BACKGROUND:Postpartum depression (PPD) is a common peripartum complication with approximately 13-17% of women being affected. About 30-50% continue to have symptoms 12 months postpartum. Earlier studies have examined women's experiences of treatments to evaluate their effectiveness in supporting women's recovery from PPD. Studies implementing a broader qualitative research focus-exploring factors associated with both personal circumstances and the health care system, and their perceived contribution to remission-are currently lacking. AIM:To identify the factors women with short- and long-term PPD symptoms view as most important for faster remission. METHOD:Participants from a Swedish cohort study (Mom2B) with depressive symptoms above the clinical cut-off of 11 on the Edinburg Postnatal Depression Scale early postpartum, were invited to participate in an interview study. Semi-structure interviews were performed online (n = 12) or via telephone (n = 6). The interviews were transcribed and analyzed using Systematic Text Condensation. RESULTS:Five themes describing factors of importance for recovery from PPD were identified; 1) Others take responsibility; 2) Practical support; 3) Emotional validation; 4) Thresholds and 5) Struggling to prioritize oneself. CONCLUSION:Synthesized from the resulting themes, a five-stage recovery process was identified: realization of symptoms, acceptance, recognizing the need for help, knowledge, and receiving help. This study highlights the key factors in PPD recovery from the perspective of affected women, providing insights to inform and improve postpartum care. The results can help staff visualize the process, which makes them better equipped to support the women effectively.

BackgroundEvidence of the relationship between breastfeeding and maternal mental health is mixed and complex, with some studies suggesting breastfeeding may lower the risk for postpartum depressive symptoms, while others report no clear or consistent effects. Given these inconsistencies, we aim to assess the association between the timing of initiation of breastfeeding and postpartum depressive symptoms 90 days after birth in Nepal.MethodologyThis longitudinal multi-centric cohort study included 898 mother-infant pairs in 9 district hospitals of Nepal. Data was collected on timing of initiation of breastfeeding, sociodemographic variables and depressive symptoms assessed through the Edinburg Postnatal Depression Scale. A Directed Acyclic Graph was constructed and multiple logistic regression, generalized mixed linear regression model and Generalized Estimating Equations (GEE) were used to assess the association of timing of breastfeeding with postpartum depressive symptoms.Principal resultsAt the 90th day postpartum, 31.4% of women reported depressive symptoms. Compared to women who had immediate breastfeeding, those who had no immediate breastfeeding had 3.47 higher odds of depressive symptoms (cOR: 3.47; 95% CI; 2.40, 5.01). After adjusting for confounding and mediating factors, the odds of depressive symptoms were 2.81 times higher among women who did not immediately breastfeed (aOR, 2.81; 95% CI; 1.76, 4.50). Using GEE modeling, there was a positive association between delayed breastfeeding and postpartum depression at 7 days (β coefficient, 0.583, p = 0.001) and at 45 days (β coefficient, 0.551, p = 0.003). Using the generalized linear mixed model, the prediction to postpartum depression score increased with delay in breastfeeding.ConclusionsThis study highlights that the delayed initiation of breastfeeding is associated with higher odds of symptoms for postpartum depression among various groups of women, especially among women from disadvantageous groups and women with no education in Nepal. Improving support to women for early initiation of breastfeeding could help reduce postpartum depression.

Background:Premenstrual disorder (PMD) and postpartum depression (PPD) have a strong phenotypic link and echo women's hormone fluctuations. Yet, the extent to which they may be cross-inherited remains poorly understood. Methods:Using the nationwide cohort of 907,841 women who born 1950-2007 and gave birth during 2001-2021 in Sweden, we estimated the cumulative incidence functions-based heritability and genetic correlation for PMD and PPD. We also analyzed genome-wide association study (GWAS) summary statistics from the largest European-ancestry cohorts for PMD (17,511 cases and 54,786 controls) and PPD (16,145 cases and 46,609 controls) using linkage disequilibrium score regression (LDSC). Fixed-effect cross-trait meta-analysis and imputed transcriptome-wide association analyses (TWAS) were conducted to identify shared loci and gene-tissue associations. Results:The register-based heritability was 0.35 (95% CI: 0.29-0.41) for PMD and 0.31 (95% CI: 0.23-0.37) for PPD, with a positive genetic correlation between these disorders (rg = 0.47, 95% CI: 0.25-0.69). LDSC also showed a positive genetic correlation between PMD and PPD (r g = 0.66, SE = 0.10, P = 1.014×10-10), indicating sizable shared heritable influences. Cross-trait meta-analysis identified two novel genome-wide significant loci jointly associated with PMD and PPD, mapping to an intronic region of PCDH9 and the 3' untranslated region of KCTD16. The KCTD16 locus implicates GABAB-mediated inhibitory signaling in both disorders. Consistent with this, TWAS revealed a hippocampus regulatory signal for KCTD16, with no detectable trend effects in other brain regions or peripheral tissues. Beyond the lead loci, TWAS suggested that the shared risk variants may partially act through genetically regulated gene expression across brain, endocrine and immune-related tissues. Conclusions:Together, these findings provide the first evidence for sizable genetic overlap between PMD and PPD and highlight novel and convergent biological mechanisms underlying the abnormal brain response of some women to gonadal hormone fluctuations.

This study explores the correlation between heat exposure and perinatal depression in four low- and middle-income countries using a spatial, time-stratified case-crossover study. Cluster-level mental health data from the Demographic and Health Surveys (DHS) of Bangladesh, Lesotho, Mozambique, and Nepal was utilized. Availability of complete data on Patient Health Questionnaire 9 (PHQ-9) was an inclusion criterion. Heat exposure data was provided by the National Aeronautics and Space Administration (NASA). Spatial alignment between DHS clusters and meteorological points was achieved using bilinear interpolation. Heat exposure was defined as the daily maximum temperature exceeding the country-specific 50th percentile. This study included 1836 perinatal women with depression. The pooled prevalence of perinatal depression was 27% (range: 19%-31%). Using distributed lag non-linear model (DLNM), in Bangladesh, lower maximum ambient temperatures (25th-centile) had 5.34 (4.28, 6.66) times higher cumulative odds for perinatal depression compared to the median temperature. In Lesotho, Mozambique, and Nepal, exposure to higher maximum ambient temperature (75th centile) had cumulative higher odds of 1.19 (0.98, 1.43), 2.51 (1.96, 3.20), and 9.41 (4.88, 18.1), respectively, in comparison to the median temperatures. The results suggest that heat exposure is correlated with perinatal depression, undermining the need for intersectoral responses that address environmental and healthcare system factors.

INTRODUCTION:Labour epidural analgesia is the most effective method for intrapartum pain relief and is associated with improved maternal outcomes. However, concerns have been raised regarding potential associations between labour epidural analgesia and adverse psycho-emotional outcomes in children. Evidence from large epidemiological studies is inconsistent and potential biological mechanisms remain unclear. Maternal immune activation during pregnancy may play a role. We aimed to investigate behavioural and psycho-emotional outcomes in children of mothers who received epidural analgesia during labour, accounting for perinatal mental health, sociodemographic characteristics and cytokine profiles. METHODS:Singleton vaginal births from the Biology, Affect, Stress, Imaging and Cognition study were included. Child behavioural outcomes were assessed by Child Behavioural Checklist scores at 18 months, 6 years and 11 years postpartum in the U-BIRTH follow-up cohort, with higher scores indicating more behavioural difficulties. The main exposure was maternal use of labour epidural analgesia. Maternal data were collected from questionnaires and medical records. RESULTS:Among 1962 mother-child dyads, 726 (37%) received labour epidural analgesia. Younger maternal age; lower resilience; inflammatory diseases; primiparity; antenatal depression; fear of childbirth; and longer duration of labour were associated with higher Child Behavioural Checklist scores at 18 months postpartum. In crude analysis, labour epidural analgesia correlated with higher Child Behavioural Checklist scores at 18 months postpartum; however, this association was not significant after adjusting for confounders. Among those with lower expression of TNFSF14 and CXCL6 cytokines, labour epidural analgesia use was associated with higher Child Behavioural Checklist scores. DISCUSSION:Use of epidural analgesia during labour was not found to be independently associated with adverse child behavioural outcomes. Variations in maternal cytokine profiles among those choosing labour epidural analgesia or not may influence susceptibility to early behavioural differences. Replication in larger cohorts and further exploration of additional immune biomarker dynamics during pregnancy are warranted.

