Bitter taste receptors in the reproductive system: Function and therapeutic implications.

Type 2 taste receptors (TAS2Rs), traditionally known for their role in bitter taste perception, are present in diverse reproductive tissues of both sexes. This review explores our current understanding of TAS2R functions with a particular focus on reproductive health. In males, TAS2Rs are believed to play potential roles in processes such as sperm chemotaxis and male fertility. Genetic insights from mouse models and human polymorphism studies provide some evidence for their contribution to male infertility. In female reproduction, it is speculated that TAS2Rs influence the ovarian milieu, shaping the functions of granulosa and cumulus cells and their interactions with oocytes. In the uterus, TAS2Rs contribute to uterine relaxation and hold potential as therapeutic targets for preventing preterm birth. In the placenta, they are proposed to function as vigilant sentinels, responding to infection and potentially modulating mechanisms of fetal protection. In the cervix and vagina, their analogous functions to those in other extraoral tissues suggest a potential role in infection defense. In addition, TAS2Rs exhibit altered expression patterns that profoundly affect cancer cell proliferation and apoptosis in reproductive cancers. Notably, TAS2R agonists show promise in inducing apoptosis and overcoming chemoresistance in these malignancies. Despite these advances, challenges remain, including a lack of genetic and functional studies. The application of techniques such as single-cell RNA sequencing and clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated endonuclease 9 gene editing could provide deeper insights into TAS2Rs in reproduction, paving the way for novel therapeutic strategies for reproductive disorders.

Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

Antenatal depression and drug use among deaf and hard-of-hearing birthing parents: results from a U.S. National Survey.

PURPOSE: This study aimed to investigate antenatal depression and drug use among deaf and hard-of-hearing (DHH) birthing parents who use American Sign Language (ASL), spoken English, or bilingually both ASL and English. METHODS: DHH participants in the United States responded to the Survey on Pregnancy Experiences of Deaf and Hard-of-Hearing Women. Respondents self-reported their antenatal depression diagnoses and drug use (i.e., pain relievers, cannabis, or illicit drugs) during their last pregnancy. Poisson regression models were used to estimate prevalence ratios, adjusting for age, race/ethnicity, education, marital status, and parity. RESULTS: The average age of respondents (n = 587) was 35 years. Respondents were predominantly non-Hispanic white (80%), college educated (60%), and married (74%). Relative to DHH English-speakers, DHH ASL-users had lower prevalence of reporting antenatal depression diagnosis (aPR = 0.40, 95% CI: 0.23 to 0.72). DHH people who reported antenatal depression diagnosis had higher prevalence of reporting antenatal drug use (PR = 2.34, 95% CI: 1.65 to 3.33). There were no significant associations between preferred language and antenatal drug use. CONCLUSIONS: DHH ASL-users are less likely to report receiving an antenatal depression diagnosis compared to DHH English-speakers. Given well-documented patient-provider communication barriers among DHH ASL-users, it is unclear if the lower prevalence observed in this study is the result of inadequate or inaccessible screening during pregnancy. Future work should consider universal use of linguistically appropriate screening tools for DHH birthing parents in both clinical and research settings.

Screening, Assessment, and Treatment of Perinatal Mental Health in Obstetrical Settings.

Perinatal mood and anxiety disorders (PMADs) are common, yet obstetricians receive little training prior to independent practice on screening, assessing, diagnosing, and treating patients with depression and anxiety. Untreated PMADs lead to adverse pregnancy and fetal outcomes. Obstetricians are in a unique position to address PMADs. The following serves as a resource for addressing PMADs in obstetric practice.

The Pressing Need to Integrate Mental Health into Obstetric Care.

Mental health and substance use conditions are prevalent among perinatal individuals. These conditions have a negative impact on the health of perinatal individuals, their infants, and families, yet are underdiagnosed and undertreated. Populations that have been marginalized disproportionately face barriers to accessing care. Integrating mental health into obstetric care could address the perinatal mental health crisis. We review perinatal mental health conditions and substance use, outline the impact associated with these conditions, and describe the promise and potential of integrating mental health into obstetric settings to improve outcomes for patients receiving obstetric and gynecologic care.

Improving front-line clinician capacity to address depression and bipolar disorder among perinatal individuals: a longitudinal analysis of the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms.

Perinatal mood disorders (PMDs) are common, yet many patients are undertreated. The Massachusetts Child Psychiatry Access Program (MCPAP) for Moms is designed to increase clinicians' willingness to address PMDs. We examined utilization of MCPAP for Moms and associations with PMDs treatment, including the more complex bipolar disorder (BD). Analyses of MCPAP for Moms data examined utilization from 7/2014 to 6/2020 and associated treatment outcomes. Participants were clinicians (n = 1006) in obstetrics/gynecology, family medicine, and pediatrics. Encounters included (1) resource and referrals and (2) psychiatric consultations (program psychiatrist consultation with clinicians or patients). Utilization sub-groups were identified using group-based trajectory modeling. Higher utilization of MCPAP for Moms was associated with increased rates of treating PMDs (incidence rate ratio [IRR] = 1.07, 95% CI: 1.06-1.07). Examining by encounter type, psychiatric consultations resulted in more frequent rates of clinicians treating PMDs than resource and referral encounters. Utilization of direct patient consultation was associated with the greatest increase in rates of clinicians treating BD (IRR = 2.12, 95% CI: 1.82-2.41). Clinicians with highest utilization rates of psychiatric consultations longitudinally had strongest predictive associations with providing direct mental healthcare to patients with BD (IRR = 13.5, 95% CI: 4.2-43.2). Utilization of MCPAP for Moms facilitates clinicians' ability to provide mental health treatment to patients.

Labor and Delivery Clinician Perspectives on Impact of Traumatic Clinical Experiences and Need for Systemic Supports.

OBJECTIVES: Few studies have elucidated the impact of work-related trauma on labor and delivery clinician or considered whether it may be a cause of burnout. This study aims to elicit labor and delivery clinician perspectives on the impact of exposure to traumatic births on their professional quality of life. METHODS: Labor and delivery clinicians (physicians, midwives, nurse practitioners, and nurses; n = 165) were recruited to complete an online questionnaire on experiences with traumatic births. The questionnaire contained measures from the Maslach Burnout Inventory and the professional quality of life scale version 5. Some participants completed an optional free-text prompt to recommend ways to support clinicians after traumatic births (n = 115). Others opted into a semi-structured phone interview (n = 8). Qualitative data was analyzed using a modified grounded theory approach. RESULTS: Self-reported adequate institutional support for clinicians after a traumatic birth was positively correlated with compassion satisfaction (r = 0.21, p < 0.01) and negatively correlated with secondary traumatic stress (r = - 0.27, p < 0.01), and burnout (r = - 0.26, p < 0.01). Qualitative themes included lack of system-wide and leadership support, lack of access to mental health resources, and suboptimal workplace culture as contributors toward secondary traumatic stress and burnout. Participants recommended proactive leadership, consistent debriefing protocols, trauma education, and improved access to counseling. CONCLUSIONS FOR PRACTICE: Multi-level barriers prevented labor and delivery clinicians from accessing needed mental health support after exposure to traumatic births. Proactive investment in healthcare system supports for clinicians may improve clinician professional quality of life.

Clinician-reported barriers to providing perinatal care to women with intellectual and developmental disabilities.

Background: Research suggests that women with intellectual and developmental disabilities are at increased risk for adverse pregnancy outcomes. Further, they report unmet perinatal care needs. This qualitative study examined clinician perspectives on barriers to providing perinatal care to women with intellectual and developmental disabilities. Method: We conducted semi-structured interviews and one focus group with US obstetric care clinicians (n=17). We used a content analysis approach to code data and analyse them for larger themes and relationships. Results: The majority of participants were white, non-Hispanic, and female. Participants reported barriers providing care to pregnant women with intellectual and developmental disabilities across individual (e.g., communication challenges), practice (e.g., identification of disability status), and system levels (e.g., lack of clinician training). Conclusions: Clinician training and evidence-based guidelines for perinatal care of women with intellectual and developmental disabilities as well as services and supports during pregnancy are needed.

Examining Pregnant Veterans' Acceptance and Beliefs Regarding the COVID-19 Vaccine.

BACKGROUND: Pregnant persons have received mixed messages regarding whether or not to receive COVID-19 vaccines as limited data are available regarding vaccine safety for pregnant and lactating persons and breastfeeding infants. OBJECTIVE: The aims of this study were to examine pregnant Veteran's acceptance of COVID-19 vaccines, along with perceptions and beliefs regarding vaccine safety and vaccine conspiracy beliefs. DESIGN AND PARTICIPANTS: We conducted a cross-sectional survey of pregnant Veterans enrolled in VA care who were taking part in an ongoing cohort study at 15 VA medical centers between January and May 2021. MAIN MEASURES: Pregnant Veterans were asked whether they had been offered the COVID-19 vaccine during pregnancy, and whether they chose to accept or refuse it. Additional questions focused on perceptions of COVID-19 vaccine safety and endorsements of vaccine knowledge and conspiracy beliefs. Logistic regression was utilized to examine predictors of acceptance of a vaccine during pregnancy. KEY RESULTS: Overall, 72 pregnant Veterans were offered a COVID-19 vaccine during pregnancy; over two-thirds (69%) opted not to receive a vaccine. Reasons for not receiving a vaccine included potential effects on the baby (64%), side effects for oneself (30%), and immunity from a past COVID-19 infection (12%). Those who received a vaccine had significantly greater vaccine knowledge and less belief in vaccine conspiracy theories. Greater knowledge of vaccines in general (aOR: 1.78; 95% CI: 1.2-2.6) and lower beliefs in vaccine conspiracies (aOR: 0.76; 95% CI: 0.6-0.9) were the strongest predictors of acceptance of a COVID-19 vaccine during pregnancy. CONCLUSIONS: Our study provides important insights regarding pregnant Veterans' decisions to accept the COVID-19 vaccine, and reasons why they may choose not to accept the vaccine. Given the high endorsement of vaccine conspiracy beliefs, trusted healthcare providers should have ongoing, open discussions about vaccine conspiracy beliefs and provide additional information to dispel these beliefs.

Factors Associated with Risk of Perinatal Depressive Symptoms Among Puerto Rican Women with Hyperglycemia.

OBJECTIVES: Rates of perinatal depression and pregnancy hyperglycemia are higher in Hispanic women as compared to non-Hispanic white women. In turn, depressive symptoms may reduce a woman's ability to engage in lifestyle changes that could reduce their subsequent diabetes risk. METHODS: We conducted a secondary analysis using data from Estudio Parto to evaluate sociodemographic, behavioral, psychosocial, and medical factors associated with perinatal depressive symptoms. Estudio Parto was a randomized controlled trial conducted in Western Massachusetts from 2013 to 17. Eligible participants had pregnancy hyperglycemia. The Edinburgh Postnatal Depression Scale (EPDS) was administered at 24-28 weeks gestation and at 6 weeks, 6 months, and 12 months postpartum. An EPDS cutpoint of 10 or greater defined the presence of depressive symptoms. RESULTS: In this sample of Puerto Rican women with pregnancy hyperglycemia, 32% and 27% showed prenatal and postpartum depressive symptoms, respectively. Among participants, 35.5% were diagnosed with GDM, 44.3% with isolated hyperglycemia, and 20.2% with impaired glucose tolerance. In multivariable models, being unmarried (OR 3.87; 95% CI 1.51-9.94), prenatal substance use (smoking or alcohol consumption; OR 2.96; 95% CI 1.41-6.18), and maternal age (1.11 for each year; 95% CI 1.04-1.18) were associated with higher odds of prenatal depressive symptoms. None of the risk factors were associated with subsequent postpartum depression in adjusted analyses. CONCLUSIONS: Identifying factors associated with prenatal and postpartum depression in Puerto Rican women with pregnancy hyperglycemia can inform targeted lifestyle interventions in this at-risk group, increase the likely adoption of healthy lifestyle behaviors, and thereby work to address health disparities. CLINICALTRIALS: gov NCT01679210; date of registration 08/07/2012.