Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. TRIAL REGISTRATION DETAILS: Not applicable.

Outside the norm: Mental health, school adjustment and community engagement in non-binary youth.

Aims: The aim of this study was to explore the role of self-reported non-binary gender identity in mental health problems, school adjustment, and wish to exert influence on municipal issues in a community sample of adolescents. Methods: In a cross-sectional design, data were collected through an anonymous survey in Uppsala County, Sweden, among 8385 students (response rate 58.2%) in grades 7, 9, and 11, aged 13-17 years. The Strengths and Difficulties Questionnaire (SDQ) self-report was used to assess mental health problems. Gender identity was measured with one item and youth were categorized into those who identified as male or female (i.e. binary youth), and those who did or could not identify with either gender (i.e. non-binary youth). Logistic regressions and qualitative content analysis were used to analyse data. Results: Youth with non-binary gender identity (n = 137; 1.6%) had higher odds of having mental problems according to the SDQ total score (OR=3.05; 1.77-5.25). The association between non-binary gender identity and mental health problems remained significant after adjusting for confounders. Additionally, compared to their binary peers, the non-binary youth reported more truancy (36.5% vs 49.6%), more often failed a subject (21.5% vs 36.5%), and were more interested in exerting influence on municipal issues such as sociopolitical development, education, municipal services, and drug and alcohol policies (25.3% vs 38.0%). Conclusions: Youth with non-binary gender identity constitute a vulnerable population regarding mental health problems and school adjustment. The willingness to exert influence on municipal issues suggests a possible pathway to engagement.

Inflammatory markers in women with postpartum depressive symptoms.

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

Worse survival after breast cancer in women with anorexia nervosa.

PURPOSE: A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. METHODS: This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. RESULTS: We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6-3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4-3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3-3.6) among Swedish and Danish women. CONCLUSIONS: We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.

Mortality in Women With Anorexia Nervosa: The Role of Comorbid Psychiatric Disorders.

OBJECTIVE: To investigate mortality in anorexia nervosa (AN) with a psychiatric comorbidity. METHODS: Using Swedish registers, data for 8069 female inpatients with AN were retrospectively collected for 1973-2010. Mortality patterns were assessed using standardized mortality ratios (SMRs), Cox regression-derived hazard ratios, and incidence rate ratios. A control cohort of 76,995 women was used. RESULTS: Patients with AN and a psychiatric comorbidity had higher mortality rates did than those without a comorbidity. The SMRs for patients with AN and a psychiatric comorbidity were 5.4 (95% confidence interval [CI] = 4.6-6.4) and 18.1 (95% CI = 15.2-21.3) for natural and unnatural causes of death, respectively. The SMRs for patients with AN without a comorbidity were 2.8 (95% CI = 2.3-3.5) and 3.1 (95% CI = 2.2-4.1) for natural and unnatural causes of death, respectively. The adjusted hazard ratios for mortality from natural or unnatural causes were 2.0 (95% CI = 1.5-2.7) and 5.7 (95% CI = 3.9-8.2), respectively. Incidence rate ratios comparing patients with AN and controls, both with psychiatric comorbidities, suggest a negative synergistic effect of comorbid AN and psychiatric disorder on mortality, which was greater for unnatural causes of death. CONCLUSIONS: Mortality in patients with AN was greater in the presence of a psychiatric comorbidity, and even more pronounced for unnatural causes of death and suicides. Substance abuse, especially alcohol use disorder, increased mortality from natural causes of death. These findings highlight the need for early detection and treatment of psychiatric comorbidity in AN, to potentially improve long-term outcomes.

Suicides during pregnancy and 1 year postpartum in Sweden, 1980-2007.

BACKGROUND: Although the incidence of suicide among women who have given birth during the past 12 months is lower than that of women who have not given birth, suicide remains one of the most common causes of death during the year following delivery in high-income countries, such as Sweden. AIMS: To characterise women who died by suicide during pregnancy and postpartum from a maternal care perspective. METHOD: We traced deaths (n = 103) through linkage of the Swedish Cause of Death Register with the Medical Birth and National Patient Registers. We analysed register data and obstetric medical records. RESULTS: The maternal suicide ratio was 3.7 per 100 000 live births for the period 1980-2007, with small magnitude variation over time. The suicide ratio was higher in women born in low-income countries (odds ratio 3.1 (95% CI 1.3-7.7)). Violent suicide methods were common, especially during the first 6 months postpartum. In all, 77 women had received psychiatric care at some point, but 26 women had no documented psychiatric care. Antenatal documentation of psychiatric history was inconsistent. At postpartum discharge, only 20 women had a plan for psychiatric follow-up. CONCLUSIONS: Suicide prevention calls for increased clinical awareness and cross-disciplinary maternal care approaches to identify and support women at risk.

Comorbidity of Cognitive Impairment and Late-Life Depression Increase Mortality: Results From a Cohort of Community-Dwelling Elderly Individuals in Rural Greece.

OBJECTIVE: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. METHODS: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. RESULTS: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. CONCLUSION: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

Folate and B12 serum levels in association with depression in the aged: a systematic review and meta-analysis.

OBJECTIVES: To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people. METHODS: Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. RESULTS: Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07-1.43, ORB12:1.20, 95%CI:1.02-1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02-1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90-2.07; ORmales:0.84, 95%CI:0.57-1.25). CONCLUSION: Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.

Cancer incidence and mortality patterns in women with anorexia nervosa.

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

Childbearing and mortality among women with anorexia nervosa.

OBJECTIVE: To assess the association between childbearing and mortality from anorexia nervosa (AN). METHOD: A total of 5,251 females, from a population-based Swedish registry, admitted with an AN diagnosis during the period 1973-2003 were included. Standardized mortality ratios (SMR) were estimated and hazard ratios (HR) were calculated using Cox regression. RESULTS: Nulliparous women had a sixfold higher mortality due to natural causes and ninefold higher mortality due to unnatural causes compared to the general population. Parous women had higher mortality compared to the general population only due to unnatural causes. Suicide was the most common cause of death. Childbearing was associated with a 65% lower mortality. One hundred forty four women out of 1,941 parous women were hospitalized perinatally for any psychiatric disorder (7.4%). DISCUSSION: Childbearing is associated with lower mortality among women with AN.

Exploring gender dysphoria and related outcomes in a prospective cohort study: protocol for the Swedish Gender Dysphoria Study (SKDS).

INTRODUCTION: There has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin. METHODS AND ANALYSIS: The Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022. ETHICS AND DISSEMINATION: The ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden.

Longitudinal assessment of inflammatory markers in the peripartum period by depressive symptom trajectory groups.

Objective: Mechanisms driving temporal fluctuations of inflammatory markers during pregnancy, and how these might differ between distinct perinatal depressive trajectories, are not well understood. The aim of this study was to investigate cytokines levels over the course of pregnancy in women with different trajectories of depressive symptoms peripartum, and relate the levels to levels of non-pregnant controls. Methods: Based on the Edinburgh Postnatal Depression Scale and/or selective serotonin reuptake inhibitors use, 131 women were categorized into: no (n = 65); antepartum (APD, n = 19), postpartum (PPD, n = 17) and persistent (n = 30) depressive symptoms. Plasma samples (n = 386) were analyzed for levels of interleukin (IL)-8, IL-18, Tumor necrosis factor-α, macrophage colony-stimulating factor (M-CSF), vascular endothelial growth factor A (VEGF-A) and fractalkine, at four different time-points (twice during pregnancy, during childbirth, and postpartum) using Bio-Plex Pro Human Cytokine Assays. Generalized linear mixed models were applied to analyze the associations between cytokine levels, time-point, perinatal depressive symptom trajectory group and their interaction. Results: For all markers but VEGF-A, pregnancy was associated with higher cytokine levels compared to the non-pregnant controls, with delivery being the most prominent time-point. For M-CSF, IL-18 and VEGF-A, levels were back to the non-pregnant status at postpartum week 8. An effect of perinatal depressive symptom trajectory groups on cytokine levels was found for VEGF-A. Women with PPD and women with APD had lower levels of VEGF-A throughout the study period compared to women with persistent depression, and women with PPD had lower levels compared to non-depressed women. Conclusions: Lower levels of VEGF-A were noted among women in some trajectories of depressive symptoms peripartum. The peripartum period is a time of tremendous immune system adaptations. Standardization of time-points for cytokine measurements in studies of perinatal depression are important in order to draw valid conclusions on the role of the immune system in perinatal depression.

Association of Media Coverage on Transgender Health With Referrals to Child and Adolescent Gender Identity Clinics in Sweden.

Importance: Increasing numbers of transgender and gender diverse children and adolescents have been referred to gender identity clinics in Sweden in the past decade, and previous studies have found an association between media attention and referral counts. Whether the tone of media stories is associated with referrals is not yet known. Objective: To investigate whether positive or negative media coverage on transgender and gender diverse issues is associated with referral counts to child and adolescent gender identity clinics. Design, Setting, and Participants: In this cross-sectional study, referrals counts were collected from all 6 specialized gender identity clinics in Sweden, along with information on referral date, sex assigned at birth, and birth year. Participants were all individuals younger than 19 years, referred to a gender identity clinic between January 1, 2017, and December 31, 2019. Data were analyzed from May 2020 to September 2021. Exposures: Exposures included 3 major media events related to transgender health care in 2019; 1 event was categorized as positive and 2 events were categorized as negative press coverage. Main Outcomes and Measures: Referral counts before and after each of the 3 major media events were assessed, and the moderating association of sex assigned at birth and age was examined with stratified analyses. Weekly referral counts and trends were assessed with interrupted time series analysis. Results: Among 1784 referrals (359 referrals [21.4%] among individuals aged <13 years; 1034 referrals [72.1%] among individuals assigned female at birth and 401 referrals [27.9%] among individuals assigned male at birth), a negative association between media coverage and referral counts was found for the first of the negative media events. In the 3 months following the event, referrals decreased by 25.4% (95% CI, -31.9% to -18.9%) overall, by 32.2% (95 CI, -41.8% to -22.8%) for individuals assigned female at birth, and by 25.3% (95 CI, -32.4% to -18.3%) for individuals aged 13 to 18 years. In the interrupted time series analysis, a mean weekly decrease of 3% in the referrals was observed in the extended time interval of 39 weeks (incidence rate ratio, 0.97; 95 CI, 0.95 to 0.99). For the other 2 media events, no changes in referral counts or time trends were observed. Conclusions and Relevance: These findings suggest that an event of negative media coverage on transgender-specific health care was negatively associated with access to health care for transgender children and adolescents; therefore, nuanced and accurate media coverage, as well as increased awareness of these mechanisms among key stakeholders, is essential.

Gender dysphoria in twins: a register-based population study.

Both genetic and environmental influences have been proposed to contribute to the variance of gender identity and development of gender dysphoria (GD), but the magnitude of the effect of each component remains unclear. We aimed to examine the prevalence of GD among twins and non-twin siblings of individuals with GD, using data derived from a large register-based population in Sweden over the period 2001-2016. Register data was collected from the Statistics Sweden and the National Board of Health and Welfare. The outcome of interest was defined as at least four diagnoses of GD or at least one diagnosis followed by gender-affirming treatment. A total of 2592 full siblings to GD cases were registered, of which 67 were twins; age at first GD diagnosis for the probands ranged from 11.2 to 64.2 years. No same-sex twins that both presented with GD were identified during the study period. The proportion of different-sex twins both presenting with GD (37%) was higher than that in same-sex twins (0%, Fisher's exact test p-value < 0.001) and in non-twin sibling pairs (0.16%). The present findings suggest that familial factors, mainly confined to shared environmental influences during the intrauterine period, seem to contribute to the development of GD.

Predicting perinatal health outcomes using smartphone-based digital phenotyping and machine learning in a prospective Swedish cohort (Mom2B): study protocol.

INTRODUCTION: Perinatal complications, such as perinatal depression and preterm birth, are major causes of morbidity and mortality for the mother and the child. Prediction of high risk can allow for early delivery of existing interventions for prevention. This ongoing study aims to use digital phenotyping data from the Mom2B smartphone application to develop models to predict women at high risk for mental and somatic complications. METHODS AND ANALYSIS: All Swedish-speaking women over 18 years, who are either pregnant or within 3 months postpartum are eligible to participate by downloading the Mom2B smartphone app. We aim to recruit at least 5000 participants with completed outcome measures. Throughout the pregnancy and within the first year postpartum, both active and passive data are collected via the app in an effort to establish a participant's digital phenotype. Active data collection consists of surveys related to participant background information, mental and physical health, lifestyle, and social circumstances, as well as voice recordings. Participants' general smartphone activity, geographical movement patterns, social media activity and cognitive patterns can be estimated through passive data collection from smartphone sensors and activity logs. The outcomes will be measured using surveys, such as the Edinburgh Postnatal Depression Scale, and through linkage to national registers, from where information on registered clinical diagnoses and received care, including prescribed medication, can be obtained. Advanced machine learning and deep learning techniques will be applied to these multimodal data in order to develop accurate algorithms for the prediction of perinatal depression and preterm birth. In this way, earlier intervention may be possible. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Swedish Ethical Review Authority (dnr: 2019/01170, with amendments), and the project fully fulfils the General Data Protection Regulation (GDPR) requirements. All participants provide consent to participate and can withdraw their participation at any time. Results from this project will be disseminated in international peer-reviewed journals and presented in relevant conferences.

Cardiovascular outcomes in transgender individuals in Sweden after initiation of gender-affirming hormone therapy.

AIMS: We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population. METHODS AND RESULTS: The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006-16). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HRs) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females (AFAB)], 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95% CI: 1.4-10.0). Assigned male at birth individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95% CI: 4.2-12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95% CI: 1.3-4.2) compared with cisgender women, and 1.7 higher compared with cisgender men (HR: 1.7, 95% CI: 1.0-2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment. CONCLUSION: The incidence of CVD among GD/GAHT individuals was low, although increased compared with matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.

Working Memory During Late Pregnancy: Associations With Antepartum and Postpartum Depression Symptoms.

Background: Few studies, with conflicting results, report on the association between memory performance and depressive symptoms during the perinatal period. In this study, we aimed to evaluate whether memory performance during late pregnancy is associated with antepartum (APD) and postpartum depression (PPD) symptoms. Method: We conducted a prospective follow-up of 283 pregnant women, nested within a large cohort of women enrolled in the BASIC study in Uppsala University hospital between 2009 and 2019. The Wechsler Digit Span Task (forward-DSF, backward-DSB and total score-DST) was performed to evaluate short-term memory/attention (DSF) and working memory (DSB) around the 38th gestational week; the Edinburgh Postnatal Depression Scale (EPDS), evaluating depressive symptoms, was filled out at 17, 32, 38 gestational weeks, as well as at 6 weeks postpartum. Unadjusted and multivariate logistic regression was used to assess the association between performance on the Digit Span Task and outcome, namely depressive symptoms (using a cut-off of 12 points on the EPDS) at 38 gestational weeks, as well as at 6 weeks postpartum. Results: APD symptoms were not significantly associated with DSF (p = 0.769) or DSB (p = 0.360). APD symptoms were significantly associated with PPD symptoms (p < 0.001). Unadjusted regression modeling showed that DSF in pregnancy was a significant predictor of PPD symptoms (OR 1.15; 95% CI, 1.00, 1.33, p = 0.049), and remained a significant predictor when adjusted for confounders (education and feeling rested at assessment; OR 1.21, 95% CI 1.03, 1.42, p = 0.022). DSF was a predictor of PPD symptoms only for women without a pre-pregnancy history of depression (OR 1.32; 95% CI 1.04, 1.67, p = 0.024) and also those without APD (OR 1.20, 95% CI 1.01, 1.43, p = 0.040). Conclusion: There was no significant association between working and short-term memory performance and APD symptoms. Among all women, but especially non-depressed earlier in life and/or at antepartum, those scoring high on the forward memory test, i.e., short-term memory, had a higher risk for PPD. Future studies are required to further explore the pathophysiology behind and the predictive value of these associations.

Differentiated mental health patterns in pregnancy during COVID-19 first two waves in Sweden: a mixed methods study using digital phenotyping.

To utilize modern tools to assess depressive and anxiety symptoms, wellbeing and life conditions in pregnant women during the first two waves of the COVID-19 pandemic in Sweden. Pregnant women (n = 1577) were recruited through the mobile application Mom2B. Symptoms of depression, anxiety and wellbeing were assessed during January 2020-February 2021. Movement data was collected using the phone's sensor. Data on Google search volumes for "Corona" and Covid-related deaths were obtained. Qualitative analysis of free text responses regarding maternity care was performed. Two peaks were seen for depressive symptoms, corresponding to the two waves. Higher prevalence of anxiety was only noted during the first wave. A moderating effect of the two waves in the association of depression, anxiety, and well-being with Covid deaths was noted; positive associations during the first wave and attenuated or became negative during the second wave. Throughout, women reported on cancelled healthcare appointments and worry about partners not being allowed in hospital. The association of mental health outcomes with relevant covariates may vary during the different phases in a pandemic, possibly due to adaptation strategies on a personal and societal/healthcare level. Digital phenotyping can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, and to adjust the support offered.

Seasonality patterns in postpartum depression.

OBJECTIVE: To investigate the possible association between postpartum depressive symptoms and season of delivery. STUDY DESIGN: During 1 year, delivering women in the Uppsala University Hospital were asked to participate in the study by filling out 3 postpartum questionnaires containing the Edinburgh Postnatal Depression scale and questions assessing life style, medical history, breastfeeding, and social support. RESULTS: Two thousand three hundred eighteen women participated. Women delivering in the last 3 months of the year had a significantly higher risk of self-reported depressive symptomatology both at 6 weeks (odds ratio, 2.02, 95% confidence interval, 1.32-3.10) and at 6 months after delivery (odds ratio, 1.82, 95% confidence interval, 1.15-2.88), in comparison to those delivering April-June, both before and after adjustment for possible confounders. CONCLUSION: Women delivering during the last quartile of the year had a significantly higher risk for depressive symptoms 6 weeks and 6 months postpartum and would thus benefit from a closer support and follow-up after delivery.

Newborn gender as a predictor of postpartum mood disturbances in a sample of Swedish women.

Postpartum depression (PPD) is a condition that affects about 10% of newly delivered women. The aim of this study was to examine the possible association between offspring gender and risk for development of PPD in Sweden. The study was undertaken as part of the UPPSAT project, a population-based longitudinal study in Uppsala, Sweden. From May 2006 to June 2007, women who gave birth at Uppsala University Hospital and fulfilled the inclusion criteria were asked to participate. The participating women filled out, at three points during the first 6 months after delivery, questionnaires containing the Edinburgh Postnatal Depression Scale as well as questions concerning various lifestyle factors, medical history, breast feeding habits, social support parameters, and diet factors. No significant difference in risk of PPD in relation to baby gender could be shown 6 weeks and 6 months after delivery. However, women who gave birth to a male offspring had a significantly higher risk of self-reported depressive symptomatology 5 days after delivery. The association remained statistically significant after adjustment for possible confounders in a logistic regression model. This longitudinal study demonstrates that, in Sweden, the gender of the offspring is not associated with a higher risk for self-reported postpartum depression in the mother 6 weeks or 6 months after delivery. The birth of a baby boy, however, gives the mother a higher risk of postpartum blues 5 days after delivery.