Stress and depression-associated shifts in gut microbiota: A pilot study of human pregnancy.

Background: Psychosocial stress and mood-related disorders, such as depression, are prevalent and vulnerability to these conditions is heightened during pregnancy. Psychosocial stress induces consequences via several mechanisms including the gut microbiota-brain axis and associated signaling pathways. Previous preclinical work indicates that prenatal stress alters maternal gut microbial composition and impairs offspring development. Importantly, although the fecal and vaginal microenvironments undergo alterations across pregnancy, we lack consensus regarding which shifts are adaptive or maladaptive in the presence of prenatal stress and depression. Clinical studies interrogating these relationships have identified unique taxa but have been limited in study design. Methods: We conducted a prospective cohort study of pregnant individuals consisting of repeated administration of psychometrics (Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D)) and collection of fecal and vaginal microbiome samples. Fecal and vaginal microbial community composition across psychometric responses were interrogated using full-length 16S rRNA sequencing followed by α and ß-diversity metrics and taxonomic abundance. Results: Early pregnancy stress was associated with increased abundance of fecal taxa not previously identified in related studies, and stress from late pregnancy through postpartum was associated with increased abundance of typical vaginal taxa and opportunistic pathogens in the fecal microenvironment. Additionally, in late pregnancy, maternal stress and depression scores were associated with each other and with elevated maternal C-C motif chemokine ligand 2 (CCL2) concentrations. At delivery, concordant with previous literature, umbilical CCL2 concentration was negatively correlated with relative abundance of maternal fecal Lactobacilli. Lastly, participants with more severe depressive symptoms experienced steeper decreases in prenatal vaginal α-diversity. Conclusion: These findings a) underscore previous preclinical and clinical research demonstrating the effects of prenatal stress on maternal microbiome composition, b) suggest distinct biological pathways for the consequences of stress versus depression and c) extend the literature by identifying several taxa which may serve critical roles in mediating this relationship. Thus, further interrogation of the role of specific maternal microbial taxa in relation to psychosocial stress and its sequelae is warranted.

Inequities in Inpatient Obstetrics Pain Management and Evaluation: Age, Race, Mental Health, and Obesity.

OBJECTIVE: To evaluate disparities of pain management among patients giving birth in inpatient Obstetrics units based on age, race, BMI, and mental health diagnoses. METHODS: A retrospective cohort study was performed and included all individuals giving birth at a tertiary-care institution in 2019. Patient-reported pain scores, and inpatient narcotic administration and dosing for pain control were collected. Models were adjusted for race, age, BMI, and diagnoses of anxiety, depression, opioid use disorder, and/or schizophrenia. RESULTS: 4788 Individuals met the inclusion criteria. A higher proportion of African American patients reported severe pain (n = 233/607, 38.4%) and received narcotics (n = 653/1141, 57.2%) compared to patients of other races. Despite controlling for several possible confounders, African American patients (OR 1.55, 95% CI 1.08-2.22), patients with increased BMI (OR 1.02, 95% CI 1.01-1.03), and patients with a mental health diagnosis (OR 2.33, 95% CI 1.32-4.12) were more likely to have worse pain at rest. Older patients were more likely to be administered narcotics (n = 447/757, 59.0%) compared to younger patients (patients aged 18-26: n = 577/1257, 52.3%; patients aged 27-35: n = 1451/2774, 52.3%; p < 0.001), despite younger patients being more likely to have severe pain (OR 1.50; 95% CI 1.20-1.86; p = 0.001). CONCLUSIONS: Patients who are Non-Hispanic African American and patients with obesity and mental health diagnoses experience inequities in postpartum pain management. Pain is complex and multifactorial and can be impacted by cultural, social, environmental factors and more. Further studies on factors that influence pain perception and management in inpatient obstetrics units are needed.

How We Do It: Student Perspectives on Changes to the Obstetrics and Gynecology Residency Application Process.

OBJECTIVE: To describe the perspectives of obstetrics and gynecology (OBGYN) residency applicants regarding new standards for the 2019 to 2020 application cycle. DESIGN: An anonymous electronic survey was sent to all OBGYN residency applicants to US programs retrospectively evaluating 5 new recommended standards for the application process. This 15-item survey assessed the importance of the proposed standards and their impact on applicants' anxiety. SETTING: The OBGYN residency application process is marked by increasing application numbers and no standardization for managing interview offers. The Association of Professors of Gynecology and Obstetrics (APGO) received a 5-year Reimagining Residency grant from the American Medical Association to improve the transition from undergraduate medical education (UME) to graduate medical education (GME) within OBGYN. The multiphase project, "Transforming the UME to GME Transition for Obstetrics and Gynecology- Right Resident, Right Program, Ready Day One (RRR)," began with Standardizing the OBGYN Application and Interview Process (SOAIP). This group recommended 5 new standards for all US OBGYN residency programs and applicants. PARTICIPANTS: Applicants for US OBGYN residency programs for the 2019 to 2020 application cycle completed the survey, with a 904/2508 (36.0%) response rate, including 762 complete responses (30.4%). RESULTS: Applicants reported that all 5 of the new standards would cause the least self-perceived anxiety (range 76.8% - 96.5%). The impact of the standards on perceived anxiety varied by student group, with International Medical Graduates (IMGs) and students with USMLE Step I scores <200 describing lesser impact compared to others. Despite these differences, all 5 standards were consistently noted to cause the least anxiety for all groups. Despite varying degrees of effects in different groups, the new OBGYN residency application standards caused the least anxiety for all subgroups of applicants. CONCLUSIONS: Implementing universal standards for the OBGYN residency application process was favorably perceived by applicants and caused the least anxiety for applicants.

