Personality and the HPA-axis in Association with Postpartum Depression

Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder

Personality and the HPA-axis in Association with Postpartum Depression

Postpartum depression is a psychiatric disorder affecting a substantial proportion of newly delivered women, and remains a significant cause of childbirth-related morbidity. The aim of the present thesis was to examine psychological, endocrine and genetic aspects of postpartum depression in a large, population-based sample of women in Uppsala, Sweden. All included studies were undertaken as parts of the BASIC-project, a longitudinal study on psychological wellbeing during pregnancy and the postpartum period. Study participants were screened for depressive symptoms in pregnancy week 17 and 32 as well as at six weeks and six months postpartum, mainly by use of the Swedish version of the Edinburgh Postnatal Depression Scale (EPDS). Furthermore, personality was assessed with the Swedish universities Scale of Personality (SSP) in pregnancy week 32. Evening cortisol levels in saliva were measured in pregnancy week 36 and at six weeks postpartum. Blood samples were obtained to measure corticotropin-releasing hormone levels (CRH) and to perform genetic analyses. The results of this thesis demonstrate that neuroticism is a strong and independent predictive factor of depressive symptoms at six weeks and six months postpartum, and has a significant mediatory role in the association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1) and postpartum depression. Furthermore, women with postpartum depressive symptoms present with a dysregulated hypothalamic-pituitary-adrenal axis activity in terms of elevated cortisol levels postpartum, as well as elevated CRH levels in mid-gestation. In conclusion, this thesis develops current knowledge on several attributes of postpartum depression. Further studies are required to replicate and expand on these results, which would further contribute to early identification of women at risk of postpartum depression and adoption of proper interventions that may moderate the short- and long-term consequences of the disorder

Mode of conception in relation to nausea and vomiting of pregnancy : a nested matched cohort study in Sweden

Nausea and vomiting of pregnancy (NVP) is a common condition reported however inconclusively among pregnancies after assisted conception. The study objective was thus to explore whether NVP is associated to mode of conception or other in vitro fertilization (IVF)-related variables. This nested matched cohort study, originating from the BASIC-project, was conducted at the Uppsala University Hospital in Sweden between 2010 and 2016. IVF pregnancies (n=210) and age and parity-matched women with spontaneous pregnancies (n=420) comprised the study sample. The study outcome was self-reported NVP at gestational week 17. IVF treatment and pregnancy data were obtained after scrutinization of the medical records. NVP with or without medications was not associated with mode of conception (chi-square test, p=0.889), even after adjusting for potential confounders. In a subgroup analysis among IVF pregnancies, NVP without medication was more frequently seen in the group who received cleavage stage embryos vs blastocysts (chi-square test, p=0.019), exhibiting a marginally significant but strongly increased effect even after adjustment [crude RRR 3.82 (95% CI 1.23-11.92) and adjusted RRR 3.42 (95% CI 0.96-12.11)]. No difference in the rate of NVP with or without medication between women that underwent fresh and frozen/thawed embryo transfers as well as IVF or ICSI was observed. Conception through IVF is not associated with NVP. Transfer of a blastocyst may decrease the risk of developing NVP and further, large-scale prospective studies are required to validate this finding

Feeling better? – Identification, interventions, and remission among women with early postpartum depressive symptoms in Sweden: a nested cohort study

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 < 0.001). Conclusions Despite screening guidelines, many women with depressive symptoms had no documentation of screening or interventions by the healthcare system. Furthermore, a significant proportion did not achieve remission despite interventions. Being identified by CHS was associated with the largest reduction of symptoms. Research is needed to understand gaps in the healthcare processes, to better identify peripartum depression

Women with prolonged nausea in pregnancy have increased risk for depressive symptoms postpartum

The aim of this population-based, longitudinal study was to assess the association between nausea and vomiting in pregnancy (NVP) and perinatal depressive symptoms. Pregnant women (N = 4239) undergoing routine ultrasound at gestational week (GW) 17 self-reported on NVP and were divided into those without nausea (G0), early (&lt;= 17 GW) nausea without medication (G1), early nausea with medication (G2), and prolonged (&gt;17 GW) nausea (G3). The Edinburgh Postnatal Depression Scale at GW 17 and 32 (cut-off &gt;= 13) and at six weeks postpartum (cut-off &gt;= 12) was used to assess depressive symptoms. Main outcome measures were depressive symptoms at GW 32 and at six weeks postpartum. NVP was experienced by 80.7%. The unadjusted logistic regression showed a positive association between all three nausea groups and depressive symptoms at all time-points. After adjustment, significant associations with postpartum depressive symptoms remained for G3, compared to G0 (aOR = 1.66; 95% CI 1.1-2.52). After excluding women with history of depression, only the G3 group was at higher odds for postpartum depressive symptoms (aOR = 2.26; 95% CI 1.04-4.92). In conclusion, women with prolonged nausea have increased risk of depressive symptoms at six weeks postpartum, regardless of history of depression

Predicting women with depressive symptoms postpartum with machine learning methods

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

Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial

STUDY QUESTION Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate? SUMMARY ANSWER Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births. WHAT IS KNOWN ALREADY Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited. STUDY DESIGN, SIZE, DURATION This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration. LIMITATIONS, REASONS FOR CAUTION The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos. WIDER IMPLICATIONS OF THE FINDINGS Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmo, Sweden. The authors have no personal conflicting interests to declare. DATE OF FIRST PATIENT'S ENROLMENT 18 February 2013

Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms

Background The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus- Pituitary-Adrenal axis response having been implicated in its pathophysiology. Methods 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. Results Women with postpartum EPDS score &gt;= 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). Conclusions Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression

Prenatal and Postpartum Evening Salivary Cortisol Levels in Association with Peripartum Depressive Symptoms

Background The biology of peripartum depression remains unclear, with altered stress and the Hypothalamus- Pituitary-Adrenal axis response having been implicated in its pathophysiology. Methods 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. Results Women with postpartum EPDS score &gt;= 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). Conclusions Women with depressive symptoms postpartum had higher postpartum cortisol levels, indicating an altered response of the HPA-axis in postpartum depression

Severe obstetric lacerations associated with postpartum depression among women with low resilience : a Swedish birth cohort study

OBJECTIVE: Women's levels of resilience and attitudes towards perineal lacerations vary greatly. Some women see them as part of the birthing process, while others react with anger, depressed mood or even self-harm thoughts. A previous study has reported increased risk of postpartum depressive (PPD) symptoms in women with severe perineal lacerations. The aim of this study was to assess the association between severe obstetric perineal lacerations and PPD. A secondary objective was to assess this association among women with low resilience. DESIGN: Nested cohort study. SETTING: Uppsala, Sweden. SAMPLE: Vaginally delivered women with singleton pregnancies (n = 2,990). METHODS: The main exposure was obstetric perineal lacerations. Resilience was assessed in gestational week 32 using the Swedish version of the Sense of Coherence Scale (SOC-29). A digital acyclic graph (DAG) was used to identify possible confounders and mediators. Logistic regression was used to estimate odds ratios and 95% confidence intervals. A sub-analysis was run after excluding women with normal or high resilience. MAIN OUTCOME MEASURES: Postpartum depression, assessed with the Depression Self-Reporting Scale (DSRS), completed at six weeks postpartum. RESULTS: There was no significant association between severe obstetric perineal lacerations and PPD at six weeks postpartum. However, a significant association was found between severe lacerations and PPD in women with low resilience (OR =4.8 95% CI = 1.2-20), persisting even after adjusting for confounding factors. CONCLUSION: Health care professionals might need to identify women with low resilience, as they are at increased risk for PPD after a severe perineal laceration