnant women’s thoughts and attitudes about breastfeeding, breastfeeding information and support, health care professionals can meet the needs and desires of women.
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| 4. |
- Eckerdal, Patricia, 1972-
(författare)
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Perinatal Complications: Associations with Postpartum depressive symptoms and Neuroticism
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Even though most pregnancies and deliveries are uncomplicated, still fifteen percent of all women in developed countries suffer pregnancy-related complications. The aim of this thesis was to explore the associations between perinatal complications and perinatal maternal health, with emphasis on postpartum depressive symptoms (PPDS) and neuroticism taking into account potential confounding or mediating factors such as history of depression, antenatal depressive symptoms and delivery experience.In the first study (n=446), the association between heavy postpartum haemorrhage and PPDS at six weeks postpartum was delineated by using path-analysis in order to provide insight into the complex mediating roles of several consequences of postpartum haemorrhage. There was no direct association between postpartum haemorrhage and PPDS, only an indirect one via anaemia at discharge and negative delivery experience.The second study (n=3888) examined the association of mode of delivery with PPDS at 6 weeks postpartum. The results indicate that the association between elective caesarean section and PPDS is highly confounded by history of depression and fear of delivery, while emergency caesarean section and vacuum extraction increase odds for PPDS by leading to postpartum complications and negative delivery experience.The third study (n=1503) investigated the association between the use of epidural analgesia during delivery and PPDS. A positive association in the crude analysis was no longer present after adjustment for sociodemographic, psychosocial and obstetrical variables, indicating that pain relief through epidural analgesia is not likely to affect risk for PPDS.In the last study (n=1969), the association between neuroticism and perinatal complications was explored. Neuroticism was not associated with adverse perinatal outcomes, except for gestational diabetes mellitus. The association, however, became statistically non-significant after adjusting for psychiatric morbidity.In summary, the current studies do no find evidence for a direct association between perinatal complications and postpartum depressive symptoms or neuroticism. However, several important mediators have been identified, among which postpartum anaemia and negative delivery experience deserve special attention. Also, earlier psychiatric history needs to be addressed as an important confounder.
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| 5. |
- Henriksson, Hanna E., 1988-
(författare)
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Seasonal aspects of peripartum depressive symptoms
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, a large proportion of pregnant and newly delivered women develop peripartum depression, a condition that may cause long-term suffering for the entire family. Although there is a lack of consensus, some studies propose an association between season and the risk of developing depression during pregnancy and the postpartum period. Furthermore, the immune system, which undergoes numerous structural changes during pregnancy, has been suggested to exhibit seasonal variations. In addition, discrepancies in metabolic profiles have been reported between women with and without depression after childbirth. This thesis aimed to investigate seasonal aspects of peripartum depressive symptoms (PPDS) and biological markers during the peripartum period. The data mainly derived from the prospective population-based Biology, Affect, Stress, Imaging, and Cognition (BASIC) study, but data were also included from the longitudinal population-based Uppsala-Athens (UPPSAT) study. The presence of depressive symptoms was primarily assessed using the Edinburgh Postnatal Depression Scale (EPDS). There were no consistent associations between season, meteorological parameters, air pollen count, and PPDS. Moreover, a number of inflammatory markers were identified as having seasonal variations among samples from pregnant women. On the contrary, only one marker had a seasonal pattern during the early postpartum period. Furthermore, metabolic profiles were not discriminatory between pregnant women with and without depressive symptoms. However, when divided into summer and winter childbirths, discrepancies were identified in metabolic profiles between summer cases and controls, as well as between summer and winter controls. In summary, the studies included in this thesis suggest that season, specifically, is not associated with PPDS. However, season may have a moderating effect on the association between depressive symptoms and the metabolic profile of pregnant women. In addition, the seasonal variations appears more prominent among inflammatory markers during late pregnancy, compared with the early postpartum period. These findings suggest that women need equal attention in clinical care regardless of the season during which they give birth. Future studies on biological aspects of PPDS and immune-associated conditions are encouraged to also assess seasonality.
