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Abstract Background As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery. Methods Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped. Results TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls. Conclusions The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.

Background: We examined differences in DNA methylation patterns in the NR3C1 and FKBP5 genes in relation to personality vulnerability to depression, resilience, and perinatal depressive symptoms, whilst also considering possible moderating effects of childhood traumatic events. Methods: N = 160 perinatal women were assessed at late pregnancy and 1 year postpartum for personality vulnerability to depression, resilience, depressive symptoms, and childhood traumatic events with self-reported questionnaires. NR3C1 and FKBP5 methylation markers were analyzed via sodium bisulfite sequencing. Associations of methylation markers with the above mentioned variables were tested using multivariable regressions. Results: NR3C1 methylation at CpGs 1, 4 and average methylation sites were negatively associated with resilience; NR3C1 methylation at CpG 2 was positively associated with postpartum depressive symptoms; methylation at CpG 4 was positively associated with prenatal depressive symptoms. The interaction between current distress due to interpersonal traumatic events and NR3C1 CpG sites in relation to personality vulnerability was significant on CpG sites 3 and 4, whereas the interaction between current distress due to total traumatic events and NR3C1 in relation to personality vulnerability was significant on CpG site 2. FKBP5 showed no significant associations with the outcomes. Conclusions: This study identified associations between NR3C1 methylation and resilience as well as perinatal depressive symptoms. Interestingly, an interaction between early trauma and personality vulnerability was noted. Our findings on these specific DNA methylation markers may, if replicated and integrated into risk prediction models, contribute to early diagnosis of mothers at risk, targeted health promotion, and early interventions.

Abstract Background Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months. Methods Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO’s Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups. Results In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p

Introduction Data suggest that micronised progesterone (mP) in menopausal hormone therapy is safer for the breast than synthetic progestins, while protection of the endometrium appears to be less effective. However, comparative randomised trial data are lacking. The objective of the Progesterone Breast Endometrial Safety Study is to investigate breast and endometrial safety of mP versus norethisterone acetate (NETA) in continuous combination with oral oestrogen.Methods and analysis This multicentre trial, conducted at three University Hospitals in Stockholm and Uppsala, Sweden, consists of two phases: part 1 focuses on breast safety and is designed as a double-blind, randomised controlled trial. 260 postmenopausal women will be randomised to 100 mg mP or 0.5 mg NETA per day in continuous combination with 1 mg oestradiol. The primary objective is to compare the treatments with respect to percentage change in mammographic breast density after 12-month treatment. Secondary outcomes are breast proliferation, endometrial histology and proliferation, bleeding pattern, gut and vaginal microbiome, hormone levels and coagulation and metabolic factors, mood, and health-related quality of life. Part 2 features an open, single-arm design to study endometrial safety of 1-year treatment with mP in continuous combination with oestradiol on endometrial pathology (hyperplasia and cancer). We will treat 260 additional women with 100 mg mP/1 mg oestradiol resulting in an endometrial safety population of 390 women. The total number of participants in part 1 and part 2 will be 520.Ethics and dissemination The study protocol was approved by the Swedish Ethical Review Authority (2021-03033) on 29 June 2021 with amendment (2023-01480-02, protocol version 3.1) on 14 March 2023. Results of the study will be published in peer-reviewed journals and presented at scientific meetings.Trial registration number NCT05586724.

Abstract Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

BackgroundPerinatal depression affects a significant number of women during pregnancy and after birth, and early identification is imperative for timely interventions and improved prognosis. Mobile apps offer the potential to overcome barriers to health care provision and facilitate clinical research. However, little is known about users’ perceptions and acceptability of these apps, particularly digital phenotyping and ecological momentary assessment apps, a relatively novel category of apps and approach to data collection. Understanding user’s concerns and the challenges they experience using the app will facilitate adoption and continued engagement. ObjectiveThis qualitative study explores the experiences and attitudes of users of the Mom2B mobile health (mHealth) research app (Uppsala University) during the perinatal period. In particular, we aimed to determine the acceptability of the app and any concerns about providing data through a mobile app. MethodsSemistructured focus group interviews were conducted digitally in Swedish with 13 groups and a total of 41 participants. Participants had been active users of the Mom2B app for at least 6 weeks and included pregnant and postpartum women, both with and without depression symptomatology apparent in their last screening test. Interviews were recorded, transcribed verbatim, translated to English, and evaluated using inductive thematic analysis. ResultsFour themes were elicited: acceptability of sharing data, motivators and incentives, barriers to task completion, and user experience. Participants also gave suggestions for the improvement of features and user experience. ConclusionsThe study findings suggest that app-based digital phenotyping is a feasible and acceptable method of conducting research and health care delivery among perinatal women. The Mom2B app was perceived as an efficient and practical tool that facilitates engagement in research as well as allows users to monitor their well-being and receive general and personalized information related to the perinatal period. However, this study also highlights the importance of trustworthiness, accessibility, and prompt technical issue resolution in the development of future research apps in cooperation with end users. The study contributes to the growing body of literature on the usability and acceptability of mobile apps for research and ecological momentary assessment and underscores the need for continued research in this area.

