Judith L. Meijer

Associations of life events during pregnancy with longitudinal change in symptoms of antenatal anxiety and depression.

OBJECTIVE to investigate the association of life events during pregnancy with change in antenatal anxiety and depression symptoms. We distinguished pregnancy related and non-pregnancy related events and assessed specificity of these associations for depressive or anxious symptoms. In addition, we investigated whether the associations were affected by personality or childhood adversities. DESIGN observational prospective cohort study SETTING primary and secondary obstetric care centres in the Netherlands PARTICIPANTS 1603 women during their first trimester of pregnancy between May 2010 and May 2012 MEASUREMENTS AND FINDINGS: we performed linear regression analyses to test the associations of pregnancy related, non-pregnancy related life events, childhood adversities and the personality traits neuroticism and extraversion with the change in symptoms of anxiety (State Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) from week 12 to week 36. Life events during pregnancy were associated with increasing antenatal symptoms of anxiety and depression. Effect sizes associated with the highest numbers of events observed ranged from 0.59 to 1.31. Pregnancy related events were specifically associated with increasing symptoms of anxiety (p=0.009), whereas non-pregnancy related events were merely associated with an increase in symptoms of depression (p<0.001). Neither personality traits nor childhood trauma influenced the associations under study. KEY CONCLUSIONS the most important finding is that pregnancy related life events during pregnancy increase levels of antenatal anxiety, whereas depression levels increase when women experience life events that are unrelated to pregnancy. Furthermore, non-pregnancy related events show stronger associations with increases in symptoms of anxiety or depression compared to pregnancy related events. IMPLICATIONS FOR PRACTICE our findings may help midwives to tailor psychosocial care to the specific risks of the pregnant woman which may eventually have a positive impact on the health of mother and child.

Predictive accuracy of Edinburgh Postnatal Depression Scale assessment during pregnancy for the risk of developing postpartum depressive symptoms: a prospective cohort study

To investigate whether the 10‐item Edinburgh Postnatal Depression Scale (EPDS) administered antenatally is accurate in predicting postpartum depressive symptoms, and whether a two‐item EPDS has similar predictive accuracy.

PRegnancy Outcomes after a Maternity Intervention for Stressful EmotionS (PROMISES): Study protocol for a randomised controlled trial

BackgroundThere is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the childs development as well as behavioural and emotional problems. In addition, we aim to study its effects on the childs development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.Methods/designWe will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women we will be able to demonstrate effect sizes of 0.35 or over on the total problems scale of the child behavioural checklist 1.5-5 with alpha 5% and power (1-beta) 80%.Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the child behaviour checklist 1.5 - 5 years.Secondary outcomes will be mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales, maternal anxiety and depression during pregnancy and postpartum, and neonatal outcomes such as birth weight, gestational age and Apgar score, health care consumption and general health status (economic evaluation).Trial RegistrationNetherlands Trial Register (NTR): NTR2242

Stressful events and continued smoking and continued alcohol consumption during mid-pregnancy

Aim to examine whether the severity of different categories of stressful events is associated with continued smoking and alcohol consumption during mid-pregnancy. Also, we explored the explanation of these associations by anxiety and depressive symptoms during pregnancy. Finally, we studied whether the severity of stressful events was associated with the amount of cigarettes and alcohol used by continued users. Method we conducted a cross-sectional analysis using data from a population-based prospective cohort study. Pregnant women were recruited via midwifery practices throughout The Netherlands. We analyzed women who continued smoking (n = 113) or quit (n = 290), and women who continued alcohol consumption (n = 124) or quit (n = 1403) during pregnancy. Smoking, alcohol consumption, and perceived severity of stressful events were measured at 19 weeks of gestation. The State Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale were filled out at 14 weeks of gestation. Odds ratios were calculated as association measures and indicated the relative increase for the odds of continuation of smoking and alcohol consumption for the maximum severity score compared to the minimum score. Findings severity of the following stressful event categories was associated with continued alcohol consumption: ‘conflict with loved ones’ (OR = 10.4, p<0.01), ‘crime related’ (OR = 35.7, p<0.05), ‘pregnancy-specific’ (OR = 13.4, p<0.05), and the total including all events (OR = 17.2, p<0.05). Adjustment for potential confounders (age, parity and educational level) did not notably change the estimates. There was no association of anxiety and depressive symptoms with continued smoking or alcohol consumption. No associations emerged for continued smoking and severity of stressful events. The amount of cigarettes and alcohol consumption among continued users was not associated with severity of stressful events. Conclusions Our findings may be relevant for health care providers, in particular midwives and general practitioners. The impact of stressful events may be considered when advising pregnant women on smoking and alcohol consumption.