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| 6. |
- Johansson, Therese
(författare)
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Leveraging genetic and population-level data to improve women’s health
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hormonal contraception (HC) and menopausal hormone therapy (MHT) are commonly used medicines, but their safety profiles are uncertain due to conflicting research. This thesis aims to examine the potential risks associated with HC and MHT by utilizing large-scale population-based cohorts.In Paper I, we prospectively examined the link between oral contraceptives (OCs) and MHT use with the risk of stroke in the UK Biobank (UKB). Cox regression with time-varying exposures was used to investigate if treatment effects vary with time and to avoid immortal time bias. We included time-varying covariates to account for potential confounding factors that change over time and might affect the exposure level. Our research showed higher stroke risk during the initial period after initiating both treatments and increased stroke risk with MHT use regardless of menopause timing.In Paper II, we calculated the hazard rate of the first incidence of depression following OC use. To avoid the influence of healthy-user bias, we estimated the risk in first-time users and excluded previous users in the reference group. A unique aspect of our study was the sibling analysis, which explored the causal relationship between OC use and depression by examining female sibling pairs in the UKB. Our findings showed that initiating OC was associated with a higher risk of depression, especially among adolescents and during the initial phase of treatment.Paper III explored the genetic predisposition to venous thromboembolism (VTE) among OC users in the UKB. Using polygenic risk scores, we demonstrated that women with a high genetic liability for VTE have a significantly increased risk when initiating OC. This suggests that genetic screening may be beneficial in personalising contraceptive advice and mitigating the risk of thrombotic events.In Paper IV, we investigated the association between different types of contemporary MHT and the risk of cardiovascular disease, building upon our findings from Paper I. We emulated a target trial using the Swedish nationwide registers to estimate the intention-to-treat and per-protocol effect. We showed that specific MHT treatments, particularly those that combine estrogen and progestin, are linked to an increased risk of ischemic heart disease (IHD) and venous thromboembolism (VTE). Tibolone was positively associated with IHD and cerebral infarction but not VTE. In Paper V, we examined the risk of depression following HC initiation using the Swedish nationwide registers. Our research expanded upon the findings of Paper II by including various types of modern HCs and employing an emulated target trial study design. We observed an increased risk of depression among various HCs and found that the risk of depression is influenced by different dosages and types of progestins rather than the route of administration.Using advanced analytical methods, we identified critical risk periods, variations in risk between different treatments and the interplay between treatment and genetics. While HC and MHT offer significant benefits, their potential side effects warrant careful consideration. Therefore, prescribing HCs and MHT should be approached with nuance, emphasising individual risk assessments and ongoing monitoring to optimise safety.
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| 7. |
- Kimmel, Mary C.
(författare)
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Pregnancy—A Critical Time for Mental Health : Interrogating Psychiatry with Microbiota-Gut-Brain Axis and Autonomic Nervous System Biomarkers
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perinatal mood and anxiety disorders (PMADs) are common and impact the parent and child beyond the perinatal period of pregnancy and postpartum. The aim of this thesis was to study biomarkers that might reflect perinatal mental health. This work focused on multiple methods of mental health characterization and the autonomic nervous system as reflected by heart rate variability (HRV), the immune system, and the gut microbiome.Three observational longitudinal cohorts of pregnant individuals from three geographic regions were studied: 1) the Biology, Affect, Stress, Imaging and Cognition (BASIC) and the follow-up study U-BIRTH from Uppsala University Hospital; 2) the University of Illinois at Chicago (UIC) MoMent cohort; and 3) the University of North Carolina at Chapel Hill (UNC) cohort.The first paper assessed HRV before and after a mental task and in relation to psychiatric diagnoses, exposure to trauma, and self-report of mental distress. The second paper studied the Perceived Stress Scale (PSS-10) in relation to microbial composition and T-cell related cytokines and chemokines. The third paper studied the Edinburgh Postnatal Depression Scale (EPDS) in relation to whole genome sequencing and Gut Brain Modules for functioning. The fourth paper assessed trajectories of infant temperament in relation to depression and anxiety from the EPDS.The PSS-10 and the EPDS factored differently in the cohorts. HRV patterns differed based on anxiety disorder type, greater trait anxiety, and greater exposure to childhood traumatic eventsut microbiome data improved the prediction of PSS-10 self-efficacy; and self-efficacy was associated with a bacteria type more beneficial in the presence of dietary fiber that also associated with an immune factor important in immune tolerance. Greatest variation in microbial community functioning was due to cortisol degradation and synthesis of inositol, menaquinone, and the short chain fatty acid (SCFA) acetate. nxiety in pregnancy was associated with children who had higher levels of sensitivity and greater negative affectivity that increased over early life.These four papers highlight: 1) the course of mental health in pregnancy is critical to the development of parent and child; 2) the characterization of perinatal mental health requires a mix of methods that recognize there may be differences in the use of the methods based on the population; and 3) biomarkers of perinatal mental health need to reflect dynamic systems, and the components may not be as important as the patterns and interactions.