Abstract The objective of this study was to investigate how placental gene expression differs in two consecutive pregnancies in same sex siblings, and its possible association with the “maternal constraint” hypothesis. Material was gathered from the BASIC study (Biological, Affect, Stress, Imaging, and Cognition in Pregnancy and the Puerperium), a population based prospective study that was started in 2009 in Uppsala. Over 900 specimens of placenta biopsies were collected and out of these 10 women gave birth twice, to the same sex child, and were included in this study. The total RNA was isolated and prepared from frozen villous tissue from the placenta and further analyzed by use of Ion AmpliSeq Human Transcriptome Gene Expression kit. A total of 234 genes differed significantly between the first and second pregnancy placentas, when adjusting for delivery mode, maternal BMI and gestational age. Of special interest was the down-regulated group of genes in the second pregnancy. Exemplified by Pentraxin 3, SRY-Box Transcription Factor 9, and Serum Amyloid A1, which all were associated with biological processes involved in the immune system and inflammation. Further, protein–protein interaction analysis visualized them as hub genes interacting with several of the other differentially expressed genes. How these altered gene expressions affect maternal constraint during pregnancy needs further validation in lager study cohorts and also future validation in functional assays.

Abstract 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.

BackgroundApproximately 10 to 20% of pregnant women worldwide experience perinatal depression (PND), a depressive episode with onset during pregnancy or after childbirth. We performed a systematic review to identify, summarize and discuss studies on inflammatory biomarkers described in relation to PND.MethodInclusion criteria defined the selection of observational studies written in English, French, Spanish or Portuguese, that evaluate analytical levels of inflammatory molecules (protein levels) in biological fluids in women, with a diagnosis of depression using ICD/DSM diagnostic criteria or depressive symptoms assessed by standardized psychometric instruments, during pregnancy and/or postpartum. Case reports, experimental studies, reviews, qualitative analysis, meta-analysis, gray literature or replicated data were excluded. Three electronic databases were used for search (Pubmed, Web of Science and PsychInfo) and quality assessment of selected studies were performed using the Newcastle-Ottawa Scale. Data extraction included study design; number of subjects; obstetric information; tools and timepoints of depression and inflammatory markers assessment.Results56 studies (sample size for cross-sectional and case-control studies ranging from 10 to 469; sample size for longitudinal studies ranging from 26 to 467), where the major aim was to analyze the association between depression and inflammatory biomarkers during pregnancy and postpartum period were included in this systematic review. Overall, the findings of our systematic review lend support to the hypothesis that several inflammatory markers may be associated with peripartum depressive symptoms. The associations were somewhat different looking at pregnancy compared to the delivery time-point and postpartum, and mainly referred to increased levels of IL-6, IL-8, CRP and TNF-α among depressed.DiscussionIn summary, our systematic review findings provide evidence supporting the hypothesis that several inflammatory markers may correlate with peripartum depressive symptoms. However, our work also highlighted notable differences in the timing of biological sampling for inflammatory markers and in the methodologies used to assess depression during the perinatal period. Additionally, variations were observed in how inflammatory biomarkers and depression were approached, including their classification as exposure or outcome variables, and the timing of assessments. It is essential for future research to investigate the influence of biological fluids and the timing of assessments for both inflammatory biomarkers and depression to gain a deeper understanding of their association. This comprehensive exploration is pivotal for elucidating the intricate relationship between inflammation and perinatal depression.

Abstract Background Postpartum depression affects around 12% of mothers in developed countries, with consequences for the whole family. Many women with depressive symptoms remain undetected and untreated. The aim of this study was to investigate to what extent women with depressive symptoms at 6 weeks postpartum are identified by the healthcare system, the interventions they received, and remission rates at 6 months postpartum. Methods Postpartum women scoring 12–30 on the Edinburgh Postnatal Depression Scale (EPDS) at 6 weeks after delivery (n = 697) were identified from the longitudinal cohort study “Biology, Affect, Stress, Imaging and Cognition” (BASIC) in Uppsala, Sweden. A total of 593 women were included. Background and remission information at 6 months was collected from the BASIC dataset. Medical records were examined to identify interventions received. Results Most women (n = 349, 58.7%) were not identified by the healthcare system as having depressive symptoms and 89% lacked any record of interventions. Remission rates at 6 months postpartum were 69% in this group. Among women identified by the healthcare system, 90% received interventions and about 50% were in remission at 6 months postpartum. The EPDS reduction during the study period was largest in the group identified by the child health services (CHS, −5.15) compared to the non-identified (−4.24, p

Purpose The current U-BIRTH cohort (Uppsala Birth Cohort) extends our previous cohort Biology, Affect, Stress, Imaging and Cognition (BASIC), assessing the development of children up to 11 years after birth. The U-BIRTH study aims to (1) assess the impact of exposure to peripartum mental illness on the children’s development taking into account biological and environmental factors during intrauterine life and childhood; (2) identify early predictors of child neurodevelopmental and psychological problems using biophysiological, psychosocial and environmental variables available during pregnancy and early post partum.Participants All mothers participating in the previous BASIC cohort are invited, and mother–child dyads recruited in the U-BIRTH study are consecutively invited to questionnaire assessments and biological sampling when the child is 18 months, 6 years and 11 years old. Data collection at 18 months (n=2882) has been completed. Consent for participation has been obtained from 1946 families of children having reached age 6 and from 698 families of children having reached age 11 years.Findings to date Based on the complete data from pregnancy to 18 months post partum, peripartum mental health was significantly associated with the development of attentional control and gaze-following behaviours, which are critical to cognitive and social learning later in life. Moreover, infants of depressed mothers had an elevated risk of difficult temperament and behavioural problems compared with infants of non-depressed mothers. Analyses of biological samples showed that peripartum depression and anxiety were related to DNA methylation differences in infants. However, there were no methylation differences in relation to infants’ behavioural problems at 18 months of age.Future plans Given that the data collection at 18 months is complete, analyses are now being undertaken. Currently, assessments for children reaching 6 and 11 years are ongoing.

