All-Cause Mortality in Women With Severe Postpartum Psychiatric Disorders

The postpartum period is associated with a high risk of psychiatric episodes. The authors studied mortality in women with first-onset severe psychiatric disorders following childbirth and compared their mortality rates with those in women from the background population including other female psychiatric patients (mothers and childless women)

Prescription patterns of benzodiazepine and benzodiazepine-related drugs in the peripartum period: A population-based study

Using prescription drugs during pregnancy is challenging and approached with caution. In this study, we present population-based information on prescription patterns of benzodiazepines and benzodiazepine-related drugs in the peripartum period. A population-based study of 1,154,817 pregnancies between 1997 and 2015 in Denmark, of which 205,406 (17.8%) pregnancies in women with a psychiatric history. Prescription drugs starting with Anatomical Therapeutic Chemical codes N05BA, N05CD, and N05CF from 12 months before pregnancy to 12 months following pregnancy were identified. We used generalised estimating equations to estimate the adjusted 5 year risk difference in the proportion of women redeeming benzodiazepines from 1 year to 5 years after. Logistic regression was used to analyze the association between characteristics and discontinuation of benzodiazepines during pregnancy. The prevalence of benzodiazepine prescriptions was 1.9% before pregnancy, 0.6% during pregnancy, and 1.3% after pregnancy. In women with a psychiatric history, the prevalence was 5–6 times higher. A significant decrease in prescriptions to women with a psychiatric history was observed, which was less profound among women with no psychiatric history. Approximately 90% of women discontinue benzodiazepines during pregnancy, with a higher percentage of women discontinuing from 1997 to 2015. The observed decrease is likely explained by changing treatment guidelines

Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway

Importance: Approximately half of women discontinue antidepressant use during pregnancy, yet this could lead to relapse in the postpartum period. Objective: To investigate the associations between longitudinal antidepressant fill trajectories during pregnancy and postpartum psychiatric outcomes. Design and setting, and participants: Cohort study using nationwide registers in Denmark and Norway. Participants included 41,475 liveborn singleton pregnancies in Denmark (1997–2016) and 16,459 in Norway (2009–2018) for women who filled at least one antidepressant prescription within six months before pregnancy. Exposures: Antidepressant prescription fills were obtained from the prescription registers. Antidepressant treatment during pregnancy was modeled using longitudinal k-means. Main outcomes and measures: Initiating psycholeptics, psychiatric emergency, or records of self-harm within one year postpartum. Hazard ratio (HR) of each psychiatric outcome was estimated using Cox regression models. Inverse probability of treatment weighting was used to control for confounding. Country-specific HRs were pooled using random-effects meta-analytic models. Results: Of 57,934 pregnancies (mean maternal age range across countries: 30.7– ?? years), [XL1] our trajectories were identified: early discontinuers (about 30% of the population), late discontinuers (previously stable users) (20–25%), late discontinuers (short-term users) (15–20%), and continuers (25–30%). Early discontinuers and late discontinuers (short-term users) had a lower probability of initiating psycholeptics and having postpartum psychiatric emergencies compared to continuers. We found a moderately increased probability of initiation of psycholeptics among late discontinuers (previously stable users) compared to continuers (HR=1.13, 95% CI: 1.03–1.24). This increase in late discontinuers (previously stable users) was more pronounced among women with previous affective disorders (HR=1.28, 95% CI: 1.12–1.47). No association between antidepressant fill trajectories and postpartum self-harm risk was found. Conclusions and Relevance: Using pooled data from Denmark and Norway, we found a moderately elevated probability of initiation of psycholeptics in late discontinuers (previously stable users) compared to continuers. [XL1]Mean (SD) age of the study population was 30.7(5.3) year

Antidepressant discontinuation before or during pregnancy and risk of psychiatric emergency in Denmark:A population-based propensity score-matched cohort study