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| 8. |
- Kullinger, Merit
(författare)
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Discrepancy between pregnancy dating methods – correlates and outcomes
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- With the introduction of obstetric ultrasound there has been a shift from last menstrual period-based to ultrasound-based estimation of gestational age. The choice of the method and timing of pregnancy dating is important because it can affect dating precision and perinatal outcomes.First, when comparing two large population-based cohorts from the Medical Birth Register, from before and after the introduction of ultrasound-based pregnancy dating, male infants on the edge of prematurity did not benefit from progress in medical care as much as female infants in terms of prematurity-related outcomes. This might reflect a bias introduced by the ultrasound-based pregnancy dating method, because of a tendency to overestimate gestational age in pregnancies with a male fetus.Second, in a large population-based cross-sectional study, the associations of discrepancies between last menstrual period-based and ultrasound-based estimates with variables such as fetal sex and maternal height, indicated that ultrasound-based pregnancy dating introduced systematic errors presumably related to the method’s use of fetal size as a proxy for gestational age. The largest effect estimates were found for maternal obesity in cases of large negative discrepancies.Third, in a large population-based cohort study, discrepancies between last menstrual period-based and ultrasound-based estimates were associated with several adverse pregnancy, delivery, and neonatal outcomes. Most importantly, a large negative discrepancy was associated with higher odds for neonatal and intrauterine fetal death, as well as for an infant being small for gestational age.Fourth, in a survey study there was overall good adherence to national guidelines, except for early pregnancy dating. However, the management of discrepancies between methods for pregnancy dating varied widely in clinical practice, which may be due to the lack of national guidelines.In summary, ultrasound-based dating can be biased by maternal or fetal characteristics. Discrepancies between methods for pregnancy dating may indicate a need for closer monitoring to optimize perinatal care during pregnancy and childbirth.
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| 9. |
- Salih Joelsson, Lana
(författare)
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Lifestyle and Reproductive Health among Women prior to Conception
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Health and lifestyle is of great importance when women intend to become pregnant, as well as during pregnancy. It is crucial that people seeking for infertility are aware of which lifestyle changes they can undertake to enhance the likelihood of treatment success. The overall aim of this project was to investigate the extent to which women comply with recommendations for lifestyle changes during the time they try to conceive and during early pregnancy and the impact of lifestyle risk factors on treatment results in sub-fertile women. Lifestyle factors and mental health at baseline and lifestyle changes women made while they were trying to conceive were assessed by a study-specific questionnaire. Both pregnant women and non-pregnant sub-fertile women in the mid-Sweden region were included. The level of pregnancy planning was associated with planning behavior. Only one-third of all pregnant women took folic acid one month prior to conception, 17% used tobacco daily and 11% used alcohol weekly three months before conception. In the sub-fertile non-pregnant women cohort, 13.2% used tobacco daily, 13.6% drank more than three cups of coffee per day, and 11.6% consumed more than two glasses of alcohol weekly. Among sub-fertile women, one-third were overweight or obese. Pregnant women who conceived with Assisted Reproductive Technology (ART) reported lower rates of anxiety and depression symptoms compared to sub-fertile women. They also showed no difference in depression and anxiety symptoms compared to women who conceived naturally. Among sub-fertile women undergoing their first IVF treatment cycle, an independent as well as a cumulative effect of smoking and BMI on the number of aspirated oocytes and the proportion of mature oocytes was observed, especially among women with low ovarian reserve. In conclusion, approximately half of the women in our studies retained habits with negative effects on fertility. This is worrying because the harmful consequences of negative lifestyle factors are well established. These negative lifestyle factors are easy to detect and adjust at an early stage in the assessment process and might allow for optimization of fertility treatment and pregnancy outcomes.
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| 10. |
- Öberg, Mariella, 1970-
(författare)
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Exposed to Violence
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Violence against women is a crime against human rights and a major global public health issue affecting the lives of millions of girls and women worldwide. Exposure to violence poses a threat to health, both in the short and the long term. To minimize the devastating consequences of violence it is central to identify girls and women who have been exposed and to find possible risk factors that may serve as targets for prevention efforts.The main aims of this thesis were to study the prevalence of sexual, physical and psychological violence among women in Sweden and to explore possible associations to violence and polyvictimization during childhood as well as sociodemographic factors.In a family planning unit, 1226 women seeking either termination of pregnancy or contraceptive counseling were recruited to answer questions about different types of violence. Of the women seeking termination of pregnancy, 29% reported experiences of intimate partner violence, compared to 22% of women seeking contraceptive counseling. Of all the women attending a family planning unit, 27% reported lifetime experiences of sexual violence.A survey containing questions about lifetime experiences of sexual, physical and/or psychological violence was sent to a national sample of 10 000 women and 10 000 men. Lifetime experiences of at least one type of severe violence were reported by over 50% of both women and men. Sexual violence was more than three times more common among women compared to men.Rape/attempted rape in adulthood was more common among women who were single, had college-level education and those who had been unemployed or had received social welfare payments.Exposure to sexual, physical and psychological violence in childhood was highly associated with rape/attempted rape in adulthood among the women respondents.Conclusion: Lifetime experiences of violence are common among women in Sweden. Multiple exposure to violence during childhood is the most potent risk factor for exposure to sexual violence in adulthood. The findings underscore the importance of detecting individuals who have been exposed in order to offer help, and may contribute to the development of effective prevention programs, especially among children and adolescents.
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