Abstract Background The COVID-19 pandemic has led to unprecedented mental stress to women after childbirth. In this study, we assessed the association of disrespectful care after childbirth and COVID-19 exposure before/during labour with postpartum depression symptoms assessed at 7 and 45 days in Nepal. Methods A longitudinal cohort study was conducted in 9 hospitals of Nepal among 898 women. The independent data collection system was established in each hospital to collection information on disrespectful care after birth via observation, exposure to COVID-19 infection before/during labour and other socio-demographic via interview. The information on depressive symptoms at 7 and 45 days was collected using the validated Edinburg Postnatal Depression Scale (EPDS) tool. Multi-level regression was performed to assess the association of disrespectful care after birth and COVID-19 exposure with postpartum depression. Result In the study, 16.5% were exposed to COVID-19 before/during labour and 41.8% of them received disrespectful care after childbirth. At 7 and 45 days postpartum, 21.3% and 22.4% of women reported depressive symptoms respectively. In the multi-level analysis, at the 7th postpartum day, women who had disrespectful care and no COVID-19 exposure still had 1.78 higher odds of having depressive symptom (aOR, 1.78; 95% CI; 1.16, 2.72). In the multi-level analysis, at 45th postpartum day, women who had disrespectful care and no COVID-19 exposure had 1.37 higher odds of having depressive symptoms (aOR, 1.37; 95% CI; 0.82, 2.30), but not statistically significant. Conclusion Disrespectful care after childbirth was strongly associated with postpartum depression symptoms irrespective of COVID-19 exposure during pregnancy. Caregivers, even during the global pandemic, should continue to focus their attention for immediate breast feeding and skin-to-skin contact, as this might reduce the risk for depressive symptoms postpartum.

Abstract 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.

Abstract Background Giving birth is often a positive experience, but 7–44% have negative experiences and about 4% develop posttraumatic stress disorder following childbirth (PTSD FC). This randomized controlled trial (RCT) investigated the effect of internet-based cognitive behaviour therapy (iCBT) for women with negative birth experiences and/or at risk for PTSD FC. Methods This was a superiority nonblinded multicentre RCT comparing iCBT combined with treatment as usual (TAU) with TAU only. Data were collected through questionnaires at baseline, at 6 weeks, 14 weeks and 1 year after randomization. The RCT was conducted at four delivery clinics in Sweden and participants were recruited from September 2013 until March 2018. Women who rated their childbirth experience as negative on a Likert scale, and/or had an immediate caesarean section or a haemorrhage of > 2000 ml were eligible. Primary outcomes were symptoms of posttraumatic stress (Traumatic Event Scale, TES) and symptoms of depression (Edinburgh Postnatal Depression Scale, EPDS). Secondary outcomes were satisfaction with life (Satisfaction With Life Scale, SWLS) and coping (Ways of Coping Questionnaire, WCQ). Results Out of 1810 eligible women, 266 women were randomised to iCBT+TAU (n = 132) or to TAU (n = 134). In the iCBT+TAU group 59 (45%) completed the treatment. ICBT+TAU did not reduce PTSD FC at 6 weeks, at 14 weeks, or at 1 year follow-up compared with TAU, according to the TES. Both the ITT and completer analyses showed significant time and quadratic time effects due to reduction of symptoms in both groups on the TES (re-experience subscale) and on the EPDS, and significant time effect on the self-controlling subscale of the WCQ (which increased over time). There was also a significant main effect of group on the SWLS where the TAU group showed higher initial satisfaction with life. Exploratory subgroup analyses (negative birth experience, immediate caesarean section, or severe haemorrhage) showed significant time effects among participants with negative birth experience on re-experience, arousal symptoms and depressive symptoms. Conclusions The ICBT intervention did not show superiority as both groups showed similar beneficial trajectories on several outcomes up to 1 year follow-up. This intervention for women with negative birth experiences and/or at risk for PTSD FC was feasible; however, the study suffered from significant drop out rate. Future studies with more narrow inclusion criteria and possibly a modified intervention are warranted. Trial registration ISRCTN39318241. Date for registration 12/01/2017.

Abstract Postpartum depression (PPD) is a serious condition associated with potentially tragic outcomes, and in an ideal world PPDs should be prevented. Risk prediction models have been developed in psychiatry estimating an individual’s probability of developing a specific condition, and recently a few models have also emerged within the field of PPD research, although none are implemented in clinical care. For the present study we aimed to develop and validate a prediction model to assess individualized risk of PPD and provide a tentative template for individualized risk calculation offering opportunities for additional external validation of this tool. Danish population registers served as our data sources and PPD was defined as recorded contact to a psychiatric treatment facility (ICD-10 code DF32-33) or redeemed antidepressant prescriptions (ATC code N06A), resulting in a sample of 6,402 PPD cases (development sample) and 2,379 (validation sample). Candidate predictors covered background information including cohabitating status, age, education, and previous psychiatric episodes in index mother (Core model), additional variables related to pregnancy and childbirth (Extended model), and further health information about the mother and her family (Extended+ model). Results indicated our recalibrated Extended model with 14 variables achieved highest performance with satisfying calibration and discrimination. Previous psychiatric history, maternal age, low education, and hyperemesis gravidarum were the most important predictors. Moving forward, external validation of the model represents the next step, while considering who will benefit from preventive PPD interventions, as well as considering potential consequences from false positive and negative test results, defined through different threshold values.