Background:Hormonal transition phases represent windows of increased neuroplasticity across the female lifespan. In this study, we aim to investigate the brain anatomical architecture of hormonal transition phases by directly comparing menarche, as a period of rising levels of steroid hormones, and menopause, as a time of declining levels. Methods:We fit linear models on cross-sectional and linear mixed-effect models on longitudinal magnetic resonance imaging (MRI) datasets, to explore the effects of menarche onset (ABCD study data, Ncross-sectional=1274, Nlongitudinal=611) and transition into menopause (UK Biobank data, Ncross-sectional=1614, Nlongitudinal=212) on 66 cortical and 135 subcortical brain volumes, and to identify brain structures with opposing but regional overlapping effects in both periods. Models were adjusted for age and corrected for multiple comparison (P <.05; FDR-corrected). Results:Cross-sectionally, using a between-subject design, 83 brain volumes showed effects of menarche-onset and 17 volumes showed effects of menopause-transition. Of these, seven brain volumes were significantly affected by both transitional periods, showing opposing directional volume changes. Longitudinally, using a within-subject design, 56 brain volumes exhibited menarche effects, of which 46 replicated cross- sectionally. No menopause effect survived correction for multiple comparison, likely due to limited longitudinal sample size. Conclusion:Our findings confirm regionally overlapping brain structural alteration between the two hormonal phases - menarche and menopause - showing the hypothesized opposite effect directions. Additionally, our results show the robustness of menarche effects, which converged across cross-sectional and longitudinal study designs. Taken together, our results contribute to a better understanding of hormone related neuroplasticity, emphasizing the importance of not only understanding individual phases, but understanding the overarching patterns across the female reproductive lifespan.

Pregnancy induces neuroanatomical changes in the human brain. Previous studies detected both traces of motherhood decades after childbirth and adaptations in fathers. It is unclear which effects can be attributed to persisting traces of pregnancy and which are effects of parenthood. We investigated effects of past birth and of pregnancy loss in women, and effects of fatherhood in men, using univariate and machine learning analyses on 205 regional brain volumes. A group of mothers and an age-matched sample of nulliparous women (N = 4357 per group, mean age 63 years) from the UK Biobank, with no past pregnancy losses, showed significant volumetric group differences in 14 regions at Bonferroni-adjusted α = 0.05. Likewise, we identified 18 significant group differences between age-matched samples of fathers and non-fathers of the same size (mean age 63.4), with 9 regions overlapping between sexes. Brain-wide association statistics for past live birth in mothers and those for fatherhood correlated (r = 0.55). XGBoost machine learning models trained to classify parenthood status separately in both datasets showed performance that was low, but significantly above chance (10-fold cross validation: AUC = 0.56, p < 1e-5 Motherhood classifier, AUC = 0.54, p < 1e-5, Fatherhood classifier, 10 k permutations). We tested the motherhood classification model on an independent test sample comprising four age-matched groups: 1. women who have never been pregnant, 2. women with past pregnancy loss but no live births, 3. women with live births but no pregnancy loss, and 4. women who experienced both. Class probability was significantly associated with live births, but not past loss. These findings may suggest that neuroanatomical patterns of past childbirth partly also reflect traces of parenthood and not solely persisting traces of past pregnancy, although a more detailed characterization of pregnancy loss data would be needed for full confirmation of this interpretation. Therefore, further research is needed to quantify the extent and understand the nature of these changes, particularly considering the known vulnerability for mental disorders associated with reproductive events.

