Brain development after intrauterine exposure to lithium: A magnetic resonance imaging study in school-age children.

OBJECTIVE: Lithium is often continued during pregnancy to reduce the risk of perinatal mood episodes for women with bipolar disorder. However, little is known about the effect of intrauterine lithium exposure on brain development. The aim of this study was to investigate brain structure in children after intrauterine exposure to lithium. METHODS: Participants were offspring, aged 8-14 years, of women with a diagnosis of bipolar spectrum disorder. In total, 63 children participated in the study: 30 with and 33 without intrauterine exposure to lithium. Global brain volume outcomes and white matter integrity were assessed using structural MRI and diffusion tensor imaging, respectively. Primary outcomes were total brain, cortical and subcortical gray matter, cortical white matter, lateral ventricles, cerebellum, hippocampus and amygdala volumes, cortical thickness, cortical surface area and global fractional anisotropy, and mean diffusivity. To assess how our data compared to the general population, global brain volumes were compared to data from the Generation R study (N = 3243). RESULTS: In our primary analyses, we found no statistically significant associations between intrauterine exposure to lithium and structural brain measures. There was a non-significant trend toward reduced subcortical gray matter volume. Compared to the general population, lithium-exposed children showed reduced subcortical gray and cortical white matter volumes. CONCLUSION: We found no differences in brain structure between lithium-exposed and non-lithium-exposed children aged 8-14 years following correction for multiple testing. While a rare population to study, future and likely multi-site studies with larger datasets are required to validate and extend these initial findings.

Neurodevelopment in school-aged children after intrauterine exposure to antipsychotics.

OBJECTIVE: Antipsychotics are increasingly prescribed in pregnancy, yet little is known about potential long-term developmental effects on children. In this study, we investigated the effect of prenatal antipsychotic exposure on neurodevelopmental functioning in school-aged children. METHODS: We performed a cross-sectional neurodevelopmental assessment of 91 children aged 6-14 years whose mothers had severe mental illness and were either exposed or unexposed to antipsychotic medication during pregnancy. Neurodevelopmental outcomes were assessed using validated neurodevelopmental assessment instruments to examine the child's IQ and global cognitive functioning, and the presence of any psychiatric disorders and/or learning problems in the child was assessed by parental report. RESULTS: No statistically significant associations were found between antipsychotic exposure during pregnancy and either adverse neurodevelopmental outcomes (IQ, neuropsychological function), likelihood of psychiatric diagnosis, or learning problems based on parental report. Analyses were likely limited in power to detect subtler differences in neurodevelopmental functioning because of small sample size and heterogeneity of the sample. CONCLUSIONS: In this exploratory cohort study, intrauterine exposure to antipsychotics was not associated with any adverse effect on IQ or neurodevelopmental functioning in a cohort of school-aged children (6-14 years).

Dialysis withdrawal and symptoms of anxiety and depression: a prospective cohort study.

BACKGROUND: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The. METHODS: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities. RESULTS: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities. DISCUSSION: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines.

The effect of prenatal lithium exposure on the neuropsychological development of the child.

OBJECTIVES: Lithium is an effective treatment for bipolar disorder, also during pregnancy to prevent the recurrence of episodes in the perinatal period. Little is known about the neuropsychological development of lithium-exposed offspring. The current study was designed to investigate neuropsychological functioning in lithium-exposed children with the aim to provide further knowledge on the long-term effects of lithium use during pregnancy. METHODS: Participants were offspring of women with a diagnosis of bipolar spectrum disorder, aged 6-14 years. In total, 99 children participated in the study, 56 were exposed to lithium in utero and 43 were not exposed to lithium. Neuropsychological tests were administered, including the Snijders-Oomen Nonverbal Intelligence Test and the NEPSY-II-NL assessment. Linear and negative binomial regression models were used to investigate the association between prenatal lithium exposure and neuropsychological functioning. In secondary analyses, the association between lithium blood level during pregnancy and neuropsychological functioning was assessed. Additionally, norm scores and percentiles for task outcomes were calculated. RESULTS: Lithium use during pregnancy was associated with the total number of mistakes made on the Auditory Attention task, but not statistically significant after full adjustment for potential confounding factors. No association between prenatal lithium exposure and IQ was found. Also, no relationship between lithium blood level during pregnancy and neuropsychological functioning was found after adjustment for potential confounders. Task outcomes in both groups were comparable to the general population. CONCLUSION: In this study, we found no evidence for significantly altered neuropsychological functioning of lithium-exposed children at the age of 6-14 years, when compared to non-lithium-exposed controls.