Abstract 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

Abstract Children of mothers with prenatal depressive symptoms (PND) have a higher risk of behavioral problems; fetal programming through DNA methylation is a possible underlying mechanism. This study investigated DNA methylation in cord blood to identify possible “at birth” signatures that may indicate susceptibility to behavioral problems at 18 months of age. Cord blood was collected from 256 children of mothers who had self-reported on symptoms of depression during pregnancy and the behavior of their child at 18 months of age. Whole genome DNA methylation was assessed using Illumina MethylationEPIC assay. The mother and child pairs were categorized into four groups, based on both self-reported depressive symptoms, PND or Healthy control (HC), and scores from the Child Behavior checklist (high or low for internalizing, externalizing, and total scores). Adjustments were made for batch effects, cell-type, and clinical covariates. Differentially methylated sites were identified using Kruskal–Wallis test, and Benjamini–Hochberg adjusted p values

Autologous hematopoietic stem cell transplantation (AHSCT) has been approved for multiple sclerosis (MS) in many European countries. A large proportion of patients are women of child-bearing age. For them, AHSCT may have negative consequences for reproductive health, since the ovaries are particularly susceptible to alkylating agents. Anti-Müllerian hormone (AMH) reflects the ovarian reserve and has been suggested as a potential biomarker of fertility in women. The aim of this study was to investigate AMH levels in relation to age and reproductive potential in MS patients treated with AHSCT. The study cohort comprised 38 female patients, aged 20-44 years, who underwent AHSCT for MS using a cyclophosphamide (200 mg/kg)/rabbit-anti-thymocyte globulin (6 mg/kg) conditioning regimen between 2013-2020. Clinal follow-up visits were made 3 months after AHSCT and then yearly. AMH was analysed in blood samples. The median age at transplantation was 28 years (interquartile range, IQR 25-33). The median AMH concentration was 23 pmol/l at baseline (IQR 6.0-30), 0.5 pmol/l at 3 months (IQR 0-1.5) and 1.1 pmol/l at 2 years (IQR 0-2.9). A multiple linear regression model was used to determine if age and/or AHSCT influenced AMH values; both significantly did (age, -0.21 per year, p = 0.018; AHSCT -19, p

Abstract Maternal distress is repeatedly reported to have negative impacts on the cognitive development in children and is linked to neurodevelopmental disorders (e.g. attention-deficit/hyperactivity disorder and autism spectrum disorder). However, studies examining the associations between maternal distress and the development of attention in infancy are few. This study investigated the longitudinal relationships between maternal distress (depressive symptoms, anxiety symptoms, and exposure to childhood trauma) and the development of focused attention in infancy in 118 mother-infant dyads. We found that maternal exposure to non-interpersonal traumatic events in childhood was associated with the less focused attention of the infants to audio-visual stimuli at 6, 10, and 18 months. In addition, exposure to interpersonal traumatic events in childhood was identified as a moderator of the negative effect of maternal anxiety during the 2nd trimester on the development of focused attention in infants. We discuss the possible mechanisms accounting for these cross-generational effects. Our findings underscore the importance of maternal mental health to the development of focused attention in infancy and address the need for early screening of maternal mental health during pregnancy.

Abstract Background Systematic reviews often conclude low confidence in the results due to heterogeneity in the reported outcomes. A Core Outcome Set (COS) is an agreed standardised collection of outcomes for a specific area of health. The outcomes included in a COS are to be measured and summarized in clinical trials as well as systematic reviews to counteract this heterogeneity. Aim The aim is to identify, compile and assess final and ongoing studies that are prioritizing outcomes in the area of pregnancy and childbirth. Methods All studies which prioritized outcomes related to pregnancy and childbirth using consensus method, including Delphi surveys or consensus meetings were included. Searches were conducted in Ovid MEDLINE, EMBASE, PsycINFO, Academic Search Elite, CINAHL, SocINDEX and COMET databases up to June 2021. For all studies fulfilling the inclusion criteria, information regarding outcomes as well as population, method, and setting was extracted. In addition, reporting in the finalized studies was assessed using a modified version of the Core Outcome Set–STAndards for Reporting. Results In total, 27 finalized studies and 42 ongoing studies were assessed as relevant and were included. In the finalized studies, the number of outcomes included in the COS ranged from 6 to 51 with a median of 13 outcomes. The majority of the identified COS, both finalized as well as ongoing, were relating to physical complications during pregnancy. Conclusion There is a growing number of Core Outcome Set studies related to pregnancy and childbirth. Although several of the finalized studies follow the proposed reporting, there are still some items that are not always clearly reported. Additionally, several of the identified COS contained a large number (n > 20) outcomes, something that possibly could hinder implementation. Therefore, there is a need to consider the number of outcomes which may be included in a COS to render it optimal for future research.

