Laboratory Analysis Techniques for the Perinatal Microbiome: Implications for Studies of Probiotic Interventions.

The microbiome is composed of many organisms and is impacted by an intricate exchange between genetics and environmental factors. The perinatal microbiome influences both the developing fetus and the pregnant person. The purpose of this article is to describe the tests that are currently available for laboratory analysis of the perinatal microbiome in relationship to probiotic interventions. This article focuses on the bacterial component of the microbiome. Although adverse outcomes associated with the perinatal microbiome have been studied, a comprehensive understanding of the physiologic perinatal microbiome is still emerging. Early efforts to influence the perinatal microbiome through probiotics are currently under investigation. Unique terminology is defined, and the microbial composition of perinatal microbiota is summarized. The outcomes of studies of antenatal probiotics are summarized. Microbiome testing and analysis are defined and compared. Implications for perinatal care and probiotics research are presented.

Vaginal and Rectal microbiome changes following administration of a multi-species antenatal probiotic: A randomized control trial.

The gut and vaginal microbiome undergo changes during pregnancy which may be protective or harmful to the birthing person. Probiotics have been found to cause protective changes to the gut and vaginal microbiomes, with the potential to improve perinatal outcomes. This randomized control trial compares the vaginal and rectal microbiomes before and after an antenatal probiotic or placebo intervention, with a diverse group of pregnant people and a special focus on racial disparities. The vaginal and rectal microbiomes reveal non-significant increased Lactobacillus in the probiotics group, with a greater increase in participants who identified as Black. Potential implications and future study are discussed.

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer.

Understanding pancreatic cancer biology is fundamental for identifying new targets and for developing more effective therapies. In particular, the contribution of the stromal microenvironment to pancreatic cancer tumorigenesis requires further exploration. Here, we report the stromal roles of the synaptic protein Netrin G1 Ligand (NGL-1) in pancreatic cancer, uncovering its pro-tumor functions in cancer-associated fibroblasts and in immune cells. We observed that the stromal expression of NGL-1 inversely correlated with patients' overall survival. Moreover, germline knockout (KO) mice for NGL-1 presented decreased tumor burden, with a microenvironment that is less supportive of tumor growth. Of note, tumors from NGL-1 KO mice produced less immunosuppressive cytokines and displayed an increased percentage of CD8 + T cells than those from control mice, while preserving the physical structure of the tumor microenvironment. These effects were shown to be mediated by NGL-1 in both immune cells and in the local stroma, in a TGF-ß-dependent manner. While myeloid cells lacking NGL-1 decreased the production of immunosuppressive cytokines, NGL-1 KO T cells showed increased proliferation rates and overall polyfunctionality compared to control T cells. CAFs lacking NGL-1 were less immunosuppressive than controls, with overall decreased production of pro-tumor cytokines and compromised ability to inhibit CD8 + T cells activation. Mechanistically, these CAFs downregulated components of the TGF-ß pathway, AP-1 and NFAT transcription factor families, resulting in a less tumor-supportive phenotype. Finally, targeting NGL-1 genetically or using a functionally antagonistic small peptide phenocopied the effects of chemotherapy, while modulating the immunosuppressive tumor microenvironment (TME), rather than eliminating it. We propose NGL-1 as a new local stroma and immunomodulatory molecule, with pro-tumor roles in pancreatic cancer. Statement of Significance: Here we uncovered the pro-tumor roles of the synaptic protein NGL-1 in the tumor microenvironment of pancreatic cancer, defining a new target that simultaneously modulates tumor cell, fibroblast, and immune cell functions. This study reports a new pathway where NGL-1 controls TGF-ß, AP-1 transcription factor members and NFAT1, modulating the immunosuppressive microenvironment in pancreatic cancer. Our findings highlight NGL-1 as a new stromal immunomodulator in pancreatic cancer.

Calcium Carbonate as a Potential Intervention to Prevent Labor Dystocia: Narrative Review of the Literature.