Background AWUom: Pelneapsreecsocnrfiibremdthaantatildlheepardeisnsgalenvteslsfaarceerethperedseilnetmedmcoarroefcwtlhy:ether or not to continue their treatment during pregnancy. Currently, limited evidence is available on the efficacy of continuing versus discontinuing antidepressant treatment during pregnancy to aid their decision. We aimed to estimate whether antidepressant discontinuation before or during pregnancy was associated with an increased risk of psychiatric emergency (ascertained by psychiatric admission or emergency room visit), a proxy measure of severe exacerbation of symptoms/mental health crisis. Methods and findings We carried out a propensity score-matched cohort study of women who gave birth to liveborn singletons between January 1, 1997 and June 30, 2016 in Denmark and who redeemed an antidepressant prescription in the 90 days before the pregnancy, identified by Anatomical Therapeutic Chemical (ATC) code N06A. We constructed 2 matched cohorts, matching each woman who discontinued antidepressants before pregnancy (N = 2,669) or during pregnancy (N = 5,467) to one who continued antidepressants based on propensity scores. Maternal characteristics and variables related to disease severity were used to generate the propensity scores in logistic regression models. We estimated hazard ratios (HRs) of psychiatric emergency in the perinatal period (pregnancy and 6 months postpartum) using stratified Cox regression. Psychiatric emergencies were observed in 76 women who discontinued antidepressants before pregnancy and 91 women who continued. There was no evidence of higher risk of psychiatric emergency among women who discontinued antidepressants before pregnancy (cumulative incidence: 2.9%, 95% confidence interval [CI]: 2.3% to 3.6% for discontinuation versus 3.4%, 95% CI: 2.8% to 4.2% for continuation; HR = 0.84, 95% CI: 0.61 to 1.16, p = 0.298). Overall, 202 women who discontinued antidepressants during pregnancy and 156 who continued had psychiatric emergencies (cumulative incidence: 5.0%, 95% CI: 4.2% to 5.9% versus 3.7%, 95% CI: 3.1% to 4.5%). Antidepressant discontinuation during pregnancy was associated with increased risk of psychiatric emergency (HR = 1.25, 95% CI: 1.00 to 1.55, p = 0.048). Study limitations include lack of information on indications for antidepressant treatment and reasons for discontinuing antidepressants. Conclusions In this study, we found that discontinuing antidepressant medication during pregnancy (but not before) is associated with an apparent increased risk of psychiatric emergency compared to continuing treatment throughout pregnancy.</p

Perinatal mental health: how nordic data sources have contributed to existing evidence and future avenues to explore

Purpose Perinatal mental health disorders affect a significant number of women with debilitating and potentially life-threatening consequences. Researchers in Nordic countries have access to high quality, population-based data sources and the possibility to link data, and are thus uniquely positioned to fill current evidence gaps. We aimed to review how Nordic studies have contributed to existing evidence on perinatal mental health. Methods We summarized examples of published evidence on perinatal mental health derived from large population-based longitudinal and register-based data from Denmark, Finland, Iceland, Norway and Sweden. Results Nordic datasets, such as the Danish National Birth Cohort, the FinnBrain Birth Cohort Study, the Icelandic SAGA cohort, the Norwegian MoBa and ABC studies, as well as the Swedish BASIC and Mom2B studies facilitate the study of prevalence of perinatal mental disorders, and further provide opportunity to prospectively test etiological hypotheses, yielding comprehensive suggestions about the underlying causal mechanisms. The large sample size, extensive follow-up, multiple measurement points, large geographic coverage, biological sampling and the possibility to link data to national registries renders them unique. The use of novel approaches, such as the digital phenotyping data in the novel application-based Mom2B cohort recording even voice qualities and digital phenotyping, or the Danish study design paralleling a natural experiment are considered strengths of such research. Conclusions Nordic data sources have contributed substantially to the existing evidence, and can guide future work focused on the study of background, genetic and environmental factors to ultimately define vulnerable groups at risk for psychiatric disorders following childbirth

Genetic liability to bipolar disorder and onset of postpartum mental disorders

Introduction Childbirth triggers a broad range of diagnoses jointly defined as postpartum mental disorders (PMDs),1 but immediate onset within the first 30 days after delivery has been linked to an increased probability of converting to bipolar disorder (BD) diagnoses later.2 Building on these specific observations, we hypothesised that PMDs occurring within the first month after delivery have a higher bipolar genetic liability, measured as polygenic score (PGS), compared with those diagnosed 31–365 days post partum, and further speculated this association is specific to the PGS for BD compared with genetic liability to other severe mental disorders, such as major depressive disorder (MDD) and schizophrenia (SCZ). Methods We conducted a cohort study linking Danish national registers to the Integrative Psychiatric Research (iPSYCH) study,3 which included 93 608 individuals diagnosed with a major mental illness and a random sample of 50 615 subjects from the entire Danish population born during 1981–2005 (the subcohort). DNA was extracted from the blood and genotyped. We identified 2974 women with genetic data who had PMD, defined as any hospital admission or outpatient contact for mental illness (International Classification of Diseases, 10th Revision (ICD-10) codes F00–F99, excluding F10–F19 and F70–F79) 0–12 months after delivery.4 We similarly defined previous psychiatric history as hospital contact for mental illness at any time before the delivery. DNA was extracted from the blood and genotyped. We derived LDpred2-auto5 PGS from the latest genome-wide association study (GWAS) by Psychiatric Genomics Consortium. We also calculated PGS using the iPSYCH individual data. We then combined the PGS obtained from summary statistics and individual-level data through a linear combination.6The sample size for the discovery GWAS without the iPSYCH sample can be found elsewhere.6 We converted PGSs into z-scores using PGS distributions in women from the subcohort born during 1981–1997. We used logistic regression to estimate the odds ratios (ORs) of PMD that occurred within 30 days vs 31–365 days after delivery by the BD PGSs in the form of both per SD increase (continuous variable) and tertiles and adjusted for all the covariates listed in table 1 and the first 10 principal components to account for population stratification.7 To show the degree of specificity for genetic liability to BD, we also calculated PGSs for MDD and SZ as negative controls, as we did not expect to find an association between these estimates and the specific early onset of PMD. Given PMD among women without a psychiatric history prior to childbirth may be a distinct psychiatric phenotype, we, for additional comparative purposes, examined the associations in women with and without previous psychiatric history separately. Since we specified the hypotheses a priori, no corrections for multiple comparisons are needed.

Maternal and infant outcomes associated with lithium use in pregnancy

Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27·5%) versus reference group (14·3%) (Pooled aOR1·62; 95% CI: 1·12–2·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7·4% versus 4·3%; pooled aOR 1·71, 95% CI: 1·07–2·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2·1% versus 1·6%; pooled aOR 1·54, 95% CI: 0·64–3·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse

Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders

It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls. Data on genetics and depressive disorders were retrieved from neonatal biobanks and the Psychiatric Central Research Register. PGSs were calculated from both individual-level genetic data and meta-analysis summary statistics from the Psychiatric Genomics Consortium. Conditional logistic regression was used to calculate the odds ratio (OR), accounting for the selection-related reproductive behavior. After adjustment for covariates, higher PGSs for severe mental disorders were associated with increased ORs of both PPD and MDD. Compared with MDD cases, MDD PGS and attention-deficit/hyperactivity disorder PGS were marginally but not statistically higher for PPD cases, with the OR of PPD versus MDD being 1.12 (95% CI: 0 .97–1.29) and 1.11 (0.97–1.27) per-standard deviation increase, respectively. The ORs of PPD versus MDD did not statistically differ by PGSs of bipolar disorder, schizophrenia, or autism spectrum disorder. Our findings suggest that relying on PGS data, there was no clear evidence of distinct genetic make-up of women with depression occurring during or outside postpartum, after taking the selection-related reproductive behavior into account

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Background The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods. Methods Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19–40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes. Findings Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe. Interpretation Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression