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[This corrects the article DOI: 10.1371/journal.pone.0280424.].

Retinoids and vitamin A are essential for multiple biological functions, including vision and immune responses, as well as the development of an embryo during pregnancy. Despite its importance, alterations in retinoid homeostasis during normal human pregnancy are incompletely understood. We aimed to characterize the temporal changes in the systemic retinoid concentrations across pregnancy and postpartum period. Monthly blood samples were collected from twenty healthy pregnant women, and plasma concentrations of retinol, all- trans -retinoic acid ( at RA), 13- cis -retinoic acid (13 cis RA), and 4-oxo-retinoic acids were measured using liquid chromatography-tandem mass spectrometry. Significant decreases in 13 cis RA concentrations over the pregnancy were observed, with rebound increases in retinol and 13 cis RA levels after delivery. Of note, at RA concentrations exhibited a unique temporal pattern with levels peaking at mid-pregnancy. While the 4-oxo- at RA concentration was below the limit of quantification, 4-oxo-13 cis RA was readily detectable, and its temporal change mimicked that of 13 cis RA. The time profiles of at RA and 13 cis RA remained similar after correction by albumin levels for plasma volume expansion adjustment. Together, the comprehensive profiling of systemic retinoid concentrations over the course of pregnancy provides insights into pregnancy-mediated changes in retinoid disposition to maintain its homeostasis.

Background Adverse childhood experiences (ACE) are highly prevalent, with long-lasting effects on physical and mental health that vary among individuals across their lifespan. Notably, ACE is associated with depression and anxiety disorders, which are major public health concerns. However, the factors involved in the detrimental effects of ACE on women in the perinatal period, a time of heightened vulnerability to physical and mental health outcomes for both mothers and their offspring, require further investigation. Methods To investigate the role of perceived stress in the association between ACE and maternal depressive and anxiety symptoms across the perinatal period, we included 138 pregnant women recruited for a prospective longitudinal study that examined the effects of increased maternal prenatal stress on pregnancy during the COVID-19 pandemic. Participants self-reported adverse childhood experiences and serial measures of perceived stress, anxiety, and depressive symptoms. Linear mixed-effects (LME) models were employed to assess the association between ACE, perceived stress, anxiety, and depressive symptoms and to determine an interaction effect between ACE and perceived stress on state anxiety, trait anxiety, and depressive symptoms. Results On average, participants were 34 years of age and at 26 weeks of gestation (gestational age; GA). We found a significant interaction between ACE and perceived stress on trait anxiety (β = 0.06, SE = 0.01, p  < .001) and depressive symptoms (β = 0.07, SE = 0.01, p  < .001) in the perinatal period. Perceived stress moderated the association between ACE and trait anxiety symptoms in the third trimester (β = 0.07, SE = 0.02, p  < .001). The association between ACE and depressive symptoms was moderated by perceived stress in the first trimester (β = 0.23, SE = 0.09, p  < .05), second trimester (β = 0.09, SE = 0.03, p  < .05), and third trimester (β = 0.04, SE = 0.02, p  < .05). Conclusion These findings underscore the importance of assessing ACE as a risk factor when evaluating maternal mental health to identify individuals susceptible to depressive and anxiety disorders in the perinatal period. Moreover, multiple mental health screenings in the perinatal period reduce the risk of missed opportunities for intervention and preventative actions.

Background Mindfulness-based interventions have been shown to improve psychological outcomes including stress, anxiety, and depression in general population studies. However, effectiveness has not been sufficiently examined in racially and ethnically diverse community-based settings. We will evaluate the effectiveness and implementation of a mindfulness-based intervention on depressive symptoms among predominantly Black women at a Federally Qualified Health Center in a metropolitan city. Methods In this 2-armed, stratified, individually randomized group-treated controlled trial, 274 English-speaking participants with depressive symptoms ages 18–65 years old will be randomly assigned to (1) eight weekly, 90-min group sessions of a mindfulness-based intervention (M-Body), or (2) enhanced usual care. Exclusion criteria include suicidal ideation in 30 days prior to enrollment and regular (>4x/week) meditation practice. Study metrics will be assessed at baseline and 2, 4, and 6 months after baseline, through clinical interviews, self-report surveys, and stress biomarker data including blood pressure, heart rate, and stress related biomarkers. The primary study outcome is depressive symptom score after 6 months. Discussion If M-Body is found to be an effective intervention for adults with depressive symptoms, this accessible, scalable treatment will widely increase access to mental health treatment in underserved, racial/ethnic minority communities. Trial registration ClinicalTrials.gov NCT03620721. Registered on 8 August 2018.

In a population-based study, prenatal exposure to topiramate, valproate, or lamotrigine was linked with an increased risk of autism. After adjustment for confounders, only valproate exposure was linked with increased risk.

Objective The primary purpose of this article is to identify factors that are associated with worsening mood and anxiety trajectories across the perinatal period among pregnant individuals receiving treatment with a selective‐serotonin reupdate inhibitor. Methods This secondary analysis of primary data from the original article, Trajectories of Depressive and Anxiety Symptoms Across Pregnancy and Postpartum in Selective Serotonin Reuptake Inhibitor‐Treated Women, explores if number of lifetime episodes of depression as characterized in the Mini‐International Neuropsychiatric Interview, elevated maternal adverse childhood experiences (ACE) score, or specific obstetric or neonatal factors from the Peripartum Events Scale (PES) were associated with membership in trajectory groups with the highest symptom burden. Results No difference in ACE scores or obstetric or neonatal factors were associated with membership in the trajectory groups using Wilcoxon rank sum tests and bi‐variable logistic regression. The trajectory group with the highest anxiety symptom burden experienced more lifetime episodes of depression compared to other groups (odds ratio = 1.17, 95% confidence intervals, 1.02–1.34, p = 0.03). Conclusions Congruent with other studies, we found a high prevalence of co‐occurring mood and anxiety symptoms and that past episodes of depression remain an important historical risk factor for perinatal symptom burden. This reinforces that past experiences of depression increase not only the risk of future symptoms but also higher symptom burden during antidepressant treatment. Highlights Past episodes of depression are associated with higher symptom burden of anxiety and depression in selective‐serotonin reupdate inhibitor (SSRI)‐treated perinatal patients. There is a high correlation between anxiety and depressive symptoms in perinatal patients. No positive correlation was found between scores on the Adverse Childhood Experience and symptoms of anxiety and depression in perinatal patients treated with SSRIs.

PurposeEstrogen levels fall sharply after parturition and have long been considered an etiologic contributor to postpartum depression (PPD); however, no differences have been reported in plasma hormone concentrations in people who develop PPD. We examine the question: What is the current view of estrogen and the neurophysiologic processes it impacts in the development and treatment of PPD?MethodsA literature review of the role of estrogen on candidate hormonal and epigenetic systems in the peripartum period was performed, including landmark historical studies and recent publications on estrogen-related research. The authors reviewed these papers and participated in reaching consensus on a conceptual framework of estrogen activity within the complexity of pregnancy physiology to examine its potential role for driving novel interventions.ResultsEstrogen fluctuations must be conceptualized in the context of multiple dramatic and interacting changes inherent in pregnancy and after birth, including progesterone, corticosteroids, inflammation, circadian biology and psychosocial challenges. Individuals who develop PPD have increased sensitivity to epigenetic alteration at estrogen-responsive genes, and these changes are highly predictive of PPD. An effective estrogen-based treatment for PPD has yet to be found, but interventions focused on associated inflammation and circadian rhythms are promising.ConclusionsOur understanding of the biological basis of PPD, one of the most common morbidities of the perinatal period, is expanding beyond changes in gynecologic hormone concentrations to include their impact on other systems. This growing understanding of the many processes influencing PPD will allow for the development of novel prevention and treatment strategies.

Objective Tracking perinatal mood and anxiety disorders is championed by the American Psychiatric Association and the International Marcé Society for Perinatal Mental Health. We conducted this study to examine trajectories of monthly depressive and anxiety symptoms through pregnancy and postpartum. Methods This is a prospective longitudinal observational cohort study of pregnant women interviewed at baseline (≤18th gestational week), every four weeks through delivery and at 6 and 14 weeks postpartum at three urban academic medical centers (N = 85) and a single rural health center (N = 3) from 2016 to 2020. Pregnant women had at least one prior episode of major depressive disorder, were not in a current episode, and were treated with sertraline, fluoxetine, citalopram, or escitalopram. Of 192 women screened, 88 (46%) women enrolled, and 77 (88%) women completed the postpartum follow‐up. Symptom trajectories were generated with scores from the Edinburgh Postnatal Depression Scale, the Quick Inventory of Depressive Symptoms, the Generalized Anxiety Disorder Scale, 7‐item, and the Patient‐Reported Outcomes Measurement Information System Global Health measure. A semi‐parametric, group‐based mixture model (trajectory analysis) was applied. Results Three relatively stable depression trajectories emerged, described as Minimal, Mild, and Subthreshold, in each group across pregnancy. Two of the four anxiety trajectories were stable, including Asymptomatic and Minimal, while the third, termed Breakthrough, was ascending with increasing symptoms and the fourth trajectory, described as Mild, had descending symptoms. Conclusions Screening for anxiety with depression for pregnant women will yield a comprehensive view of psychiatric symptoms and treatment targets in perinatal women. Highlights Question: What are the trajectories of depression and anxiety symptoms across pregnancy and postpartum in women who continue to take Selective serotonin reuptake inhibitor (SSRI) antidepressants? Findings: In this prospective longitudinal observational cohort study of pregnant women with antidepressant‐treated remitted depression (N = 88), a substantive proportion of women had mild depression (32%) or anxiety (23%). Three trajectories were observed for depression, all relatively stable across time, and four were observed for anxiety, three stable and one increasing across time. Meaning: There is a relative stability of mild symptoms at study entry and across gestation in depression and anxiety symptom course, with three depression and four anxiety trajectories. There was one unique trajectory in anxiety symptom course with one group with ascending symptoms. Clinicians may use measures that are already part of perinatal visits to track and treat those women who fall into these trajectories to improve their mental health.

Determination of the relationships between drug dosage, maternal and infant (cord blood) plasma drug concentrations, and serotonin reuptake inhibitor (SRI) bioeffect on offspring neurobehavior is crucial to assessing the effects of gestational SRI exposure. Measurement of maternal and cord blood platelet serotonin (5-HT) provides an index of inhibitory bioeffect at the 5-HT transporter and complements other measures of drug exposure. Three groups of mother-infant pairs were evaluated: (1) mothers with depression untreated with SRIs (DEP, n  = 17), (2) mothers treated for depression with SRIs (DEP + SRI, n  = 17), and (3) mothers who were not depressed and untreated (ND, n  = 29). Fetal movement was assessed using a standardized ultrasound imaging and rating protocol. Maternal and cord blood platelet 5-HT levels were obtained from all participants. For the SRI + DEP group, maternal and infant plasma drug concentrations and an estimate of third-trimester maternal SRI drug exposure were obtained. As expected, substantially lower median platelet 5-HT levels were observed in the DEP + SRI group than in the non-exposed, combined ND and DEP groups. In non-exposed mothers and infants, platelet 5-HT levels were not affected by the presence of maternal depression. Lower maternal and infant platelet 5-HT levels were associated with more immature fetal movement quality. Although these data are limited by small sample size, the bioeffect index of in vivo platelet 5-HT transporter inhibition appears to provide a valuable approach for elucidating and possibly predicting the effects of gestational SRI exposure on fetal and perinatal neurobehavior.

Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3–2% of pregnancies and is defined by dehydration, ketonuria, and more than 5% body weight loss. Initial pharmacologic treatment for HG includes a combination of doxylamine and pyridoxine. Additional interventions include ondansetron or dopamine antagonists such as metoclopramide or promethazine. The options are limited for women who are not adequately treated with these medications. We suggest that mirtazapine is a useful drug in this context and its efficacy has been described in case studies. Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antidepressant, anxiolytic, antiemetic, sedative, and appetite-stimulating effects. Mirtazapine is not associated with an independent increased risk of birth defects. Further investigation of mirtazapine as a treatment for HG holds promise to expand treatment options for women suffering from HG.