Complications and Healthcare Consumption of Pregnant Women with a Migrant Background: Could There be an Association with Psychological Distress?

OBJECTIVE: Previous studies reported less prenatal healthcare consumption and more perinatal complications in women with a migrant background. Hence, we investigated in a country with free healthcare access whether women with a migrant background differed with respect to pregnancy complications, healthcare consumption and in terms of associations with psychological distress in comparison to native Dutch. METHODS: We included 324 native Dutch and 303 women with a migrant background, who visited two hospitals in Amsterdam for antenatal care between 2014 and 2015. Participants completed the Edinburgh Postnatal Depression Scale, the Hospital Depression and Anxiety Scale, and sociodemographic questions. Complications and healthcare consumption during pregnancy were extracted from medical records. Regression analyses were used with adjustment for covariates. RESULTS: Except for gestational diabetes [adjusted OR = 3.09; 95% CI = (1.51, 6.32)], no differences were found between groups in perinatal complications [OR = 1.15; 95% CI = (0.80, 1.64)], nor in healthcare consumption [OR = 0.87; 95% CI = (0.63, 1.19)]. Women with a migrant background reported more depressive symptoms [Cohen's d = 0.25; 95% CI = (0.10, 0.41)], even after adjustment for socio-economic factors. Psychological distress was associated with more hospital admissions during pregnancy. When experiencing depressive symptoms, women with a migrant background had an increased risk to be admitted [OR = 1.11; 95% CI = (1.01, 1.21)]. CONCLUSIONS FOR PRACTICE: This cohort study found no differences in pregnancy-related complications, except for diabetes, nor different healthcare consumption, in women with a migrant background versus native Dutch, in a country with free health care access. However, women with a migrant background experienced more depressive symptoms, and when depressed their risk for hospital admission increased. Additional research is warranted to improve healthcare for this population.

The influence of perioperative interventions targeting psychological distress on clinical outcome after total knee arthroplasty.

Our aim was to assess the effect of perioperative interventions targeting psychological distress on clinical outcome after total knee arthroplasty (TKA). We searched studies on the effect of perioperative interventions focused on psychological distress used in conjunction with TKA on pain, function, and quality of life (QoL) on PubMed, Embase.com, PsycINFO/OVID, CENTRAL, the Cochrane Database of Systematic Reviews, Scopus, and Web of Science. We included 40 studies (22 RCTs, ten cohort studies, and eight quasi-experimental studies) with a total of 3846 patients. We graded the quality of evidence as low for pain and function and as moderate for QoL. Patients receiving music, education, cognitive behavioural therapy, guided imagery, pain coping skills training, Reiki, occupational therapy with self-monitoring, and biofeedback-assisted progressive muscles relaxing training had lower pain scores or declined opioid prescriptions after TKA. Pain coping skills training, audio recording-guided imagery scripts, video promoting self-confidence, psychological therapies by video, Reiki, music, occupational therapy with self-monitoring, education, and psychotherapy improved postoperative functional outcome. Education through an app improved QoL after TKA. The studies in our systematic review show that perioperative interventions targeting psychological distress for patients receiving TKA seem to have a positive effect on postoperative pain, function, and QoL. RCTs with strict methodological safeguards are still needed to determine if perioperative interventions focused on psychological distress should be used in conjunction with TKA. These studies should also assess which type of intervention will be most effective in improving patient-reported outcome measures and declining opioid prescriptions.