Abstract Purpose The COVID-19 pandemic posed substantial challenges to cancer care, raising concerns about the safety of ongoing endocrine therapy in women with breast cancer. However, real-world evidence on the association between endocrine therapy and COVID-19 outcomes in population-based cohorts remains limited. Methods A nationwide, register-based matched cohort study was conducted in Sweden, including women aged ≥ 55 years who received endocrine therapy for breast cancer during 2020. A total of 31,678 women were included: 8,879 treated with tamoxifen, 21,384 with aromatase inhibitors, and 1,415 with sequential therapy. Exposed women were matched 1:1 by age and region to population controls without breast cancer or estrogen-modulating therapy. Stage-stratified analyses were performed for early-stage and locally advanced breast cancer. Outcomes included COVID-19–related mortality (primary outcome), all-cause mortality, intensive care unit admission, COVID-19–related hospitalization, and laboratory-confirmed SARS-CoV-2 infection. Results COVID-19–related mortality did not differ between women receiving endocrine therapy and their matched population controls. Intensive care unit admission risk were comparable across groups. Tamoxifen was associated with lower all-cause mortality in early-stage breast cancer, whereas aromatase inhibitors were linked to higher all-cause mortality and increased COVID-19-related hospitalization in locally advanced disease. A modestly increased risk of SARS-CoV-2 infection was observed among tamoxifen users. Conclusion In this nationwide Swedish cohort, adjuvant endocrine therapy was not associated with increased COVID-19–specific mortality. These findings support the continued use of adjuvant endocrine therapy in women with breast cancer without added COVID-19 mortality risk and highlight stage-specific differences in outcomes, reinforcing the safety of endocrine therapy during pandemic conditions.

Change in cohabitation status could influence the economic security and well-being of parents and their children. However, literature concerning the association between the duration of perinatal depression (PND) exposure and change in parental cohabitation status is limited. Therefore, this study aimed to assess whether the presence and persistence of maternal PND symptoms are associated with changes in parental cohabitation status up to six years postpartum. Using data from 4,344 persons in the Swedish BASIC and U-BIRTH cohort studies, maternal depressive symptoms were assessed at three time points (during pregnancy, 6 weeks, and 6 months postpartum) using the Edinburgh Postnatal Depression Scale. Cohabitation status was measured at 6 weeks and 6 years postpartum. Logistic regressions estimated odds ratios (ORs) for non-cohabitation associated with the number of PND-positive time points. Mothers with positive screenings at more than one time point for depressive symptoms had higher odds of not cohabiting at both 6 weeks and 6 years postpartum. At 6 years, mothers with depressive symptoms at all three time points had over four times the odds of not cohabiting (OR 4.1, 95% CI 1.7-9.5). However, most associations lost significance after full adjustment for sociodemographic and psychosocial factors, except the association between prolonged PND (3 positive screenings) and non-cohabitation at six years postpartum. Prolonged PND symptoms may increase the risk of long-term parental separation. Although confounding factors reduce the strength of this association, findings underscore the need for extended mental health monitoring and support for perinatal persons.

Background:Transgender and gender-diverse (TGD) people experience elevated mortality risk, yet population-based estimates of cause-specific mortality remain limited. Prior studies have focused on narrow subgroups or outdated cohorts, leaving gaps in understanding current mortality disparities. Therefore, the purpose of this study is to quantify all-cause and cause-specific mortality among all TGD adults with a diagnosis of gender dysphoria in Sweden. Methods:This cohort study provides national cause-specific mortality estimates among TGD adults in Sweden using registry data (2001-2023). TGD people were identified using ICD-10 codes for "gender dysphoria" and matched to approximately 10 cisgender controls of each sex by age and county. Age-standardized mortality rates, absolute mortality risk differences, mortality rate ratios (MRR), and years of potential life lost (YPLL) were calculated overall and stratified by sex assigned at birth. Findings:A total of 9038 TGD people were identified, among them, 211 deaths were observed. All-cause mortality risk was almost twice that of the cisgender comparison group (MRR = 1.9, 95% confidence interval [CI] 1.7, 2.2). Stratified analyses showed distinct mortality patterns for transfeminine (assigned male sex at birth) and transmasculine (assigned female sex at birth) people, with higher risk from ill-defined diseases among transfeminine people (cisgender women as reference: MRR = 4.9, 95% CI 2.3, 10.3; cisgender men: MRR = 5.5, 95% CI 2.6, 11.4) and transmasculine people from neoplasms (cisgender women: MRR = 2.4, 95% CI 1.4, 4.1; cisgender men: MRR = 1.8, 95% CI 1.1, 3.1). These disparities resulted in a mean of 6.3 YPLL for transfeminine people compared to cisgender men and 9.0 YPLL for transmasculine people compared to cisgender women. Interpretation:These findings highlight persistent health inequities and underscore the need for targeted public health interventions and an evaluation of data collection processes to improve health monitoring and support TGD populations in Sweden. Funding:The present study was funded by a Starting Grant (2023-01397) and a project grant (2021-01968) from the Swedish Research Council for Health, Working Life and Welfare (FORTE).

Perinatal depression (PND) is a common mental health disorder associated with childbirth, which has high societal costs affecting up to 10% of individuals during pregnancy or postpartum. Whilst socially assistive robots (SARs) have recently proven to be useful tools in mental healthcare, and our previous work has investigated different stakeholders' perspectives on SARs in PND screening through interview studies, gaps remain in understanding how primary users (i.e., prospective patients) perceive and interact with such technologies. In this article, we use a participatory design methodology with semi-structured interviews of women in Sweden with previous experience of PND to explore the roles that SARs could play in addressing PND challenges and identify design factors for SARs in PND screening. We design and evaluate in a user study a robot prototype in two new interaction contexts for SARs with different levels of human oversight. The results show that SARs are welcomed by most participants, who appreciated the potentially faster assessment process and felt more comfortable opening up with a robot versus a human clinician. However, we found that there is no single solution that fits all, as other participants preferred the flexibility of self-reported digital surveys or interaction with a human clinician. Moreover, results show that transparency and human oversight are crucial requirements to consider when implementing robot-delivered PND screening questionnaires and diagnostic interviews. We reflect on ethical considerations, provide design recommendations and urge HRI designers to carefully consider whom SARs benefit, whom they may not, and which safeguarding factors are necessary to prevent potential negative outcomes.

Abstract Introduction Menopausal hormone therapy (MHT) is used to manage menopausal symptoms. Dispensing patterns are influenced by evolving guidelines, clinical practice, and public perceptions, which have shifted considerably over the past two decades. This study aims to describe patterns and age‐specific trajectories of MHT dispensing in Sweden in a closed cohort of women aged 45–60 years at baseline, followed from 2006 to 2020. Material and Methods A population‐based closed cohort study linking several Swedish national health registers was performed. A total of 951 455 women aged 45–60 years residing in Sweden were included on January 1, 2006, and followed up until December 31, 2020. MHT dispensing was examined through three approaches: 1) local or no MHT versus systemic MHT, 2) oral versus transdermal estrogen, and 3) based on progestogen type and administration route. Analyses were also stratified by age at baseline (45–49, 50–54, 55–60 years). Results Systemic MHT dispensing was 9.6% in 2006 and 3.8% in 2020, while 6.7% and 16.7% used local MHT, respectively. The oldest age group consistently dispensed systemic MHT to a greater extent through the years. Oral estrogen dominated, although relative transdermal estrogen use increased modestly toward the end of follow‐up. Dispensing of systemic MHT was less common among women born outside Europe, while dispensing of transdermal estrogen, compared to oral, was higher among those with higher education and income. Synthetic progestogens remained the most common type of progestogen, whereas dispensing of bioidentical progesterone/dydrogesterone and hormonal intrauterine devices was rare. Conclusions In this large, population‐based, closed cohort of women in Sweden, dispensing of systemic MHT declined with increasing age, while local MHT increased. Dispensing patterns, including route of estrogen administration and type of progestogen, varied by age cohort and sociodemographic characteristics. These findings illustrate how MHT dispensing is shaped by aging, cohort effects, evolving clinical practices, and updated guidelines, as well as by social determinants of health. Overall, the results underscore the importance of continued monitoring of MHT dispensing and efforts to ensure that prescribing remains evidence‐based and equitable.