Stakeholder Perspectives on Standardizing the Residency Application and Interview Processes.

OBJECTIVE: The purpose of this study was to examine stakeholder perspectives on recommended standards for the obstetrics and gynecology (OBGYN) residency application and interview processes proposed for the 2019 to 2020 application cycle. The authors aimed to assess the acceptance and perception of key stakeholders on the feasibility of implementing the standards as well as the effect of these changes on applicant anxiety. DESIGN AND SETTING: The authors electronically distributed an anonymous survey in February 2020 to OBGYN residency applicants, clerkship directors, student affairs deans, program directors, and program managers. Participants received a 15-item survey, with questions assessing the importance and adoption of the guidelines, as well as their effect on perceived applicants' anxiety. Responses were measured on a 5-item Likert scale. Multiple regression analysis was used to explore which residency factors were associated with compliance with the standards. IRB exemption was granted by the University of Michigan. PARTICIPANTS: A total of 1358 participants completed the survey for an overall response rate of 39.26%. Response rates were 36.04% for applicants (904/2508), 46.67% for CDs (105/225), 34.84% for members of GSAs (34/155), 59.43% for program directors (167/281), and 51.03% for program managers (148/290). RESULTS: The overall response rate was 39.26% (1358/3459) with 36.04% of applicants (904/2508), 46.67% of clerkship directors (105/225), 34.84% of student affairs deans (34/155), 59.43% of program directors (167/281), and 51.03% of program managers (148/290). The recommendations were perceived as important by all stakeholders. More than 90% of program directors reported compliance with some or all of the recommendations and more than 90% of all applicants, clerkship directors and student affairs deans reported that the standards reduced applicant anxiety. All stakeholders rated each guideline to be important to extremely important. CONCLUSIONS: This study demonstrates the feasibility and acceptance of universal standards for the residency application process in the field of OBGYN. The vast majority of stakeholders surveyed supported the initiative and participated in the guidelines. Applicant respondents perceived the guidelines to be important and to decrease anxiety surrounding the application and interview timelines. These findings are important for other specialties when considering similar interventions.

Effectiveness of Cessation Messages Targeting Pregnant and Nonpregnant Female Smokers in the United States: A Cross-Sectional Analysis into the Impact of Pregnancy, Self-Efficacy, and Risk Perception.

OBJECTIVES: Roughly 10% of pregnant women are current smokers. Improving smoking cessation in this population before and during pregnancy is essential to prevent adverse fetal outcomes. This study aimed to examine cessation messages targeting American women. METHODS: An obstetrics-gynecological clinic-based sample of female, current smokers of reproductive age (18-44 years old) was recruited (n = 135) from January to May 2019; half (51.2%) were currently pregnant. Participants completed a within-subjects study with a randomized set of gain- and loss-framed text-only pregnancy-related cessation messages (5 each). Each individual message was rated on a validated, 10-point scale for perceived effectiveness; responses to the seven items were averaged. Regression analyses examined differences in effectiveness ratings by message framing. RESULTS: Study participants (female smokers) rated the gain-framed messages as slightly more effective than loss-framed messages (7.9 versus 7.7, p < 0.01). After adjusting for quit intention and pregnancy, the relationship between gain- and loss-framing and effectiveness ratings was modified by both self-efficacy and risk perceptions. Women who perceived high risks of smoking during pregnancy had higher effectiveness ratings of both gain- and loss-framed cessation messages, compared to women who perceived low risks. Lower cessation self-efficacy was significantly associated with lower effectiveness ratings for gain- and loss-framed messages (1.53 and 1.92, respectively; p < 0.05). CONCLUSIONS FOR PRACTICE: Women with lower self-efficacy and low risk perception of smoking risks had the lowered effectiveness ratings for both frames of cessation messages. Enhancing self-efficacy and risk perceptions through clinical interventions may improve the effectiveness of targeted messages to promote quitting smoking before or during pregnancy.

The relationship between progestin hormonal contraception and depression: a systematic review.

OBJECTIVE: We performed a systematic review to look for an association between progestin-only contraception and depression. METHODS: We searched PubMed, Ovid and Web of Science for English-language articles including progestin-only contraception and depression from database inception to September 2016. We evaluated study quality with the procedures guiding reviews for the United States Preventive Services Task Force and the Cochrane Risk of Bias Tools. We included studies that evaluated progestin-only contraception and depression, focusing on externally validated depression measures. We excluded case studies, review articles and other psychiatric disorders. RESULTS: We identified 26 studies that met the inclusion criteria, including 5 randomized controlled trials, 11 cohort studies and 10 cross-sectional studies. We found minimal association between progestin-only methods and depression. No correlation with depression was found in five low-quality, high-risk-of-bias progestin subdermal implant studies and four out of five varying-quality and medium-risk-of-bias levonorgestrel intrauterine device studies. Three medroxyprogesterone acetate intramuscular injection trials with varying levels of quality and bias show no difference in depression. Two progestin-only contraceptive pill studies with varying levels of quality and bias indicate no increase in depression scores, while one good-quality, medium-bias study shows an association between progestin-only pills, the intrauterine device and depression. CONCLUSION: Despite perceptions in the community of increased depression following the initiation of progestin contraceptives, the preponderance of evidence does not support an association based on validated measures (mostly level II-1 evidence, moderate quality, low risk of bias).

Combined hormonal contraception and its effects on mood: a critical review.

OBJECTIVES: Adverse mood changes are sometimes cited as a reason for discontinuing combined hormonal contraception (CHC). A systematic review of recent literature was undertaken to characterise the nature of these side effects and identify characteristics that might predispose women to such effects. METHODS: A MEDLINE review of studies from the past 30 years that focused on CHC and mood was performed. Database search was supplemented with studies found through citations and references. RESULTS: The research literature on this topic is limited by a lack of prospective studies, a variety of measurements of mood, and a consolidation of many disparate types of contraceptives studied together in a single cohort. Common themes that emerge from review of these papers include (1) most women using CHC demonstrate no effect or a beneficial effect on mood, with a low incidence of adverse effects; (2) contraceptives containing less androgenic progestins may have fewer adverse effects on mood; (3) continuous and perhaps non-oral dosing of CHC has the fewest mood effects; (4) women with underlying mood disorders may be predisposed to mood effects, but this may reflect factors related to choice of contraception rather than the mood disorder itself. CONCLUSION: Inconsistent research methods and lack of uniform assessments make it difficult to make strong conclusions about which CHC users are at risk for adverse mood effects. Until more prospective data is available, clinicians should recognise that such effects are infrequent and CHC may be prescribed with confidence.

Stress and the commensal microbiota: importance in parturition and infant neurodevelopment.

The body is colonized by an enormous array of microbes that are collectively called the microbiota. During quiescent periods, microbial communities within the gut are relatively resistant to change. However, several factors that disrupt homeostasis can also significantly change gut microbial community structure. One factor that has been shown to change the composition of the gut microbiota is exposure to psychological stressors. Studies demonstrate that the commensal microbiota are involved in stressor-induced immunomodulation, but other biological effects are not yet known. This review discusses emerging evidence that the microbiota can impact the brain and behavior and indicates that stressor-induced alterations in the composition of gut microbial communities contribute to stressor-induced behavioral changes. This review will also discuss the evidence that such effects are most evident early in life, where both stress and the microbiota have been linked to birth outcomes, such as prematurity, and neurodevelopment. When considered together, a paradigm emerges in which stressor-induced alterations in commensal microbial populations significantly impact parturition and infant neurodevelopment.

The effect of mental illness and psychotropic medication on gametes and fertility: a systematic review.

BACKGROUND: Psychiatric disorders during the reproductive years and their treatment with psychotropic medications are increasingly common, and their effect on the reproductive system is an important area of research. OBJECTIVE: To review the effect of mental illness and psychotropic medication on gametes and fertility. DATA SOURCES: Searches of the PubMed database were conducted for English-language articles containing the keywords gametes, fertility, psychotropic, oocyte, sperm, mental illness, depression, and/or anxiety, in the title or abstract. The searches yielded 3,603 citations. STUDY SELECTION: Studies were evaluated for relevance. Those not pertinent to the clinical question, not written in English, and focusing on invertebrates were excluded. Full texts of 50 articles were obtained for further evaluation. Additional articles were identified from reference lists. Ultimately, a total of 37 studies were deemed suitable and reviewed. RESULTS: Clinical studies have not demonstrated a deleterious effect of psychotropic medication on oocytes in terms of retrieval and pregnancy rates. Clinical studies demonstrate inconclusive results regarding the effect on sperm, with several studies suggesting increased sperm motility and quantity with certain psychotropics. Decreased sperm quantity and motility are described in a number of studies, including in vitro and in vivo studies. Maternal psychiatric illness is associated with decreased reproductive success, including lower rates of oocyte retrieval, lower rates of ongoing pregnancy, and dysregulation of the stress system in a majority (n = 11) but not all (n = 3) studies reviewed. Male depression did not appear to affect sperm, but anxiety did have an effect (n = 1). CONCLUSIONS: Given the detrimental effect of untreated mental illness, current literature is not robust enough to influence the use of psychotropics in males or females who are considering reproduction.