The Effectiveness of a Guided Internet-Based Tool for the Treatment of Depression and Anxiety in Pregnancy (MamaKits Online): Randomized Controlled Trial.

BACKGROUND: Pregnant women with symptoms of depression or anxiety often do not receive adequate treatment. In view of the high incidence of these symptoms in pregnancy and their impact on pregnancy outcomes, getting treatment is of the utmost importance. A guided internet self-help intervention may help to provide more women with appropriate treatment. OBJECTIVE: This study aimed to examine the effectiveness of a guided internet intervention (MamaKits online) for pregnant women with moderate to severe symptoms of anxiety or depression. Assessments took place before randomization (T0), post intervention (T1), at 36 weeks of pregnancy (T2), and 6 weeks postpartum (T3). We also explored effects on perinatal child outcomes 6 weeks postpartum. METHODS: This randomized controlled trial included pregnant women (<30 weeks) with depressive symptoms above threshold (ie, Center for Epidemiological Studies Depression scale [CES-D] >16) or anxiety above threshold (ie, Hospital Anxiety and Depression Scale-Anxiety subscale [HADS-A] >8) or both of them. Participants were recruited via general media and flyers in prenatal care waiting rooms or via obstetricians and midwives. After initial assessment, women were randomized to (1) MamaKits online in addition to treatment as usual or (2) treatment as usual (control condition). MamaKits online is a 5-week guided internet intervention based on problem solving treatment. Guidance was was provided by trained students pursuing a Master's in Psychology. Outcomes were based on a Web-based self-report. Women in the control condition were allowed to receive the intervention after the last assessment (6 weeks postpartum). RESULTS: Of the 159 included women, 79 were randomized to MamaKits online, 47% (79/37) of whom completed the intervention. Both groups showed a substantial decrease in affective symptoms on the CES-D, HADS-A, and Edinburgh Postnatal Depression Scale over time. In the intervention group, affective symptoms decreased more than that in the control group, but between-group effect sizes were small to medium (Cohen d at T3=0.45, 0.21, and 0.23 for the 3 questionnaires, respectively) and statistically not significant. Negative perinatal child outcomes did not differ between the 2 groups (χ21=0.1; P=.78). Completer analysis revealed no differences in outcome between the treatment completers and the control group. The trial was terminated early for reasons of futility based on the results of an interim analysis, which we performed because of inclusion problems. CONCLUSIONS: Our study did show a significant reduction in affective symptoms in both groups, but the differences in reduction of affective symptoms between the intervention and control groups were not significant. There were also no differences in perinatal child outcomes. Future research should examine for which women these interventions might be effective or if changes in the internet intervention might make the intervention more effective. TRIAL REGISTRATION: Netherlands Trial Register NL4162; https://tinyurl.com/sdckjek.

Anxiety Symptoms, Mortality, and Hospitalization in Patients Receiving Maintenance Dialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients treated at 10 dialysis centers in the Netherlands between 2012 and 2016. EXPOSURES: Time-varying symptoms of anxiety and depression using the Beck Anxiety Inventory and Beck Depression Inventory. OUTCOMES: All-cause mortality, 1-year hospitalization rate, and hospital length of stay. ANALYTICAL APPROACH: Cox proportional hazards and Poisson regression models adjusted for sociodemographic and clinical variables. Sensitivity analyses included multiple imputation of missing data and restriction to incident patients only. RESULTS: 687 patients were included, composed of 433 prevalent and 242 incident dialysis patients. Median follow-up time was 3.1 (IQR, 3.0-3.5) years, during which 172 deaths occurred. 22% of patients had anxiety symptoms and 42% had depressive symptoms. Anxiety symptoms were associated with all-cause mortality and 1-year hospitalization rate and length of stay in all multivariable models. Anxiety symptoms showed a clear dose-response relationship with mortality. LIMITATIONS: Depression and anxiety often coexist and share symptoms. The observational design of this study limits inferences about causal mechanisms between anxiety and clinical outcomes. CONCLUSIONS: Anxiety symptoms are independently associated with increased risk for mortality and 1-year hospitalization. Anxiety symptoms are a clinically relevant risk factor for morbidity and mortality in dialysis patients and warrant further research on effective treatment.

Dimensions of Depressive Symptoms and Their Association With Mortality, Hospitalization, and Quality of Life in Dialysis Patients: A Cohort Study.

OBJECTIVE: Unraveling specific dimensions of depressive symptoms may help to improve screening and treatment in dialysis patients. We aimed to identify the best-fitting factorial structure for the Beck Depression Inventory-II (BDI) in dialysis patients and to assess the relation of these structure dimensions with quality of life (QoL), hospitalization, and mortality. METHODS: This prospective study included chronic dialysis patients from 10 dialysis centers in five hospitals between 2012 and 2017. Dimensions of depressive symptoms within the BDI were analyzed using confirmatory factor analysis. To investigate the clinical impact of these dimensions, the associations between symptom dimensions and QoL, hospitalization rate, and mortality were investigated using logistic, Poisson, and Cox proportional hazard regression models. Multivariable regression models included demographic, social, and clinical variables. RESULTS: In total, 687 dialysis patients were included. The factor model that included a general and a somatic factor provided the best-fitting structure of the BDI-II. Only the somatic dimension scores were associated with all-cause mortality (hazard ratio of 1.7 [1.2-2.5], p < .007) in the multivariable model. All dimensions were associated with increased hospitalization rate and reduced QoL. CONCLUSIONS: The somatic dimension of the BDI-II in dialysis patients was associated with all-cause mortality, increased hospitalization rate, and reduced QoL. Other dimensions were associated with hospitalization rate and decreased QoL. These findings show that symptom dimensions of depression have differential association with adverse clinical outcomes. Future studies should take symptom dimensions into account when investigating depression-related pathways, screening, and treatment effects in dialysis patients.

Longitudinal Associations Between Inflammation and Depressive Symptoms in Chronic Dialysis Patients.

OBJECTIVE: Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients. METHODS: Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1ß, IL-6, IL-10, and tumor necrosis factor α) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses. RESULTS: A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (ß = 0.9, confidence interval [CI] = 0.4-1.4) and 6-month follow-up (ß = 1.1, CI = 0.3-2.0), and between IL-1ß and depressive symptoms at 6-month follow-up (ß = 1.3, CI = 0.8-1.8) and 12-month follow-up (ß = 1.2, CI = 0.4-1.9). Inflammation makers (HsCRP, IL-6, IL-1ß, IL-10, and tumor necrosis factor α) at baseline were not associated with depressive symptoms at follow-up and vice versa. CONCLUSIONS: We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.

The (cost) effectiveness of guided internet-based self-help CBT for dialysis patients with symptoms of depression: study protocol of a randomised controlled trial.

BACKGROUND: Only a minority of dialysis patients with depressive symptoms are diagnosed and receive treatment. Depressive symptoms are highly prevalent in this population and are associated with adverse clinical outcomes. Underlying factors for this undertreatment may be the lack of evidence for the safety and effectivity of antidepressant medication, the reluctance of patients to adhere to antidepressant medication, the lack of mental healthcare provision in somatic healthcare environments and end-stage renal disease (ESRD) related physical limitations that complicate face-to-face psychotherapy. Guided Internet-based self-help treatment has demonstrated to be effective for depressive symptoms in other chronic patient populations and may overcome these barriers. The aim of this study is to investigate the (cost) effectiveness of a guided Internet-based self-help intervention for symptoms of depression in dialysis patients. METHODS: This study is a cluster randomized controlled trial (RCT) that investigates the effectiveness of a 5-week Internet-based self-help Problem Solving Therapy (PST) for depressive symptoms in dialysis patients. Depressive symptoms will be measured using the Beck Depression Inventory - second edition (BDI-II), with a cut-off score of ≥10. We aim to include 206 dialysis patients with depressive symptoms who will be cluster randomized to the intervention or the Care as Usual (CAU) control group. Secondary outcomes will include anxiety symptoms, quality of life, economic costs and clinical outcomes, such as inflammatory factors and hair cortisol levels. Assessments will take place at baseline (T0), 2 weeks after intervention (T1) and 6 months (T2), 12 months (T3) and 18 months (T4) after intervention. The control group will be measured at the same time points. Analysis will be based on the intention-to-treat principle. Mixed models will be used to assess the changes within each condition between pre-treatment and post-treatment. DISCUSSION: If demonstrated to be (cost) effective, Internet-based PST will offer new possibilities to treat dialysis patients with depressive symptoms and to improve their quality of care. TRIAL REGISTRATION: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017).

Diabetes distress is associated with adverse pregnancy outcomes in women with gestational diabetes: a prospective cohort study.

BACKGROUND: Around 12% of pregnant women develop gestational diabetes mellitus (GDM), which is associated with increased health risks for both mother and child and pre- and postpartum depression. Little is known about the relationship of GDM with diabetes-specific emotional distress (diabetes distress). The aims of this study are to assess the prevalence of diabetes distress in GDM and its association with adverse pregnancy outcomes. METHODS: A prospective cohort study was carried out in an Amsterdam based teaching hospital with an ethnic diverse population. Women diagnosed with GDM completed a set of questionnaires at three time points. Questionnaires consisted of Problem Areas in Diabetes Scale 5 (PAID-5) for diabetes distress (T0-T1), Patient Health Questionnaire 9 (PHQ-9) for depressive symptoms (T0-T2), and questions to assess adverse pregnancy outcomes (T2). Adverse pregnancy outcomes (collected via self-report and if feasible from the medical records) were defined as hypertension, pre-eclampsia, caesarean section, severe perineal tearing, postpartum hemorrhage, postpartum depression, shoulder dystocia, neonatal hospitalization, macrosomia, jaundice, hypoglycemia and other (among which low heart rate, fever, hypoxia). Adverse pregnancy outcomes were dichotomized into none and 1 or more. Additional information was collected from the medical charts. Missing data were imputed via predictive mean matching and a multivariable logistic regression analysis was performed with diabetes distress, depressive symptoms, socioeconomic status, parity and ethnicity as predictors and age, HbA1c, and BMI as covariates. RESULTS: A total of 100 women were included, mean age 32.5 (4.1), mean BMI 26.7 (4.8), 71% were of non-Dutch ethnic background. Elevated diabetes distress (PAID score ≥ 8) was reported by 36% of the women. Multivariable logistic regression analyses revealed that both high diabetes distress (OR 4.70, p = .02) and parity (OR 0.21, p = .02) but not antepartum depressive symptoms were related to adverse pregnancy outcomes. CONCLUSIONS: Diabetes distress is likely in women with GDM and our findings suggest an association between both diabetes distress, parity and adverse pregnancy outcomes in women with GDM. This warrants replication and further research into the underlying mechanisms explaining the impact of diabetes distress in GDM and potential interventions to reduce distress.

Preventing post-traumatic stress disorder following childbirth and traumatic birth experiences: a systematic review.

INTRODUCTION: Between 9 and 44% of women experience giving birth as traumatic, and 3% of women develop a post-traumatic stress disorder following childbirth. Knowledge on risk factors is abundant, but studies on treatment are limited. This study aimed to present an overview of means to prevent traumatic birth experiences and childbirth-related post-traumatic stress disorder. MATERIAL AND METHODS: Major databases [Cochrane; Embase; PsycINFO; PubMed (Medline)] were searched using combinations of the key words and their synonyms. RESULTS: After screening titles and abstracts and reading 135 full-text articles, 13 studies were included. All evaluated secondary prevention, and none primary prevention. Interventions included debriefing, structured psychological interventions, expressive writing interventions, encouraging skin-to-skin contact with healthy newborns immediately postpartum and holding or seeing the newborn after stillbirth. The large heterogeneity of study characteristics precluded pooling of data. The writing interventions to express feelings appeared to be effective in prevention. A psychological intervention including elements of exposure and psycho-education seemed to lead to fewer post-traumatic stress disorder symptoms in women who delivered via emergency cesarean section. CONCLUSIONS: No research has been done on primary prevention of traumatic childbirth. Research on secondary prevention of traumatic childbirth and post-traumatic stress disorder following delivery provides insufficient evidence that the described interventions are effective in unselected groups of women. In certain subgroups, results are inhomogeneous.

The Stability of Type D Personality in Dialysis Patients.

PURPOSE: Type D personality has been identified as an independent risk factor for survival in cardiovascular disease (CVD) patients. As CVD is present in about 50% of dialysis patients, it is of clinical interest to assess the prevalence of type D personality, the association with depressive and anxiety symptoms, and stability of type D personality in dialysis patients. METHODS: Data was used from two consecutive measurements of the DIVERS study, a prospective cohort study among chronic dialysis patients in the Netherlands. Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and the Type D Scale-14 (DS14) were used to assess depressive and anxiety symptoms and type D personality, respectively. The association of type D personality was assessed with analysis of variance F test. Stability of type D personality, depressive, and anxiety symptoms were determined by calculating Cohen's κ, and by determining the positive agreement. RESULTS: In total, 349 patients were included of which 249 patients had two measurement points. The prevalence of type D personality was 21% and type D personality was associated with depressive and anxiety symptoms (P < 0.01). Over a 6-month period, Cohen's κ was 0.52, 0.56, and 0.61 for type D personality, depressive, and anxiety symptoms, respectively. Sixty-one, 73, and 73% had a stable type-D personality, depressive, and anxiety symptoms, respectively. CONCLUSION: The presence of type D personality varies over time in dialysis patients. Therefore, type D personality is possibly more a state instead of a trait phenomenon.

The role of tryptophan degradation in the association between inflammatory markers and depressive symptoms in chronic dialysis patients.

BACKGROUND: Among chronic dialysis patients, associations have been found between inflammatory markers and depressive symptoms. In this population, no studies have examined the mechanism linking the association between inflammatory markers and depressive symptoms. We examined whether the association between inflammatory markers and depressive symptoms is mediated by tryptophan (TRP) degradation along the kynurenine (KYN) pathway. METHODS: The data are part of an observational, prospective cohort study in five urban dialysis centres in The Netherlands. Depressive symptoms were determined with the Beck Depression Inventory. Peripheral blood was collected before dialysis to measure inflammatory markers [high sensitivity C-reactive protein (HsCRP), interleukin (IL)-1ß, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)], TRP, KYN and 3-hydroxykynurenine. The KYN/TRP ratio was used as a measure of TRP degradation. The association between inflammatory markers and depressive symptoms was determined using linear regression analysis and adjusted for the KYN/TRP ratio. RESULTS: In total, 490 chronic dialysis patients were included. HsCRP [ ß = 3.8; confidence interval (CI): 1.0-6.6], IL-6 ( ß = 9.1; CI: 4.0-14.1) and TNF-α ( ß = 1.3; CI: 0.9-1.7) were associated with the KYN/TRP ratio. We found significant associations between HsCRP ( ß = 0.8; CI: 0.3-1.3) and IL-6 ( ß = 1.2; CI: 0.3-2.2) levels and depressive symptoms. However, this association was not attenuated after adjustment for the KYN/TRP ratio. Also, no significant associations were found between the KYN/TRP ratio and depressive symptoms. CONCLUSION: The association between inflammatory markers and depressive symptoms in chronic dialysis patients was not mediated by TRP degradation along the KYN pathway.

Pregnancy-specific anxiety and its association with background characteristics and health-related behaviors in a low-risk population.

BACKGROUND: Pregnancy-specific anxiety is an important risk factor for adverse pregnancy outcomes. It is therefore needed to gain insight in which women are at risk for elevated levels (> 85th percentile) of pregnancy-specific anxiety. Additionally, given that unhealthy behaviour has been suggested as a possible pathway linking pregnancy-specific anxiety to adverse pregnancy outcomes, it is important to examine whether higher levels of pregnancy-specific anxiety are associated with negative health-related behaviours (smoking, alcohol use and too much weight gain). METHODS: Using a study sample of 4541 low-risk pregnant women who filled in the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R), we first examined which socio-demographic, pregnancy-related and psychological background characteristics were significantly associated with a PRAQ-R score above the 85th percentile. Secondly, we examined the association between pregnancy-specific anxiety and self-reported health-related behaviours (smoking, alcohol use and too much weight gain) while controlling for significant background characteristics. For both research questions, backward regression analysis was applied. RESULTS: Results showed that nulliparity (OR=2.33, 95% confidence interval (CI)=1.97-2.77), anxious or depressed mood (OR=3.29, 95% CI=2.74-3.94) and non-Dutch ethnicity, especially Turkish (OR=3.47, 95% CI=2.16-5.59) or Moroccan (OR=2.97, 95% CI=1.84-4.81), were most strongly associated with elevated pregnancy-specific anxiety levels. Women with higher pregnancy-specific anxiety levels were more likely to gain too much weight during pregnancy (odds ratio (OR) linear term=1.49, 95% CI=1.21-1.83), while both very low and high levels of pregnancy-specific anxiety were associated with smoking (OR linear term=0.13, 95% CI=0.04-0.45, OR quadratic term=1.81, 95% CI=1.32-2.47). No association with alcohol use was found. CONCLUSIONS: In conclusion, our results show nulliparity, anxious or depressed mood and non-Dutch ethnicity as three major vulnerability factors for elevated levels of pregnancy-specific anxiety. Furthermore, our results show an association between pregnancy-specific anxiety and negative health-related behaviours, which is worth examining in future studies.

Use of antidepressants during pregnancy in the Netherlands: observational study into postpartum interventions.

BACKGROUND: Psychiatric disorders and use of selective antidepressants during pregnancy can have negative effects on mother and infant postpartum. This study aimed to provide evidence-based recommendations on observation of antidepressant-exposed mother-infant dyads. METHODS: In this observational study, mother-infant dyads were observed for possible consequences of either the maternal psychiatric disorder or fetal exposure to selective antidepressants during pregnancy. These possible complications can lead to medical interventions, including 1. adjustment of antidepressants 2. admission to the psychiatric department 3. additional investigations due to indistinctness about the origin of neonatal symptoms 4. treatment of poor neonatal adaptation and 5. consultation of an external organization for additional care. The type, number and time to medical interventions were analyzed. RESULTS: In 61% of the 324 included mother-infant dyads one or more intrventions were performed. Adjustment of antidepressants and treatment of poor neonatal adaptation were most prevalent. In 75% of dyads the final intervention was performed within 48 h. CONCLUSIONS: The high prevalence and type of medical interventions requires professional observation of all mother-infant dyads exposed to selective antidepressants. In the absence of specialized home care, hospital admission is indicated whereby an observational period of 48 h seems sufficient for most dyads.

The effect of an elective cesarean section on maternal request on peripartum anxiety and depression in women with childbirth fear: a systematic review.

BACKGROUND: Obstetricians are often reluctant to grant requests for an elective cesarean section (ECS) due to childbirth fear. To date, it is unknown if an ECS on request improves mental well-being in the mother in the peripartum period and if possible beneficial effects on anxiety and depression could outweigh the increased risk of complications associated with a surgical delivery. A systematic review was conducted to explore the effect of ECS on request on peripartum anxiety and depression. METHODS: We searched on PubMed, PsychoInfo and Embase. Studies were included with primary data on anxiety and/or depression postpartum in women with childbirth fear who had requested an ECS. After full-text evaluation of 65 papers and quality analysis of four papers, three papers were included. Of one paper additional and yet unpublished data were provided. Studies varied in outcome measures, hence no meta-analysis was performed. RESULTS: Women who requested an ECS had higher antepartum depression and anxiety levels but no different postpartum depression levels than women who delivered vaginally. One study of good quality examined the effect of vaginal delivery in women preferring ECS: These women had significantly higher symptom levels of post-traumatic stress disorder (PTSD) and depression than women with normal vaginal delivery. CONCLUSIONS: The prospect of an ECS does not lower antepartum anxiety and/or depression levels in women requesting an ECS. If women resolutely persist in wishing an ECS despite adequate counselling and/or psychiatric treatment, the risk of developing depressive and PTSD symptoms in case of vaginal delivery should be taken into account, and an ECS may be considered as a valid alternative.

Increased postpartum haemorrhage, the possible relation with serotonergic and other psychopharmacological drugs: a matched cohort study.

BACKGROUND: Postpartum haemorrhage is a major obstetric risk worldwide. Therefore risk factors need to be investigated to control for this serious complication. A recent systematic review and meta-analysis revealed that the use of both serotonergic and non-serotonergic antidepressants in pregnancy are associated with a higher risk of postpartum haemorrhage. However, use of antidepressants in pregnancy is often necessary because untreated depression in pregnancy is associated with adverse maternal and neonatal outcome, such as postpartum depression, preterm birth and dysmaturity. Therefore it is of utmost importance to unravel the possible association between postpartum haemorrhage and the use of serotonergic and other psychopharmacological medication during pregnancy. METHODS: We performed a matched cohort observational study consecutively including all pregnant women using serotonergic medication (n = 578) or other psychopharmacological medication (n = 50) visiting two teaching hospitals in Amsterdam between 2010 and 2014. The incidence of postpartum haemorrhage in women using serotonergic medication or other psychopharmacological medication was compared with the incidence of postpartum haemorrhage in 641,364 pregnant women not using psychiatric medication selected from the database of the Netherlands Perinatal Registry foundation (Perined). Matching took place 1:5 for nine factors, i.e., parity, maternal age, ethnicity, socioeconomic status, macrosomia, gestational duration, history of postpartum haemorrhage, labour induction and hypertensive disorder. RESULTS: Postpartum haemorrhage occurred in 9.7% of the women using serotonergic medication. In the matched controls this was 6.6% (p = 0.01). The adjusted odds ratio (aOR) before matching was 1.6 (95% CI 1.2-2.1) and after matching 1.5 (95% CI 1.1-2.1). Among the women using other psychopharmacological medication, the incidence of postpartum haemorrhage before matching was 12.0% versus 6.1% (p = 0.08) with OR 2.1 (95% CI 0.9-4.9), and after matching 12.1% versus 4.4% (p = 0.03) with aOR of 3.3 (95% CI 1.1-9.8). CONCLUSIONS: Pregnant women using serotonergic medication have an increased risk of postpartum haemorrhage, but this high risk is also seen in pregnant women using other psychopharmacological medication. We suggest that this higher risk of postpartum haemorrhage could not only be explained by serotonin, but also by other mechanisms. An additional explanation could be the underlying psychiatric disorder.

Serotonin and poor neonatal adaptation after antidepressant exposure in utero.

OBJECTIVE: Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non-specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA. METHODS: In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared. RESULTS: The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p≤0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship. CONCLUSIONS: A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role.