The occurrence of treatment resistance in women with postpartum depression (PPD) and risk factors for treatment resistance remain less studied. This study aimed to determine the rate of treatment resistance and the associated risk factors among women with PPD in a nationwide setting. Here we conducted a nationwide register-based cohort study of 58,618 patients with a first-ever PPD during 2006-2021 in Sweden. Information on demographics, pregnancy characteristics, pre-existing physical and psychiatric conditions and treatment was retrieved from Swedish national registers. The outcome was treatment-resistant PPD (TRPPD) within 1 year following PPD diagnosis. Associations between potential risk factors and TRPPD were assessed using multivariable Poisson regression. Among the 58,618 patients with PPD, 3,522 (6.0%) met the criteria for TRPPD during 1 year after PPD diagnosis. Lower educational level, lower household income, being non-cohabiting, smoking in early pregnancy, delivery by cesarean section, pre-existing physical conditions and pre-existing psychiatric disorders were significantly associated with a higher risk of TRPPD. In addition, patients with two births (versus primiparity) or with a prior premenstrual disorder had a lower risk of TRPPD. Treatment resistance in patients with PPD is common and is notably associated with specific demographic and clinical profiles. These findings may provide grounds for practical risk assessment at PPD diagnosis and highlight the need for personalized management strategies.

Background The peripartum period encompasses physiological, endocrine, and immunological adaptations that ensure maternal health and fetal development. Notably, the molecular correlates of these adaptations in healthy women remain limited, particularly at the transcriptomic level. This study aimed to identify systemic transcriptomic differences between late pregnancy and the early postpartum period in a large cohort of healthy women. Methods RNA sequencing was performed on 112 samples from peripheral blood collected at gestational week 38 (gw38; n = 40) and postpartum week 8 (ppw8; n = 72). The transcriptome was compared while adjusting for age and BMI. Additional covariate-adjusted analyses were performed considering cell-type composition, sex of the fetus, and gestational length. Results A total of 293 differentially expressed genes (DEGs) were identified when comparing ppw8 vs. gw38, with the majority being downregulated in the postpartum period. The postpartum phase was marked by the lower expression of genes involved in erythropoiesis and innate, granulocyte-driven immunity, as well as higher levels of adaptive, antibody-mediated defense transcripts. The directionality and functional patterns of DEGs were largely preserved, while accounting for shifts in cellular heterogeneity from pregnancy to postpartum, alongside the emergence of DEGs in cell-intrinsic regulatory pathways. Conclusions Our results reveal systemic transcriptomic differences from late pregnancy to postpartum, particularly a shift from innate to adaptive immune signatures as well as hematopoietic processes, cellular and metabolic pathways. These findings provide reference data for further understanding of peripartum adaptation and establish a molecular baseline for future investigations into perinatal biology and related disorders.

Objective: Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors. Method: A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I^2) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines. Results: Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior. Conclusions and Relevance: Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.

Mental health conditions, including perinatal suicidality, remains a significant health burden representing a leading cause of maternal mortality in the United States. Although the etiology of perinatal suicidal ideation (SI) is not well understood, DNA methylation may provide meaningful mechanistic insights and/or serve as clinical biomarkers during the peripartum period. Using data provided by the Swedish BASIC cohort, we performed a retrospective analysis of DNA methylation changes associated with perinatal SI at three perinatal timepoints (17- and 38-weeks gestation and 8 weeks post-partum) through a targeted and genome-wide approach. Targeted analysis of a priori genes revealed 1, 10, and 4 significantly differentially methylated probes at each timepoint and implicated genes associated with the hypothalamic-pituitary-adrenal axis. Genome-wide results identified 465, 2,880, and 510 differentially methylated probes and 7, 25, and 12 differentially methylated regions at each timepoint. Pathway analysis at 38-weeks gestation identified vitamin digestion and absorption as the top term differentially methylated in perinatal SI. Additionally, genes implicated in estrogen and oxytocin signaling were also significantly differentially methylated. Post-partum ideation-risk was successfully predicted using the top ten genome-wide differentially methylated probes at 17 weeks (AUC=66.9%), with prediction accuracy highest when DNA methylation and depression severity were combined (AUC=93.2%). Furthermore, the prediction accuracy for identifying novel SI in the post-partum period increased to 86.2% with 17-week biomarkers. Our results deliver novel insights regarding the role of DNA methylation and perinatal SI, with biomarkers providing both mechanistic insights and clinical usefulness, contributing to the field of perinatal psychiatry and epigenetics.