Through the Microbial Looking Glass: Premature Labor, Preeclampsia, and Gestational Diabetes: A Scoping Review.

The influence of microbial factors on adverse perinatal outcomes has become the focal point of recent investigations, with particular interest in the role of the microbiome and probiotic interventions. The purpose of this scoping review was to identify and critique the most recent evidence about these factors as they relate to pregnancies complicated by preeclampsia (PEC), preterm birth (PTB), and gestational diabetes mellitus (GDM). Four databases (PubMed, EMBASE, Web of Science, and Cochrane) were searched for articles published in English in the last 10 years with the concepts of the microbiome, probiotics, and PEC, PTB, or GDM. Forty-nine articles were eligible for full-text review. Five articles were excluded, leaving 44 articles that met all the eligibility criteria. The relationships between the microbiome and the risk for PEC, PTB, and GDM are not fully elucidated, although probiotic interventions seem beneficial in decreasing PEC and GDM risk. Probiotic interventions targeting bacterial vaginosis and elimination of infection in women at risk for PTB appear to be beneficial. More research is needed to understand the contributions of the microbiome to adverse perinatal outcomes. Probiotic interventions appear to be effective in reducing risk for select outcomes.

Complement Activation During Early Pregnancy and Clinical Predictors of Preterm Birth in African American Women.

Complement activation is essential for select physiologic processes during pregnancy; however, excess activation has been associated with an increased risk for preterm birth (PTB). African American (AA) women experience disproportionately higher rates of inflammation-associated PTB than other groups of women; thus, the purpose of this study was to explore the relationship between complement activation and perinatal outcomes among AA women. A plasma sample was collected between 8 and 14 weeks' gestation from a cohort of healthy AA women (N = 144) enrolled in a larger PTB cohort study. Medical record review was conducted to collect information on clinical factors (cervical length, health behaviors, gestational age at delivery). Multiple regression analysis was used to explore the relationships between complement marker (C3a/Bb) concentrations and the outcomes of interest after adjusting for baseline characteristics. C3a/Bb concentrations were not significant predictors of the gestational age at delivery, cervical length, or behavioral risk factors for PTB in this sample. Complement markers may not influence pregnancy outcomes among AA women in the same way as in predominantly white populations; however, more studies are needed to define complement dysregulation and the relationship with outcomes among AA women.

Maternal Microbiome and Pregnancy Outcomes That Impact Infant Health: A Review.

The maternal microbiome is recognized as a key determinant of a range of important maternal and child health outcomes, and together with perinatal factors influences the infant microbiome. This article provides a summary review of research investigating (1) the role of the maternal microbiome in pregnancy outcomes known to adversely influence neonatal and infant health, including preterm birth, cardiometabolic complications of pregnancy such as preeclampsia and gestational diabetes, and excessive gestational weight gain; (2) factors with an established link to adverse pregnancy outcomes that are known to influence the composition of the maternal microbiome; and (3) strategies for promoting a healthy maternal microbiome, recognizing that much more research is needed in this area.

Factors Associated with Vaginal Lactobacillus Predominance Among African American Women Early in Pregnancy.

Background: Vaginal Lactobacillus is considered protective of some adverse reproductive health outcomes, including preterm birth. However, factors that increase or decrease the likelihood of harboring Lactobacillus in the vaginal microbiome remain largely unknown. In this study, we sought to identify risk and protective factors associated with vaginal Lactobacillus predominance within a cohort of pregnant African American women. Materials and Methods: Vaginal microbiome samples were self-collected by African American women (N = 436) during their 8-14th week of pregnancy. Sociodemographic information and measures of health behaviors, including substance use, antibiotic exposure, sexual practices, frequency of vaginal intercourse, and the use of vaginal products, were collected through participant self-report. The V3-V4 region of the 16S rRNA gene was targeted for amplification and sequencing using Illumina HiSeq, with bacterial taxonomy assigned using the PECAN classifier. Univariate and a series of multivariate logistic regression models identified factors predictive of diverse vaginal microbiota or Lactobacillus predominance. Results: Participants who used marijuana in the past 30 days (aOR 1.80, 95% CI 1.08-2.98) were more likely to have diverse non-Lactobacillus-predominant vaginal microbiota, as were women not living with their partners (aOR 1.90, 95% CI 1.20-3.01). Cohabitating or marijuana usage were not associated with type of Lactobacillus (non-iners Lactobacillus vs. Lactobacillus iners) predominance (aOR 1.11, 95% CI 0.52-2.38 and aOR 0.56, 95% CI 0.21-1.47, respectively). Conclusions: Living with a partner is conducive to vaginal Lactobacillus predominance. As such, cohabitation may be in important covariate to consider in vaginal microbiome studies.

The Maternal Infant Microbiome: Considerations for Labor and Birth.

The human microbiome plays a role in maintaining health, but is also thought to attenuate and exacerbate risk factors for adverse maternal-child health outcomes. The development of the microbiome begins in utero; however, factors related to the labor and birth environment have been shown to influence the initial colonization process of the newborn microbiome. This "seeding" or transfer of microbes from the mother to newborn may serve as an early inoculation process with implications for the long-term health outcomes of newborns. Studies have shown that there are distinct differences in the microbiome profiles of newborns born vaginally compared with those born by cesarean. Antibiotic exposure has been shown to alter the microbial profiles of women and may influence the gut microbial profiles of their newborns. Considering that the first major microbial colonization occurs at birth, it is essential that labor and birth nurses be aware of factors that may alter the composition of the microbiome during the labor and birth process. The implications of various activities and factors unique to the labor and birth environment that may influence the microbiome of women and newborns during the labor and birth process (e.g., route of birth, antibiotic use, nursing procedures) are presented with a focus on the role of labor nurses and the potential influence of nursing activities on this process.

The Microbiome and Complement Activation: A Mechanistic Model for Preterm Birth.

Preterm birth (PTB, <37 completed weeks' gestation) is one of the leading obstetrical problems in the United States, affecting approximately one of every nine births. Even more concerning are the persistent racial disparities in PTB, with particularly high rates among African Americans. There are several recognized pathophysiologic pathways to PTB, including infection and/or exaggerated systemic or local inflammation. Intrauterine infection is a causal factor linked to PTB thought to result most commonly from inflammatory processes triggered by microbial invasion of bacteria ascending from the vaginal microbiome. Trials to treat various infections have shown limited efficacy in reducing PTB risk, suggesting that other complex mechanisms, including those associated with inflammation, may be involved in the relationship between microbes, infection, and PTB. The complement system, a key mediator of the inflammatory response, is an innate defense mechanism involved in both normal physiologic processes that occur during pregnancy implantation and processes that promote the elimination of pathogenic microbes. Recent research has demonstrated an association between this system and PTB. The purpose of this article is to present a mechanistic model of inflammation-associated PTB, which hypothesizes a relationship between the microbiome and dysregulation of the complement system. Exploring the relationships between the microbial environment and complement biomarkers may elucidate a potentially modifiable biological pathway to PTB.

Perineal Injury During Childbirth Increases Risk of Postpartum Depressive Symptoms and Inflammatory Markers.

INTRODUCTION: Perineal lacerations during childbirth affect more than 65% of women in the United States. Little attention has been given to the long-term biologic consequences associated with perineal lacerations or possible associations with postpartum mental health. In this article, we describe the results of a study that explored inflammatory cytokines in women who reported perineal lacerations during childbirth and the relationship with stress and depressive symptoms during the first 6 months postpartum. METHODS: A repeated measures design was used to explore the relationship between varying degrees of perineal lacerations, inflammatory cytokines, postpartum stress, and depressive symptoms in 153 women over 6 months. Depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS), and maternal stress was measured using the Perceived Stress Scale. Plasma was analyzed for proinflammatory (tumor necrosis factor alpha, interleukin 6 (IL-6), interleukin-1 beta, interferon gamma) and anti-inflammatory (interleukin 10) cytokines. Levels of cytokines were compared between women with or without varying degrees of injury. RESULTS: A relationship was identified between symptoms of depression and a second-degree or more severe perineal laceration starting at one month postpartum (P = .04) and continuing through 3 months postpartum (P = .03). Similarly, stress symptoms were higher at 3 months postpartum (P = .02). Markers of inflammation were significantly higher among this group, with IL-6 increased at 2 weeks postpartum (P = .02) and remaining elevated through 2 months postpartum (P = .003); there were also significant differences in pro- to anti-inflammatory cytokine ratios out to 6 months postpartum. Regression analysis indicated that second-degree or more severe lacerations accounted for 5.9% of the variance in EPDS score at one month postpartum (P = .024, F = 2.865, t = 2.127), increasing substantially when the one month stress score was included as well. DISCUSSION: This study suggests that perineal lacerations, inflammation, stress, and depressed mood are associated; however, more research is needed to elucidate the actual relationship between inflammation and mental health in women who experience such injuries.