Associations between maternal awakening salivary cortisol levels in mid-pregnancy and adverse birth outcomes.

PURPOSE: Elevated levels of maternal cortisol have been hypothesized as the intermediate process between symptoms of depression and psychosocial stress during pregnancy and adverse birth outcomes. Therefore, we examined associations between cortisol levels in the second trimester of pregnancy and risks of three common birth outcomes in a nested case-control study. METHODS: This study was embedded in the PRIDE Study (n = 3,019), from which we selected all cases with preterm birth (n = 64), low birth weight (n = 49), and small-for-gestational age (SGA; n = 65), and 260 randomly selected controls, among the participants who provided a single awakening saliva sample in approximately gestational week 19 in 2012-2016. Multivariable linear and logistic regression was performed to assess the associations between continuous and categorized cortisol levels and the selected outcomes. RESULTS: We did not observe any associations between maternal cortisol levels and preterm birth and low birth weight. However, high cortisol levels (≥ 90th percentile) seemed to be associated with SGA (adjusted odds ratio 2.1, 95% confidence interval 0.9-4.8), in particular among girls (adjusted odds ratio 3.7, 95% confidence interval 1.1-11.9, based on eight exposed cases) in an exploratory analysis. CONCLUSION: The results of this study showed no suggestions of associations between maternal awakening cortisol levels in mid-pregnancy and adverse birth outcomes, except for an increased risk of SGA.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Questionnaires and salivary cortisol to measure stress and depression in mid-pregnancy.

The hypothalamic-pituitary-adrenal axis, with cortisol as its final metabolite, has been proposed as a potential underlying biological mechanism for associations between depression and stress symptoms during pregnancy and adverse perinatal outcomes. In this study, we explored associations between salivary cortisol as a potential biomarker for stress and depressive symptoms and several self-completed psychological measurement scales among pregnant women. In total, 652 pregnant women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study completed the Edinburgh Depression Scale (EDS), Patient Health Questionnaire-2 (PHQ-2), Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), and Tilburg Pregnancy Distress Scale (TPDS) and collected a single awakening salivary cortisol sample around gestational week 17. Odds ratios, Spearman's correlation coefficients (ρs) and Cohen's Kappa coefficients (κ) were calculated to examine the associations between the EDS, PHQ-2, PRAQ-R, TPDS, and maternal cortisol levels. The overall correlation coefficient between the score on the EDS and the salivary cortisol level was 0.01 (p = 0.89) with κ = -0.01 (95% confidence interval [CI] -0.08-0.06). We did not observe agreement between the PHQ-2 and cortisol levels either (κ = 0.06 (95% CI -0.02-0.14)). The results for the PRAQ-R and TPDS were similar with overall correlations with maternal cortisol levels of ρs = 0.01 (p = 0.81) and ρs = 0.06 (p = 0.35) and agreements of κ = 0.02 (95% CI -0.06-0.09) and κ = -0.02 (95% CI -0.11-0.07), respectively. Maternal awakening salivary cortisol levels and measures of maternal psychological distress, anxiety, depressive symptoms, and pregnancy-related anxiety, assessed by self-completed questionnaires, did not seem to be related in mid-pregnancy.

Most response-inducing strategies do not increase participation in observational studies: a systematic review and meta-analysis.

OBJECTIVES: To evaluate response-inducing strategies for observational studies using health-related questionnaires or interviews. STUDY DESIGN AND SETTING: We searched PubMed, EMBASE, CINAHL, PsycINFO, and Web of Science up to December 28, 2017. Studies evaluating the effect of a response-inducing strategy on participation rates of observational studies were included. For each strategy, we estimated pooled response ratios with 95% confidence intervals (CIs) in a Hartung-Knapp/Sidik-Jonkman random effects model with the final participation rate as outcome, stratified for type of participants and method of data collection. RESULTS: The search yielded 168 eligible studies involving 367,616 potential participants and 33 strategies. Among patients, response-inducing strategies for paper-based questionnaires included unconditional monetary incentives (response ratio 1.15; 95% CI 1.09-1.21) and shorter questionnaires (1.04; 1.02-1.06). Among nonpatients, a personalized mode of delivery (1.47; 1.24-1.74), more expensive mailing type (1.25; 1.00-1.56), unconditional monetary incentives (1.24; 1.12-1.38), prenotification (1.12; 1.03-1.22), unconditional scratch lottery tickets (1.09; 1.01-1.18), and shorter questionnaires (1.06; 1.02-1.11) increased response rates to paper-based questionnaires. For Web-based questionnaires and interviews among nonpatients, response rates were increased by conditional lottery tickets (1.17; 1.02-1.34) and conditional monetary incentives (1.39; 1.01-1.91), respectively. CONCLUSION: Although the majority of strategies evaluated were unsuccessful, some may increase response rates to observational studies, particularly among nonpatients.

Depression and anxiety during pregnancy: The influence of maternal characteristics.