Objectives Internet-based interventions are often hampered by high dropout rates. The number of individuals who decline to participate or dropout are reported, but reasons for dropout are not. Identification of barriers to participation and predictors of dropout may help improve the efficacy of internet-based clinical trials. The aim was to investigate a large number of possible predictors for non-participation and dropout in a randomised controlled trial for women with a negative birth experience and/or post-traumatic stress following childbirth.Setting A childbirth clinic at a university hospital in Sweden.Participants The sample included 1523 women who gave birth between September 2013 and February 2018. All women who rated an overall negative birth experience on a Likert scale, and/or had an immediate caesarean section (CS), and/or severe postpartum haemorrhage (≥ 2000 mL) were eligible.Methods Demographic, antepartum, and labour-related/postpartum predictors were investigated for non-participation (eligible but denied participation), pre-treatment dropout (prior to intervention start), treatment dropout, and loss to follow-up. Descriptive statistics and logistic regression were used in the data analysis.Results A majority (80.3 %) were non-participants. Non-participation was predicted by lower level of education, being foreign-born, no experience of counselling for fear of childbirth, multiparity, vaginal delivery (vs CS and vacuum-assisted delivery) and absence of: preeclampsia, anal sphincter injury and intrapartum fetal distress. Pretreatment dropout was predicted by the absence of severe haemorrhage. Treatment dropout was predicted by vaginal delivery (vs immediate CS), vertex presentation and good overall birth experience. Loss to follow-up was predicted by vaginal delivery (vs immediate CS or vacuum-assisted delivery) and absence of intrapartum fetal distress.Conclusions Mothers with no obstetric complications were more likely to not participate and dropout at different time points. Both demographic, antepartum and obstetrical variables are important to attend to while designing procedures to maximise participation in internet-delivered cognitive–behavioral therapy.Trial registration number ISRCTN39318241

Abstract The aim of this study was to examine the validity of the Gender Dysphoria (GD) diagnoses in the Swedish National Patient Register (NPR), to discuss different register-based definitions of GD and to investigate incidence trends. We collected data on all individuals with registered GD diagnoses between 2001 and 2016 as well as data on the coverage in the NPR. We regarded gender confirming medical intervention (GCMI) as one proxy for a clinically valid diagnosis and calculated the positive predictive value (PPV) for receiving GCMI for increasing number of registered GD diagnoses. We assessed crude and coverage-adjusted time trends of GD during 2004–2015 with a Poisson regression, using assigned sex and age as interaction terms. The PPV for receiving GCMI was 68% for ≥ 1 and 79% for ≥ 4 GD-diagnoses. The incidence of GD was on average 35% higher with the definition of ≥ 1 compared to the definition of ≥ 4 diagnoses. The incidence of GD, defined as ≥ 4 diagnoses increased significantly during the study period and mostly in the age categories 10–17 and 18–30 years, even after adjusting for register coverage. We concluded that the validity of a single ICD code denoting clinical GD in the Swedish NPR can be questioned. For future research, we propose to carefully weight the advantages and disadvantages of different register-based definitions according to the individual study’s needs, the time periods involved and the age-groups under study.

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.

Abstract Fetal growth restriction is a strong risk factor for perinatal morbidity and mortality. Reliable standards are indispensable, both to assess fetal growth and to evaluate birthweight and early postnatal growth in infants born preterm. The aim of this study was to create updated Swedish reference ranges for estimated fetal weight (EFW) from gestational week 12–42. This prospective longitudinal multicentre study included 583 women without known conditions causing aberrant fetal growth. Each woman was assigned a randomly selected protocol of five ultrasound scans from gestational week 12 + 3 to 41 + 6. Hadlock’s 3rd formula was used to estimate fetal weight. A two-level hierarchical regression model was employed to calculate the expected median and variance, expressed in standard deviations and percentiles, for EFW. EFW was higher for males than females. The reference ranges were compared with the presently used Swedish, and international reference ranges. Our reference ranges had higher EFW than the presently used Swedish reference ranges from gestational week 33, and higher median, 2.5th and 97.5th percentiles from gestational week 24 compared with INTERGROWTH-21st. The new reference ranges can be used both for assessment of intrauterine fetal weight and growth, and early postnatal growth in children born preterm.

Abstract Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive–compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.

Abstract Postpartum depression (PPD) is a detrimental health condition that affects 12% of new mothers. Despite negative effects on mothers’ and children’s health, many women do not receive adequate care. Preventive interventions are cost-efficient among high-risk women, but our ability to identify these is poor. We leveraged the power of clinical, demographic, and psychometric data to assess if machine learning methods can make accurate predictions of postpartum depression. Data were obtained from a population-based prospective cohort study in Uppsala, Sweden, collected between 2009 and 2018 (BASIC study, n = 4313). Sub-analyses among women without previous depression were performed. The extremely randomized trees method provided robust performance with highest accuracy and well-balanced sensitivity and specificity (accuracy 73%, sensitivity 72%, specificity 75%, positive predictive value 33%, negative predictive value 94%, area under the curve 81%). Among women without earlier mental health issues, the accuracy was 64%. The variables setting women at most risk for PPD were depression and anxiety during pregnancy, as well as variables related to resilience and personality. Future clinical models that could be implemented directly after delivery might consider including these variables in order to identify women at high risk for postpartum depression to facilitate individualized follow-up and cost-effectiveness.

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.

Abstract Ultrasonic assessment of fetal growth is an important part of obstetric care to prevent adverse pregnancy outcome. However, lack of reliable reference ranges is a major barrier for accurate interpretation of the examinations. The aim of this study was to create updated Swedish national reference ranges for intrauterine size and growth of the fetal head, abdomen and femur from gestational week 12 to 42. This prospective longitudinal multicentre study included 583 healthy pregnant women with low risk of aberrant fetal growth. Each woman was examined up to five times with ultrasound from gestational week 12 + 3 to 41 + 6. The assessed intrauterine fetal biometric measurements were biparietal diameter (outer–inner), head circumference, mean abdominal diameter, abdominal circumference and femur length. A two-level hierarchical regression model was employed to account for the individual measurements of the fetus and the number of repeated visits for measurements while accounting for the random effect of the identified parameterization of gestational age. The expected median and variance, expressed in both standard deviations and percentiles, for each individual biometric measurement was calculated. The presented national reference ranges can be used for assessment of intrauterine size and growth of the fetal head, abdomen and femur in the second and third trimester of pregnancy.

Background: Prenatal depression is common, with an estimate that up to one in five pregnant women suffers from depressive symptoms. Maternal depression is associated with poor pregnancy outcomes such as preterm birth and low birth-weight. Such outcomes possibly affect offspring development. Previous studies suggest placental RNA levels of the glucocorticoid receptor are altered by maternal depression or anxiety; this stress may affect the placenta of male and female foetuses differently. However, it is unknown if the protein levels and activity of this receptor are additionally affected in women with depressive symptoms or being pharmacologically treated for depression. Methods: In this study, we investigated whether the glucocorticoid receptor (NR3C1) in the placenta is affected by maternal depression and/or selective serotonin reuptake inhibitor (SSRIs) treatment. Placentas from 45 women with singleton, term pregnancies were analysed by Western blot to determine glucocorticoid receptor levels, and by DNA-binding capacity to measure glucocorticoid receptor activation. Results: There were no differences in levels of the glucocorticoid receptor or activity between groups (control, depressive symptoms, and SSRI treatment; n = 45). Similarly, there was no difference in placental glucocorticoid receptor levels or activity dependent upon foetal sex. Conclusion: Maternal depression and SSRI treatment do not affect the glucocorticoid receptors in the placenta.

BackgroundFew 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.MethodWe 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.ResultsAPD 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).ConclusionThere 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.

IntroductionSleep problems are common in pregnancy but many studies have relied only on self-reported sleep measures. We studied the association between objectively measured sleep and peripartum depressive symptoms in pregnant women.Material and MethodsSleep was assessed using Actiwatch accelerometers in a sample of 163 pregnant women in the late first (weeks 11–15) or early second trimester (weeks 16–19). Depressive symptoms were assessed in gestational weeks 17, 32 and at 6 weeks post-partum using the Edinburgh Postnatal Depression Scale (EPDS). Multiple linear regression and logistic regression analyses, adjusting for age, BMI, pre-pregnancy smoking, ongoing mental health problems, trimester and season of sleep assessment were carried out to test the association between sleep and depression. Sleep was measured by total sleep time and sleep efficiency, whereas depression was indicated by depressive symptoms and depression caseness. Results are presented as unstandardized beta (B) coefficients or adjusted odds ratios (AOR) and 95% confidence intervals (CI).ResultsTotal sleep time ranged from 3 to 9 h (mean 7.1, SD 0.9) and average sleep efficiency was 83% (SD 6.0). Women with the shortest total sleep time, i.e., in the lowest quartile (

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

Abstract Background Antenatal depression affects 10–20% of pregnant women. Around 2–4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy. Methods Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal–Wallis test. Results Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p

Abstract Background 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 guidelines. Methods All units in Sweden that performed ultrasound-based pregnancy dating were asked to complete a web-based questionnaire comprising multiple-response questions and commentary fields. Information was collected regarding baseline information, current and previous clinical practice, and management of discrepancies between last-menstrual-period- and ultrasound-based methods for pregnancy dating. Results The response rate was 79%. Half of the units offered first-trimester ultrasound to all pregnant women. However, contrary to the guidelines, the crown–rump length was not used for ultrasound-based pregnancy dating in most units. Instead, ultrasound-based pregnancy dating was performed only if the biparietal diameter was between 21 and 55 mm. Management of discrepancies between methods for pregnancy dating varied widely. Conclusions The units reported high adherence to national guidelines, except for early pregnancy dating, for which many units followed unwritten or informal guidelines. The management of discrepancies between last-menstrual-period-based and ultrasound-based estimated day of delivery varied widely. These findings emphasize the need for regular updating of national written guidelines and efforts to improve their implementation in all units.

Background: Experiences of sexual violence among women can lead to ill health and increase the risk of lifetime co-occurrence of violence. Identifying risk factors and victims facilitates development of effective programmes for treatment and prevention of additional violence. The primary aim of this study was to assess the prevalence and correlates of sexual violence experiences among women seeking care at a family planning unit in Sweden. A secondary aim was to examine associations between sexual violence and other types of violence. Methods: Women (n = 1226) seeking services at a family planning unit, Uppsala University Hospital, Sweden, answered a questionnaire and were interviewed about experiences of sexual violence. Bivariate associations were examined using the chi-square test. Results: Experiences of sexual violence were reported by 27% of the participants, of which 57% were exposed when they were younger than 18 years old. Women with experiences of sexual violence were more likely to have lower education (P = 0.024), were students or without occupation (P = 0.037), and were not in a current relationship (P

Abstract Background Depressive symptoms negatively impact on breastfeeding duration, whereas early breastfeeding initiation after birth enhances the chances for a longer breastfeeding period. Our aim was to investigate the interplay between depressive symptoms during pregnancy and late initiation of the first breastfeeding session and their effect on exclusive breastfeeding at six weeks postpartum. Methods In a longitudinal study design, web-questionnaires including demographic data, breastfeeding information and the Edinburgh Postnatal Depression Scale (EPDS) were completed by 1217 women at pregnancy weeks 17–20, 32 and/or at six weeks postpartum. A multivariable logistic regression model was fitted to estimate the effect of depressive symptoms during pregnancy and the timing of the first breastfeeding session on exclusive breastfeeding at six weeks postpartum. Results Exclusive breastfeeding at six weeks postpartum was reported by 77% of the women. Depressive symptoms during pregnancy (EPDS> 13); (OR:1.93 [1.28–2.91]) and not accomplishing the first breastfeeding session within two hours after birth (OR: 2.61 [1.80–3.78]), were both associated with not exclusively breastfeeding at six weeks postpartum after adjusting for identified confounders. Τhe combined exposure to depressive symptoms in pregnancy and late breastfeeding initiation was associated with an almost 4-fold increased odds of not exclusive breastfeeding at six weeks postpartum. Conclusions Women reporting depressive symptoms during pregnancy seem to be more vulnerable to the consequences of a postponed first breastfeeding session on exclusive breastfeeding duration. Consequently, women experiencing depressive symptoms may benefit from targeted breastfeeding support during the first hours after birth.

Background: Postpartum depression (PPD) is a devastating disease requiring improvements in diagnosis and prevention. Blood metabolomics identifies biological markers discriminatory between women with and those without antenatal depressive symptoms. Whether this cutting-edge method can be applied to postpartum depressive symptoms merits further investigation.Methods: As a substudy within the Biology, Affect, Stress, Imagine and Cognition Study, 24 women with PPD symptom (PPDS) assessment at 6 weeks postpartum were included. Controls were selected as having a score of ≤ 6 and PPDS cases as ≥12 on the Edinburgh Postnatal Depression Scale. Blood plasma was collected at 10 weeks postpartum and analyzed with gas chromatography–mass spectrometry metabolomics.Results: Variations of metabolomic profiles within the PPDS samples were identified. One cluster showed altered kidney function, whereas the other, a metabolic syndrome profile, both previously associated with depression. Five metabolites (glycerol, threonine, 2-hydroxybutanoic acid, erythritol, and phenylalanine) showed higher abundance among women with PPDSs, indicating perturbations in the serine/threonine and glycerol lipid metabolism, suggesting oxidative stress conditions.Conclusions: Alterations in certain metabolites were associated with depressive pathophysiology postpartum, whereas diversity in PPDS physiologies was revealed. Hence, plasma metabolic profiling could be considered in diagnosis and pathophysiological investigation of PPD toward providing clues for treatment. Future studies require standardization of various subgroups with respect to symptom onset, lifestyle, and comorbidities.

The development of gaze following begins in early infancy and its developmental foundation has been under heavy debate. Using a longitudinal design (N = 118), we demonstrate that attachment quality predicts individual differences in the onset of gaze following, at six months of age, and that maternal postpartum depression predicts later gaze following, at 10 months. In addition, we report longitudinal stability in gaze following from 6 to 10 months. A full path model (using attachment, maternal depression and gaze following at six months) accounted for 21% of variance in gaze following at 10 months. These results suggest an experience-dependent development of gaze following, driven by the infant's own motivation to interact and engage with others (the social-first perspective).

Abstract 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 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.

Abstract Background Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders. Methods It was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP. Results The genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04–2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity. Conclusions The HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.

IntroductionThere is evidence demonstrating that certain lifestyle factors have a detrimental effect on fertility. Since such factors often coexist, possible synergistic effects merit further investigation. Thus we aimed to examine the cumulative impact of lifestyle factors on in vitro fertilization (IVF) early reproductive treatment outcomes and their interaction with measures of ovarian reserve.Materials and methodsBy following women who were starting their first fresh IVF cycle in 2 cohorts, the "Lifestyle study cohort" (hypothesis generating cohort, n = 242) and the "UppSTART study" (validation cohort, n = 432) in Sweden, we identified two significant risk factors acting independently, smoking and BMI, and then further assessed their cumulative effects.ResultsWomen with both these risk factors had an Incidence Rate Ratio (IRR) of 0.75 [(95% CI 0.61-0.94)] regarding the number of aspirated oocytes compared to women without these risk factors. Concerning the proportion of mature oocytes in relation to the total number of aspirated oocytes, the interaction between BMI and Antral Follicle Count (AFC) was significant (p-value 0.045): the lower the value of AFC, the more harmful the effect of BMI with the outcome.ConclusionsData shows that there is an individual as well as a cumulative effect of smoking and BMI on the number of aspirated and mature oocytes in fresh IVF treatment cycles. AFC might modify associations between BMI and the proportion of mature oocytes in relation to the total number of aspirated oocytes. These results highlight the importance of lifestyle factors on IVF early reproductive outcomes and provide additional evidence for the importance of preconception guidance for the optimization of IVF cycle outcome.

IntroductionPostpartum depression predisposes to maternal affective and somatic disorders. It is important to identify which women are at an increased risk of subsequent morbidity and would benefit from an intensified follow-up. Self-harm thoughts (SHTs), with or without other depressive symptomatology, might have prognostic value for maternal health beyond the postpartum period.AimThis study is to investigate the somatic and psychiatric morbidity of postpartum women with SHTs, with or without other depressive symptoms, over a 7-year follow-up period.Materials and methodsThe subjects for this study are derived from a population-based Swedish cohort of women who gave birth at Uppsala University Hospital (May 2006–June 2007) and who answered the Edinburgh Postnatal Depression Scale (EPDS) at 5 days, 6 weeks, and 6 months postpartum. Three groups were included: women reporting SHTs (SHT group, n = 107) on item 10 of the EPDS; women reporting depressive symptoms, i.e., EPDS ≥ 12 at 6 weeks and/or 6 months postpartum, without SHTs (DEP group, n = 94); and randomly selected controls screening negatively for postpartum depression (CTL group, n = 104). The number of diagnostic codes for somatic and psychiatric morbidity according to the International Statistical Classification of Diseases and Related Health Problems system, and the number of medical interventions were retrieved from medical records over 7 years following childbirth and were used as the outcome measures, together with any prescription of antidepressants and sick leave during the follow-up.ResultsThe SHT group had the highest psychiatric morbidity of all groups and more somatic morbidity than controls. Affective disorders were more common in the SHT and the DEP groups compared with controls, as well as antidepressant prescriptions and sick leave. One-fifth of women with SHTs did not screen positive for depressive symptoms; nevertheless, they had more somatic and psychiatric morbidity than the control group.ConclusionWomen reporting thoughts of self-harm in the postpartum period are at an increased risk of somatic and psychiatric morbidity during a follow-up of 7 years after delivery, and this increased risk may not be fully attributed to depressive symptoms. Results underline the importance of screening for self-harm symptoms postpartum and point to a need for individualized follow-up.

Breastfeeding rates in Sweden are declining, and it is important to identify women at risk for early cessation of exclusive breastfeeding.The aim of this study was to investigate factors associated with exclusive breastfeeding lasting less than two months postpartum.A population-based longitudinal study was conducted at Uppsala University Hospital, Sweden. Six hundred and seventy-nine women were included in this sub-study. Questionnaires were sent at five days, six weeks and six months postpartum, including questions on breastfeeding initiation and duration as well as several other background variables. The main outcome measure was exclusive breastfeeding lasting less than two months postpartum. Multivariable logistic regression analysis was used in order to calculate adjusted Odds Ratios (AOR) and 95% Confidence Intervals (95% CI).Seventy-seven percent of the women reported exclusive breastfeeding at two months postpartum. The following variables in the multivariate regression analysis were independently associated with exclusive breastfeeding lasting less than two months postpartum: being a first time mother (AOR 2.15, 95% CI 1.32-3.49), reporting emotional distress during pregnancy (AOR 2.21, 95% CI 1.35-3.62) and giving birth by cesarean section (AOR 2.63, 95% CI 1.34-5.17).Factors associated with shorter exclusive breastfeeding duration were determined. Identification of women experiencing emotional distress during pregnancy, as well as scrutiny of caregiving routines on cesarean section need to be addressed, in order to give individual targeted breastfeeding support and promote longer breastfeeding duration.

OBJECTIVES:To explore the association between postpartum haemorrhage (PPH) and postpartum depression (PPD), taking into account the role of postpartum anaemia, delivery experience and psychiatric history. METHODS:A nested cohort study (n = 446), based on two population-based cohorts in Uppsala, Sweden. Exposed individuals were defined as having a bleeding of ≥1000 ml (n = 196) at delivery, and non-exposed individuals as having bleeding of

The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus-Pituitary-Adrenal axis response having been implicated in its pathophysiology.The current study was undertaken as a part of the BASIC project (Biology, Affect, Stress, Imaging, Cognition), a population-based longitudinal study of psychological wellbeing during pregnancy and the postpartum period in Uppsala County, Sweden, in order to assess the association between evening salivary cortisol levels and depressive symptoms in the peripartum period. Three hundred and sixty-five pregnant women from the BASIC cohort were recruited at pregnancy week 18 and instructed to complete a Swedish validated version of the Edinburgh Postnatal Depression Scale at the 36th week of pregnancy as well as the sixth week after delivery. At both times, they were also asked to provide evening salivary samples for cortisol analysis. A comprehensive review of the relevant literature is also provided.Women with postpartum EPDS score ≥ 10 had higher salivary evening cortisol at six weeks postpartum compared to healthy controls (median cortisol 1.19 vs 0.89 nmol/L). A logistic regression model showed a positive association between cortisol levels and depressive symptoms postpartum (OR = 4.1; 95% CI 1.7-9.7). This association remained significant even after controlling for history of depression, use of tobacco, partner support, breastfeeding, stressful life events, and sleep problems, as possible confounders (aOR = 4.5; 95% CI 1.5-14.1). Additionally, women with postpartum depressive symptoms had higher postpartum cortisol levels compared to both women with depressive symptoms antenatally and controls (p = 0.019 and p = 0.004, respectively).Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression.

Marked endocrine alterations occur after delivery. Most women cope well with these changes, but the postpartum period is associated with an increased risk of depressive episodes. Previous studies of emotion processing have focused on maternal-infant bonding or postpartum depression (PPD), and longitudinal studies of the neural correlates of emotion processing throughout the postpartum period in healthy women are lacking. In this study, 13 women, without signs of post partum depression, underwent fMRI with an emotional face matching task and completed the MADRS-S, STAI-S, and EPDS within 48 h (early postpartum) and 4-6 weeks after delivery (late postpartum). Also, data from a previous study including 15 naturally cycling controls assessed in the luteal and follicular phase of the menstrual cycle was used. Women had lower reactivity in insula, middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) in the early as compared to the late postpartum assessment. Insular reactivity was positively correlated with anxiety in the early postpartum period and with depressive symptoms late postpartum. Reactivity in insula and IFG were greater in postpartum women than in non-pregnant control subjects. Brain reactivity was not correlated with serum estradiol or progesterone levels. Increased reactivity in the insula, IFG, and MFG may reflect normal postpartum adaptation, but correlation with self-rated symptoms of depression and anxiety in these otherwise healthy postpartum women, may also suggest that these changes place susceptible women at increased risk of PPD. These findings contribute to our understanding of the neurobiological aspects of the postpartum period, which might shed light on the mechanisms underlying affective puerperal disorders, such as PPD.