New advances in DPYD genotype and risk of severe toxicity under capecitabine

Background Deficiency in dihydropyrimidine dehydrogenase (DPD) enzyme is the main cause of severe and lethal fluoropyrimidine-related toxicity. Various approaches have been developed for DPD-deficiency screening, including DPYD genotyping and phenotyping. The goal of this prospective observational study was to perform exhaustive exome DPYD sequencing and to examine relationships between DPYD variants and toxicity in advanced breast cancer patients receiving capecitabine. Methods Two-hundred forty-three patients were analysed (88.5% capecitabine monotherapy). Grade 3 and grade 4 capecitabine-related digestive and/or neurologic and/or hemato-toxicities were observed in 10.3% and 2.1% of patients, respectively. DPYD exome, along with flanking intronic regions 3’UTR and 5’UTR, were sequenced on MiSeq Illumina. DPD phenotype was assessed by pre-treatment plasma uracil (U) and dihydrouracil (UH2) measurement. Results Among the 48 SNPs identified, 19 were located in coding regions, including 3 novel variations, each observed in a single patient (among which, F100L and A26T, both pathogenic in silico). Combined analysis of deleterious variants *2A, I560S (*13) and D949V showed significant association with grade 3–4 toxicity (sensitivity 16.7%, positive predictive value (PPV) 71.4%, relative risk (RR) 6.7, p<0.001) but not with grade 4 toxicity. Considering additional deleterious coding variants D342G, S492L, R592W and F100L increased the sensitivity to 26.7% for grade 3–4 toxicity (PPV 72.7%, RR 7.6, p<0.001), and was significantly associated with grade 4 toxicity (sensitivity 60%, PPV 27.3%, RR 31.4, p = 0.001), suggesting the clinical relevance of extended targeted DPYD genotyping. As compared to extended genotype, combining genotyping (7 variants) and phenotyping (U>16 ng/ml) did not substantially increase the sensitivity, while impairing PPV and RR. Conclusions Exploring an extended set of deleterious DPYD variants improves the performance of DPYD genotyping for predicting both grade 3–4 and grade 4 toxicities (digestive and/or neurologic and/or hematotoxicities) related to capecitabine, as compared to conventional genotyping restricted to consensual variants *2A, *13 and D949V.

Psychological treatment of antenatal depression and anxiety : Effects on obstetric outcomes

Objective/Background It has been estimated that around 10-20% of all pregnant women suffer from antenatal depressive or anxiety symptoms. These symptoms have been associated with multiple adverse child outcomes including obstetric problems, e.g. preterm delivery, Apgar score and low birth weight. Therefore, considerable health gains may be achieved if depression and anxiety during the perinatal period are adequately treated. Nevertheless, to date, no previous trials have published on the effects of Cognitive Behavioral Therapy (CBT) during pregnancy on child outcomes. Methods The ´Pregnancy Outcomes After a Maternity Intervention for Stressful Emotions´ (PROMISES) trial is a randomized controlled trial, which compares the effects of CBT vs. care as usual (CAU) during pregnancy among a group of women with (sub)clinically depressive and/or anxiety symptoms (n=226) on both maternal and child outcomes. Child outcomes comprise a range of obstetric outcomes including birth weight, Apgar score, and gestational age. Independent samples t-tests were performed to investigate differences in mean values. Results No significant differences were found between the CBT- and the CAU-groups, in gestational age (39+0 vs 39+2 weeks+days, p=.99), birth weight (3447 vs 3509 grams, p=.24), or Apgar score at 1 (8.6 vs 8.6, p=.99), 5 (9.5 vs 9.6, p=.31), and 10 minutes (9.7 vs 9.8, p=.26). Conclusion/discussion Although CBT as early treatment of antenatal depression and anxiety is most likely to be effective for prevention of postpartum depression, CBT seems to have no effect on major obstetric outcomes.

Low socioeconomic status increases effects of negative life events on antenatal anxiety and depression

PROBLEM Low socioeconomic status and prior negative life events are documented risk factors for antenatal anxiety and depression, preterm birth and birth weight. We aimed to asses whether the adverse effects of prior negative life events increase with lower socioeconomic status and which aspects of socioeconomic status are most relevant. METHODS We performed a population-based cohort study in the Netherlands including 5398 women in their first trimester of pregnancy. We assessed the number of negative life events prior to pregnancy, aspects of paternal and maternal socio-economic position and symptoms of anxiety and depression. Associations of the number of prior negative life events with anxiety, depression, low birth weight and gestational age were quantified. FINDINGS The number of prior negative life events, particularly when they had occurred in the two years before pregnancy and maternal aspects of low socioeconomic status (educational level, unemployment and income) were associated with antenatal anxiety and depression. Furthermore, low socioeconomic status increased the adverse effects of prior negative life events. Obstetric outcomes showed similar trends, although mostly not statistically significant. DISCUSSION Low socioeconomic status and prior negative life events both have an adverse effect on antenatal anxiety and depression. Furthermore, low socioeconomic status increases the adverse impact of prior negative life events on anxiety and depressive symptoms in pregnancy. CONCLUSION Interventions for anxiety and depression during pregnancy should be targeted particularly to unemployed, less-educated or low-income women who recently experienced negative life events.

Low socio-economic position increases the adverse effect of negative life events on anxiety and depression during pregnancy

Background Prevention, identification, and treatment of maternal psychopathology may be favourable for both mother and child. Both a low socio-economic position (SEP) and adverse life events are considered risk factors for symptoms of anxiety and depression during pregnancy. It is unknown whether the effect of adverse life events is modified by SEP. Objective To investigate the relationship between symptoms of anxiety and depression in pregnancy and adverse life events, and how this relationship is modified by SEP. Methods The population based Pregnancy, Anxiety and Depression (PAD) Study is a prospective study in Dutch obstetric care. We assessed symptoms of anxiety and depression in pregnant women, SEP (educational level of mother and partner, work status of mother and partner and family income), and the number of adverse life events, categorised by period in life. The association of the number of adverse life events with anxiety and depression, as well as effect modification by SEP was tested using linear regression analyses. Results We included 4272 participants. The number of life events and low SEP were independantly associated with symptoms of both anxiety and depression during pregnancy. Additionally, we found that aspects of SEP: low maternal educational level, maternal unemployment, and low family income may increase the adverse effect of adverse life events. Conclusion A low SEP increases the adverse impact of adverse life events. In an early screening for anxiety and depression, the number of adverse life events and more important the above-mentioned aspects of SEP should play a key role.