Explore the vast range of titles available.

During pregnancy, the woman’s body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (~gw38) and 114 in the postpartum period (~w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.

AbstractObjectiveTo determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters.DesignNationwide, register based study.SettingSwedish national registers, 1 January 2001 to 31 December 2018.Participants86 551 women with a first ever diagnosis of perinatal depression ascertained through specialised care and use of antidepressants, and 865 510 women who did not have perinatal depression were identified and matched based on age and calendar year at delivery. To address familial confounding factors, comparisons were made between 270 586 full sisters (women with perinatal depression (n=24 473) and full sisters who did not have this disorder (n=246 113)), who gave at least one singleton birth during the study period.Main outcome measuresPrimary outcome was death due to any cause. Secondary outcome was cause specific deaths (ie, unnatural and natural causes). Multivariable Cox regression was used to estimate hazard ratios of mortality comparing women with perinatal depression to unaffected women and sisters, taking into account several confounders. The temporal patterns of perinatal depression and differences between antepartum and postpartum onset of perinatal depression were also studied.Results522 deaths (0.82 per 1000 person years) were reported among women with perinatal depression diagnosed at a median age of 31.0 years (interquartile range 27.0 to 35.0) over up to 18 years of follow-up. Compared with women who did not have perinatal depression, women with perinatal depression were associated with an increased risk of death (adjusted hazard ratio 2.11 (95% confidence interval 1.86 to 2.40)); similar associations were reported among women who had and did not have pre-existing psychiatric disorder. Risk of death seemed to be increased for postpartum than for antepartum depression (hazard ratio 2.71 (95% confidence interval 2.26 to 3.26) v 1.62 (1.34 to 1.94)). A similar association was noted for perinatal depression in the sibling comparison (2.12 (1.16 to 3.88)). The association was most pronounced within the first year after perinatal depression but remained up to 18 years after start of follow up. An increased risk was associated with both unnatural and natural causes of death among women with perinatal depression (4.28 (3.44 to 5.32) v (1.38 (1.16 to 1.64)), with the strongest association noted for suicide (6.34 (4.62 to 8.71)), although suicide was rare (0.23 per 1000 person years).ConclusionsEven when accounting for familial factors, women with clinically diagnosed perinatal depression were associated with an increased risk of death, particularly during the first year after diagnosis and because of suicide. Women who are affected, their families, and health professionals should be aware of these severe health hazards after perinatal depression.

Fast Facts

ObjectiveWomen with premenstrual disorder (PMD) display heightened sensitivity to hormonal changes and may be at risk for psychiatric disorders during other hormonally dynamic periods such as pregnancy and postpartum. While PMD has been linked to perinatal depression, associations with the full spectrum of perinatal psychiatric disorders (PNPDs), including anxiety and psychosis, remain largely unexplored. This study aimed to investigate whether a history of PMD is associated with increased risk of a first-onset PNPD.DesignNationwide register-based cohort study from 2003 to 2020.SettingSwedish national and regional population and healthcare registers.Participants1 052 977 women with 1 799 010 pregnancies recorded in the Swedish Medical Birth Register. Individuals with PMD prior to pregnancy were identified through clinical diagnoses or prescribed medications in Swedish healthcare registers.Primary and secondary outcome measuresFirst-onset PNPDs diagnosed from pregnancy start to 12 months postpartum were identified through Swedish healthcare registers. PNPDs were categorised into eight subgroups: depression, anxiety, stress-related disorders, bipolar disorder, psychosis, alcohol use disorder, drug use disorder and other. Multivariable logistic regression models were used to estimate ORs and 95% CIs, adjusting for demographic and clinical covariates. Sibling analyses were also conducted to address potential familial confounding.ResultsAmong the 1 052 977 women included, 13 382 women (1.3%), corresponding to 17 514 (1%) pregnancies, had a diagnosis of PMD prior to pregnancy. In the type-specific analysis, an increased likelihood was found for all subtypes of disorders, except for perinatal psychosis. The strongest associations were observed for bipolar disorder (adjusted OR 3.98, 95% CI 3.15 to 5.04), followed by perinatal depression (adjusted OR 2.74, 95% CI 2.56 to 2.94). Associations were present in both antepartum and postpartum periods and were stronger among women without psychiatric history. Sibling comparisons showed attenuated but statistically significant associations.ConclusionOur findings highlight that women with a history of PMD face an increased likelihood of developing PNPDs, particularly depression and bipolar disorder, both during pregnancy and postpartum. Given frequent perinatal healthcare contact, these findings may help inform targeted risk identification and early intervention strategies.

Oocytes can be effectively cryopreserved and stored for future use in in-vitro fertilisation. Oocyte cryopreservation (OC) can therefore mitigate different threats to female fertility, but attitudes and policies often seem more favourable in medical rather than age-related fertility preservation scenarios. The value of OC for potential candidates may be perceived differently depending on the indications, although relevant empirical data are lacking. An adequately powered sample of Swedish female university students (n = 270; median age 25; range 19–35) were randomly delivered a medical (n = 130) or age-related (n = 140) fertility preservation scenario within an online survey. Sociodemographic factors, reproductive experiences, and awareness about OC were not significantly different between the groups. Differences in four outcomes were studied: proportions of respondents (1) positive to the use of OC, (2) positive to public funding for OC, or (3) open to considering OC; and (4) willingness-to-pay (WTP) for OC, measured in thousand Swedish krona (K SEK) through contingent valuation. There were no significant differences in the proportions of respondents positive to the use of OC (medical: 96%; age-related: 93%) or open to consider it (medical: 90%; age-related: 88%) in each scenario. However, public funding had significantly greater support in the medical scenario (85%) than in the age-related one (64%). The median WTP (45 K SEK ≈ 4.15 K EUR) approximated the current Swedish market price for a single elective cycle and was not significantly different between the scenarios (Cliff’s delta − 0.009; 95%CI − 0.146, 0.128). These findings suggest that it may be inappropriate to justify counselling and priority policies only on the assumption that fertility preservation with OC for medical indications is more beneficial to women than when the same technique is used for age-related reasons. However, it would be interesting to investigate further why public funding appears more debatable than the treatment itself.

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 < 0.05 were considered significant. The analysis was also stratified by sex of the child. Among boys, we observed higher and correlated DNA methylation of one CpG-site in the promoter region of TPP1 in the HC group, with high externalizing scores compared to HC with low externalizing scores. Boys in the PND group showed lower DNA methylation in NUDT15 among those with high, compared to low, internalizing scores; the DNA methylation levels of CpGs in this gene were positively correlated with the CBCL scores. Hence, the differentially methylated CpG sites could be of interest for resilience, regardless of maternal mental health during pregnancy. The findings are in a relatively healthy study cohort, thus limiting the possibility of detecting strong effects associated with behavioral difficulties. This is the first investigation of cord blood DNA methylation signs of fetal programming of PND on child behavior at 18 months of age and thus calls for independent replications.

IntroductionPerinatal 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 analysisAll 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 disseminationEthical 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.

Premenstrual disorders (PMDs) and perinatal depression (PND) share symptomology and the timing of symptoms of both conditions coincide with natural hormonal fluctuations, which may indicate a shared etiology. Yet, there is a notable absence of prospective data on the potential bidirectional association between these conditions, which is crucial for guiding clinical management. Using the Swedish nationwide registers with prospectively collected data, we aimed to investigate the bidirectional association between PMDs and PND. With 1,803,309 singleton pregnancies of 1,041,419 women recorded in the Swedish Medical Birth Register during 2001 to 2018, we conducted a nested case-control study to examine the risk of PND following PMDs, which is equivalent to a cohort study, and transitioned that design into a matched cohort study with onward follow-up to simulate a prospective study design and examine the risk of PMDs after PND (within the same study population). Incident PND and PMDs were identified through clinical diagnoses or prescribed medications. We randomly selected 10 pregnant women without PND, individually matched to each PND case on maternal age and calendar year using incidence density sampling (N: 84,949: 849,482). We (1) calculated odds ratio (OR) and 95% confidence intervals (CIs) of PMDs using conditional logistic regression in the nested case-control study. Demographic factors (country of birth, educational level, region of residency, and cohabitation status) were adjusted for. We (2) calculated the hazard ratio (HR) and 95% CIs of PMDs subsequent to PND using stratified Cox regression in the matched cohort study. Smoking, BMI, parity, and history of psychiatric disorders were further controlled for, in addition to demographic factors. Pregnancies from full sisters of PND cases were identified for sibling comparison, which contrasts the risk within each set of full sisters discordant on PND. In the nested case-control study, we identified 2,488 PMDs (2.9%) before pregnancy among women with PND and 5,199 (0.6%) among controls. PMDs were associated with a higher risk of subsequent PND (OR 4.76, 95% CI [4.52,5.01]; p < 0.001). In the matched cohort with a mean follow-up of 7.40 years, we identified 4,227 newly diagnosed PMDs among women with PND (incidence rate (IR) 7.6/1,000 person-years) and 21,326 among controls (IR 3.8). Compared to their matched controls, women with PND were at higher risk of subsequent PMDs (HR 1.81, 95% CI [1.74,1.88]; p < 0.001). The bidirectional association was noted for both prenatal and postnatal depression and was stronger among women without history of psychiatric disorders (p for interaction < 0.001). Sibling comparison showed somewhat attenuated, yet statistically significant, bidirectional associations. The main limitation of this study was that our findings, based on clinical diagnoses recorded in registers, may not generalize well to women with mild PMDs or PND. In this study, we observed a bidirectional association between PMDs and PND. These findings suggest that a history of PMDs can inform PND susceptibility and vice versa and lend support to the shared etiology between both disorders.

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.

PurposeWith the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.ParticipantsFrom September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16–18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.Findings to dateIn addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case–control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic–pituitary–adrenal axis and immune system.Future plansIn parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.