Anecdotally, there are attestations from clinicians of calcium carbonate being used successfully for laboring people experiencing labor dystocia. The goal of this narrative review was to provide a synopsis of pertinent literature on calcium use in obstetrics to explore the potential benefit of calcium carbonate as a simple and low-cost intervention for prevention or treatment of labor dystocia. To answer how calcium and carbonate physiologically contribute to myometrium contractility, we conducted a literature search of English-language peer-reviewed articles, with no year limitation, consisting of the keywords "calcium," "calcium carbonate," "calcium gluconate," "pregnancy," "hemorrhage," and variations of "smooth muscle contractility" and "uterine contractions." Though no overt evidence on calcium carbonate's ability to prevent labor dystocia was identified; relevant information was found regarding smooth muscle contractility, calcium's influence on uterine muscle contractility, and carbonate's potential impact on reducing amniotic fluid lactate levels to restore uterine contractility during labor. Studies reporting the potential effectiveness of calcium gluconate and sodium bicarbonate in preventing labor dystocia offer background, safety information, and rationale for a future randomized control trial to evaluate the ability of calcium carbonate to prevent labor dystocia and reduce rates of cesarean section.

A randomized controlled trial of an oral probiotic to reduce antepartum group B Streptococcus colonization and gastrointestinal symptoms.

BACKGROUND: Probiotics have been suggested as a strategy to reduce antenatal group B Streptococcus colonization. Although probiotics are known to improve gastrointestinal symptoms, this has not been studied during pregnancy. OBJECTIVE: This study aimed to evaluate the efficacy of a probiotic to reduce: (1) standard-of-care antenatal group B Streptococcus colonization and colony counts and (2) gastrointestinal symptoms of pregnancy. STUDY DESIGN: In a double-blind fashion, 109 healthy adult pregnant people were randomized to Florajen3 probiotic or placebo capsules once daily from 28 weeks' gestation until labor onset. Baseline vaginal and rectal study swabs for group B Streptococcus colony-forming units and microbiome analysis were collected at 28 and 36 weeks' gestation. Standard-of-care vaginal to rectal group B Streptococcus swabs were collected from all participants at 36 weeks' gestation and determined the need for intrapartum antibiotic prophylaxis. Data collection included solicitation of adverse events, demographic information, Antepartum Gastrointestinal Symptom Assessment score, yogurt ingestion, sexual activity, and vaginal cleaning practices. RESULTS: A total of 83 participants completed the study to 36 weeks' gestation with no adverse events. Standard-of-care group B Streptococcus colonization was 20.4% in the control group and 15.4% in probiotic group participants (-5%; P=.73). The relative risk for positive standard-of-care vaginal-rectal group B Streptococcus colonization was 1.33 (95% confidence interval, 0.5-3.40) times higher in the control group than in the probiotic group (P=.55). There were no differences in median vaginal (P=.16) or rectal (P=.20) group B streptococcus colony-forming units at baseline or at 36 weeks (vaginal P>.999; rectal P=.56). Antepartum Gastrointestinal Symptom Assessment scores were similar at baseline (P=.19), but significantly decreased in probiotic group participants at 36 weeks (P=.02). No covariates significantly altered group B Streptococcus colonization. Significantly more Florajen3 bacteria components were recovered from the vaginal-rectal samples of probiotic group participants (32%; P=.04) compared with controls. CONCLUSION: The findings of this study provided insufficient evidence for the clinical application of the Florajen3 probiotic intervention to reduce standard-of-care vaginal-rectal group B Streptococcus colonization. The prevalence of group B Streptococcus was lower than expected in the study population, and intervention adherence was poor. Probiotic bacteria colonization of the genitourinary tract occurred more in intervention group participants than in controls and significantly reduced gastrointestinal symptoms of pregnancy.

Probiotic interventions to reduce antepartum Group B streptococcus colonization: A systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyse studies of the efficacy of probiotics to reduce antenatal Group B Streptococcus (GBS) colonisation. PARTICIPANTS: Antenatal participants with known positive GBS colonisation or unknown GBS status. INTERVENTION: Probiotic interventions containing species of Lactobacillus or Streptococcus. DESIGN: Systematic review and meta-analysis. MEASUREMENTS AND FINDINGS: The systematic review included 10 studies. Five articles contained in vitro studies of probiotic interventions to determine antagonistic activity against GBS. Six clinical trials of probiotics to reduce antenatal GBS were systematically reviewed and meta-analysed. The meta-analysis revealed that the use of an antenatal probiotic decreased the probability of a positive GBS result by 44% (OR = 0.56, 95% CI = 8.7%, 194.1%, p = 0.02) (n = 709). However, only one clinical trial of 10 had a low risk of bias. KEY CONCLUSIONS: The probiotic interventions subjected to in vitro testing showed antagonistic activity against GBS through the mechanisms of acidification, immune modulation, and adhesion. The findings of the meta-analysis of the clinical trials revealed that probiotics are a moderately effective intervention to reduce antenatal GBS colonisation. More well-controlled trials with diverse participants and with better elucidation of variables influencing GBS colonisation rates are needed. IMPLICATIONS FOR PRACTICE: Probiotic interventions appear to be a safe and effective primary prevention strategy for antenatal GBS colonisation. Application of this low-risk intervention needs more study but may reduce the need for intrapartum antibiotic prophylaxis in countries or regions where antenatal GBS screening is used. Midwives can be instrumental in conducting and supporting larger well-controlled clinical trials.

Dancing During Labor: Are Women Down to Boogie?

Recent social media trends have demonstrated increased interest in dancing during the final weeks of pregnancy and labor. However, there is limited evidence about dancing during labor and its impact on labor pain and duration as well as patient satisfaction. Before conducting a prospective study, given that enrollment is often challenging, our feasibility study aimed to assess the willingness of pregnant women to participate in a future study evaluating low-impact dance during labor. We anonymously surveyed a convenience sample of English-speaking/reading pregnant women who presented for prenatal care at 1 of 3 clinics from June 2019 to July 2019. Questions related to women's interest in dancing during labor and limited demographic information were collected and analyzed. Overall, 88.6% of pregnant women who completed the survey expressed interest in participating in a future study on low-impact dance during labor, with Caucasian patients and those ≥35 years of age being less interested in future participation (P<0.05 for both). Interest in participating was not influenced by any other demographic characteristic, pregnancy history, or current activity level. Given sufficient interest among pregnant women in participating in a study aimed at evaluating the potential benefits of low-impact dance during labor, enrollment numbers may be easier to achieve than previously expected.

Dancing During Labor: Social Media Trend or Future Practice?

Over the past 30 years, medical interventions in pregnancy and childbirth have increased. Some pregnant women seek less invasive and nonpharmacological options to manage discomforts during labor. While exercise during pregnancy is recommended, less is known about exercise, specifically dancing, during labor. While anecdotal evidence is supportive, little is known about the implications of exercise and dance during the first stage of labor for pain reduction and labor progression. Some movements common in dance, such as expanding hip circles that loosen and relax muscles of the pelvic floor, may be beneficial to women during labor. Available evidence suggests that dancing during the first stage of labor may decrease duration and intensity of pain and increase patient satisfaction, but further study is warranted. Ultimately, before assessing the implications of dance during labor, a feasibility study should be conducted to determine pregnant women's willingness to participate in a prospective or randomized controlled trial.

Validity and Reliability of the Antepartum Gastrointestinal Symptom Assessment Instrument.

OBJECTIVE: To examine the psychometric properties of the nine-item Antepartum Gastrointestinal Symptom Assessment (AP-GI-SA) instrument. DESIGN: Single-group prospective design. SETTING: Urban prenatal clinic serving a diverse population. PARTICIPANTS: Convenience sample of 45 pregnant women. METHODS: Participants completed the AP-GI-SA before a scheduled prenatal care appointment. We used Bayesian structural equation modeling to evaluate the construct validity of the scale and assessed known-groups validity. We assessed reliability through maximal reliability coefficient estimate and measured internal consistency with Cronbach's alpha coefficient. RESULTS: Participants completed the instrument in 2 minutes or less. Construct validity was supported by confirmatory factor analysis (posterior predictive p value = 0.49, gamma-hat = 0.970, and root mean square error of approximation = 0.065), which indicated that the single-factor model is a plausible data-generative model for GI symptoms. The maximal reliability coefficient of 0.75 and Cronbach's alpha coefficient of 0.67 supported reliability. Average AP-GI-SA scores were the highest for women in the third trimester. Of all nine GI symptoms, heartburn in the third trimester received the highest score. CONCLUSION: Our findings provide preliminary support for the validity and reliability of the AP-GI-SA. The instrument may be used as a measure in intervention studies where GI symptoms of pregnancy are an outcome. The AP-GI-SA could also be useful in clinical settings to quickly evaluate GI symptoms.