BACKGROUND: Depression and anxiety during pregnancy are associated with adverse health outcomes for both mother and child. This study aims to investigate the occurrence of symptoms of depression and anxiety in early and late pregnancy, the longitudinal changes from early to late pregnancy, and factors associated with symptoms of depression and anxiety in pregnant women in the Netherlands. METHODS: We studied 2897 women participating in the PRegnancy and Infant DEvelopment (PRIDE) Study. To assess symptoms of depression and anxiety, web-based questionnaires including the Hospital Anxiety and Depression Scale (HADS) and multiple questions on maternal characteristics were completed in early and late pregnancy. Cross-sectional and longitudinal multivariable linear regression analyses were conducted. RESULTS: The depressive symptoms in our population increased, with a prevalence of probable depression from 5.4% in early pregnancy to 10.0% in late pregnancy (P < .001), whereas the anxiety symptoms decreased, with a prevalence of probable anxiety from 17.9% to 14.2% (P < .001). Characteristics associated with depressive or anxiety symptoms included low level of education, multiparity, a history of depression, severe nausea, extreme fatigue, lack of physical exercise, and negative life events. Being non-Dutch, not living with a partner, and having an unplanned pregnancy or a long time to pregnancy were associated with the depressive and/or anxiety symptoms in early pregnancy only. DISCUSSION: Symptoms of depression and anxiety are common in both early and late pregnancy. Screening for risk factors in early pregnancy is important, since prenatal depression and anxiety may be related to adverse maternal and child health outcomes.

Epidemiological evaluation of the Patient Health Questionnaire-2 in a pregnant population.

INTRODUCTION: The Patient Health Questionnaire-2 (PHQ-2) is a commonly used 2-item screening tool for depressive symptoms among pregnant women in primary care settings. However, its validity has not been assessed for large-scale epidemiological studies. Therefore, the aim of this study was to provide an epidemiological evaluation of the PHQ-2 among pregnant women. METHOD: A total of 3033 pregnant women participating in the PRegnancy and Infant DEvelopment Study completed the PHQ-2 as well as the Hospital Anxiety Depression Scale-Depression (HADS-D) or the Edinburgh Depression Scale (EDS) three times throughout pregnancy. The validity of the PHQ-2 was assessed with the HADS-D/EDS as reference standard. RESULTS: Sensitivity and specificity of the PHQ-2 were 69-84% and 79-84%, respectively. The positive predictive values (range 19-26%) were substantially lower than the negative predictive values (96-99%). CONCLUSION: Despite the relatively high number of false-positive screens, initial screening for depression by two questions only may enhance routine evaluation of depressive symptoms among pregnant women.

Single awakening salivary measurements provide reliable estimates of morning cortisol levels in pregnant women.

Mood disorders during pregnancy have been associated with adverse effects on maternal as well as fetal health. Since mood, anxiety, and stress disorders are related with elevated cortisol levels, salivary cortisol may be a useful biomarker. Although multiple samples are generally recommended, a single measurement of awakening salivary cortisol could be a simpler and more cost-effective method to determine whether women have elevated morning cortisol levels during a specific period of pregnancy. Therefore, the aim of this validation study among 177 women in the PRIDE Study was to examine whether one awakening salivary cortisol measurement will suffice to classify pregnant women as having normal or elevated cortisol levels compared to awakening salivary cortisol measurements on three consecutive working days. We calculated intraclass correlation coefficients (ICC) and Cohen's kappa statistics (κ) overall as well as in sub-analyses within strata based on maternal age, level of education, net household income, pre-pregnancy BMI, parity, complications during pregnancy, caffeine consumption, gestational week of sampling, and awakening time. The mean cortisol concentrations were 8.98ng/ml (SD 5.32) for day one, 8.62ng/ml (SD 4.55) for day two, and 8.39ng/ml (SD 4.58) for day three. The overall ICC was 0.86 (95% CI 0.82-0.89) while the κ was 0.75 (95% CI 0.64-0.86). For the ICCs calculated within sub-analyses, a maximum difference of 0.11 was observed between the strata. For the κ statistics, most strata did not differ more than 0.12, except for pre-pregnancy BMI, severe nausea, and extreme fatigue with differences up to 0.22. In conclusion, one awakening salivary cortisol measurement is as reliable for the classification of pregnant women into normal and elevated morning cortisol levels as salivary cortisol measurements on three consecutive working days.

Neurodevelopmental problems at 18 months among children exposed to paracetamol in utero: a propensity score matched cohort study.

Background: Previous studies showed that children exposed to paracetamol during fetal life might have an increased risk of neurodevelopmental problems. Since paracetamol is one of the most commonly used medications during pregnancy, even small increases in the risk of neurodevelopmental problems may have considerable implications for public health. Methods: Using data from the Norwegian Mother and Child Cohort Study, we applied propensity score (PS) matching to examine associations between prenatal paracetamol exposure and neurodevelopmental problems among children at 18 months of age. Paracetamol use was classified into short-term (< 28 days) and long-term (≥ 28 days) of exposure. Results: Of the 51 200 pregnancies included in our study, 40.5% of mothers ( n = 20 749) used paracetamol at least once during pregnancy. In the PS-matched analyses, long-term paracetamol exposure during pregnancy was associated with communication problems [odds ratio (OR): 1.38, 95% confidence interval (CI) 0.98-1.95) and delayed motor milestone attainment (OR: 1.35, 95% CI 1.07-1.70). We did not observe increased risks after short-term exposure. Sensitivity analyses for several indications showed similar effects as the PS-matched analyses, suggesting no confounding by indication. Conclusion: Long-term exposure to paracetamol in utero was associated with modestly increased risks of motor milestone delay and impaired communication skills among children at 18 months. Caution is warranted when considering long-term use of paracetamol during pregnancy; however, women with severe pain conditions should not be deprived of appropriate pharmacotherapy.

Age as an independent prognostic factor for survival of localised synovial sarcoma patients.

BACKGROUND: We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients. METHODS: Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan-Meier survival curves and multivariable Cox-proportional hazards modelling. RESULTS: A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups. CONCLUSIONS: We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment.